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What's new for 'Trypanosomatids' in PubMed

2012-02-11T04:26:00.000-08:00

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Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 9 of 9

1.	Clin Vaccine Immunol. 2012 Feb 8. [Epub ahead of print] Killed but metabolically active Leishmania as a novel whole-cell vaccine for visceral leishmaniasis. Birnbaum R, Haskell J, Vanchinathan V, Greger S, Narayan R, Chang PL, Tran TA, Hickerson SM, Beverley SM, Wilson ME, Bruhn KW, Craft N. Source Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502 USA. Abstract There are currently no effective vaccines for visceral leishmaniasis, the second most deadly parasitic infection in the world. Here we describe a novel whole-cell vaccine approach using Leishmania infantum chagasi promastigotes treated with the psoralen compound amotosalen (S-59) and low doses of ultraviolet A radiation. This treatment generates permanent, covalent DNA crosslinks within parasites, and results in Leishmania organisms termed killed but metabolically active (KBMA). In this report, we characterize the in vitro growth characteristics of both KBMA-L. major and KBMA-L. infantum chagasi (KBMA-Lic). Concentrations of S-59 that generate optimally attenuated parasites were identified. Like live L. infantum chagasi, KBMA-Lic parasites were able to initially enter liver cells in vivo after intravenous infection. However, whereas live L. infantum chagasi infection leads to hepatosplenomegaly in mice after six months, KBMA-Lic were undetectable in the organs of mice at this time point. In vitro, KBMA-Lic retained the ability to enter macrophages and induce nitric oxide production. These characteristics of KBMA-Lic correlated with the ability to prophylactically protect mice via subcutaneous vaccination at levels similar to vaccination with live, virulent organisms. Splenocytes from mice vaccinated with either live L. infantum chagasi or KBMA-Lic displayed similar cytokine patterns in vitro. These results suggest that KBMA technology is a potentially safe and effective novel vaccine strategy against the intracellular protozoan L. infantum chagasi. This approach may represent a new method for whole-cell vaccination against other complex intracellular pathogens.
	PMID: 22323556 [PubMed - as supplied by publisher]
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2.	BMC Microbiol. 2012 Feb 9;12(1):22. [Epub ahead of print] A comparison of two distinct murine macrophage gene expression profiles in response to Leishmania amazonensis infection. Probst CM, Silva RA, Menezes JP, Almeida TF, Gomes IN, Dallabona AC, Ozaki LS, Buck GA, Pavoni DP, Krieger MA, Veras PS. Abstract ABSTRACT: BACKGROUND: The experimental murine model of leishmaniasis has been widely used to characterize the immune response against Leishmania. CBA mice develop severe lesions, while C57BL/6 present small chronic lesions under L. amazonensis infection. Employing a transcriptomic approach combined with biological network analysis, the gene expression profiles of C57BL/6 and CBA macrophages, before and after L. amazonensis infection in vitro, were compared. These strains were selected due to their different degrees of susceptibility to this parasite. RESULTS: The genes expressed by C57BL/6 and CBA macrophages, before and after infection, differ greatly, both with respect to absolute number as well as cell function. Uninfected C57BL/6 macrophages express genes involved in the deactivation pathway of macrophages at lower levels, while genes related to the activation of the host immune inflammatory response, including apoptosis and phagocytosis, have elevated expression levels. Several genes that participate in the apoptosis process were also observed to be up-regulated in C57BL/6 macrophages infected with L. amazonensis, which is very likely related to the capacity of these cells to control parasite infection. By contrast, genes involved in lipid metabolism were found to be up-regulated in CBA macrophages in response to infection, which supports the notion that L. amazonensis probably modulates parasitophorous vacuoles in order to survive and multiply in host cells. CONCLUSION: The transcriptomic profiles of C57BL/6 macrophages, before and after infection, were shown to be involved in the macrophage pathway of activation, which may aid in the control of L. amazonensis infection, in contrast to the profiles of CBA cells.
	PMID: 22321871 [PubMed - as supplied by publisher]
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3.	Trans R Soc Trop Med Hyg. 2012 Feb 7. [Epub ahead of print] Prevalence of antibodies against three species of Leishmania (L. mexicana, L. braziliensis, L. infantum) and possible associated factors in dogs from Mérida, Yucatán, Mexico. Arjona-Jiménez G, Villegas N, López-Céspedes A, Marín C, Longoni SS, Bolio-González ME, Rodríguez-Vivas RI, Sauri-Arceo CH, Sánchez-Moreno M. Source Campus de Ciencias Biológicas y Agropecuarias, Universidad Autónoma de Yucatán, México. Km 15.5 Carretera Mérida-Xmatkuil, Mérida, Yucatán, México. Abstract Leishmania spp. has been recorded in humans and in dogs, and numerous studies have demonstrated that dogs act as reservoirs for visceral leishmaniasis. The objective of this study was to determine the prevalence of three species of the Leishmania genus and possible associated factors in sera of 218 dogs from two different populations in Mérida, Yucatán (Mexico). The sera were analyzed to detect antibodies against L. mexicana, L. braziliensis, and L. infantum using the superoxide dismutase- enzyme-linked immunosorbent assay (SOD-ELISA) and Western blot as confirmation. The Fe-SOD excreted was used as the antigenic fraction for the three Leishmania species. The prevalence values found were 30.2% (L. mexicana), 8.2% (L. braziliensis), and 11.9% (L. infantum), with L. mexicana seroprevalence being greater than L. braziliensis and L. infantum (p<0.05). Five percent (11/218) of the dogs showed antibodies against L. mexicana/L. braziliensis, 5.5% (12/218) with L. mexicana/L. infantum and 1.8% (4/218) with L. mexicana/L. braziliensis/L. infantum. No relationship (p>0.05) was found between antibodies against L. mexicana and breed, age, physical condition, or cutaneous lesions in dogs. This study provides evidence of antibodies against L. mexicana, L. braziliensis and L. infantum in dog populations from Mérida, Mexico. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
	PMID: 22321575 [PubMed - as supplied by publisher]
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4.	PLoS Comput Biol. 2011 Oct;7(10):e1002178. Epub 2011 Oct 13. Large-scale conformational changes of Trypanosoma cruzi proline racemase predicted by accelerated molecular dynamics simulation. de Oliveira CA, Grant BJ, Zhou M, McCammon JA. Source Departments of Chemistry and Biochemistry, Howard Hughes Medical Institute, Center for Theoretical Biological Physics, University of California, San Diego, La Jolla, California, United States of America. cesar@mccammon.ucsd.edu Abstract Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is a life-threatening illness affecting 11-18 million people. Currently available treatments are limited, with unacceptable efficacy and safety profiles. Recent studies have revealed an essential T. cruzi proline racemase enzyme (TcPR) as an attractive candidate for improved chemotherapeutic intervention. Conformational changes associated with substrate binding to TcPR are believed to expose critical residues that elicit a host mitogenic B-cell response, a process contributing to parasite persistence and immune system evasion. Characterization of the conformational states of TcPR requires access to long-time-scale motions that are currently inaccessible by standard molecular dynamics simulations. Here we describe advanced accelerated molecular dynamics that extend the effective simulation time and capture large-scale motions of functional relevance. Conservation and fragment mapping analyses identified potential conformational epitopes located in the vicinity of newly identified transient binding pockets. The newly identified open TcPR conformations revealed by this study along with knowledge of the closed to open interconversion mechanism advances our understanding of TcPR function. The results and the strategy adopted in this work constitute an important step toward the rationalization of the molecular basis behind the mitogenic B-cell response of TcPR and provide new insights for future structure-based drug discovery. PMCID: PMC3192803 Free PMC Article
	PMID: 22022240 [PubMed - indexed for MEDLINE]
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5.	Insect Mol Biol. 2011 Dec;20(6):775-86. doi: 10.1111/j.1365-2583.2011.01107.x. Epub 2011 Sep 12. Prolixicin: a novel antimicrobial peptide isolated from Rhodnius prolixus with differential activity against bacteria and Trypanosoma cruzi. Ursic-Bedoya R, Buchhop J, Joy JB, Durvasula R, Lowenberger C. Source Simon Fraser University, Department of Biological Sciences, 8888 University Drive, Burnaby, BC, Canada. Abstract We identified and characterized the activity of prolixicin, a novel antimicrobial peptide (AMP) isolated from the hemipteran insect, Rhodnius prolixus. Sequence analysis reveals one region of prolixicin that may be related to the diptericin/attacin family of AMPs. Prolixicin is an 11-kDa peptide containing a putative 21 amino acid signal peptide, two putative phosphorylation sites and no glycosylation sites. It is produced by both adult fat body and midgut tissues in response to bacterial infection of the haemolymph or the midgut. Unlike most insect antibacterial peptides, the prolixicin gene does not seem to be regulated by NF-κB binding sites, but its promoter region contains several GATA sites. Recombinant prolixicin has strong activity against the Gram-negative bacterium Escherichia coli and differential activity against several Gram-negative and Gram-positive bacteria. No significant toxicity was demonstrated against Trypanosoma cruzi, the human parasite transmitted by R. prolixus. © 2011 The Authors. Insect Molecular Biology © 2011 The Royal Entomological Society.
	PMID: 21906194 [PubMed - indexed for MEDLINE]
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6.	Mem Inst Oswaldo Cruz. 2011 Jun;106(4):445-50. Distribution and infection of triatomines (Hemiptera: Reduviidae) by Trypanosoma cruzi in the state of Michoacán, Mexico. Martínez-Ibarra JA, Valencia-Navarro I, León-Saucedo S, Ibáñez-Cervantes G, Bustos-Saldaña R, Montañez-Valdez OD, Cervantes Díaz OI, Nogueda-Torres B. Source Centro Universitario del Sur, Universidad de Guadalajara, Jalisco, México. aibarra@cusur.udg.mx Abstract An entomological study of triatomine species was carried out to assess their prevalence in 10 localities of the state of Michoacán, Mexico. Entomological indices were calculated to estimate the risk for vector-borne transmission of Trypanosoma cruzi to the human population in this area. Four triatomine species (Triatoma barberi, Triatoma dimidiata, Meccus pallidipennis and Meccus longipennis) were collected from the study area. This is the first report of M. longipennis and T. dimidiata in Michoacán. M. pallidipennis was significantly (p < 0.05) more abundant than any of the other species collected in the study area. Infection indices were greater than 50% for each of the four collected triatomine species. Significantly more triatomines were collected from intradomiciliary areas than from peridomiciliary or sylvatic areas. Infestation, crowding and density indices were low, whereas colonisation indices were high in five localities. The current vectorial conditions in the study area require continuous entomological and serological surveillance to diminish the risk of T. cruzi transmission to human populations. Free Article
	PMID: 21739032 [PubMed - indexed for MEDLINE]
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7.	Mem Inst Oswaldo Cruz. 2011 Jun;106(4):416-23. A high corticosterone/DHEA-s ratio in young rats infected with Tryp anosoma cruzi is associated with increased susceptibility. Pérez AR, Bertoya AA, Revelli S, García F. Source Instituto de Inmunología, Facultad de Ciencias Médicas de Rosario, Universidad Nacional de Rosario, Rosario, Argentina. Abstract We have previously established that young male rats are more susceptible to the effects of Trypanosoma cruzi infection than adult rats. To explore underlying age-associated differences in disease outcome, we simultaneously assessed hormone levels and cytokine release throughout the acute infection period in young and adult rats infected with T. cruzi. Young rats were inoculated with 1 x 10(6) and adult rats with 7 x 10(6) blood trypomastigotes, according to their relative body weight. At zero, seven, 14, 21 and 28 days after infection, blood was collected for the determination of gonadal and adrenal hormones, tumor necrosis factor α (TNF-α), interleukin (IL)-10 and specific IgM and IgG subtypes. Young animals displayed significantly higher parasitaemia values and an endocrine pattern that was characterised by elevated values in corticosterone (CT) and the CT/dehydroepiandrosterone-sulfate ratio, which favours immunosuppression and susceptibility. In contrast, adult male rats were able to restrict the parasite burden, which likely resulted from increased IgG antibody synthesis and oestradiol levels. Adult rats also showed a reduced TNF-α/IL-10 ratio and less tissue damage. We conclude that young animals exhibited increased vulnerability to T. cruzi infection compared with adults and this is associated with an unsuitable immunoendocrine milieu. Free Article
	PMID: 21739028 [PubMed - indexed for MEDLINE]
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8.	Curr Pharm Des. 2011;17(20):2074-99. The uniqueness of the Trypanosoma cruzi mitochondrion: opportunities to ident ify new drug target for the treatment of Chagas disease. Lisvane Silva P, Mantilla BS, Barisón MJ, Wrenger C, Silber AM. Source Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brasil. Abstract Trypanosoma cruzi is the causative agent of Chagas' disease, which affects some 8 - 10 million people in the Americas. The only two drugs approved for the etiological treatment of the disease in humans were launched more than 40 years ago and have serious drawbacks. In the present work, we revisit the unique characteristics of T. cruzi mitochondria and mitochondrial metabolism. The possibility of taking advantage of these peculiarities to target new drugs against this parasite is also discussed.
	PMID: 21718252 [PubMed - indexed for MEDLINE]
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9.	ChemMedChem. 2011 Sep 5;6(9):1581-6. doi: 10.1002/cmdc.201100189. Epub 2011 Jun 15. Development of antitrypanosomal and antiplasmodial nonpeptidic cysteine protease inhibitors based on N-protected-guanidino-furan and -pyrrole building blocks. Langolf S, Machon U, Ehlers M, Sicking W, Schirmeister T, Büchhold C, Gelhaus C, Rosenthal PJ, Schmuck C. Source Institute of Organic Chemistry, University of Duisburg-Essen, Universitätstrasse 7, 45141 Essen, Germany.
	PMID: 21678556 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-02-10T04:18:00.000-08:00

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
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Sent on Friday, 2012 February 10
Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 4 of 4

1.	Parasit Vectors. 2012 Feb 9;5(1):31. [Epub ahead of print] Current epidemiological profile and features of visceral leishmaniasis in People's Republic of China. Wang JY, Cui G, Chen HT, Zhou XN, Gao CH, Yang YT. Abstract ABSTRACT: BACKGROUND: Visceral leishmaniasis (VL) is still an important public health problem in China. In recent years endemic regions spread, prevalence increased, and even an outbreak of the disease occurred in China due to global warming and population movement. It is essential to elucidate the current epidemic situation and epidemiological characteristics of VL for designing control policy. In the present study we describe the current epidemiological profile and characteristics of VL in China based on retrospectively reviewing of VL cases reported between 2005 and 2010 by a passive surveillance system. METHODS: The present study was a retrospective review of VL cases notified between 2005 and 2010 based on the passive surveillance data. The data were tabulated, diagrammatized and analyzed through descriptive statistics in a Microsoft Excel spreadsheet. RESULTS: A total of 2450 VL cases were notified, with a mean of 408 cases per year. 61 counties were identified as endemic area with 2224 autochthonous cases, and the other 118 counties as non-endemic areas with 226 imported cases. 97.71% of cases were concentrated in Xinjiang, Gansu and Sichuan Provinces. 9 major counties reported a mean of 10 cases per year, with a total of 1759 cases reported. Different types of VL revealed distinct epidemiological characteristics. CONCLUSIONS: The number of VL cases and endemic counties both increased in the period 2005-2010 in China. Different type or sub-type of VL revealed distinct epidemiological characteristics. Therefore, differential control measures must be taken in different endemic areas against incidence increase and endemic area spread.
	PMID: 22316234 [PubMed - as supplied by publisher]

2.	Vet Res. 2012 Feb 8;43(1):10. [Epub ahead of print] Extracellular matrix alterations in experimental Leishmania amazonensis infection in susceptible and resistant mice. Silva-Almeida M, Carvalho LO, Abreu-Silva AL, Souza CS, Hardoim DJ, Calabrese KS. Abstract ABSTRACT: Leishmania is inoculated, by the bite of an infected sandfly, into the skin of the host, where the promastigotes are phagocyted by dermal macrophages. The dermal region comprises cells and abundant extracellular matrix. Studies show that matrix metalloproteinases play an important role in host defense responses against pathogens in mammals and that their activities lead to the production of antimicrobial peptides. The aim of this study is to evaluate the changes in the distribution of fibronectin and laminin as well as in the elastic system fibres during the course of infection caused by Leishmania amazonensis in mice with distinct genetic backgrounds of susceptibility to this parasite. The results showed that BALB/c presented an enhancement of fibronectin during the course of infection when compared to their control group while the infected or non-infected C3H.He showed a decrease of this protein at end of the experiment. Laminin, on the other hand, remained unaltered in both strains. Also in both BALB/c and C3H.He mice the elastic and elaunin fibres remained unchanged while the oxytalan fibres decreased along the experiment. Ninety days after the infection C3H.He mice had recovered their capacity to produce oxytalan fibres.
	PMID: 22316002 [PubMed - as supplied by publisher]

3.	Adv Exp Med Biol. 2012;710:59-70. Ecological niche modeling as a tool for understanding distributions and interactions of vectors, hosts, and etiologic agents of Chagas disease. Costa J, Peterson AT. Source Laboratório de Biodiversidade Entomológica, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil. jcosta@ioc.fiocruz.br Abstract Chagas disease, or American Trypanosomiasis, is a tropical parasitic disease caused by the flagellate protozoan Trypanosoma cruzi, which is in turn transmitted by blood-sucking insects of the subfamily Triatominae (family Reduviidae). Because no drugs or vaccines are available to cure Chagas disease in its chronic phase, vectorial control (i.e., insecticide spraying) constitutes the principal means by which to impair Chagas disease transmission. Environmental and social factors have caused changes in the epidemiology of this disease-it was originally restricted to Latin America, but is now becoming a global heath concern in non-endemic areas as a consequence of human migrations. In Brazil, despite the fact that the most effective vector has been controlled, other triatomine species infest and colonize domiciliary habitats and can transmit the pathogen. As a consequence, Chagas disease transmission continues: the prevalence of the disease remains at ∼12 million people, with ∼200,000 new cases per year in 15 countries of Latin America, making control actions still necessary. Understanding the environmental requirements and geographic distributions of vectors is key to guiding control measures, and understanding better epidemiologic aspects of the disease. Ecologic niche modeling is a relatively new tool that permits such insights--as a consequence, here, we present an overview of insights gained using this approach in understanding of Chagas disease.
	PMID: 22127886 [PubMed - indexed for MEDLINE]
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4.	Med Microbiol Immunol. 2011 Nov;200(4):209-18. Epub 2011 Mar 24. Trypanosoma cruzi antigen immunization induces a higher B cell survival in BALB/c mi ce, a susceptible strain, compared to C57BL/6 B lymphocytes, a resistant strain to cardiac autoimmunity. Pellegrini A, Carrera-Silva EA, Arocena A, Cano RC, Aoki MP, Gea S. Source Inmunología, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, CIBICI-CONICET, Universidad Nacional de Córdoba, Ciudad Universitaria, Haya de la Torre y Medina Allende S/N, 5000 Córdoba, Argentina. apellegrini@fcq.unc.edu.ar Abstract Chagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and represents the most common infectious myocarditis worldwide. Autoimmunity is one of the mechanisms contributing to its pathogenesis. Although the cellular interactions that promote this autoimmune response are still poorly understood, several studies have demonstrated a key role for B lymphocytes since they secrete antibodies, cytokines and present antigens. Recently, we reported that immunization with cruzipain, an immunodominant T. cruzi antigen, induces a higher activation state in B cells from BALB/c mice (susceptible to cardiac autoimmunity) than B lymphocytes from C57BL/6 (a resistant strain). Here, we focused on the study of B cell survival in both mouse strains after cruzipain immunization and demonstrated an increased survival rate of B cells from BALB/c compared to C57BL/6 mice. This phenomenon was associated with a decreased expression of Fas/FasL and an increased expression of anti-apoptotic Bcl-2/Bcl-xL proteins. With the purpose to gain more knowledge about the mechanisms involved, we found that IL-4 produced by BALB/c B cells played a key role in the survival in an autocrine way whereas the addition of this bioactive cytokine rescued C57BL/6 B lymphocytes from apoptosis. Our findings suggest that in the absence of infection, both enhanced B cell activation induced by the immunization with a single parasite antigen and insufficient negative regulation can potentially contribute to autoimmunity seen in cruzipain immune BALB/c mice. © Springer-Verlag 2011
	PMID: 21431877 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-02-09T04:10:00.000-08:00

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
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Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 10 of 27

1.	J Trop Med. 2012;2012:858657. Epub 2012 Jan 18. Studies on the Feeding Habits of Lutzomyia (Lutzomyia) longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) Populations from Endemic Areas of American Visceral Leishmaniasis in Northeastern Brazil. Afonso MM, Duarte R, Miranda JC, Caranha L, Rangel EF. Source Laboratório de Transmissores de Leishmanioses, Laboratório de Referência em Vigilância Entomológica, Taxonomia e Ecologia de Vetores das Leishmanioses do Instituto Oswaldo Cruz, FIOCRUZ, Avenida Brasil, 4365, 21040-360 Manguinhos, RJ, Brazil. Abstract The aim of this study was to identify potential blood feeding sources of L. (L.) longipalpis specimens from populations in Northeastern Brazil, endemic areas of American Visceral Leishmaniasis (AVL) and its correlation with the transmission of L. (L.) i. chagasi. The ELISA technique was applied using bird, dog, goat, opossum, equine, feline, human, sheep, and rodent antisera to analyze 609 females, resulting in an overall positivity of 60%. In all municipalities, females showed higher positivity for bird followed by dog antiserum and sand fly specimens were also positive for equine, feline, human, sheep, goat, opossum, and rodent antisera. The finding for 17 combinations of two or three types of blood in some females corroborates the opportunistic habit of this sand fly species. The results demonstrating the association between L. (L.) longipalpis and opossum suggest the need for further evaluation of the real role of this synanthropic mammal in the eco-epidemiology of AVL.
	PMID: 22315621 [PubMed - in process]

2.	J Trop Med. 2012;2012:652803. Epub 2012 Jan 19. Distribution and abundance of phlebotominae, vectors of leishmaniasis, in Argentina: spatial and temporal analysis at different scales. Quintana MG, Fernández MS, Salomón OD. Source Instituto Superior de Entomología, FCN, Universidad Nacional de Tucumán-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Miguel Lillo 205, T4000 JFE San Miguel de Tucumán, Argentina. Abstract The spatial-temporal analysis of the abundance of insects, vectors of tegumentary leishmaniasis (TL) and visceral leishmaniasis (VL), was performed in Argentina using spatial-temporal increasing scales. In the microscale (microfocal), the effect of the primary vegetation-crop interface in vector abundance was observed, and also how the shelters, food sources, and other environmental characteristics contribute to habitat microheterogeneity and so to a microheterogeneous vector distribution. In the mesoscale (locality or epidemic focus), the results from different foci of TL (rural and periurban) and VL (urban) suggested a metapopulation structure determined partially by quantifiable habitat variables that could explain the increase of risk associated to an increase of vector-human contact due to climatic or anthropogenic changes. In the macroscale (regional), captures of vectors and records of human cases allowed the construction of risk maps and predictive models of vector distribution. In conclusion, in order to obtain valid results transferrable to control programs from spatial studies, special attention should be paid in order to assure the consistency between the spatial scales of the hypotheses, data, and analytical tools of each experimental or descriptive design.
	PMID: 22315620 [PubMed - in process]

3.	J Trop Med. 2012;2012:642910. Epub 2012 Jan 18. Microspatial distributional patterns of vectors of cutaneous leishmaniasis in pernambuco, northeastern Brazil. Donalisio MR, Peterson AT, Costa PL, da Silva FJ, Valença HF, Shaw JJ, Brandão Filho SP. Source Departmento de Medicina Preventiva e Social, Faculdade de Ciências Médicas, UNICAMP, Rua Tessalia Vieira de Camargo 126, 13083-887, Campinas, São Paulo, Brazil. Abstract The purpose of this study is to analyze the spatial distribution and population trends through time of Lutzomyia species in a long-term focus of cutaneous leishmaniasis transmission in an Atlantic Forest area, northeastern Brazil. Sand fly populations of different ecological niches were monitored spatiotemporally in 2009. To summarize vegetation characteristics and phenology, we calculated the Normalized Difference Vegetation Index from Landsat images. Using niche modeling approaches, we assessed suites of environmental factors to identify areas of transmission risk. Although 12 species were detected, L. whitmani was the most abundant and broadly distributed across the area, particularly in peridomiciliary locations, and associated negatively with denser vegetation areas. On the other hand, L. complexa, L. sordelli, and L. tupynambai were found almost exclusively in forested areas (P < 0.05), and associated positively with denser vegetation. Lutzomyia species' occurrences are related to specific environmental combinations (with contrast among species) in the region.
	PMID: 22315619 [PubMed - in process]

4.	Antimicrob Agents Chemother. 2012 Feb 6. [Epub ahead of print] Induction of Oxidative Stress in Trypanosoma brucei by the Antitrypanosomal Dihydroquinoline OSU-40. He S, Dayton A, Kuppusamy P, Werbovetz KA, Drew ME. Source Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio. Abstract Dihydroquinoline derivative OSU-40 (1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate) is selectively potent against T. b. rhodesiense in vitro (IC(50) = 14 nM, selectivity index = 1700), and has been proposed to cause the formation of reactive oxygen species (ROS) in African trypanosomes (Fotie, J., M. Kaiser, D. A. Delfin, J. Manley, C. S. Reid, J. M. Paris, T. Wenzler, L. Maes, K. V. Mahasenan, C. L. Li, and K. A. Werbovetz. 2010. J. Med. Chem. 53:966-982). In the present study, we sought to provide further support for the hypothesis that OSU-40 kills trypanosomes through oxidative stress. Inducible RNA interference (RNAi) was applied to down-regulate key enzymes in parasite antioxidant defense, including trypanothione synthetase (TbTryS) and a superoxide dismutase (TbSODB). Both TbTryS RNAi-induced and TbSODB RNAi-induced cells showed impaired growth and increased sensitivity towards OSU-40 by 2.4-fold and 3.4-fold respectively. Decreased expression of key parasite antioxidant enzymes was thus associated with an increased sensitivity to OSU-40, consistent with the hypothesis that OSU-40 acts through oxidative stress. Finally, the dose-dependent formation of free radicals was observed after incubation of T. brucei with OSU-40 utilizing electron spin resonance (ESR) spectroscopy. These data support the notion that the mode of antitrypanosomal action for this class of compounds is to induce oxidative stress.
	PMID: 22314522 [PubMed - as supplied by publisher]

5.	Parasite. 2012 Feb;19(1):81-4. Identification of the causative agent of cutaneous leishmaniasis in Chichaoua province, Morocco. Rhajaoui M, Sebti F, Fellah H, Alam MZ, Nasereddin A, Abbasi I, Schönian G. Source Département de parasitologie, Institut National d'Hygiène, Rabat, Morocco. rhajaouimed@yahoo.fr. Abstract Cutaneous leishmaniasis (CL) in Morocco is caused by three species, Leishmania major, L. tropica and L. infantum. CL has been known in Chichaoua province since 2000. Using DNA extracted from microscopic slides and parasite cultures, collected in the years 2006 and 2009, we identified for the first time L. tropica as the causative agent of CL in this region. Species identification was achieved by performing the ITS1-PCR-RFLP approach. By using this method it was possible to identify parasites in Giemsa stained slides containing less than five parasites per oil-immersion field even they were conserved for up to four months.
	PMID: 22314244 [PubMed - in process]

6.	Parasite. 2012 Feb;19(1):77-80. [A case of feline leishmaniasis in the south of France]. [Article in French] Pocholle E, Reyes-Gomez E, Giacomo A, Delaunay P, Hasseine L, Marty P. Source Université de Liège, boulevard de Colonster 20, 4000 Liège (Sart Tilman), Belgique. emiliepocholle@gmail.fr. Abstract We report a case of disseminated feline leishmaniasis in a FIV-seropositive 14-year-old male cat (Felis catus) living in the Alpes-Maritimes (south of France). The cat presented with erythematous ulcerated papules on the head and withers, and with an ulcerated proliferative lesion on the left pinnae. The condition was diagnosed, along with a squamous cell carcinoma of the pinnae, after histopathological examination of the cutaneous lesions. Total remission of the cutaneous lesions was obtained after oral administration of 100 mg of allopurinol once a day for four months. Necropsic samples revealed that the parasite was still present in the organism after six months of treatment. This case discusses of the cat sensibility to the leishmaniasis pathology and of his potential ability of being a reservoir host.
	PMID: 22314243 [PubMed - in process]

7.	Parasite. 2012 Feb;19(1):63-70. In silico analysis of a therapeutic target in Leishmania infantum: the guanosine-dipho spho-D-mannose pyrophosphorylase. Pomel S, Rodrigo J, Hendra F, Cavé C, Loiseau PM. Source Université Paris-Sud 11, Faculté de Pharmacie, UMR 8076 CNRS, Chimiothérapie Antiparasitaire, 5, rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France. Abstract Leishmaniases are tropical and sub-tropical diseases for which classical drugs (i.e. antimonials) exhibit toxicity and drug resistance. Such a situation requires to find new chemical series with antileishmanial activity. This work consists in analyzing the structure of a validated target in Leishmania: the GDP-mannose pyrophosphorylase (GDP-MP), an enzyme involved in glycosylation and essential for amastigote survival. By comparing both human and L. infantum GDP-MP 3D homology models, we identified (i) a common motif of amino acids that binds to the mannose moiety of the substrate and, interestingly, (ii) a motif that is specific to the catalytic site of the parasite enzyme. This motif could then be used to design compounds that specifically inhibit the leishmanial GDP-MP, without any effect on the human homolog.
	PMID: 22314241 [PubMed - in process]

8.	Parasitology. 2012 Feb 8:1-9. [Epub ahead of print] The development of Psychodiella sergenti (Apicomplexa: Eugregarinorida) in Phlebotomus sergenti (Diptera: Psychodidae). Lantova L, Volf P. Source Department of Parasitology, Faculty of Science, Charles University in Prague, Czech Republic. Abstract SUMMARYPsychodiella sergenti is a recently described specific pathogen of the sand fly Phlebotomus sergenti, the main vector of Leishmania tropica. The aim of this study was to examine the life cycle of Ps. sergenti in various developmental stages of the sand fly host. The microscopical methods used include scanning electron microscopy, transmission electron microscopy and light microscopy of native preparations and histological sections stained with periodic acid-Schiff reaction. Psychodiella sergenti oocysts were observed on the chorion of sand fly eggs. In 1st instar larvae, sporozoites were located in the ectoperitrophic space of the intestine. No intracellular stages were found. In 4th instar larvae, Ps. sergenti was mostly located in the ectoperitrophic space of the intestine of the larvae before defecation and in the intestinal lumen of the larvae after defecation. In adults, the parasite was recorded in the body cavity, where the sexual development was triggered by a bloodmeal intake. Psychodiella sergenti has several unique features. It develops sexually exclusively in sand fly females that took a bloodmeal, and its sporozoites bear a distinctive conoid (about 700 nm long), which is more than 4 times longer than conoids of the mosquito gregarines.
	PMID: 22313575 [PubMed - as supplied by publisher]

9.	J Exp Med. 2012 Feb 6. [Epub ahead of print] Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5. Buxadé M, Lunazzi G, Minguillón J, Iborra S, Berga-Bolaños R, Del Val M, Aramburu J, López-Rodríguez C. Source Immunology Unit, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), 08003 Barcelona, Spain. Abstract Toll-like receptors (TLRs) engage networks of transcriptional regulators to induce genes essential for antimicrobial immunity. We report that NFAT5, previously characterized as an osmostress responsive factor, regulates the expression of multiple TLR-induced genes in macrophages independently of osmotic stress. NFAT5 was essential for the induction of the key antimicrobial gene Nos2 (inducible nitric oxide synthase [iNOS]) in response to low and high doses of TLR agonists but is required for Tnf and Il6 mainly under mild stimulatory conditions, indicating that NFAT5 could regulate specific gene patterns depending on pathogen burden intensity. NFAT5 exhibited two modes of association with target genes, as it was constitutively bound to Tnf and other genes regardless of TLR stimulation, whereas its recruitment to Nos2 or Il6 required TLR activation. Further analysis revealed that TLR-induced recruitment of NFAT5 to Nos2 was dependent on inhibitor of κB kinase (IKK) β activity and de novo protein synthesis, and was sensitive to histone deacetylases. In vivo, NFAT5 was necessary for effective immunity against Leishmania major, a parasite whose clearance requires TLRs and iNOS expression in macrophages. These findings identify NFAT5 as a novel regulator of mammalian anti-pathogen responses.
	PMID: 22312110 [PubMed - as supplied by publisher]
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10.	Eur J Immunol. 2012 Feb 6. doi: 10.1002/eji.201141926. [Epub ahead of print] Leishmania amazonensis impairs DC function by inhibiting CD40 expression via A(2B) adenosine receptor activation. Figueiredo AB, Serafim TD, Marques-da-Silva EA, Meyer-Fernandes JR, Afonso LC. Source Laboratório de Imunoparasitologia, Departamento de Ciências Biológicas, ICEB/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil. Abstract Dendritic cells (DCs) play an essential role in the modulation of immune responses and several studies have evaluated the interactions between Leishmania parasites and DCs. While extracellular ATP exhibits pro-inflammatory properties, adenosine is an important anti-inflammatory mediator. Here we investigated the effects of Leishmania infection on DC responses and the participation of purinergic signalling in this process. BMDCs from C57BL/6J mice infected with Leishmania amazonensis, Leishmania braziliensis or Leishmania major metacyclic promastigotes showed decreased MHC class II and CD86 expression and increased ectonucleotidase expression as compared with uninfected cells. In addition, L. amazonensis-infected DCs, which had lower CD40 expression, exhibited a decreased ability to induce T-cell proliferation. The presence of MRS1754, a highly selective A(2B) adenosine receptor antagonist at the time of infection increased MHC class II, CD86 and CD40 expression in L. amazonensis-infected DCs and restored the ability of the infected DCs to induce T-cell proliferation. Similar results were obtained through the inhibition of extracellular ATP hydrolysis using suramin. In conclusion, we propose that A(2B) receptor activation may be used by L. amazonensis to inhibit DC function and evade the immune response. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
	PMID: 22311598 [PubMed - as supplied by publisher]
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What's new for 'Trypanosomatids' in PubMed

2012-02-07T04:11:00.000-08:00

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Sent on Tuesday, 2012 February 07
Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 8 of 8

1.	Eukaryot Cell. 2012 Feb 3. [Epub ahead of print] Delta-aminolevulinate-induced host-parasite porphyric disparity for selective photolysis of transgenic Leishmania in the phagolysosomes of mononuclear phagocytes: A potential novel platform for vaccine delivery. Dutta S, Chang C, Kolli BK, Sassa S, Yousef M, Showe M, Showe L, Chang KP. Source Department of Microbiology/Immunology, Chicago Medical School/RFUMS, North Chicago, IL 60064. Abstract Leishmania double transfectants (DT), expressing the 2(nd) and 3(rd) enzymes in heme biosynthetic pathway, were previously reported to show neogenesis of uroporphyrin I (URO) when induced with delta-aminolevulinate (ALA) - the product of the 1(st) enzyme in this pathway. The ensuing accumulation of URO in DT promastigotes rendered them light-excitable to produce ROS, resulting in their cytolysis. Evidence is presented here, showing that the DTs retained wildtype infectivity to their host cells; and that the intra-phagolysosomal/parasitophorous vacuolar (PV) DTs remained ALA-inducible for uroporphyrinogenesis/photolysis. Exposure of DT-infected cells to ALA was noted by fluorescence microscopy to result in host-parasite differential porphyrinogenesis: porphyrin fluorescence emerged first in the host cells and then in the intra-PV amastigotes. DT-infected and control cells differed qualitatively and quantitatively in their porphyrin species, consistent with the expected multi- and mono-porphyrinogenic specificities of the host cells and the DTs, respectively. After ALA removal, the neogenic porphyrins were rapidly lost from the host cells, but persisted as URO in the intra-PV DTs. These DTs were thus extremely light-sensitive and lysed selectively by illumination under non-stringent conditions in the relatively ROS-resistant phagolysosomes. Photolysis of the intra-PV DTs returned the distribution of MHC Class II molecules and the global gene expression profiles of host cells toward their pre-infection patterns and, when transfected with ovalbumin, released this antigen for co-presentation with MHC Class I molecules. These Leishmania mutants thus have considerable potential as a novel model of universal vaccine carrier for photodynamic immuno-therapy/-prophylaxis.
	PMID: 22307976 [PubMed - as supplied by publisher]

2.	Acta Trop. 2012 Jan 24. [Epub ahead of print] Twenty-four new human cases of cutaneous leishmaniasis due to Leishmania killicki in Metlaoui, southwestern Tunisia. Probable role of Phlebotomus sergenti in the transmission. Jaouadi K, Depaquit J, Haouas N, Chaara D, Gorcii M, Chargui N, Dedet JP, Pratlong F, Boubabous R, Babba H. Source Laboratoire de Parasitologie-Mycologie (99UR/08-05), Département de biologie clinique, Faculté de Pharmacie de Monastir-Tunisie et direction de santé et de soin de base de Gafsa, Tunisia; JE 2533 - USC ANSES "Transmission vectorielle et épidémiosurveillance de maladies parasitaires (VECPAR)", Université de Reims Champagne-Ardenne, 51 rue Cognacq-Jay, 51096 Reims, France. Abstract Metlaoui district in the South-west of Tunisia is a classical focus of cutaneous leishmaniasis (CL) due to Leishmania major. Since 2005, a single case of CL due to L. killicki has been reported. We report twenty four human cases due to this parasite, affecting men and women from 2 to 70 years old. Leishmania killicki have been typed using molecular techniques: polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) and gene sequencing. Four strains from patients have been successfully cultured on NNN medium and isoenzymatically typed as L. killicki MON-8. Our results strongly suggests that Metlaoui is a new L. killicki focus with a stable transmission cycle. Sand flies fauna in the same focus was also studied. 1400 Phlebotomine sand flies (785 males/615 females) have been caught during an entomological survey. Leishmania major DNA has been found in one P. papatasi female, the most abundant species, whereas L. killicki DNA has been found in one Phlebotomus sergenti female emphasizing the probable role of this species as vector of this zoonotic parasite. Copyright © 2012 Elsevier B.V. All rights reserved.
	PMID: 22306359 [PubMed - as supplied by publisher]

3.	Exp Parasitol. 2012 Jan 24. [Epub ahead of print] Characterization of a compensatory mutant of Leishmania major that lacks ether lipids but exhibits normal growth, and G418 and hygromycin resistance. Zufferey R, Bibis SS, Zhu T, Dhalladoo S. Source Department of Biological Sciences, St. John's University, 8000 Utopia Parkway, Jamaica, NY 11439, USA. Abstract Ether glycerolipid biosynthesis in Leishmania major initiates with the acylation of dihydroxyacetonephosphate by the glycosomal dihydroxyacetonephosphate acyltransferase LmDAT. We previously reported that a null mutant of LmDAT is severely affected in logarithmic growth, survival during stationary phase, and in virulence in mice. In addition, it lacks all ether glycerolipids, produces altered forms of the ether-lipid based virulence factors lipophosphoglycan and increased levels of GPI-anchored protein gp63. Here, we describe the characterization of a compensatory mutant of a null strain of LmDAT, Δlmdat/Δlmdat(rev). Similarly to the null mutant, the Δlmdat/Δlmdat(rev) strain formed altered forms of lipophosphoglycan and increased levels of gp63, and was avirulent in mice infection. Further, dihydroxyacetonephosphate acyltransferase activity was absent in the revertant clone, indicating that a mutation in another acyltransferase gene did not confer dihydroxyacetonephosphate specificity. In contrast, the revertant grew normally but still exhibited poor survival during stationary phase. In addition, agarose gel analysis of its genomic DNA failed to detect any amplified DNA. Surprisingly, its sensitivity to aminoglycoside based antibiotics G418 and hygromycin was lower than that of the null mutant, wild type and complemented line. Copyright © 2012 Elsevier Inc. All rights reserved.
	PMID: 22306069 [PubMed - as supplied by publisher]

4.	Emerg Infect Dis. 2012 Feb;18(2):354-5. doi: 10.3291/eid1802.110924. Leishmania infantum and Human Visceral Leishmaniasis, Argentina. Barrio A, Parodi CM, Locatelli F, Mora MC, Basombrío MA, Korenaga M, Hashiguchi Y, Bustos MF, Gentile A, Marco JD. Abstract TO THE EDITOR: In Argentina, 14 autochthonous human cases of visceral leishmaniasis (VL) were reported during 1925-1989. These cases occurred in different localities in Salta, Jujuy, Santiago del Estero, and Chaco Provinces of northwestern Argentina (Figure A1), where cutaneous leishmaniasis (CL) caused principally by Leishmania (Viannia) braziliensis is endemic.
	PMID: 22305425 [PubMed - in process]

5.	Emerg Infect Dis. 2012 Feb;18(2):287-9. doi: 10.3201/eid1802.111479. Multiorgan Dysfunction Caused by Travel-associated African Trypanosomiasis. Cottle LE, Peters JR, Hall A, Bailey JW, Noyes HA, Rimington JE, Beeching NJ, Squire SB, Beadsworth MB. Abstract We describe a case of multiorgan dysfunction secondary to Trypanosoma brucei rhodesiense infection acquired on safari in Zambia. This case was one of several recently reported to ProMED-mail in persons who had traveled to this region. Trypanosomiasis remains rare in travelers but should be considered in febrile patients who have returned from trypanosomiasis-endemic areas of Africa.
	PMID: 22305185 [PubMed - in process]

6.	Bioorg Med Chem. 2012 Jan 14. [Epub ahead of print] Investigation of trypanothione reductase inhibitory activity by 1,3,4-thiadiazolium-2-aminide derivatives and molecular docking studies. Rodrigues RF, Castro-Pinto D, Echevarria A, Dos Reis CM, Del Cistia CN, Sant'anna CM, Teixeira F, Castro H, Canto-Cavalheiro M, Leon LL, Tomás A. Source Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Tripanosomatídeos, Av. Brasil, 4365, Pavilhão 26, sala 405, Manguinhos, Rio de Janeiro, RJ 21045-900, Brazil. Abstract The biological activities of a series of mesoionic 1,3,4-thiadiazolium-2-aminide derivatives have been studied. The most active compounds (MI-HH; MI-3-OCH(3); MI-4-OCH(3) and MI-4-NO(2)) were evaluated to determine their effect on trypanothione reductase (TryR) activity in Leishmania sp. and Trypanosoma cruzi. Among the assayed compounds, only MI-4-NO(2) showed enzyme inhibition effect on extracts from different cultures of parasites, which was confirmed using the recombinant enzyme from T. cruzi (TcTryR) and Leishmania infantum (LiTryR). The enzyme kinetics determined with LiTryR demonstrated a non-competitive inhibition profile of MI-4-NO(2). A molecular docking study showed that the mesoionic compounds could effectively dock into the substrate binding site together with the substrate molecule. The mesoionic compounds were also effective ligands of the NADPH and FAD binding sites and the NADPH binding site was predicted as the best of all three binding sites. Based on the theoretical results, an explanation at the molecular level is proposed for the MI-4-NO(2) enzyme inhibition effect. Given TryR as a molecular target, it is important to continue the study of mesoionic compounds as part of a drug discovery campaign against Leishmaniasis or Chagas' disease. Copyright © 2012 Elsevier Ltd. All rights reserved.
	PMID: 22304847 [PubMed - as supplied by publisher]

7.	BMJ. 2011 Dec 16;343:d8198. doi: 10.1136/bmj.d8198. Excessive mortality in Central African Republic is out of control, warns charity. Moszynski P.
	PMID: 22180448 [PubMed - indexed for MEDLINE]
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8.	An Acad Bras Cienc. 2011 Sep;83(3):1041-4. Epub 2011 Jul 1. Chagas disease in prehistory. Ferreira LF, Jansen AM, Araújo A. Source Laboratório de Paleoparasitologia, Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil. Abstract The classical hypothesis proposes that Chagas disease has been originated in the Andean region among prehistoric people when they started domesticating animals, changing to sedentary habits, and adopting agriculture. These changes in their way of life happened nearly 6,000 years ago. However, paleoparasitological data based on molecular tools showed that Trypanosoma cruzi infection and Chagas disease were commonly found both in South and North American prehistoric populations long before that time, suggesting that Chagas disease may be as old as the human presence in the American continent. The study of the origin and dispersion of Trypanosoma cruzi infection among prehistoric human populations may help in the comprehension of the clinical and epidemiological questions on Chagas disease that still remain unanswered. Free Article
	PMID: 21739083 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-02-04T05:25:00.000-08:00

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
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Sent on Saturday, 2012 February 04
Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 10 of 12

1.	PLoS Negl Trop Dis. 2012 Jan;6(1):e1501. Epub 2012 Jan 31. Using Molecular Data for Epidemiological Inference: Assessing the Prevalence of Trypanosoma brucei rhodesiense in Tsetse in Serengeti, Tanzania. Auty HK, Picozzi K, Malele I, Torr SJ, Cleaveland S, Welburn S. Source Division of Pathway Medicine and Centre for Infectious Diseases, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, United Kingdom. Abstract BACKGROUND: Measuring the prevalence of transmissible Trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. Although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of immature non-transmissible infections. Diagnostic tests to measure the prevalence of T. b. rhodesiense in tsetse are applied and interpreted inconsistently, and discrepancies between studies suggest this value is not consistently estimated even to within an order of magnitude. METHODOLOGY/PRINCIPAL FINDINGS: Three approaches were used to estimate the prevalence of transmissible Trypanosoma brucei s.l. and T. b. rhodesiense in Glossina swynnertoni and G. pallidipes in Serengeti National Park, Tanzania: (i) dissection/microscopy; (ii) PCR on infected tsetse midguts; and (iii) inference from a mathematical model. Using dissection/microscopy the prevalence of transmissible T. brucei s.l. was 0% (95% CI 0-0.085) for G. swynnertoni and 0% (0-0.18) G. pallidipes; using PCR the prevalence of transmissible T. b. rhodesiense was 0.010% (0-0.054) and 0.0089% (0-0.059) respectively, and by model inference 0.0064% and 0.00085% respectively. CONCLUSIONS/SIGNIFICANCE: The zero prevalence result by dissection/microscopy (likely really greater than zero given the results of other approaches) is not unusual by this technique, often ascribed to poor sensitivity. The application of additional techniques confirmed the very low prevalence of T. brucei suggesting the zero prevalence result was attributable to insufficient sample size (despite examination of 6000 tsetse). Given the prohibitively high sample sizes required to obtain meaningful results by dissection/microscopy, PCR-based approaches offer the current best option for assessing trypanosome prevalence in tsetse but inconsistencies in relating PCR results to transmissibility highlight the need for a consensus approach to generate meaningful and comparable data.
	PMID: 22303496 [PubMed - in process]
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2.	PLoS Negl Trop Dis. 2012 Jan;6(1):e1484. Epub 2012 Jan 31. Comparative Study of rK39 Leis hmania Antigen for Serodiagnosis of Visceral Leishmaniasis: Systematic Review with Meta-Analysis. Maia Z, Lírio M, Mistro S, Mendes CM, Mehta SR, Badaro R. Source Department of Medicine, Federal University of Bahia Salvador, Bahia, Brazil. Abstract BACKGROUND: The rK39 recombinant protein is derived from a specific antigen produced by the Leishmania donovani complex, and has been used in the last two decades for the serodiagnosis of visceral leishmaniasis. We present here a systematic review and meta-analysis of studies evaluating serologic assays to diagnose visceral leishmaniasis to determine the accuracy of rK39 antigen in comparison to the use of other antigen preparations. METHODOLOGY/PRINCIPAL FINDINGS: A systematic review with meta-analysis of the literature was performed to compare the rK39 strip-test and ELISA formats against serological tests using promastigote antigens derived from whole or soluble parasites for Direct Aglutination Test (DAT), Indirect Immunofluorescence test (IFAT) and ELISA with a promastigote antigen preparation (p-ELISA). Gold standard diagnosis was defined by the demonstration of amastigotes on hematological specimens. A database search was performed on Medline, Lilacs, Scopus, Isi Web of Science, and Cochrane Library. Quality of data was assessed using the QUADAS questionnaire. A search of the electronic databases found 352 papers of which only 14 fulfilled the selection criteria. Three evaluated the rK39 ELISA, while 13 evaluated the rK39 immunochromatographic strip test. The summarized sensitivity for the rK39-ELISA was 92% followed by IFAT 88% and p-ELISA 87%. The summarized specificity for the three diagnostic tests was 81%, 90%, and 77%. Studies comparing the rK39 strip test with DAT found a similar sensitivity of 94%, although the DAT had a slightly higher specificity. The rK39 strip test was more sensitive and specific than the IFAT and p-ELISA. We did not detect any difference in the sensitivity and specificity between strips produced by different manufacturers. CONCLUSIONS: The rK39 protein used either in a strip test or in an ELISA, and the DAT are the best choices for implementation of rapid, easy and efficient test for serodiagnosis of VL.
	PMID: 22303488 [PubMed - in process]
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3.	Parasitol Res. 2012 Feb 3. [Epub ahead of print] Biomarkers of antimony resistance: need for expression analysis of multiple genes to distinguish resistance phenotype in clinical isolates of Leishmania donovani. Kumar D, Singh R, Bhandari V, Kulshrestha A, Negi NS, Salotra P. Source National Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India. Abstract Resistance to antimony is a major cause of failure to therapy in a large proportion of visceral leishmaniasis cases. Methods to distinguish resistant and sensitive parasite are urgently needed as the standard in vitro intracellular drug susceptibility assays are cumbersome and time consuming. Differential expression profiling studies have led to the identification of several antimony resistance-associated genes; however, their efficacy as a potential biomarker for monitoring antimony resistance remains imprecise. We analysed the expression of eight genes [antimony metabolism-associated genes-multidrug resistance protein A (MRPA), γ-glutamylcysteine synthetase (γ-GCS) and aquaporin-1 (AQP1)-and genes identified by proteome/transcriptome profiling-heat shock protein 83, mitogen-activated protein kinase 1 and histones H1, H2A and H4) in antimony-resistant (n = 10) and antimony-sensitive (n = 4) clinical isolates of Leishmania donovani by quantitative real-time PCR, in comparison with a lab-generated resistant and a standard sensitive isolate. We observed a significant differential expression of MRPA, histone H1 (p < 0.01), γ-GCS, HSP83 (p < 0.005) and histone H2A and H4 (p < 0.0001) in a group of sodium antimony gluconate-resistant isolates compared to sensitive isolates. Preferential AQP1 expression was observed in all the sensitive isolates (p < 0.0001). Overall, expression profile in field isolates for all the genes studied showed altered expression in majority of isolates, while in some, the expression was static. All the isolates showed a mosaic of expression pattern of the genes analysed indicating constellation of genes contributes towards the drug susceptibility of parasite. As none of the genes exhibit an absolute correlation with phenotype, targeted expression analysis of a set of genes should be considered as biomarker for distinguishing the antimony-resistant and antimony-sensitive parasite.
	PMID: 22302478 [PubMed - as supplied by publisher]
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4.	J Infect Dis. 2012 Feb 1. [Epub ahead of print] Therapeutic Vaccination With Recombinant Adenovirus Reduces Splenic Parasite Burden in Experimental Visceral Leishmaniasis . Maroof A, Brown N, Smith B, Hodgkinson MR, Maxwell A, Losch FO, Fritz U, Walden P, Lacey CN, Smith DF, Aebischer T, Kaye PM. Source Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, Heslington, United Kingdom. Abstract Therapeutic vaccines, when used alone or in combination therapy with antileishmanial drugs, may have an important place in the control of a variety of forms of human leishmaniasis. Here, we describe the development of an adenovirus-based vaccine (Ad5-KH) comprising a synthetic haspb gene linked to a kmp11 gene via a viral 2A sequence. In nonvaccinated Leishmania donovani-infected BALB/c mice, HASPB- and KMP11-specific CD8(+) T cell responses were undetectable, although IgG1 and IgG2a antibodies were evident. After therapeutic vaccination, antibody responses were boosted, and IFNγ(+)CD8(+) T cell responses, particularly to HASPB, became apparent. A single vaccination with Ad5-KH inhibited splenic parasite growth by ∼66%, a level of efficacy comparable to that observed in early stage testing of clinically approved antileishmanial drugs in this model. These studies indicate the usefulness of adenoviral vectors to deliver leishmanial antigens in a potent and host protective manner to animals with existing L. donovani infection.
	PMID: 22301630 [PubMed - as supplied by publisher]
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5.	Sci Transl Med. 2012 Feb 1;4(119):119re1. The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis. Wyllie S, Patterson S, Stojanovski L, Simeons FR, Norval S, Kime R, Read KD, Fairlamb AH. Source Division of Biological Chemistry and Drug Discovery, Wellcome Trust Biocentre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK. Abstract Safer and more effective oral drugs are required to treat visceral leishmaniasis, a parasitic disease that kills 50,000 to 60,000 people each year in parts of Asia, Africa, and Latin America. Here, we report that fexinidazole, a drug currently in phase 1 clinical trials for treating African trypanosomiasis, shows promise for treating visceral leishmaniasis. This 2-substituted 5-nitroimidazole drug is rapidly oxidized in vivo in mice, dogs, and humans to sulfoxide and sulfone metabolites. Both metabolites of fexinidazole were active against Leishmania donovani amastigotes grown in macrophages, whereas the parent compound was inactive. Pharmacokinetic studies with fexinidazole (200 mg/kg) showed that fexinidazole sulfone achieves blood concentrations in mice above the EC(99) (effective concentration inhibiting growth by 99%) value for at least 24 hours after a single oral dose. A once-daily regimen for 5 days at this dose resulted in a 98.4% suppression of infection in a mouse model of visceral leishmaniasis, equivalent to that seen with the drugs miltefosine and Pentostam, which are currently used clinically to treat this tropical disease. In African trypanosomes, the mode of action of nitro drugs involves reductive activation via a NADH (reduced form of nicotinamide adenine dinucleotide)-dependent bacterial-like nitroreductase. Overexpression of the leishmanial homolog of this nitroreductase in L. donovani increased sensitivity to fexinidazole by 19-fold, indicating that a similar mechanism is involved in both parasites. These findings illustrate the potential of fexinidazole as an oral drug therapy for treating visceral leishmaniasis.
	PMID: 22301556 [PubMed - in process]
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6.	Trans R Soc Trop Med Hyg. 2012 Jan 31. [Epub ahead of print] Clinical features and epidemiology of cutaneous leishmaniasis and Leishmania major/HIV co-infec tion in Cameroon: results of a large cross-sectional study. Ngouateu OB, Kollo P, Ravel C, Dereure J, Kamtchouing P, Same-Ekobo A, von Stebut E, Maurer M, Dondji B. Source Department of Animal Biology and Physiology, University of Yaoundé I, Yaoundé, Cameroon; Mokolo District Hospital, Mokolo, Cameroon; Department of Dermatology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany; Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany. Abstract Cutaneous leishmaniasis (CL) is endemic in Central Africa, including Cameroon. However, data on its prevalence and co-infection with HIV are scarce. Here we present the results of a large cross-sectional study reporting the prevalence, clinical features and species identification of CL and HIV co-infection in northern Cameroon. A total of 32 466 subjects were clinically screened for CL during a door-to-door survey, followed by parasitological diagnosis in the field laboratory. Amongst the subjects surveyed, 146 (0.4%) were diagnosed with active CL. Seven (4.8%) of these 146 CL patients tested positive for HIV-1 and/or HIV-2. The number of lesions per CL patient ranged from 1 to 20. Three of the five subjects with >10 active lesions were co-infected with HIV. In both CL and HIV co-infected subjects, three successful parasite isolates were identified as Leishmania major by PCR. This first report of L. major/HIV co-infection in Cameroon and Central Africa confirms the endemicity of CL in the region and highlights a worsened CL pathology in HIV co-infected individuals. These findings provide important data necessary for the development and implementation of successful control programmes against CL and HIV in this geographical area. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
	PMID: 22301076 [PubMed - as supplied by publisher]
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7.	Trends Parasitol. 2012 Jan 31. [Epub ahead of print] Parasite-specific aptamers as biosynthetic reagents and potential pharmaceuticals. Göringer HU. Source Genetics, Darmstadt University of Technology, Schnittspahnstrasse 10, 64287 Darmstadt, Germany. Abstract Aptamers are short, synthetic nucleic acid molecules. They are generated by a Darwinian-type in vitro evolution method known as 'systematic evolution of ligands by exponential enrichment' (SELEX). SELEX represents an experimental platform to identify rare ligands with predetermined functionality from combinatorial nucleic acid libraries. Since its discovery about 20 years ago the method has been instrumental in identifying a large number of aptamers that recognize targets of very different chemistry and molecular complexity. Although aptamers have been converted into sophisticated biomolecular tools for a diverse set of technologies, only a limited number of aptamers have been selected as binding reagents for parasites or parasite-derived molecules. Here the published examples of aptamers that target Leishmania-, Trypanosoma- and Plasmodia-specific molecules are reviewed. Copyright © 2012 Elsevier Ltd. All rights reserved.
	PMID: 22300805 [PubMed - as supplied by publisher]
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8.	Southeast Asian J Trop Med Public Health. 2011 Nov;42(6):1405-9. Cavernicolous species of phlebotomine sand flies from Kanchanaburi Province, with an updated species list for Thailand. Apiwathnasorn C, Samung Y, Prummongkol S, Phayakaphon A, Panasopolkul C. Source Department of Medical Entomology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. tmcaw@mahidol.ac.th Abstract During 2008-2009 2,401 Phlebotomine sand flies were collected in 14 limestone caves in Kanchanaburi Province, Thailand to determine the prevalence and type of cavernicolous species that have the potential to be leishmaniasis vectors. Twenty species belonging to the genera Chinius, Nemopalpus, Phlebotomus and Sergentomyia were identified. An additional man-biting species, P. major major was recorded for the first time in Thailand. Ecological observations of the habitats were made. It is expected the diversity of cavernicolous sand flies is more than currently known. An updated list of 26 phlebotomine species for Thailand is provided.
	PMID: 22299409 [PubMed - in process]
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9.	Southeast Asian J Trop Med Public Health. 2011 Nov;42(6):1395-404. Distri bution of cave-dwelling phlebotomine sand flies and their nocturnal and diurnal activity in Phitsanulok Province, Thailand. Polseela R, Vitta A, Nateeworanart S, Apiwathnasorn C. Source Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University Phitsanulok, Thailand. raxsinap@nu.ac.th Abstract An entomological survey of sand flies was conducted in Naresuan Cave in Noen Maprang District, Phitsanulok Province, during November 2009 to December 2010. A total of 10,115 cave-dwelling sand flies were collected with CDC light traps nocturnally (06:00 AM and 06:00 PM) and diurnally (06:00 PM and 06:00 AM). The ratio between male and female sand flies was 1:1.3 (4,363:5,752). The ratio between the number of sand flies caught nocturnally and diurnally was 2.6:1 (7,268:2,847). In this study, 13 species belonging to 4 genera were identified, of which 4 belonged to the genus Phlebotomus, 7 to Sergentomyia, 1 to Nemopalpus and 1 to Chinius. An abundance of species were observed: Nemopalpus vietnamensis (49.15%), P. argentipes (20.15%), C. barbazani (15.79%), P. teshi (9.53%), and S. anodontis (3.21%). Less common species (<1%) were S. barraudi (0.63%), P. stantoni (0.57%), S. dentata (0.49%), S.quatei (0.17%), P. philippinensis gouldi (0.12%), S.silvatica (0.10%), S. gemmea (0.05%), and S. iyengari (0.04%). The predominant species in the Naresuan Cave was Nemopalpus vietnamensis (49.15%). The data demonstrates variability in sand fly prevalence, species composition, and relative abundance in caves. P. argentipes was found throughout the day in the caves, which is important because it is believed to be the Leishmania spp vector. This study highlights the diurnal activity of the sand fly and the day-time risk of leishmaniasis. In conclusion, although leishmaniasis has not been reported in Phitsanulok, there should be heightened awareness of infection in these areas with vectors of the protozoa.
	PMID: 22299408 [PubMed - in process]
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10.	Biochemistry (Mosc). 2011 Jul;76(7):727-8. doi: 10.1134/S0006297911070017. Microbial Carbohydrates. Knirel YA.
	PMID: 22103014 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-02-03T04:18:00.001-08:00

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Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 9 of 9

1.	PLoS One. 2012;7(1):e31059. Epub 2012 Jan 27. Developmentally Regulated Sphingolipid Degradation in Leishmania major. Zhang O, Xu W, Balakrishna Pillai A, Zhang K. Source Department of Biological Sciences, Texas Tech University, Lubbock, Texas, United States of America. Abstract Leishmania parasites alternate between extracellular promastigotes in sandflies and intracellular amastigotes in mammals. These protozoans acquire sphingolipids (SLs) through de novo synthesis (to produce inositol phosphorylceramide) and salvage (to obtain sphingomyelin from the host). A single ISCL (Inositol phosphoSphingolipid phospholipase C-Like) enzyme is responsible for the degradation of both inositol phosphorylceramide (the IPC hydrolase or IPCase activity) and sphingomyelin (the SMase activity). Recent studies of a L. major ISCL-null mutant (iscl(-)) indicate that SL degradation is required for promastigote survival in stationary phase, especially under acidic pH. ISCL is also essential for L. major proliferation in mammals. To further understand the role of ISCL in Leishmania growth and virulence, we introduced a sole IPCase or a sole SMase into the iscl(-) mutant. Results showed that restoration of IPCase only complemented the acid resistance defect in iscl(-) promastigotes and improved their survival in macrophages, but failed to recover virulence in mice. In contrast, a sole SMase fully restored parasite infectivity in mice but was unable to reverse the promastigote defects in iscl(-). These findings suggest that SL degradation in Leishmania possesses separate roles in different stages: while the IPCase activity is important for promastigote survival and acid tolerance, the SMase activity is required for amastigote proliferation in mammals. Consistent with these findings, ISCL was preferentially expressed in stationary phase promastigotes and amastigotes. Together, our results indicate that SL degradation by Leishmania is critical for parasites to establish and sustain infection in the mammalian host.
	PMID: 22299050 [PubMed - in process]

2.	Ceylon Med J. 2011 Dec;56(4):179-80. doi: 10.4038/cmj.v56i4.3904. First successful in vitro culture of Leishmania sp. causing autochthonous visceral leishmaniasis in Sri Lanka. Ranasinghe PH, Abeygunasekera PH, Athauda SB, Chandrasekharan NV, Mendis AS, Hulangamuwa CS, Wickremasinghe DR. Source Department of Parasitology, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka. ishalindra@yahoo.com.
	PMID: 22298217 [PubMed - in process]

3.	Parasitol Res. 2012 Feb 2. [Epub ahead of print] Antileishmanial activity of cryptolepine analogues and apoptotic effects of 2,7-dibromocryptolepine against Leishmania donovani promastigotes. Hazra S, Ghosh S, Debnath S, Seville S, Prajapati VK, Wright CW, Sundar S, Hazra B. Source Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India. Abstract Cryptolepine (5-methyl-10H-indolo [3, 2-b] quinoline), an indoloquinoline alkaloid (1) isolated from a medicinal plant traditionally used in Western Africa for treatment of malaria, has been shown to possess broad spectrum biological activity in addition to its antiplasmodial effect. Here, the antileishmanial properties of 11 synthetic derivatives of cryptolepine against Leishmania donovani parasites have been evaluated for the first time. 2,7-Dibromocryptolepine (8; IC(50) 0.5 ± 0.1 μM) was found to be the most active analogue against the promastigote form of a classical L. donovani strain (AG83) in comparison to the natural alkaloid, cryptolepine (1; IC(50) 1.6 ± 0.1 μM). Further, 8 was found to substantially inhibit the intracellular amastigote forms of two clinical isolates, one of them being an SbV-resistant strain of L. donovani. Moreover, the toxicity of 8 against normal mouse peritoneal macrophage cells was markedly lower than that of 1 (IC(50) values: 9.0 ± 1.2 and 1.1 ± 0.3 μM, respectively), indicating 8 to be a prospective "lead" towards novel antileishmanial therapy. This was supported by studies on the mechanism of cytotoxicity induced by 8 in L. donovani promastigotes (AG83), which revealed the cytoplasmic and nuclear features of metazoan apoptosis. Light microscopic observation demonstrated a gradual decline in the motility, cell volume, and survival of the treated parasites with increasing incubation time. Flow cytometric analysis of phosphatidylserine externalization and distribution of cells in different phases of cell cycle confirmed the presence of a substantial percentage of cells in early apoptotic stage. Disruption of mitochondrial membrane integrity in terms of depolarization of membrane potential, and finally degradation of chromosomal DNA into oligonucleosomal fragments-the hallmark event of apoptosis-characterized the mode of cell death in L. donovani promastigotes.
	PMID: 22297912 [PubMed - as supplied by publisher]

4.	Res Vet Sci. 2012 Jan 30. [Epub ahead of print] Monitoring the reverse to normal of clinico-pathological findings and the disease free interval time using four different treatment protocols for canine leishmaniosis in an endemic area. Paradies P, Sasanelli M, Amato ME, Greco B, De Palo P, Lubas G. Source Department of Public Health and Animal Sciences, Faculty of Veterinary Medicine, University of Bari, Italy. Abstract Twenty-four dogs naturally infected by Leishmania spp. were treated with four different protocols using meglumine antimoniate (aNm) and allopurinol in combination or in monotherapy. Aiming to compare the efficacy of the different treatments the reverse to normal of clinico-pathological findings and the disease free interval time (DFIT) were evaluated. Treated dogs were monitored for 1year and, in absence of relapses, the DFIT was postponed to the last available follow-up. Seven dogs treated with aNm alone showed relapses during the year of observation. In the group of dogs treated with the combination of aNm (50mg/kg/SC 12 hourly up to clinico-pathological recovery) and allopurinol (15mg/kg/PO 12 hourly administered for 6months) no relapses were registered in the year of monitoring and the DFIT reached up to 65months. Our results showed that this combination represents the best choice to treat canine leishmaniosis compared to other protocols. Copyright © 2012 Elsevier Ltd. All rights reserved.
	PMID: 22296941 [PubMed - as supplied by publisher]

5.	Chem Biol Drug Des. 2012 Feb 1. doi: 10.1111/j.1747-0285.2012.01329.x. [Epub ahead of print] Comparative Analysis of Different DNA Binding Drugs for Leishmaniasis Cure: A Pharmacoinformatics Approach. Chauhan N, Vidyarthi AS, Poddar R. Source Department of Biotechnology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835215 (INDIA). Abstract Several experiments have been performed to test DNA binding drugs to cure Leishmania infection. However, there are no details of pharmacoinformatics study. Herein, we have selected a good number of compounds from experimentally verified studies and performed a comparative analysis based on Pharmacoinformatics techniques. In silico docking study were performed to observe the molecular level interactions of these known ligands with the DNA receptor by automated computational docking using Glide. A comparison between the calculated interaction energies and in silico ADME/T study was made. In agreement of drug likeness rules, our study suggests that, Seco-hydroxy-aza-CBI-TMI (compound 4b; GScore: -12.058) is a potential molecule for targeting the DNA to cure Leishmaniasis. © 2012 John Wiley & Sons A/S. © 2012 John Wiley & Sons A/S.
	PMID: 22296858 [PubMed - as supplied by publisher]

6.	Mol Microbiol. 2012 Feb 2. doi: 10.1111/j.1365-2958.2012.07988.x. [Epub ahead of print] Expression of the RNA Recognition Motif protein RBP10 promotes a bloodstream-form transcript pattern in Trypanosoma brucei. Wurst M, Seliger B, Jha BA, Klein C, Queiroz R, Clayton C. Source Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, D69120 Heidelberg. Abstract When Trypanosoma brucei differentiates from the bloodstream form to the procyclic form, there are decreases in the levels of many mRNAs encoding proteins required for the glycolytic pathway, and the mRNA encoding the RNA Recognition Motif protein RBP10 decreases in parallel. We show that RBP10 is a cytoplasmic protein that is specific to bloodstream-form trypanosomes, where it is essential. Depletion of RBP10 caused decreases in many bloodstream-form-specific mRNAs, with increases in mRNAs associated with the early stages of differentiation. The changes were similar to, but more extensive than, those caused by glucose deprivation. Conversely, forced RBP10 expression in procyclics induced a switch towards bloodstream-form mRNA expression patterns, with concomitant growth inhibition. Forced expression of RBP10 prevented differentiation of bloodstream forms in response to cis-aconitate, but did not prevent expression of key differentiation markers in response to glucose deprivation. RBP10 was not associated with heavy polysomes, showed no detectable in vivo binding to RNA, and was not stably associated with other proteins. Tethering of RBP10 to a reporter mRNA inhibited translation, and halved the abundance of the bound mRNA. We suggest that RBP10 may prevent the expression of regulatory proteins that are specific to the procyclic form. © 2012 Blackwell Publishing Ltd. © 2012 Blackwell Publishing Ltd.
	PMID: 22296558 [PubMed - as supplied by publisher]

7.	Cad Saude Publica. 2011 Oct;27(10):1917-29. [Seroprevalence for Trypanosoma cruzi infection and associated factors in an endemic area of Venezuela]. [Article in Spanish] Bonfante-Cabarca s R, Rodríguez-Bonfante C, Vielma BO, García D, Saldivia AM, Aldana E, Curvelo JL. Source Decanato de Ciencias de la Salud, Universidad Centroccidental Lisandro Alvarado, Venezuela. rcabarca@ucla.edu.ve Abstract This study investigated risk factors associated with positive serological status for Trypanosoma cruzi antibodies in 26 rural communities including 905 households, 2,156 humans, and 333 dogs in Lara State, Venezuela. Serology was performed with ELISA and MABA. Data were obtained from entomological, demographic, and clinical surveys. Risk factors were determined through binary logistic regression. Seroprevalence was 7.24% in humans and 6.9% in canines. Positive serological status was positively associated with the Rhodnius prolixus vector, age, maternal history of Chagas disease, tobacco chewing, presence of mammals and birds in the household, household disarray, mud-and-wattle outbuildings, and animal nests and burrows in the peridomicile, and negatively associated with tobacco and alcohol consumption, history of cancer, and storage deposits in the peridomile. In conclusion, Chagas disease in this rural area is an old phenomenon transmitted by R. prolixus or by the transplacental route, associated with socio-cultural habits related to poverty, sylvatic surroundings, and the host's medical history. Free Article
	PMID: 22031196 [PubMed - indexed for MEDLINE]
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8.	J Bioenerg Biomembr. 2011 Aug;43(4):419-24. Epub 2011 Jul 6. Role of Trypanosoma cruzi peroxiredoxins in mitoc hondrial bioenergetics. Peloso Ede F, Vitor SC, Ribeiro LH, Piñeyro MD, Robello C, Gadelha FR. Source Universidade Estadual de Campinas, Instituto de Biologia, Departamento de Bioquímica, IB, UNICAMP, Campinas, São Paulo, Brazil. Abstract Trypanosoma cruzi cytosolic (TcCPx) and mitochondrial tryparedoxin peroxidase (TcMPx) play a fundamental role in H(2)O(2) detoxification. Herein, mitochondrial bioenergetics was evaluated in cells that overexpressed TcCPx (CPx) and TcMPx (MPx) and in pTEX. In MPx, a higher expression was observed for TcCPx, and the same correlation was true for CPx. Differences in H(2)O(2) release among the overexpressing cells were detected when the mitochondrial respiratory chain was inhibited using antimycin A or thenoyltrifluoroacetone. MPx had higher O(2) consumption rates than pTEX and CPx, especially in the presence of oligomycin. In all of the cells, the mitochondrial membrane potential and the ATP levels were similar. Because of the mild uncoupling that was observed in MPx, the presence or induction of a proton transporter in the mitochondrial membrane is suggested when TcMPx is expressed at higher levels. Our results show a possible interplay between the cytosolic and mitochondrial antioxidant systems in a trypanosomatid.
	PMID: 21732175 [PubMed - indexed for MEDLINE]
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9.	J Bioenerg Biomembr. 2011 Aug;43(4):409-17. Epub 2011 Jul 6. O2 consumption rates along the growth curve: new insights into Trypanosoma cruzi mitochond rial respiratory chain. Silva TM, Peloso EF, Vitor SC, Ribeiro LH, Gadelha FR. Source Departamento de Bioquímica, Universidade Estadual de Campinas, Instituto de Biologia, Campinas, São Paulo, Brazil. Abstract Understanding the energy-transduction pathways employed by Trypanosoma cruzi, the etiological agent of Chagas disease, may lead to the identification of new targets for development of a more effective therapy. Herein, the contribution of different substrates for O(2) consumption rates along T. cruzi epimastigotes (Tulahuen 2 and Y strains) growth curve was evaluated. O(2) consumption rates were higher at the late stationary phase not due to an increase on succinate-dehydrogenase activity. Antimycin A and cyanide did not totally inhibit the mitochondrial respiratory chain (MRC). Malonate at 10 or 25 mM was not a potent inhibitor of complex II. Comparing complex II and III, the former appears to be the primary site of H(2)O(2) release. An update on T. cruzi MRC is presented that together with our results bring important data towards the understanding of the parasite's MRC. The findings mainly at the stationary phase could be relevant for epimastigotes transformation into the metacyclic form, and in this sense deserves further attention.
	PMID: 21732174 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-02-02T04:12:00.001-08:00

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Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 2 of 2

1.	Infect Genet Evol. 2012 Jan 25. [Epub ahead of print] Horizontal gene transfer confers fermentative metabolism in the respiratory-deficient plant trypanosomatid Phytomonas serpens. Ienne S, Pappas G Jr, Benabdellah K, González A, Zingales B. Source Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, São Paulo, SP CEP 05508-000, Brazil. Abstract Among trypanosomatids, the genus Phytomonas is the only one specifically adapted to infect plants. These hosts provide a particular habitat with a plentiful supply of carbohydrates. Phytomonas sp. lacks a cytochrome-mediated respiratory chain and Krebs cycle, and ATP production relies predominantly on glycolysis. We have characterised the complete gene encoding a putative pyruvate/indolepyruvate decarboxylase (PDC/IPDC) (548 amino acids) of P. serpens, that displays high amino acid sequence similarity with phytobacteria and Leishmania enzymes. No orthologous PDC/IPDC genes were found in Trypanosoma cruzi or T. brucei. Conservation of the PDC/IPDC gene sequence was verified in 14 Phytomonas isolates. A phylogenetic analysis shows that Phytomonas protein is robustly monophyletic with Leishmania spp. and C. fasciculata enzymes. In the trees this clade appears as a sister group of indolepyruvate decarboxylases of γ-proteobacteria. This supports the proposition that a horizontal gene transfer event from a donor phytobacteria to a recipient ancestral trypanosome has occurred prior to the separation between Phytomonas, Leishmania and Crithidia. We have measured the PDC activity in P. serpens cell extracts. The enzyme has a Km value for pyruvate of 1.4mM. The acquisition of a PDC, a key enzyme in alcoholic fermentation, explains earlier observations that ethanol is one of the major end-products of glucose catabolism under aerobic and anaerobic conditions. This represents an alternative and necessary route to reoxidise part of the NADH produced in the highly demanding glycolytic pathway and highlights the importance of this type of event in metabolic adaptation. Copyright © 2012. Published by Elsevier B.V.
	PMID: 22293462 [PubMed - as supplied by publisher]

2.	Vet Parasitol. 2011 Feb 10;175(3-4):237-44. Epub 2010 Oct 20. Acetylcholinesterase activity and lipid peroxidation in the brain and spinal cord of rats infected with Trypanosoma evansi. da Silva AS, Monteiro SG, Gonçalves JF, Spanevello R, Oliveira CB, Costa MM, Jaques JA, Morsch VM, Schetinger MR, Mazzanti CM, Lopes ST. Source Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Brazil. aleksandro ss@yahoo.com.br Abstract Neurological and locomotor clinical signs are described in animals infected with Trypanosoma evansi. These disturbances may be related to changes in the amount of acetylcholine (neurotransmitter) in the synaptic cleft. Therefore, changes in acetylcholinesterase (AChE) activity and lipid peroxidation in brain and spinal cord of T. evansi-infected rats were investigated. Each rat was intraperitoneally infected with 10(6) trypomastigotes kept in fresh (group A; n=13) and cryopreserved blood (group B; n=13). Thirteen served as uninfected (not-infected; group C). In days 4 and 30 post-infection (PI) the rats were anesthetized and subsequently decapitated to obtain the brain and the spinal cord (between vertebrae L1 and S2). The brain was removed and dissected (cerebellum, cerebral cortex, striatum and hippocampus) to measure the activity of AChE and lipid peroxidation, determined by TBARS levels. To verify if T. evansi was present in the central nervous system (CNS), brain structures of three rats of each group were processed by PCR T. evansi-specific. AChE activity was significantly increased in all brain structures and decrease in spinal cord in infected rats in 4 PI (P<0.05). The levels of TBARS were decreased in the brain structures, differently from spinal cord, which showed increased lipid peroxidation in 4 PI. The AChE activity in striatum, cerebral cortex, hippocampus and spinal cord reduced concomitantly with the increase of the enzyme in cerebellum of the infected rats (P<0.05), and the TBARS levels increased in cerebellum, striatum and spinal cord of infected rats compared to non-infected animals in 30 PI. The PCR was positive for T. evansi in all structures of the brain, confirming the presence of the parasite in the CNS. Based on the results, we conclude that the changes in AChE activity and lipid peroxidation in the CNS are induced by infection with T. evansi, suggesting that the parasite interferes with the cholinergic neurotransmission in this experimental condition. Copyright Â© 2010 Elsevier B.V. All rights reserved.
	PMID: 21055876 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-02-01T04:16:00.000-08:00

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PubMed Results

Items 1 - 7 of 7

1.	PLoS Negl Trop Dis. 2012 Jan;6(1):e1469. Epub 2012 Jan 24. Impact of Continuous Axenic Cultivation in Leishmania infantum Virulence. Moreira D, Santarém N, Loureiro I, Tavares J, Silva AM, Amorim AM, Ouaissi A, Cordeiro-da-Silva A, Silvestre R. Source Parasite Disease Group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal. Abstract Experimental infections with visceral Leishmania spp. are frequently performed referring to stationary parasite cultures that are comprised of a mixture of metacyclic and non-metacyclic parasites often with little regard to time of culture and metacyclic purification. This may lead to misleading or irreproducible experimental data. It is known that the maintenance of Leishmania spp. in vitro results in a progressive loss of virulence that can be reverted by passage in a mammalian host. In the present study, we aimed to characterize the loss of virulence in culture comparing the in vitro and in vivo infection and immunological profile of L. infantum stationary promastigotes submitted to successive periods of in vitro cultivation. To evaluate the effect of axenic in vitro culture in parasite virulence, we submitted L. infantum promastigotes to 4, 21 or 31 successive in vitro passages. Our results demonstrated a rapid and significant loss of parasite virulence when parasites are sustained in axenic culture. Strikingly, the parasite capacity to modulate macrophage activation decreased significantly with the augmentation of the number of in vitro passages. We validated these in vitro observations using an experimental murine model of infection. A significant correlation was found between higher parasite burdens and lower number of in vitro passages in infected Balb/c mice. Furthermore, we have demonstrated that the virulence deficit caused by successive in vitro passages results from an inadequate capacity to differentiate into amastigote forms. In conclusion, our data demonstrated that the use of parasites with distinct periods of axenic in vitro culture induce distinct infection rates and immunological responses and correlated this phenotype with a rapid loss of promastigote differentiation capacity. These results highlight the need for a standard operating protocol (SOP) when studying Leishmania species.
	PMID: 22292094 [PubMed - in process]
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2.	PLoS One. 2012;7(1):e30746. Epub 2012 Jan 26. Leishmania donovani: Immunostimulatory Cellular Responses of Membrane and Soluble Protein Fractions of Splenic Amastigotes in Cured Patient and Hamsters. Kumari S, Misra P, Tandon R, Samant M, Sundar S, Dube A. Source Parasitology Division, Central Drug Research Institute, CSIR, Lucknow, Uttar Pradesh, India. Abstract Visceral leishmaniasis (VL), caused by the intracellular parasite Leishmania donovani, L. chagasi and L. infantum is characterized by defective cell-mediated immunity (CMI) and is usually fatal if not treated properly. An estimated 350 million people worldwide are at risk of acquiring infection with Leishmania parasites with approximately 500,000 cases of VL being reported each year. In the absence of an efficient and cost-effective antileishmanial drug, development of an appropriate long-lasting vaccine against VL is the need of the day. In VL, the development of a CMI, capable of mounting Th1-type of immune responses, play an important role as it correlate with recovery from and resistance to disease. Resolution of infection results in lifelong immunity against the disease which indicates towards the feasibility of a vaccine against the disease. Most of the vaccination studies in Leishmaniasis have been focused on promastigote- an infective stage of parasite with less exploration of pathogenic amastigote form, due to the cumbersome process of its purified isolation. In the present study, we have isolated and purified splenic amastigotes of L. donovani, following the traditional protocol with slight modification. These were fractionated into five membranous and soluble subfractions each i.e MAF1-5 and SAF1-5 and were subjected for evaluation of their ability to induce cellular responses. Out of five sub-fractions from each of membrane and soluble, only four viz. MAF2, MAF3, SAF2 and SAF3 were observed to stimulate remarkable lymphoproliferative, IFN-γ, IL-12 responses and Nitric Oxide production, in Leishmania-infected cured/exposed patients and hamsters. Results suggest the presence of Th-1 type immunostimulatory molecules in these sub-fractions which may further be exploited for developing a successful subunit vaccine from the less explored pathogenic stage against VL.
	PMID: 22292030 [PubMed - in process]
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3.	J Infect Dis. 2012 Jan 30. [Epub ahead of print] Pharmacolog ical Validation of Trypanosoma brucei Phosphodiesterases as Novel Drug Targets. de Koning HP, Gould MK, Sterk GJ, Tenor H, Kunz S, Luginbuehl E, Seebeck T. Source Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom. Abstract The development of drugs for neglected infectious diseases often uses parasite-specific enzymes as targets. We here demonstrate that parasite enzymes with highly conserved human homologs may represent a promising reservoir of new potential drug targets. The cyclic nucleotide-specific phosphodiesterases (PDEs) of Trypanosoma brucei, causative agent of the fatal human sleeping sickness, are essential for the parasite. The highly conserved human homologs are well-established drug targets. We here describe what is to our knowledge the first pharmacological validation of trypanosomal PDEs as drug targets. High-throughput screening of a proprietary compound library identified a number of potent hits. One compound, the tetrahydrophthalazinone compound A (Cpd A), was further characterized. It causes a dramatic increase of intracellular cyclic adenosine monophosphate (cAMP). Short-term cell viability is not affected, but cell proliferation is inhibited immediately, and cell death occurs within 3 days. Cpd A prevents cytokinesis, resulting in multinucleated, multiflagellated cells that eventually lyse. These observations pharmacologically validate the highly conserved trypanosomal PDEs as potential drug targets.
	PMID: 22291195 [PubMed - as supplied by publisher]
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4.	Genomics Proteomics Bioinformatics. 2011 Dec;9(6):218-28. Comparative multivariate analysis of codon and amino Acid usage in three leishmania genomes. Chauhan N, Vidyarthi AS, Poddar R. Source Department of Biotechnology, Birla Institute of Technology, Mesra, Ranchi-835215, India. Abstract Multivariate analysis of codon and amino acid usage was performed for three Leishmania species, including L. donovani, L. infantum and L. major. It was revealed that all three species are under mutational bias and translational selection. Lower GC(12) and higher GC(3S) in all three parasites suggests that the ancestral highly expressed genes (HEGs), compared to lowly expressed genes (LEGs), might have been rich in AT-content. This also suggests that there must have been a faster rate of evolution under GC-bias in LEGs. It was observed from the estimation of synonymous/non-synonymous substitutions in HEGs that the HEG dataset of L. donovani is much closer to L. major evolutionarily. This is also supported by the higher d(N) value as compared to d(S) between L. donovani and L. major, suggesting the conservation of synonymous codon positions between these two species and the role of translational selection in shaping the composition of protein-coding genes. Copyright © 2011 Beijing Genomics Institute. Published by Elsevier Ltd. All rights reserved.
	PMID: 22289478 [PubMed - in process]
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5.	Clin Exp Immunol. 2012 Mar;167(3):505-13. doi: 10.1111/j.1365-2249.2011.04536.x. Multifunctional CD4(+) T cells in patients with American cutaneous leishmaniasis. Macedo AB, Sánchez-Arcila JC, Schubach AO, Mendonça SC, Marins-Dos-Santos A, de Fatima Madeira M, Gagini T, Pimentel MI, De Luca PM. Source Laboratório de Imunoparasitologia Plataforma de Citometria de Fluxo, Instituto Oswaldo Cruz Laboratório de Vigilância em Leishmanioses, Instituto de Pesquisa Clínica Evandro Chagas (IPEC), Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. Abstract Leishmaniasis is a group of important parasitic diseases affecting millions worldwide. To understand more clearly the quality of T helper type 1 (Th1) response stimulated after Leishmania infection, we applied a multiparametric flow cytometry protocol to evaluate multifunctional T cells induced by crude antigen extracts obtained from promastigotes of Leishmania braziliensis (LbAg) and Leishmania amazonensis (LaAg) in peripheral blood mononuclear cells from healed cutaneous leishmaniasis patients. Although no significant difference was detected in the percentage of total interferon (IFN)-γ-producing CD4(+) T cells induced by both antigens, multiparametric flow cytometry analysis revealed clear differences in the quality of Th1 responses. LbAg induced an important proportion of multifunctional CD4(+) T cells (28% of the total Th1 response evaluated), whereas LaAg induced predominantly single-positive cells (68%), and 57% of those were IFN-γ single-positives. Multifunctional CD4(+) T cells showed the highest mean fluorescence intensity (MFI) for the three Th1 cytokines assessed and MFIs for IFN-γ and interleukin-2 from those cells stimulated with LbAg were significantly higher than those obtained after LaAg stimulation. These major differences observed in the generation of multifunctional CD4(+) T cells suggest that the quality of the Th1 response induced by L. amazonensis antigens can be involved in the mechanisms responsible for the high susceptibility observed in L. amazonensis-infected individuals. Ultimately, our results call attention to the importance of studying a Th1 response regarding its quality, not just its magnitude, and indicate that this kind of evaluation might help understanding of the complex and diverse immunopathogenesis of American tegumentary leishmaniasis. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.
	PMID: 22288594 [PubMed - in process]
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6.	Mol Microbiol. 2012 Jan 31. doi: 10.1111/j.1365-2958.2012.07978.x. [Epub ahead of print] Involvement of TatD nuclease during programmed cell death in the protozoan parasite Trypanosoma brucei. Gannavaram S, Debrabant A. Source Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892, USA. Abstract In this report, we describe the involvement of TatD nuclease during programmed cell death (PCD) in the human protozoan parasite Trypanosoma brucei. T. brucei TatD nuclease showed intrinsic DNase activity, was localized in the cytoplasm and translocated to the nucleus when cells were treated with inducers previously demonstrated to cause PCD in T. brucei. Overexpression of TatD nuclease resulted in elevated PCD and conversely, loss of TatD expression by RNAi conferred significant resistance to the induction of PCD in T. brucei. Co-immunoprecipitation studies revealed that TatD nuclease interacts with endonucleaseG suggesting that these two nucleases could form a DNA degradation complex in the nucleus. Together, biochemical activity, RNAi and subcellular localization results demonstrate the role of TatD nuclease activity in DNA degradation during PCD in these evolutionarily ancient eukaryotic organisms. Further, in conjunction with endonucleaseG, TatD may represent a critical nuclease in a caspase-independent PCD pathway in trypanosomatid parasites since caspases have not been identified in these organisms. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
	PMID: 22288397 [PubMed - as supplied by publisher]
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7.	Ann Trop Med Parasitol. 2011 Sep;105(6):425-30. Lack of assoc iation between blood-based detection of Trypanosoma cruzi DNA and cardiac involvement in a non-endemic area. Norman FF, Pérez-Ayala A, Pérez-Molina JA, Flores-Chavez M, Cañavate C, López-Vélez R. Source Tropical Medicine and Clinical Parasitology, Infectious Diseases Department, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain. ffnorman@gmail.com Abstract Cases of chronic Chagas disease have been increasing in non-endemic areas due to the growth in immigration. This study examined the association between positive Trypanosoma cruzi-DNA detection in blood by PCR and presence of chagasic cardiac involvement in a cohort of immigrants in a European city. No association was found in this study between the positive T. cruzi blood PCR and cardiac involvement.
	PMID: 22117851 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-01-31T04:16:00.000-08:00

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Sent on Tuesday, 2012 January 31
Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 10 of 12

1.	Virulence. 2012 Jan 1;3(1). [Epub ahead of print] Haptoglobin-hemoglobin receptor independent killing of African trypanosomes by human serum. Bullard W, Kieft R, Capewell P, Veitch NJ, Macleod A, Hajduk S. Source Department of Biochemistry and Molecular Biology; University of Georgia; Athens, GA USA. Abstract The haptoglobin-hemoglobin receptor (HpHbR) of African trypanosomes plays a critical role in human innate immunity against these parasites. Localized to the flagellar pocket of the veterinary pathogen Trypanosoma brucei brucei this receptor binds Trypanosome Lytic Factor-1 (TLF-1), a subclass of human high-density lipoprotein (HDL) facilitating endocytosis, lysosomal trafficking and subsequent killing. Recently, we found that group 1 Trypanosoma brucei gambiense does not express a functional HpHbR. We now show that loss of the TbbHpHbR reduces the susceptibility of T. b. brucei to human serum and TLF-1 by 100- and 10,000-fold respectively. The relatively high concentrations of human serum and TLF-1 needed to kill trypanosomes lacking the HpHbR indicates that high affinity TbbHpHbR binding enhances the cytotoxicity; however in the absence of TbbHpHbR other receptors or fluid phase endocytosis are sufficient to provide some level of susceptibility. Human serum contains a second innate immune factor, TLF-2, that has been suggested to kill trypanosomes independently of the TbbHpHbR. We found that T. b. brucei killing by TLF-2 was reduced in TbbHpHbR deficient cells but to a lesser extent than TLF-1. This suggests that both TLF-1 and TLF-2 can be taken up via the TbbHpHbR but that alternative pathways exist for the uptake of these toxins. Together the findings reported here extend our previously published studies and suggest that group 1 T. b. gambiense has evolved multiple mechanisms to avoid killing by trypanolytic human serum factors.
	PMID: 22286709 [PubMed - as supplied by publisher]

2.	Rev Chilena Infectol. 2011 Dec;28(6):520-8. Epub 2012 Jan 5. [Travellers to South america]. [Article in Spanish] Lloveras SC. Source Área de Medicina del Viajero, Centro Municipal de Patologías Regionales Argentinas y Medicina Tropical, Hospital F. J. Muñiz, Buenos Aires, Argentina. Abstract The geography, tourist attractions and the multiple sites of historical and cultural interest make South America as an important destination chosen by travelers. The continent has a wide climatic variation from north to south, making exposure to risk different between the tropics and the temperate or cold regions. In the countries of tropical South America, the greatest risk is associated with the possibility of acquiring vector-borne diseases, like yellow fever, dengue, malaria and leishmaniasis. The risk of acquiring traveler's diarrhea and food-borne illness is similar across the continent, with some variations according to country and to visit urban or rural areas. Rabies, pertussis and diphtheria have appeared as epidemics in several countries and other diseases such as rickettsiosis, hantavirosis and viral encephalitis have expanded their distribution. The geographic and epidemiological diversity of South America, promotes a challenge for travel medicine specialists because during the pre-travel advice they have to take in account the kind of trip, traveller's medical history, exposure to risk and the dynamics of endemic emerging and reemerging diseases in the region.
	PMID: 22286674 [PubMed - in process]

3.	Nat Methods. 2012 Jan 29. doi: 10.1038/nmeth.1859. [Epub ahead of print] In vivo protein crystallization opens new routes in structural biology. Koopmann R, Cupelli K, Redecke L, Nass K, Deponte DP, White TA, Stellato F, Rehders D, Liang M, Andreasson J, Aquila A, Bajt S, Barthelmess M, Barty A, Bogan MJ, Bostedt C, Boutet S, Bozek JD, Caleman C, Coppola N, Davidsson J, Doak RB, Ekeberg T, Epp SW, Erk B, Fleckenstein H, Foucar L, Graafsma H, Gumprecht L, Hajdu J, Hampton CY, Hartmann A, Hartmann R, Hauser G, Hirsemann H, Holl P, Hunter MS, Kassemeyer S, Kirian RA, Lomb L, Maia FR, Kimmel N, Martin AV, Messerschmidt M, Reich C, Rolles D, Rudek B, Rudenko A, Schlichting I, Schulz J, Seibert MM, Shoeman RL, Sierra RG, Soltau H, Stern S, Strüder L, Timneanu N, Ullrich J, Wang X, Weidenspointner G, Weierstall U, Williams GJ, Wunderer CB, Fromme P, Spence JC, Stehle T, Chapman HN, Betzel C, Duszenko M. Source 1] Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany. [2]. Abstract Protein crystallization in cells has been observed several times in nature. However, owing to their small size these crystals have not yet been used for X-ray crystallographic analysis. We prepared nano-sized in vivo-grown crystals of Trypanosoma brucei enzymes and applied the emerging method of free-electron laser-based serial femtosecond crystallography to record interpretable diffraction data. This combined approach will open new opportunities in structural systems biology.
	PMID: 22286384 [PubMed - as supplied by publisher]

4.	Eukaryot Cell. 2012 Jan 27. [Epub ahead of print] Dynamic localization of Trypanosoma brucei mitochondrial DNA polymerase ID. Concepción-Acevedo J, Luo J, Klingbeil MM. Source Department of Microbiology, University of Massachusetts, Amherst, Massachusetts 01003. Abstract Trypanosomes contain a unique form of mitochondrial DNA called kinetoplast DNA (kDNA) that is a catenated network composed of minicircles and maxicircles. Several proteins are essential for network replication and most of these localize to the antipodal sites or the kinetoflagellar zone. Essential components for kDNA synthesis include three mitochondrial DNA polymerases (TbPOLIB, IC, ID). In contrast to other kDNA replication proteins, TbPOLID was previously reported to localize throughout the mitochondrial matrix. This spatial distribution suggests that TbPOLID would require redistribution to engage in kDNA replication. Here we characterize the subcellular distribution of TbPOLID with respect to the Trypanosoma brucei cell cycle using immunofluorescence microscopy. Our analyses demonstrate that in addition to the previously reported matrix localization, TbPOLID was detected as discrete foci near the kDNA. TbPOLID foci colocalized with replicating minicircles at antipodal sites in a specific subset of the cells during stage II-III of kDNA replication. Additionally, the TbPOLID foci were stable following inhibition of protein synthesis, detergent extraction and DNase treatment. Together, these data demonstrate that TbPOLID has a dynamic localization that allows it to be spatially and temporally available to perform its role in kDNA replication.
	PMID: 22286095 [PubMed - as supplied by publisher]

5.	Phytomedicine. 2012 Jan 27. [Epub ahead of print] Effects of (-) mammea A/BB isolated from Calophyllum brasiliense leaves and derivatives on mitochondrial membrane of Leishmania amazonensis. Brenzan MA, Santos AO, Nakamura CV, Filho BP, Ueda-Nakamura T, Young MC, Côrrea AG, Júnior JA, Morgado-Díaz JA, Cortez DA. Source Pós-doutoranda em Ciências Farmacêuticas, Departamento de Farmácia e Farmacologia, Universidade Estadual de Maringá, Av. Colombo 5790, 87020-900 Maringá, PR, Brazil. Abstract We have previously demonstrated antileishmanial activity on Leishmania amazonensis of the natural (1-2), synthetic (7) and derivatives of coumarin (-) mammea A/BB (3-6) isolated from the dichloromethane extract of Calophyllum brasiliense leaves. The aim of the present study was to evaluate morphological and ultrastructural alterations in Leishmania amazonensis induced by these compounds. In promastigote forms, all seven compounds produced significant morphological and ultrastructural alterations, as revealed by scanning and transmission electron microscopy. The compound 5,7-dihydroxy-8-(2-methylbutanoyl)-6-(3-methylbutyl)-4-phenyl-chroman-2-one (3), the most active antileishmanial with LD(50) of 0.9μM), induced cell shrinkage and a rounded appearance of the cells. Parasites incubated in the presence of compound (3) showed ultrastructural changes, such as the appearance of mitochondrial swelling with a reduction in the density of the mitochondrial matrix and the presence of vesicles inside the mitochondrion, indicating damage and significant change in this organelle; abnormal chromatin condensation, alterations in the nuclear envelope, intense atypical cytoplasmic vacuolization, and the appearance of autophagic vacuoles were also observed. In addition, the compound (3) may be acting to depolarize the mitochondrial membrane potential of the cells, leading to death of the parasite. Copyright © 2011 Elsevier GmbH. All rights reserved.
	PMID: 22285848 [PubMed - as supplied by publisher]

6.	J Struct Biol. 2012 Jan 25. [Epub ahead of print] Cryo-electron tomography and 3-D analysis of the intact flagellum in Trypanosoma brucei. Höög JL, Bouchet-Marquis C, McIntosh RJ, Hoenger A, Gull K. Source The Boulder Laboratory for 3-D Electron Microscopy of Cells, MCD-Biology, University of Colorado at Boulder, Boulder, CO 80309-0347, USA; The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Abstract Trypanosoma brucei is a uni-cellular protist that causes African sleeping sickness. These parasites have a flagellum that is attached to the cell body and is indispensible for its motility. The flagellum consists of a canonical 9+2 axoneme and a paraflagellar rod (PFR), an intricate tripartite, fibrous structure that is connected to the axoneme. In this paper we describe results from cryo-electron tomography of unperturbed flagella. This method revealed novel structures that are likely involved in attaching the flagellum to the cell. We also show the first cryo-electron tomographic images of a basal body in situ, revealing electron dense structures inside its triplet microtubules. Sub-tomogram averaging of the PFR revealed that its distal region is organized as an orthorhombic crystal. Copyright © 2012 Elsevier Inc. All rights reserved.
	PMID: 22285651 [PubMed - as supplied by publisher]

7.	Infect Genet Evol. 2012 Jan 21. [Epub ahead of print] Multiple infections of Trypanosoma brucei gambiense in blood and cerebrospinal fluid of human African trypanosomosis patients from Angola: Consequences on clinical course and treatment outcome. Truc P, Tiouchichine ML, Cuny G, Vatunga G, Josenando T, Simo G, Herder S. Source Institut de Recherche pour le Développement, Unité Mixte de Recherche 177 IRD-CIRAD, Campus International de Baillarguet, TA A17/G, 34398 Montpellier Cedex 5, France. Abstract Human African trypanosomosis, caused by Trypanosoma brucei gambiense, is a chronic disease, although various clinical patterns have been observed, from asymptomatic to acute forms. Since 2001 in Angola, 80% of patients have been found to be in the meningoencephalitic stage of the disease. The existence of an acute form of the disease caused by virulent strains of trypanosomes was suspected. To test this hypothesis, four sensitive and polymorphic microsatellite markers were used to characterize the trypanosome DNA extracted from the blood and cerebrospinal fluid of 100 patients in the meningoencephalitic stage. Twenty-three patients were found with mixed T. b. gambiense genotypes in the blood and/or cerebrospinal fluid. The absence of association between the number of infecting genotypes, the presence of neurological signs and white blood cell counts in the cerebrospinal fluid, seems to indicate, at least in the context of the present study, the absence of virulent strains. However, out of five patients who died from encephalopathy syndrome during treatment with eflornithine, three harbored multiple infections. Copyright © 2012. Published by Elsevier B.V.
	PMID: 22285307 [PubMed - as supplied by publisher]

8.	Bioorg Med Chem. 2012 Jan 2. [Epub ahead of print] Synthesis and antimalarial and antituberculosis activities of a series of natural and unnatural 4-methoxy-6-styryl-pyran-2-ones, dihydro analogues and photo-dimers. McCracken ST, Kaiser M, Boshoff HI, Boyd PD, Copp BR. Source School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. Abstract Previous studies have identified the 3,6-dialkyl-4-hydroxy-pyran-2-one marine microbial metabolites pseudopyronines A and B to be modest growth inhibitors of Mycobacterium tuberculosis and a range of tropical diseases including Plasmodium falciparum and Leishmania donovani. In an effort to expand the structure-activity relationship of this compound class towards infectious diseases, a library of natural product and natural product-like 4-methoxy-6-styryl-pyran-2-ones and a subset of catalytically reduced examples were synthesized. In addition, the photochemical reactivity of several of the 4-methoxy-6-styryl-pyran-2-ones were investigated yielding head-to-head and head-to-tail cyclobutane dimers as well as examples of asymmetric aniba-dimer A-type dimers. All compounds were evaluated for cytotoxicity and activity against M. tuberculosis, P. falciparum, L. donovani, Trypanosoma brucei rhodesiense and Trypanosoma cruzi. Of the styryl-pyranones, natural product 3 and non-natural styrene and naphthalene substituted examples 13, 18, 21, 22 and 23 exhibited antimalarial activity (IC(50) <10μM) with selectivity indices (SI) >10. Δ(7) Dihydro analogues were typically less active or lacked selectivity. Head-to-head and head-to-tail photodimers 5 and 34 exhibited moderate IC(50)s of 2.3 to 17μM towards several of the parasitic organisms, while the aniba-dimer-type asymmetric dimers 31 and 33 were identified as being moderately active towards P. falciparum (IC(50) 1.5 and 1.7μM) with good selectivity (SI ∼80). The 4-tert-butyl aniba-dimer A analogue 33 also exhibited activity towards L. donovani (IC(50) 4.5μM), suggesting further elaboration of this latter scaffold could lead to the identification of new leads for the dual treatment of malaria and leishmaniasis. Copyright © 2011 Elsevier Ltd. All rights reserved.
	PMID: 22285027 [PubMed - as supplied by publisher]

9.	Vet Parasitol. 2012 Jan 10. [Epub ahead of print] Coinfection of Leishmania chagasi with Toxoplasma gondii, Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) in cats from an endemic area of zoonotic visceral leishmaniasis. Sobrinho LS, Rossi CN, Vides JP, Braga ET, Gomes AA, de Lima VM, Perri SH, Generoso D, Langoni H, Leutenegger C, Biondo AW, Laurenti MD, Marcondes M. Source Department of Clinics, Surgery and Animal Reproduction, College of Veterinary Medicine, São Paulo State University, Araçatuba, São Paulo 16050-680, Brazil. Abstract The aim of the present study was to determine the coinfection of Leishmania sp. with Toxoplasma gondii, Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) in a population of cats from an endemic area for zoonotic visceral leishmaniasis. An overall 66/302 (21.85%) cats were found positive for Leishmania sp., with infection determined by direct parasitological examination in 30/302 (9.93%), by serology in 46/302 (15.23%) and by both in 10/302 (3.31%) cats. Real time PCR followed by amplicon sequencing successfully confirmed Leishmania infantum (syn Leishmania chagasi) infection. Out of the Leishmania infected cats, coinfection with FIV was observed in 12/66 (18.18%), with T. gondii in 17/66 (25.75%) and with both agents in 5/66 (7.58%) cats. FeLV was found only in a single adult cat with no Leishmania infection. A positive association was observed in coinfection of Leishmania and FIV (p<0.0001), but not with T. gondii (p>0.05). In conclusion, cats living in endemic areas of visceral leishmaniasis are significantly more likely to be coinfected with FIV, which may present confounding clinical signs and therefore cats in such areas should be always carefully screened for coinfections. Copyright © 2012 Elsevier B.V. All rights reserved.
	PMID: 22285010 [PubMed - as supplied by publisher]

10.	Trans R Soc Trop Med Hyg. 2012 Jan 25. [Epub ahead of print] Risk factors for cutaneous leishmaniasis in Cukurova region, Turkey. Votýpka J, Kasap OE, Volf P, Kodym P, Alten B. Source Department of Parasitology, Charles University, Vinicna 7, Prague 128 44, Czech Republic. Abstract We conducted a case-control study to evaluate risk factors for cutaneous leishmaniasis caused by Leishmania infantum outbreaks in villages in the Cukurova region, South Anatolia, Turkey. 282 respondents from eight villages were interviewed using structured questionnaires. Epidemiological and clinical characteristics, personal protection and knowledge of leishmania were analyzed. Young people, aged from 5-19 years, were found to be the most endangered group of villagers. The concurrent presence of both lesions and scars in nine persons may indicate repeated infections. Sleeping without bed nets, ownership of a dog and cattle ownership (living close to a barn and storage of dried dung according univariate analyses) were associated with a significantly increased risk of leishmania infection. Non-impregnated bed nets provided only partial protection, but their use decreased the risk approximately 1.6 times. Further research on the role of dogs in the transmission cycle and the effect of suitable interventions are needed to design the best strategy for disease control. Results suggest that personal protection should be increased, particularly among outdoor sleepers, with insecticide-treated bed nets suggested as the best choice. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
	PMID: 22284721 [PubMed - as supplied by publisher]

What's new for 'Trypanosomatids' in PubMed

2012-01-28T04:37:00.000-08:00

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
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Sender's message:

Sent on Saturday, 2012 January 28
Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 7 of 7

1.	J Am Soc Nephrol. 2012 Jan 26. [Epub ahead of print] Renal Leishmaniasis as Unusual Cause of Nephrotic Syndrome in an HIV Patient. Amann K, Bogdan C, Harrer T, Rech J. Source *Abt. für Nephropathologie, Pathologisches Institut. Abstract Renal involvement is a rare complication in HIV-1-infected patients leading to various pathologies and clinical symptoms. In addition to the classic HIV-1-associated nephropathy with collapsing-type focal segmental glomerulosclerosis and characteristic tubulocystic changes, which is more common in Afro-American than in Caucasian HIV-1 patients, immune complex GNs such as membranous GN and membranoproliferative GN are particularly common renal manifestations. Besides HIV-1 itself, a number of opportunistic infections may cause renal disease in HIV-1-infected patients. In this study, we report an unusual case of HIV-1 infection with a severe renal manifestation of systemic leishmaniasis that developed years after repeated visits to Mediterranean countries. The case presents several remarkable clinical, pathologic, and therapeutic aspects that may be important for daily clinical practice.
	PMID: 22282598 [PubMed - as supplied by publisher]

2.	An Bras Dermatol. 2011 Dec;86(6):1141-4. Combining diagnostic procedures for the management of leishmaniasis in areas with high prevalence of Leishmania guyanensis. Benicio Ede A, Nunes Gadelha EP, Talhari A, Silva RM Jr, Ferreira LC, Santos MC, Mira MT, Oliveira CM, Talhari C, Talhari S, Machado PR, Schriefer A. Abstract BACKGROUND: The Amazon region corresponds to approximately 40% of the cases of leishmaniasis in Brazil. We report a prospective study with 180 patients conducted in a health care unit that diagnoses 10% of the cases of leishmaniasis in the Brazilian Amazon. The study addresses how a combination of procedures improves diagnosis in areas with high prevalence of Leishmania guyanensis. OBJECTIVES: to evaluate diagnostic methods in areas with high prevalence of Leishmania guyanensis. METHODS: All subjects were amastigote-positive by direct microscopic examination of lesion scarifications. We conducted skin biopsy and histopathology, polymerase chain reaction and parasite cultivation. RESULTS: Polymerase chain reaction detected almost ninety percent of infections when two amplification protocols were used (mini-exon and HSP-70). HSP-70 specific polymerase chain reaction matched the sensitivity of parasite cultivation plus histopathology. CONCLUSION: The best combination was polymerase chain reaction plus histopathology, which increased diagnostic sensitivity to 94%. Species discrimination by polymerase chain reaction disclosed prevalence of human infections with Leishmania guyanensis of 94% and with Leishmania braziliensis of 6% for this region.
	PMID: 22281902 [PubMed - in process]

3.	An Bras Dermatol. 2011 Dec;86(6):1092-1101. A randomized clinical trial comparing meglumine antimoniate, pentamidine and amphotericin B for the treatment of cutaneous leishmaniasis by Leishmania guyanensis. [Article in English, Portuguese] Neves LO, Talhari AC, Gadelha EP, Silva Júnior RM, Guerra JA, Ferreira LC, Talhari S. Source Programa de Pós-Graduação em Medicina Tropical, Fundação de Medicina Tropical Heitor Vieira Dourado, Universidade do Estado do Amazonas. Abstract FUNDAMENTALS: American tegumentary leishmaniasis (ATL) treatment remains a challenge, since most available drugs are injectable and only a small number of comparative, randomized clinical trials have been performed to support their use. Moreover, treatment outcome may depend on the causative species of Leishmania. OBJECTIVES: To evaluate and compare the efficacy and tolerability of meglumine antimoniate, pentamidine isethionate, and amphotericin B in the treatment of ATL caused by Leishmania (Viannia) guyanensis. METHODS: 185 patients were selected according to the eligibility criteria and randomly allocated into three groups - two groups with 74 patients each, and one group with 37 patients, which underwent meglumine, pentamidine and amphotericin B treatment, respectively. Doses, mode of administration and time periods of treatment followed the current recommendations for each drug. Patients were re-examined one, two and six months after completion of treatment. RESULTS: No differences were observed among the therapeutic groups in relation to gender, age, number or site of lesions. Intention-to-treat (ITT) analysis showed efficacy of 58.1% for pentamidine and 55.5% for meglumine (p=0.857). The amphotericin B group was analyzed separately, since 28 patients (75.7%) in this group refused to continue participating in the study. Mild or moderate adverse effects were reported by 74 (40%) patients, especially arthralgia (20.3%) in the meglumine group, and pain (35.1%) or induration (10.8%) at the site of injection in the pentamidine group. CONCLUSION: Pentamidine and meglumine show similar efficacy in the treatment of ATL caused by L. guyanensis. Given the low efficacy of both drugs, there is an urgent need for new therapeutical approaches.
	PMID: 22281895 [PubMed - as supplied by publisher]

4.	Int J Parasitol. 2012 Jan 11. [Epub ahead of print] Acylation-dependent and independent membrane targeting and distinct functions of small myristoylated proteins (SMPs) in Leishmania major. Tull D, Heng J, Gooley PR, Naderer T, McConville MJ. Source Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia. Abstract Trypanosomatid parasites express a number of mono- and diacylated proteins that are targeted to distinct regions of the plasma membrane including the cell body, the flagellum and the flagellar pocket. The extent to which the acylation status and other protein motifs regulate the targeting and/or retention of these proteins to the distinct membrane domains is poorly defined. We have previously described a family of small myristoylated proteins (SMPs) that are either monoacylated (myristoylated) or diacylated (myristoylated and palmitoylated) and targeted to distinct plasma membrane domains. Diacylated SMP-1 is a major constituent of the flagellar membrane, whereas monoacylated SMP-2 resides in the flagellar pocket in Leishmania major. Here, we show that a third SMP family member, monoacylated SMP-4, localizes predominantly to the pellicular membrane. Density gradient centrifugation of detergent-insoluble membranes indicated that SMP-4 was associated with detergent-insoluble domains but was not tightly associated with the subpellicular cytoskeleton. Based on the localisation of truncated SMP proteins, we conclude that the flagellum targeting of SMP-1 is primarily dependent on the dual-acylation motif. In contrast, the localisation of SMP-4 to the cell body membrane was dependent on N-terminal myristoylation and a C-terminal peptide subdomain with a predicted α-helical structure. Strikingly, a SMP-1 chimera containing the SMP-4 C-terminal extension was selectively trafficked to the distal tip of the flagellum and failed to complement the loss of native SMP-1 in a Δsmp1/2 double knockout strain. Collectively, these results suggest that dual acylation is sufficient to target some SMP proteins to the flagellum, while the unique C-terminal extensions of these proteins may confer additional membrane targeting signals that are important for both localisation and SMP function. Copyright © 2012. Published by Elsevier Ltd.
	PMID: 22281304 [PubMed - as supplied by publisher]

5.	Acta Trop. 2012 Jan 18. [Epub ahead of print] Anti-Trypanosoma cruzi activity of nicotinamide. Soares MB, Silva CV, Bastos TM, Guimarães ET, Figueira CP, Smirlis D, Azevedo WF Jr. Source Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão, 121, Candeal 40296-710, Salvador, BA, Brazil; Hospital São Rafael, Av. São Rafael, 2152, São Marcos 41253-190, Salvador, BA, Brazil. Abstract Inhibition of Trypanosoma brucei and Leishmania spp. sirtuins has shown promising antiparasitic activity, indicating that these enzymes may be used as targets for drug discovery against trypanosomatid infections. In the present work we carried out a virtual screening focused on the C pocket of Sir2 from Trypanosoma cruzi. Using this approach, the best ligand found was nicotinamide. In vitro tests confirmed the anti-T. cruzi activity of nicotinamide on epimastigote and trypomastigote forms. Moreover, treatment of T. cruzi-infected macrophages with nicotinamide caused a significant reduction in the number of amastigotes. In addition, alterations in the mitochondria and an increase in the vacuolization in the cytoplasm were observed in epimastigotes treated with nicotinamide. Analysis of the complex of Sir2 and nicotinamide revealed the details of the possible ligand-target interaction. Our data reveal a potential use of TcSir2 as a target for anti-T. cruzi drug discovery. Copyright © 2012 Elsevier B.V. All rights reserved.
	PMID: 22281243 [PubMed - as supplied by publisher]

6.	Exp Parasitol. 2012 Jan 20. [Epub ahead of print] Effectiveness of liposomal buparvaquone in an experimental hamster model of Leishmani a (L.) infantum chagasi. Reimão JQ, Colombo FA, Pereira-Chioccola VL, Tempone AG. Source Department of Parasitology, Instituto Adolfo Lutz, Avenida Dr. Arnaldo, 351, 8° Andar. Cerqueira César, CEP 01246-902 São Paulo, SP, Brazil. Abstract The objective of this study was to develop a novel liposomal formulation, containing phosphatidylserine (PS), of buparvaquone (BPQ) and to evaluate its in vivo effectiveness in Leishmania (L.) infantum chagasi-infected hamsters. The activity of BPQ was evaluated against both the promastigote forms of different Leishmania species and the intracellular amastigotes of L. (L.) infantum chagasi. Buparvaquone was entrapped in PS-liposomes (BPQ-PS-LP), and the drug was quantified by ultra-high-performance liquid chromatography. The treatment was quantified by detecting the RNA of the living amastigotes in the spleen and the liver by real-time PCR. In vitro assays with L. (L.) infantum chagasi intracellular amastigotes were performed in peritoneal macrophages for the evaluation of the 50% inhibitory concentration (IC(50)). BPQ-PS-LP at 0.33mg/kg/day for eight consecutive days reduced the number of amastigotes by 89.4% (P<0.05) in the spleen and by 67.2% (P>0.05) in the liver, compared to 84.3% (P<0.05) and 99.7% (P<0.05), respectively, following Glucantime® treatment at 50mg/kg/day. Free BPQ at 20mg/kg/day failed to treat the hamsters when compared to the untreated group. BPQ was significantly (P<0.05) selective against L. (L.) infantum chagasi intracellular amastigotes, with an IC(50) value of 1.5μM; no in vitro mammalian cytotoxicity could be detected. Other cutaneous species were also susceptible to BPQ, with IC(50) values in the range 1-4μM. BPQ-PS-LP caused a significant reduction in the parasite burden at a 60-fold lower dose than did the free BPQ. These results show the potential of PS-liposome formulations for the successful targeted delivery of BPQ in visceral leishmaniasis. Copyright © 2012. Published by Elsevier Inc.
	PMID: 22281156 [PubMed - as supplied by publisher]

7.	Braz J Biol. 2011 May;71(2):491-500. Prevalence and intensity of infection, metacyclogenesis and nuclear phenotypes in Panstrongylus megistus (Burmeister, 1835) after ingestion of Trypanosoma cruzi (Chagas, 1909) II and subjection to heat shock. Garcia SL, Rodrigues VL, Garcia NL, Mello ML. Source Departamento de Anatomia, Biologia Celular e Fisiologia e Biofísica, Universidade Estadual de Campinas, Campinas, SP, Brazil, 13083-863. Abstract This study aimed to contribute to our knowledge of the parasite-vector interaction associated with Trypanosoma cruzi (Chagas, 1909) infection in Panstrongylus megistus (Burmeister, 1835), an important vector of Chagas' disease in Brazil. The prevalence and intensity of T. cruzi infection, the incidence of metacyclogenesis and the frequency of nuclear phenotypes in Malpighian tubules were investigated in nymphs of P. megistus, reared at 28 °C and subjected to heat shock (40 °C, 1 hour) two days after infection with T. cruzi II (Y strain). Following the 45-day post-infection period, the frequency of epimastigotes was much higher than that of trypomastigotes in both heat-shocked and non-shocked insects, and the prevalence of infection was not altered by heat shock. Fewer epimastigotes and trypomastigotes were found in the infected insects subjected to the heat shock, indicating that the multiplication and metacyclogenesis of the parasites were affected by the stress. In infected specimens heat shock promoted an increased frequency of cell nuclei with heterochromatin decondensation, a cell survival response to stress, and did not affect insect survival. The effects of infection and heat shock, especially on the multiplication and metacyclogenesis of T. cruzi, and the observed resistance to heat shock developed by P. megistus nymphs are suggestive that they should be considered when adequate conditions for rearing these infected insects in the laboratory are pursued. Free Article
	PMID: 21755168 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-01-27T04:20:00.001-08:00

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Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 10 of 13

1.	PLoS One. 2012;7(1):e30367. Epub 2012 Jan 18. Cytokinesis in Bloodstream Stage Trypanosoma brucei Requires a Family of Katanins and Spastin. Benz C, Clucas C, Mottram JC, Hammarton TC. Source Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. Abstract Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell division.
	PMID: 22279588 [PubMed - in process]
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2.	J Res Med Sci. 2011 Aug;16(8):1032-9. In vitro and in v ivo activities of Peganum harmala extract against Leishmania major. Rahimi-Moghaddam P, Ebrahimi SA, Ourmazdi H, Selseleh M, Karjalian M, Haj-Hassani G, Alimohammadian MH, Mahmoudian M, Shafiei M. Source Department of Pharmacology, Razi Institute for Drug Research, Medical School, Tehran University of Medical Sciences, Tehran, Iran. Abstract BACKGROUND: In vitro and in vivo antileishmanial activities of crude hydroalcoholic extract of peganum harmala seeds were investigated against Leishmania major. METHODS: The extract of aerial parts of P harmala was obtained by maceration. The in vitro experiments were performed on promastigotes to assess antileishmanial activity of the extract using amphotericin B as a reference. The in vivo studies were carried out on cutaneous leishmaniasis in outbred mice to evaluate the effects of topical application of the ointment-based extract. RESULTS: The in vitro experiments showed a concentration-dependent decrease of parasites number caused by the extract with an IC50 value of 59.4 μg/ml. In vivo studies demonstrated a significant post-treatment decrease in the lesion size and parasite count in infected animals, compared to placebo and control groups. High performance liquid chromatography (HPLC) of the crude extract demonstrated the existence of harmaline and harmine as beta-carboline alkaloids. CONCLUSIONS: P harmala seeds extract showed significant in vitro and in vivo antileishmanial activities. Most biological activity of the extract could be attributed to its beta-carboline content. However, another alkaloid of P harmala seeds extract, peganine, has also been reported to have antileishmanial activity. These beneficial effects can be attributed to the cumulative effects of various biologically active components present in it.
	PMID: 22279479 [PubMed - in process]
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3.	J Clin Microbiol. 2012 Jan 25. [Epub ahead of print] Post Kala-azar Dermal Leishmaniasis in a patient treated with Injectable Paromomycin for Visceral leishm aniasis-First case report from India. Pandey K, Das V, Singh D, Das S, Lal C, Verma N, Bimal S, Topno R, Siddiqui N, Verma R, Sinha P, Das P. Source Rajendra Memorial Research Institute of Medical Sciences, (Indian Council of Medical Research), Agamkuan, Patna, Bihar, India. 800007. Abstract Post Kala-azar Dermal Leishmaniasis (PKDL) is a skin manifestation that usually develops after treatment of Visceral Leishmaniasis (VL), a major public health problem in India. The diagnosis and management of PKDL is complex. This is the first case report from India in which PKDL occurred after paromomycin treatment for VL in an Indian patient.
	PMID: 22278840 [PubMed - as supplied by publisher]
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4.	Biomol NMR Assign. 2012 Jan 26. [Epub ahead of print] Backbone and side chain (1)H, (15)N & (13)C chemical shift assignments of the holo-acyl carrier protein (ACP) of Leishmania major. Kumar A, Surolia A, Sundd M. Source National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India. Abstract Acyl carrier protein (ACP) is a small acidic protein, an important cofactor involved in fatty acid biosynthesis. Its main function is to protect the growing acyl chain from the hydrophilic environment during fatty acid biosynthesis and simultaneously, present it to the active site of fatty acid pathway enzymes, liable for its elongation. The ACP molecule is expressed as apo-ACP (inactive) and is post-transitionally modified to the holo form (active) by the enzyme holo ACP synthase (ACPS). Here we report the complete backbone and side chain chemical shift assignments of the holo-ACP molecule of Leishmania major.
	PMID: 22278299 [PubMed - as supplied by publisher]
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5.	Nature. 2012 Jan 25. doi: 10.1038/nature10771. [Epub ahead of print] High-throughput decoding of antitrypanosomal drug efficacy and resistance. Alsford S, Eckert S, Baker N, Glover L, Sanchez-Flores A, Leung KF, Turner DJ, Field MC, Berriman M, Horn D. Source London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. Abstract The concept of disease-specific chemotherapy was developed a century ago. Dyes and arsenical compounds that displayed selectivity against trypanosomes were central to this work, and the drugs that emerged remain in use for treating human African trypanosomiasis (HAT). The importance of understanding the mechanisms underlying selective drug action and resistance for the development of improved HAT therapies has been recognized, but these mechanisms have remained largely unknown. Here we use all five current HAT drugs for genome-scale RNA interference target sequencing (RIT-seq) screens in Trypanosoma brucei, revealing the transporters, organelles, enzymes and metabolic pathways that function to facilitate antitrypanosomal drug action. RIT-seq profiling identifies both known drug importers and the only known pro-drug activator, and links more than fifty additional genes to drug action. A bloodstream stage-specific invariant surface glycoprotein (ISG75) family mediates suramin uptake, and the AP1 adaptin complex, lysosomal proteases and major lysosomal transmembrane protein, as well as spermidine and N-acetylglucosamine biosynthesis, all contribute to suramin action. Further screens link ubiquinone availability to nitro-drug action, plasma membrane P-type H(+)-ATPases to pentamidine action, and trypanothione and several putative kinases to melarsoprol action. We also demonstrate a major role for aquaglyceroporins in pentamidine and melarsoprol cross-resistance. These advances in our understanding of mechanisms of antitrypanosomal drug efficacy and resistance will aid the rational design of new therapies and help to combat drug resistance, and provide unprecedented molecular insight into the mode of action of antitrypanosomal drugs.
	PMID: 22278056 [PubMed - as supplied by publisher]
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6.	J Invest Dermatol. 2012 Jan 26. doi: 10.1038/jid.2011.454. [Epub ahead of print] Priming of Leishmania-Reactive CD8(+) T cells In Vivo Does Not Require LMP7-Containing Immunoproteasomes. Brosch S, Tenzer S, Akkad N, Lorenz B, Schild H, Stebut EV. Source Department of Dermatology, Universitätsmedizin, Johannes Gutenberg-University, Mainz, Germany.
	PMID: 22277939 [PubMed - as supplied by publisher]
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7.	Comp Immunol Microbiol Infect Dis. 2012 Jan 23. [Epub ahead of print] New Rickettsia sp. in tsetse flies from Senegal. Mediannikov O, Audoly G, Diatta G, Trape JF, Raoult D. Source Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes: URMITE, UMR IRD/CNRS 198/6236, Université de la Méditerranée, Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille, France; Institut de Recherche pour le Développement (IRD), Campus commun UCAD-IRD of Hann, URMITE UMR 198, BP 1386 CP 18524 Dakar, Senegal. Abstract Tsetse flies are blood-sucking insects transmitting African trypanosomiasis. They are known to harbor also three intracellular bacteria that play important role in their lifecycle: Wigglesworthia glossinidia, Sodalis glossinidius and Wolbachia sp. We have studied 78 Glossina morsitans submorsitans collected in Senegal. In all studied flies we amplified genes of bacterium phylogenetically close to obligate intracellular pathogen Rickettsia felis, the agent of spotted fever in humans. We also visualized this rickettsia in the cells of tsetse flies by fluorescence in situ hybridization. The role of this probable fourth endosymbiotic bacterium of tsetse flies in Glossina lifecycle and possible pathogenecity for humans should be further investigated. Copyright © 2012 Elsevier Ltd. All rights reserved.
	PMID: 22277830 [PubMed - as supplied by publisher]
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8.	Mol Ecol Resour. 2012 Jan 25. doi: 10.1111/j.1755-0998.2012.03117.x. [Epub ahead of print] DNA barcoding for identification of sand flies (Diptera: Psychodidae) in India. Kumar NP, Srinivasan R, Jambulingam P. Source Vector Control Research Centre Field Station (ICMR), Kottayam 686002, Kerala, India Vector Control Research Centre (ICMR), Puducherry 605006, India. Abstract About 50 species of sand flies have been reported to be prevalent in India. We explored the utility of the DNA barcode approach towards species identification of these medically important insects. A total of 62 specimens belonging to seven morphologically identified species of two genera, Phlebotomus and Sergentomyia, collected from Puducherry Union Territory, Maharashtra and Rajasthan states of India were subjected to the analysis. Neighbor-joining (NJ) analysis of DNA barcode sequences identified the individuals of seven morphological species into eight distinct species, as presented in the designed NJ tree. This methodology delineated morphologically identified species, S. bailyi, into two genetically isolated groups. Also, this study characterizes DNA barcodes of P. argentipes and P. papatasi, the vector species of leishmaniasis in India, for the first time. © 2012 Blackwell Publishing Ltd.
	PMID: 22277023 [PubMed - as supplied by publisher]
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9.	Tidsskr Nor Laegeforen. 2011 Dec 13;131(24):2486. [In Process Citation]. [Article in Norwegian] Flægstad T. S ource Barneavdelingen, Universitetssykehuset Nord-Norge og Universitetet i Tromsø, Norway. trond.flaegstad@unn.no Comment on Tidsskr Nor Laegeforen. 2011 Dec 13;131(24):2482-6. Free Article
	PMID: 22170137 [PubMed - indexed for MEDLINE]
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10.	Tidsskr Nor Laegeforen. 2011 Dec 13;131(24):2482-6. A 15-month-old girl with fever and pancytopenia. [Article in English, Norwegian] Skram MK, Bjering S, Hermansen NO, Dini L, Hellebostad M. Source Department of Paediatric Medicine, Oslo University Hospital, Ullevål, Norway. Comment in Tidsskr Nor Laegeforen. 2011 Dec 13;131(24):2486. Abstract A 15 month-old girl was admitted after a couple of months' history of illness with remittent fever, increasing pallor and a swollen abdomen. On admission she was highly febrile, with palpably enlarged liver and spleen. Blood tests revealed pancytopenia, a high CRP level and a high serum ferritin level. We describe the diagnostic evaluation, interpretation and treatment. Free Article
	PMID: 22170136 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-01-26T04:27:00.001-08:00

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
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Sender's message:

Sent on Thursday, 2012 January 26
Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 8 of 8

1.	PLoS One. 2012;7(1):e28266. Epub 2012 Jan 20. First Detection of Leishmania major DNA in Sergentomyia (Spelaeomyia) darlingi from Cutaneous Leishmaniasis Foci in Mali. Berdjane-Brouk Z, Koné AK, Djimdé AA, Charrel RN, Ravel C, Delaunay P, Del Giudice P, Diarra AZ, Doumbo S, Goita S, Thera MA, Depaquit J, Marty P, Doumbo OK, Izri A. Source Parasitologie, Hôpital Avicenne, Université de Paris 13, Paris, France. Abstract BACKGROUND: Leishmania major complex is the main causative agent of zoonotic cutaneous leishmaniasis (ZCL) in the Old World. Phlebotomus papatasi and Phlebotomus duboscqi are recognized vectors of L. major complex in Northern and Southern Sahara, respectively. In Mali, ZCL due to L. major is an emerging public health problem, with several cases reported from different parts of the country. The main objective of the present study was to identify the vectors of Leishmania major in the Bandiagara area, in Mali. METHODOLOGY/PRINCIPAL FINDINGS: An entomological survey was carried out in the ZCL foci of Bandiagara area. Sandflies were collected using CDC miniature light traps and sticky papers. In the field, live female Phlebotomine sandflies were identified and examined for the presence of promastigotes. The remaining sandflies were identified morphologically and tested for Leishmania by PCR in the ITS2 gene. The source of blood meal of the engorged females was determined using the cyt-b sequence. Out of the 3,259 collected sandflies, 1,324 were identified morphologically, and consisted of 20 species, of which four belonged to the genus Phlebotomus and 16 to the genus Sergentomyia. Leishmania major DNA was detected by PCR in 7 of the 446 females (1.6%), specifically 2 out of 115 Phlebotomus duboscqi specimens, and 5 from 198 Sergentomyia darlingi specimens. Human DNA was detected in one blood-fed female S. darlingi positive for L. major DNA. CONCLUSION: Our data suggest the possible involvement of P. duboscqi and potentially S. darlingi in the transmission of ZCL in Mali.
	PMID: 22276095 [PubMed - in process]

2.	PLoS Pathog. 2012 Jan;8(1):e1002417. Epub 2012 Jan 19. Progressive Visceral Leishmaniasis Is Driven by Dominant Parasite-induced STAT6 Activation and STAT6-dependent Host Arginase 1 Expression. Osorio EY, Zhao W, Espitia C, Saldarriaga O, Hawel L, Byus CV, Travi BL, Melby PC. Source Research Service, Department of Veterans Affairs Medical Center, South Texas Veterans Health Care System, San Antonio, Texas, United States of America. Abstract The clinicopathological features of the hamster model of visceral leishmaniasis (VL) closely mimic active human disease. Studies in humans and hamsters indicate that the inability to control parasite replication in VL could be related to ineffective classical macrophage activation. Therefore, we hypothesized that the pathogenesis of VL might be driven by a program of alternative macrophage activation. Indeed, the infected hamster spleen showed low NOS2 but high arg1 enzyme activity and protein and mRNA expression (p<0.001) and increased polyamine synthesis (p<0.05). Increased arginase activity was also evident in macrophages isolated from the spleens of infected hamsters (p<0.05), and arg1 expression was induced by L. donovani in primary hamster peritoneal macrophages (p<0.001) and fibroblasts (p<0.01), and in a hamster fibroblast cell line (p<0.05), without synthesis of endogenous IL-4 or IL-13 or exposure to exogenous cytokines. miRNAi-mediated selective knockdown of hamster arginase 1 (arg1) in BHK cells led to increased generation of nitric oxide and reduced parasite burden (p<0.005). Since many of the genes involved in alternative macrophage activation are regulated by Signal Transducer and Activator of Transcription-6 (STAT6), and because the parasite-induced expression of arg1 occurred in the absence of exogenous IL-4, we considered the possibility that L. donovani was directly activating STAT6. Indeed, exposure of hamster fibroblasts or macrophages to L. donovani resulted in dose-dependent STAT6 activation, even without the addition of exogenous cytokines. Knockdown of hamster STAT6 in BHK cells with miRNAi resulted in reduced arg1 mRNA expression and enhanced control of parasite replication (p<0.0001). Collectively these data indicate that L. donovani infection induces macrophage STAT6 activation and STAT6-dependent arg1 expression, which do not require but are amplified by type 2 cytokines, and which contribute to impaired control of infection.
	PMID: 22275864 [PubMed - in process]

3.	J Cell Sci. 2012 Jan 24. [Epub ahead of print] Structure-function relationship of the Polo-like kinase in Trypanosoma brucei. Yu Z, Liu Y, Li Z. Abstract Polo-like kinases (Plks) play multiple roles in mitosis and cytokinesis in eukaryotes and are characterized by the C-terminal Polo-box domain (PBD) implicated in binding to Plk substrates, targeting Plk, and regulating Plk activity. The Plk homolog in Trypanosoma brucei possesses a similar architecture, but it lacks the crucial residues involved in substrate binding and regulates cytokinesis but not mitosis. Despite these, little is known about the regulation of TbPLK and the role of the PBD in TbPLK localization and function. Here, we addressed the requirement of the kinase activity and the PBD for TbPLK localization and function through coupling RNAi of endogenous TbPLK with ectopic expression of TbPLK mutants. We demonstrate that the kinase activity and phosphorylation of two threonine residues, Thr198 and Thr202, in the activation loop (T-loop) of the kinase domain are essential for TbPLK function but not for TbPLK localization. Deletion of the PBD abolishes TbPLK localization, but the PBD itself is not correctly targeted, indicating that TbPLK localization requires both the PBD and the kinase domain. Surprisingly, the kinase domain of TbPLK, but not the PBD, binds to its substrates, TbCentrin2 and p110, suggesting that TbPLK may interact with its substrate through different mechanisms. Finally, the PBD interacts with the kinase domain of TbPLK and inhibits its activity, and this inhibition is relieved when Thr198 is phosphorylated. Together, these results suggest an essential role of T-loop phosphorylation in TbPLK activation and crucial roles of the PBD in regulating TbPLK activity and localization.
	PMID: 22275435 [PubMed - as supplied by publisher]

4.	J Biol Chem. 2012 Jan 23. [Epub ahead of print] High-throughput screening against the peroxidase cascade of African trypanosomes identifies antiparasitic compounds that inactivate tryparedoxin. Fueller F, Jehle B, Putzker K, Lewis JD, Krauth-Siegel RL. Source Biochemie-Zentrum der Universitaet Heidelberg, Germany; Abstract In African trypanosomes, the detoxification of broad-spectrum hydroperoxides relies on a unique cascade composed of trypanothione [T(SH)2], trypanothione reductase (TR), tryparedoxin (Tpx) and nonselenium glutathione peroxidase-type enzymes (Px). All three proteins are essential for Trypanosoma brucei. Here we subjected the complete system to a high-throughput screening approach with nearly 80,000 chemicals. Twelve compounds inhibited the peroxidase system. Except one, all of them carried chloroalkyl substituents. The detailed kinetic analysis showed that two compounds weakly inhibited TR but none of them specifically interacted with the peroxidase. They proved to be time-dependent inhibitors of Tpx modifying Cys40, the first cysteine of its active site WCPPC motif. Importantly, gel shift assays verified Tpx as target in the intact parasites. T(SH)2, present in the in vitro assays and in the cells in high molar excess, did not interfere with Tpx inactivation. The compounds inhibited the proliferation of bloodstream T. brucei with EC50-values down to <1 microM and exerted up to 83-fold lower toxicity towards HeLa cells. Irreversible inhibitors are traditionally regarded as unfavourable. However, a large number of antimicrobials and anticancer therapeutics act covalently with their target protein. The compounds identified here also interacted with recombinant human thioredoxin, a distant relative of Tpx. This finding might even be exploited for thioredoxin-based anticancer drug development approaches reported recently. The fact that the T(SH)2/Tpx couple occupies a central position within the trypanosomal thiol metabolism and delivers electrons also for the synthesis of DNA precursors, renders the parasite-specific oxidoreductase an attractive drug target molecule.
	PMID: 22275351 [PubMed - as supplied by publisher]

5.	Proteins. 2011 Dec 22. doi: 10.1002/prot.24019. [Epub ahead of print] Insights into internal dynamics of 6-phosphogluconolactonase from trypanosoma brucei studied by NMR and molecular dynamics. Calligari PA, Salgado GF, Pelupessy P, Lopes P, Ouazzani J, Bodenhausen G, Abergel D. Source Département de Chimie, Ecole Normale Supérieure, 24 rue Lhomond, 75231 Paris Cedex 05, France; Université Pierre-et-Marie Curie, Place Jussieu, 75005 Paris, France; UMR 7203 CNRS, 24 rue Lhomond, 75231 Paris Cedex 05, France. Abstract Nuclear magnetic resonance (NMR) is used to investigate the backbone dynamics in 6-phosphogluconolactonase from T. brucei (Tb6PGL) with (holo-) and without (apo-) 6-phosphogluconic acid (6PGA) as ligand. Relaxation data were analyzed using the model-free (MF) approach and reduced spectral density mapping (SDM). Comparison of predictions, based on 77 ns molecular dynamics (MD) simulations, with the observed relaxation rates gives insight into dynamical properties of the protein and their alteration upon ligand binding. Data indicate dynamics changes in the vicinity of the binding site. Maybe more interesting is the presence of perturbations located in remote regions of this well-structured globular protein in which no large amplitude regional motion is involved. This is reminiscent of other studies in the literature, and suggests that delocalized dynamics changes upon binding could be a general feature of protein-target interactions. Proteins 2011. © 2011 Wiley-Liss, Inc. Copyright © 2011 Wiley-Liss, Inc.
	PMID: 22275079 [PubMed - as supplied by publisher]

6.	Exp Parasitol. 2012 Jan;130(1):13-21. Epub 2011 Oct 19. Differential expression of cruzipain- and gp63-like molecules in the phytoflagellate trypanosomatid Phytomonas serpens induced by exogenous proteins. Elias CG, Chagas MG, Souza-Gonçalves AL, Pascarelli BM, d'Avila-Levy CM, Branquinha MH, Santos AL. Source Laboratório de Estudos Integrados em Bioquímica Microbiana, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Bloco E-subsolo, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Av Carlos Chagas Filho, 373 Cidade Universitária, Rio de Janeiro 21941-902, Brazil. Abstract Phytomonas serpens synthesizes metallo- and cysteine-proteases that are related to gp63 and cruzipain, respectively, two virulence factors produced by pathogenic trypanosomatids. Here, we described the cellular distribution of gp63- and cruzipain-like molecules in P. serpens through immunocytochemistry and confocal fluorescence microscopy. Both proteases were detected in distinct cellular compartments, presenting co-localization in membrane domains and intracellular regions. Subsequently, we showed that exogenous proteins modulated the production of both protease classes, but in different ways. Regarding the metalloprotease, only fetal bovine serum (FBS) influenced the gp63 expression, reducing its surface exposition (≈30%). Conversely, the cruzipain-like molecule was differentially modulated according to the proteins: human and bovine albumins reduced its expression around 50% and 35%, respectively; mucin and FBS did not alter its production, while IgG and hemoglobin drastically enhanced its surface exposition around 7- and 11-fold, respectively. Additionally, hemoglobin induced an augmentation in the cell-associated cruzipain-like activity in a dose-dependent manner. A twofold increase of the secreted cruzipain-like protein was detected after parasite incubation with 1% hemoglobin compared to the parasites incubated in PBS-glucose. The results showed the ability of P. serpens in modulating the expression and the activity of proteolytic enzymes after exposition to exogenous proteins, with emphasis in its cruzipain-like molecules. Copyright © 2011 Elsevier Inc. All rights reserved.
	PMID: 22033075 [PubMed - indexed for MEDLINE]
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7.	Homeopathy. 2011 Oct;100(4):237-43. Different forms of administration of biotherapy 7dH in mice experimentally infected by Trypanosoma cruzi pr oduce different effects. Ferraz FN, Simoni GK, do Nascimento A, de Melo CS, Aleixo DL, Gomes ML, Spack M, de Araújo SM. Source Basic Health Science Department, Universidade Estadual de Maringá, Paraná, Brazil. fabiana_nabarro@hotmail.com Abstract OBJECTIVE: To evaluate the effects of different forms of administration of the blood trypomastigotes biotherapy 7dH in mice experimentally infected with Trypanosoma cruzi. MATERIAL AND METHODS: Male swiss mice were inoculated with 1400 blood trypomastigotes of the Y strain of T. cruzi and allocated into 5 treatment groups: IC (distilled water); TCBZ (benznidazole); TBA(7dH) (biotherapy 7dH 20 days after infection); TBB(7dH)7 (biotherapy 7dH seven days before infection); TBB(7dH)30 (biotherapy 7dH 30 days before infection). Parasitological parameters assessed included pre-patent and patent periods, parasitemia peak, total parasitemia, mortality and survival rates. Cure index was obtained by fresh blood examination, hemoculture and polymerase chain reaction (PCR). RESULTS: The TBB(7dH)7 group showed a reduction in parasitemia peak, parasitemia area under the curve and total parasitemia. TBB(7dH)30 showed a tendency to increased pre-patent and survival periods, peak parasitemia was increased without increased total parasitemia. TBA(7dH) did not present significant alterations in the parasitological parameters analyzed. CONCLUSIONS: Biotherapy 7dH given before infection (7 or 30 days) produces different effects suggesting modulation of the host's immune system. The effects range from reduced parasitemia to its effective increase. The use of biotherapy to treat T. cruzi infection including dose, potency and schedule deserves further investigation. Copyright © 2011 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.
	PMID: 21962198 [PubMed - indexed for MEDLINE]
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8.	Int J Epidemiol. 2011 Aug;40(4):862-7. Epub 2010 Aug 30. Cohort profile: the Bambui (Brazil) Cohort Study of Ageing. Lima-Costa MF, Firmo JO, Uchoa E. Source Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil. lima-costa@cpqrr.fiocruz.br
	PMID: 20805109 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-01-25T04:15:00.000-08:00

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Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 8 of 8

1.	PLoS Negl Trop Dis. 2012 Jan;6(1):e1467. Epub 2012 Jan 17. Should I get screened for sleeping sickness? A qualitative study in kasai province, democratic republic of congo. Mpanya A, Hendrickx D, Vuna M, Kanyinda A, Lumbala C, Tshilombo V, Mitashi P, Luboya O, Kande V, Boelaert M, Lefèvre P, Lutumba P. Source Programme National de Lutte contre la Trypanosomiase Humaine Africain (PNLTHA), Kinshasa, Democratic Republic of Congo. Abstract BACKGROUND: Control of human African trypanosomiasis (sleeping sickness) in the Democratic Republic of Congo is based on mass population active screening by mobile teams. Although generally considered a successful strategy, the community participation rates in these screening activities and ensuing treatment remain low in the Kasai-Oriental province. A better understanding of the reasons behind this observation is necessary to improve regional control activities. METHODS: Thirteen focus group discussions were held in five health zones of the Kasai-Oriental province to gain insights in the regional perceptions regarding sleeping sickness and the national control programme's activities. PRINCIPAL FINDINGS: Sleeping sickness is well known among the population and is considered a serious and life-threatening disease. The disease is acknowledged to have severe implications for the individual (e.g., persistence of manic periods and trembling hands, even after treatment), at the family level (e.g., income loss, conflicts, separations) and for communities (e.g., disruption of community life and activities). Several important barriers to screening and treatment were identified. Fear of drug toxicity, lack of confidentiality during screening procedures, financial barriers and a lack of communication between the mobile teams and local communities were described. Additionally, a number of regionally accepted prohibitions related to sleeping sickness treatment were described that were found to be a strong impediment to disease screening and treatment. These prohibitions, which do not seem to have a rational basis, have far-reaching socio-economic repercussions and severely restrict the participation in day-to-day life. CONCLUSIONS/SIGNIFICANCE: A mobile screening calendar more adapted to the local conditions with more respect for privacy, the use of less toxic drugs, and a better understanding of the origin as well as better communication about the prohibitions related to treatment would facilitate higher participation rates among the Kasai-Oriental population in sleeping sickness screening and treatment activities organized by the national HAT control programme.
	PMID: 22272367 [PubMed - in process]

2.	PLoS Negl Trop Dis. 2012 Jan;6(1):e1463. Epub 2012 Jan 17. Genetic Polymorphisms and Drug Susceptibility in Four Isolates of Leishmania tropica Obtained from Canadian Soldiers Returning from Afghanistan. Plourde M, Coelho A, Keynan Y, Larios OE, Ndao M, Ruest A, Roy G, Rubinstein E, Ouellette M. Source Centre de Recherche en Infectiologie du Centre de Recherche du CHUQ and Département de Microbiologie, Immunologie et Infectiologie, Faculté de Médecine, Université Laval, Québec, Québec, Canada. Abstract BACKGROUND: Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease characterized by the presence of one or more lesions on the skin that usually heal spontaneously after a few months. Most cases of CL worldwide occur in Southwest Asia, Africa and South America, and a number of cases have been reported among troops deployed to Afghanistan. No vaccines are available against this disease, and its treatment relies on chemotherapy. The aim of this study was to characterize parasites isolated from Canadian soldiers at the molecular level and to determine their susceptibility profile against a panel of antileishmanials to identify appropriate therapies. METHODOLOGY/PRINCIPAL FINDINGS: Parasites were isolated from skin lesions and characterized as Leishmania tropica based on their pulsed field gel electrophoresis profiles and pteridine reductase 1 (PTR1) sequences. Unusually high allelic polymorphisms were observed at several genetic loci for the L. tropica isolates that were characterized. The drug susceptibility profile of intracellular amastigote parasites was determined using an established macrophage assay. All isolates were sensitive to miltefosine, amphotericin B, sodium stibogluconate (Pentostam) and paromomycin, but were not susceptible to fluconazole. Variable levels of susceptibility were observed for the antimalarial agent atovaquone/proguanil (Malarone). Three Canadian soldiers from this study were successfully treated with miltefosine. CONCLUSIONS/SIGNIFICANCE: This study shows high heterogeneity between the two L. tropica allelic versions of a gene but despite this, L. tropica isolated from Afghanistan are susceptible to several of the antileishmanial drugs available.
	PMID: 22272366 [PubMed - in process]

3.	PLoS Negl Trop Dis. 2012 Jan;6(1):e1430. Epub 2012 Jan 17. Identification of Proteins in Promastigote and Amastigote-like Leishmania Using an Immunoproteomic Approach. Coelho VT, Oliveira JS, Valadares DG, Chávez-Fumagalli MA, Duarte MC, Lage PS, Soto M, Santoro MM, Tavares CA, Fernandes AP, Coelho EA. Source Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Abstract BACKGROUND: The present study aims to identify antigens in protein extracts of promastigote and amastigote-like Leishmania (Leishmania) chagasi syn. L. (L.) infantum recognized by antibodies present in the sera of dogs with asymptomatic and symptomatic visceral leishmaniasis (VL). METHODOLOGY/PRINCIPAL FINDINGS: Proteins recognized by sera samples were separated by two-dimensional electrophoresis (2DE) and identified by mass spectrometry. A total of 550 spots were observed in the 2DE gels, and approximately 104 proteins were identified. Several stage-specific proteins could be identified by either or both classes of sera, including, as expected, previously known proteins identified as diagnosis, virulence factors, drug targets, or vaccine candidates. Three, seven, and five hypothetical proteins could be identified in promastigote antigenic extracts; while two, eleven, and three hypothetical proteins could be identified in amastigote-like antigenic extracts by asymptomatic and symptomatic sera, as well as a combination of both, respectively. CONCLUSIONS/SIGNIFICANCE: The present study represents a significant contribution not only in identifying stage-specific L. infantum molecules, but also in revealing the expression of a large number of hypothetical proteins. Moreover, when combined, the identified proteins constitute a significant source of information for the improvement of diagnostic tools and/or vaccine development to VL.
	PMID: 22272364 [PubMed - in process]

4.	Int J Otolaryngol. 2012;2012:809056. Epub 2012 Jan 4. Epistaxis in visceral leishmaniasis with hematological correlation. Sigdel B, Bhandary S, Rijal S. Source Department of Otorhinolaryngology and Head and Neck Surgery, Gandaki Medical College, Pokhara, Nepal. Abstract Objective. To study the prevalence of epistaxis in visceral leismaniasis and its correlation with hematological profile. Methods. Out of 80 diagnosed cases of visceral leishmaniasis, 19 patients with epistaxis were included in the study. Diagnosis was made by Rk-39 from peripheral smear and LD bodies from bone marrow. Before starting anti-kala-azar treatment, nasal examination findings and hematological profile were noted. Study Design. Prospective cross-sectional hospital-based study. Results. Epistaxis was found in the age group of 7-66 years. Epistaxis was observed in 19 (23.8%) cases. One patient died because of epistaxis and neck hematoma. Conclusion. Epistaxis is a common ENT finding in endemic area of visceral leishmaniasis like our case.
	PMID: 22272206 [PubMed - in process]

5.	J Immunol. 2012 Jan 23. [Epub ahead of print] Reciprocal Regulation of Protein Kinase C Isoforms Results in Differential Cellular Responsiveness. Sudan R, Srivastava N, Pandey SP, Majumdar S, Saha B. Source National Centre for Cell Science, Ganeshkhind, Pune 411 007, India. Abstract Immunological homeostasis is often maintained by counteractive functions of two different cell types or two different receptors signaling through different intermediates in the same cell. One of these signaling intermediates is protein kinase C (PKC). Ten differentially regulated PKC isoforms are integral to receptor-triggered responses in different cells. So far, eight PKC isoforms are reported to be expressed in macrophages. Whether a single receptor differentially uses PKC isoforms to regulate counteractive effector functions has never been addressed. As CD40 is the only receptor characterized to trigger counteractive functions, we examined the relative role of PKC isoforms in the CD40-induced macrophage functions. We report that in BALB/c mouse macrophages, higher doses of CD40 stimulation induce optimum phosphorylation and translocation of PKCα, βI, βII, and ε whereas lower doses of CD40 stimulation activates PKCδ, ζ, and λ. Infection of macrophages with the protozoan parasite Leishmania major impairs PKCα, βI, βII, and ε isoforms but enhances PKCδ, ζ, and λ isoforms, suggesting a reciprocity among these PKC isoforms. Indeed, PKCα, βI, βII, and ε isoforms mediate CD40-induced p38MAPK phosphorylation, IL-12 expression, and Leishmania killing; PKCδ and ζ/λ mediate ERK1/2 phosphorylation, IL-10 production, and parasite growth. Treatment of the susceptible BALB/c mice with the lentivirally expressed PKCδ- or ζ-specific short hairpin RNA significantly reduces the infection and reinstates host-protective IFN-γ-dominated T cell response, defining the differential roles for PKC isoforms in immune homeostasis and novel PKC-targeted immunotherapeutic and parasite-derived immune evasion strategies.
	PMID: 22271653 [PubMed - as supplied by publisher]

6.	Vet Parasitol. 2012 Jan 5. [Epub ahead of print] Leishmania tropica experimental infection in the rat using luciferase-transfected parasites. Talmi-Frank D, Jaffe CL, Nasereddin A, Baneth G. Source School of Veterinary Medicine, Hebrew University, P.O. Box 12, Rehovot 76100, Israel. Abstract Leishmania tropica is the causative agent of zoonotic cutaneous leishmaniasis in different parts of the Old World. Although it is a common cause of disease in some areas of the world, there is insufficient knowledge on the pathogenicity of this parasite in mammalian hosts and animal models. L. tropica luciferase-transfected metacyclic-stage promastigotes were inoculated into the footpad or ear of Sprague Dawley (SD) rats. Parasite DNA was detected by kDNA real time PCR in the blood at varying levels from 2days to 5weeks post infection (PI) in the absence of clinical signs. Parasite DNA was found in the spleen of all rats at the end of the study, and the parasitic load was up to 40 times higher in the spleen when compared with inoculation sites. Parasites were cultured from the spleen, and skin inoculation sites 5weeks PI. Bioluminescent parasites were observed by in vivo imaging at one day PI, but the technique was not sufficiently sensitive to follow parasite spread after this time. This study provides new evidence for the viscerotropic spread of L. tropica in the rat and demonstrates that the rat can serve as a model for persistent visceralizing infection with this parasite. Copyright © 2012 Elsevier B.V. All rights reserved.
	PMID: 22270032 [PubMed - as supplied by publisher]

7.	J Leukoc Biol. 2011 Dec;90(6):1079-87. Epub 2011 Sep 13. Tregs and infections: on the potential value of modifying their function. Sehrawat S, Rouse BT. Source Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. ss1@wi.mit.edu Abstract CD4(+) T cells, which express a master transcription factor, Foxp3, have been recognized as bona fide Tregs. These cells are essential to maintain immune homeostasis in healthy as well as infected mice and humans. Extensive investigations in the last decade have provided ways to manipulate the Foxp3(+) Treg response therapeutically so the role of such cells in microbe-induced inflammatory reactions can be evaluated. This review focuses on our current understanding of the mechanisms required for the generation and sustenance of Tregs in vivo and the potential value of modulating Tregs to control microbe-induced immunopathological responses. PMCID: PMC3236550 [Available on 2012/12/1]
	PMID: 21914856 [PubMed - indexed for MEDLINE]
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8.	Eur J Pharm Biopharm. 2011 Aug;78(3):377-84. Epub 2011 Mar 17. Benznidazole microcrystal preparation by solvent ch ange precipitation and in vivo evaluation in the treatment of Chagas disease. Maximiano FP, de Paula LM, Figueiredo VP, de Andrade IM, Talvani A, Sá-Barreto LC, Bahia MT, Cunha-Filho MS. Source Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto-MG, Brazil. Abstract Benznidazole (BNZ) is traditionally used to treat Chagas disease. Despite its common use, BNZ has a poor water solubility and a variable bioavailability. The purpose of this study was to prepare BNZ microcrystals by solvent change precipitation and to study the effects of BNZ micronisation on therapeutic efficiency using a murine model of Chagas disease. The solvent change precipitation procedure was optimised in order to obtain stable and homogeneous particles with a small particle size, high yield and fast dissolution rate. The thermal and crystallographic analysis showed no polymorphic change in the microcrystals, and microscopy confirmed a significant reduction in particle size. A marked improvement in the drug dissolution rate was observed for micronised BNZ particles and BNZ tablets in comparison with untreated BNZ and commercial Rochagan. In vivo studies showed a significant increase in the therapeutic efficacy of the BNZ microparticles, corroborating the dissolution results. Copyright © 2011 Elsevier B.V. All rights reserved.
	PMID: 21397015 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-01-24T04:10:00.000-08:00

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
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Sender's message:

Sent on Tuesday, 2012 January 24
Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 10 of 10

1.	J Biol Chem. 2012 Jan 20. [Epub ahead of print] A Mitochondrial membrane complex that contains proteins necessary for tRNA import in Trypanosoma brucei. Seidman D, Johsnon D, Gerbasi V, Golden D, Orlando R, Hajduk S. Source The University of Georgia, United States; Abstract The mitochondrial genome of Trypanosoma brucei does not contain genes encoding tRNAs, instead this protozoan parasite must import nuclear encoded tRNAs from the cytosol for mitochondrial translation. Previously, it has been shown that mitochondrial tRNA import requires ATP hydrolysis and a proteinaceous mitochondrial membrane component. However, little is known about the mitochondrial membrane proteins involved in tRNA binding and translocation into the mitochondrion. Here we report the purification of a mitochondrial membrane complex using tRNA affinity purification and have identified several protein components of the putative tRNA translocon by mass spectrometry. Using an in vivo tRNA import assay, in combination with RNA interference, we have verified that two of these proteins, Tb11.01.4590 and Tb09.v1.0420, are involved in mitochondrial tRNA import. Using PTP-tagged Tb11.01.4590, additional associated proteins were identified including Tim17 and other mitochondrial proteins necessary for mitochondrial protein import. Results presented here identify and validate two novel protein components of the putative tRNA translocon and provide additional evidence that mitochondrial tRNA and protein import have shared components in trypanosomes.
	PMID: 22267727 [PubMed - as supplied by publisher]

2.	Bioorg Med Chem. 2011 Dec 27. [Epub ahead of print] Quinol derivatives as potential trypanocidal agents. Capes A, Patterson S, Wyllie S, Hallyburton I, Collie IT, McCarroll AJ, Stevens MF, Frearson JA, Wyatt PG, Fairlamb AH, Gilbert IH. Source Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. Abstract Quinols have been developed as a class of potential anti-cancer compounds. They are thought to act as double Michael acceptors, forming two covalent bonds to their target protein(s). Quinols have also been shown to have activity against the parasite Trypanosoma brucei, the causative organism of human African trypanosomiasis, but they demonstrated little selectivity over mammalian MRC5 cells in a counter-screen. In this paper, we report screening of further examples of quinols against T. brucei. We were able to derive an SAR, but the compounds demonstrated little selectivity over MRC5 cells. In an approach to increase selectivity, we attached melamine and benzamidine motifs to the quinols, because these moieties are known to be selectively concentrated in the parasite by transporter proteins. In general these transporter motif-containing analogues showed increased selectivity; however they also showed reduced levels of potency against T. brucei. Copyright © 2011 Elsevier Ltd. All rights reserved.
	PMID: 22264753 [PubMed - as supplied by publisher]

3.	Lipids Health Dis. 2012 Jan 20;11(1):13. [Epub ahead of print] Synthesis of lipophilic tyrosyl esters derivatives and assessment of their antimicrobial and antileishmania activities. Aissa I, Sghair RM, Bouaziz M, Laouini D, Sayadi S, Gargouri Y. Abstract ABSTRACT: BACKGROUND: Preparation of tyrosyl lipophilic derivatives was carried out as a response to the food, cosmetic and pharmaceutical industries' increasing demand for new lipophilic antioxidants. RESULTS: A large series of tyrosyl esters (TyC2 to TyC18:1) with increasing lipophilicity was synthesized in a good yield using lipase from Candida antarctica (Novozyme 435). Spectroscopic analyses of purified esters showed that the tyrosol was esterified on the primary hydroxyl group. Synthetized compounds were evaluated for either their antimicrobial activity, by both diffusion well and minimal inhibition concentration (MIC) methods, or their antileishmanial activity against Leishmania major and Leishmania infantum parasite species. Among all the tested compounds, our results showed that only TyC8, TyC10 and TyC12 exhibited antibacterial and antileishmanial activities. When MIC and IC50 values were plotted against the acyl chain length of each tyrosyl derivative, TyC10 showed a parabolic shape with a minimum value. This nonlinear dependency with the increase of the chain length indicates that biological activities are probably associated to the surfactant effectiveness of lipophilic derivatives. CONCLUSION: These results open up potential applications to use medium tyrosyl derivatives surfactants, antioxidants, antimicrobial and antileishmanial compounds in cosmetic, food and pharmaceutical industries.
	PMID: 22264330 [PubMed - as supplied by publisher]

4.	Vet Rec. 2011 Nov 19;169(21):541. New approach to cattle vaccination. [No authors listed]
	PMID: 22102345 [PubMed - indexed for MEDLINE]
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5.	Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19288-92. Epub 2011 Nov 14. Socially tra nsmitted gut microbiota protect bumble bees against an intestinal parasite. Koch H, Schmid-Hempel P. Source Institute of Integrative Biology, Swiss Federal Institute of Technology, ETH, Zürich, CH-8092 Zürich, Switzerland. Abstract Populations of important pollinators, such as bumble bees and honey bees, are declining at alarming rates worldwide. Parasites are likely contributing to this phenomenon. A distinct resident community of bacteria has recently been identified in bumble bees and honey bees that is not shared with related solitary bee species. We now show that the presence of these microbiota protects bee hosts against a widespread and highly virulent natural parasite (Crithidia bombi) in an experimental setting. We add further support to this antagonistic relationship from patterns found in field data. For the successful establishment of these microbiota and a protective effect, exposure to feces from nest mates was needed after pupal eclosion. Transmission of beneficial gut bacteria could therefore represent an important benefit of sociality. Our results stress the importance of considering the host microbiota as an "extended immune phenotype" in addition to the host immune system itself and provide a unique perspective to understanding bees in health and disease. PMCID: PMC3228419 [Available on 2012/5/29]
	PMID: 22084077 [PubMed - indexed for MEDLINE]
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6.	Am J Pathol. 2011 Oct;179(4):1894-904. Epub 2011 Aug 3. Mast cell function and death in Trypanosoma cruzi infection. Meuser-Batista M, Corrêa JR, Carvalho VF, de Carvalho Britto CF, da Cruz Moreira O, Batista MM, Soares MJ, Filho FA, E Silva PM, Lannes-Vieira J, Silva RC, Henriques-Pons A. Source Laboratório de Inovações em Terapias, Ensino, e Bioprodutos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. meuser@ioc.fiocruz.br Abstract Although the roles of mast cells (MCs) are essential in many inflammatory and fibrotic diseases, their role in Trypanosoma cruzi-induced cardiomyopathy is unexplored. In this study, we treated infected CBA mice with cromolyn, an MC stabilizer, and observed much greater parasitemia and interferon-γ levels, higher mortality, myocarditis, and cardiac damage. Although these data show that MCs are important in controlling acute infection, we observed MC apoptosis in the cardiac tissue and peritoneal cavity of untreated mice. In the heart, pericardial mucosal MC die, perhaps because of reduced amounts of local stem cell factor. Using RT-PCR in purified cardiac MCs, we observed that infection induced transcription of P2X(7) receptor and Fas, two molecules reportedly involved in cell death and inflammatory regulation. In gld/gld mice (FasL(-/-)), apoptosis of cardiac, but not peritoneal, MCs was decreased. Conversely, infection of P2X(7)(-/-) mice led to reduced peritoneal, but not cardiac, MC death. These data illustrate the immunomodulatory role played by MCs in T. cruzi infection and the complexity of molecular interactions that control inflammatory pathways in different tissues and compartments. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. PMCID: PMC3181382 [Available on 2012/10/1]
	PMID: 21819958 [PubMed - indexed for MEDLINE]
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7.	Asian Pac J Trop Med. 2011 Mar;4(3):234-40. Epub 2011 Apr 12. Choice of providers for treating a neglected tropical disease: an empirical anal ysis of kala azar in Nepal. Adhikari SR, Supakankunti S, Khan MM. Source Patan Multiple Campus, Tribhuvan University, Nepal. sssadhikari@yahoo.com Abstract OBJECTIVE: To examine the choice of healthcare providers for treating kala azar (KA) in Nepal. METHODS: Information was collected from clinically diagnosed KA patients seeking care from public hospitals located in KA endemic districts. The survey collected information from more than 25 percent of total KA cases in the country. For empirical estimation of probability of choosing a provider-type as a first contact healthcare provider, a multinomial logit model was defined with five alternative options with self care as the reference category. RESULTS: The empirical model found that price of medical care services, income of households, knowledge of patients on KA and KA treatment, borrowing money, age of patient, perceived quality of provider types, etc. determine the likelihood of seeking care from the alternative options considered in the analysis. All variables have expected signs and are consistent with earlier studies. The price and income elasticity were found to be very high indicating that poorer households are very sensitive to price and income changes, even for a severe disease like KA. Using the empirical models, we have analyzed two policy instruments: demand side financing and interventions to improve the knowledge index about KA. CONCLUSIONS: Due to high price elasticity of KA care and high spillover effects of KA on the society, policy makers may consider demand side financing as an instrument to encourage utilization of public hospitals. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.
	PMID: 21771461 [PubMed - indexed for MEDLINE]
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8.	Microbiology. 2011 Oct;157(Pt 10):2818-30. Epub 2011 Jul 14. Characterization of a porin channel in the endosymbiont of the trypanosomatid p rotozoan Crithidia deanei. Andrade Ida S, Vianez-Júnior JL, Goulart CL, Homblé F, Ruysschaert JM, Almeida von Krüger WM, Bisch PM, de Souza W, Mohana-Borges R, Motta MC. Source Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Abstract Crithidia deanei is a trypanosomatid protozoan that harbours a symbiotic bacterium. The partners maintain a mutualistic relationship, thus constituting an excellent model for studying metabolic exchanges between the host and the symbiont, the origin of organelles and cellular evolution. According to molecular analysis, symbionts of different trypanosomatid species share high identity and descend from a common ancestor, a β-proteobacterium of the genus Bordetella. The endosymbiont is surrounded by two membranes, like Gram-negative bacteria, but its envelope presents special features, since phosphatidylcholine is a major membrane component and the peptidoglycan layer is highly reduced, as described in other obligate intracellular bacteria. Like the process that generated mitochondria and plastids, the endosymbiosis in trypanosomatids depends on pathways that facilitate the intensive metabolic exchanges between the bacterium and the host protozoan. A search of the annotated symbiont genome database identified one sequence with identity to porin-encoding genes of the genus Bordetella. Considering that the symbiont outer membrane has a great accessibility to cytoplasm host factors, it was important to characterize this single porin-like protein using biochemical, molecular, computational and ultrastructural approaches. Antiserum against the recombinant porin-like molecule revealed that it is mainly located in the symbiont envelope. Secondary structure analysis and comparative modelling predicted the protein 3D structure as an 18-domain β-barrel, which is consistent with porin channels. Electrophysiological measurements showed that the porin displays a slight preference for cations over anions. Taken together, the data presented herein suggest that the C. deanei endosymbiont porin is phylogenetically and structurally similar to those described in Gram-negative bacteria, representing a diffusion channel that might contribute to the exchange of nutrients and metabolic precursors between the symbiont and its host cell.
	PMID: 21757490 [PubMed - indexed for MEDLINE]
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9.	Int J Parasitol. 2008 Nov;38(13):1533-43. Epub 2008 May 24. Molecular epidemiology of domestic and sylvatic Trypanoso ma cruzi infection in rural northwestern Argentina. Cardinal MV, Lauricella MA, Ceballos LA, Lanati L, Marcet PL, Levin MJ, Kitron U, Gürtler RE, Schijman AG. Source Laboratorio de Eco-Epidemiología, Departamento de Ecología, Genética y Evolución, Universidad de Buenos Aires, Buenos Aires, Argentina. Abstract Genetic diversity of Trypanosoma cruzi populations and parasite transmission dynamics have been well documented throughout the Americas, but few studies have been conducted in the Gran Chaco ecoregion, one of the most highly endemic areas for Chagas disease, caused by T. cruzi. In this study, we assessed the distribution of T. cruzi lineages (identified by PCR strategies) in Triatoma infestans, domestic dogs, cats, humans and sylvatic mammals from two neighbouring rural areas with different histories of transmission and vector control in northern Argentina. Lineage II predominated amongst the 99 isolates characterised and lineage I amongst the six isolates obtained from sylvatic mammals. T. cruzi lineage IIe predominated in domestic habitats; it was found in 87% of 54 isolates from Tr. infestans, in 82% of 33 isolates from dogs, and in the four cats found infected. Domestic and sylvatic cycles overlapped in the study area in the late 1980s, when intense domestic transmission occurred, and still overlap marginally. The introduction of T. cruzi from sylvatic into domestic habitats is likely to occur very rarely in the current epidemiological context. The household distribution of T. cruzi lineages showed that Tr. infestans, dogs and cats from a given house compound shared the same parasite lineage in most cases. Based on molecular evidence, this result lends further support to the importance of dogs and cats as domestic reservoir hosts of T. cruzi. We believe that in Argentina, this is the first time that lineage IIc has been isolated from naturally infected domestic dogs and Tr. infestans. PMCID: PMC3143243 Free PMC Article
	PMID: 18585717 [PubMed - indexed for MEDLINE]
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10.	Int J Parasitol. 2008 Nov;38(13):1481-92. Epub 2008 May 21. Some components of the cardiac β-adrenergic system are altered in the chronic indeterminate form of experimental Trypanosoma cruzi infection. Silvina Lo Presti M, Walter Rivarola H, Bustamante JM, Fernández AR, Enders JE, Levin G, Juaneda E, Fretes R, Fernanda Triquell M, Paglini-Oliva PA. Source Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, PC 5000 Córdoba, Argentina. Abstract The chronic indeterminate form of Trypanosoma cruzi infection could be the key to knowing which patients will develop chagasic myocardiopathy. Infected mice present a period in which cardiac functional and structural alterations are different from those described for acute or chronic phases. We studied some components of the cardiac β-adrenergic system in mouse hearts infected with T. cruzi Tulahuen strain or SGO-Z12 isolate during the chronic indeterminate phase of infection. We determined: (i) the primary messenger (epinephrine and norepinephrine) levels in plasma by reverse-phase-HPLC; (ii) the cardiac β-adrenergic receptors' (β-AR) density and affinity by binding with tritiated dihidroalprenolol and by immunofluorescence; (iii) the cardiac concentration of the second messenger (cAMP) (by ELISA) given its importance for the phosphorylation of the proteins involved in cardiac contraction; (iv) the cardiac contractility and functional studies of the β-ARs as a response to the ligand binding to the receptor; and (v) the left ventricular ejection fraction as a measure of in vivo cardiac function. Plasma catecholamines levels remained similar to those found in uninfected controls. The β-ARs' affinity decreased in both infected groups compared with the uninfected group (P<0.05) while the receptors' density increased only in the SGO-Z12 group (P<0.01). Cyclic AMP levels were higher in both infected groups (P<0.01) relative to controls, and were higher in SGO-Z12-infected mice compared with those infected with the Tulahuen strain. However, the basal contractile force remained unchanged and the response to catecholamines only increased in the Tulahuen group (P<0.05). The left ventricular ejection fraction, on the other hand, was diminished in SGO-Z12-infected mice. Heterogeneity between T. cruzi strains determine, in the chronic indeterminate form, alterations in the signaling pathways of the β-adrenergic system at different levels: (i) between catecholamines and the β(1)-receptors; (ii) between the receptors' activation and the adenylyl-cyclase activation; and/or (iii) between cAMP and the contractile response.
	PMID: 18582889 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-01-21T04:30:00.000-08:00

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Sent on Saturday, 2012 January 21
Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 5 of 5

1.	Emerg Infect Dis. 2012 Jan;18(1):165-7. doi: 10.3201/eid1801.111384. Urban transmission of human african trypanosomiasis, Gabon. Simon F, Mura M, Pagès F, Morand G, Truc P, Louis F, Gautret P. Abstract TO THE EDITOR: We describe a confirmed case of human African trypanosomiasis (HAT) in an expatriate returning to France from Gabon after a probable tsetse fly bite in the urban setting of Libreville. This case indicates a possible urban transmission of HAT in Gabon and stresses the need for entomologic studies in Libreville.
	PMID: 22261276 [PubMed - in process]

2.	Parasit Vectors. 2012 Jan 19;5(1):20. [Epub ahead of print] The transmission of Leishmania in fantum chagasi by the bite of the Lutzomyia longipalpis to two different vertebrates. Secundino NF, Freitas VC, Monteiro CC, Pires AC, David BA, Pimenta PF. Abstract ABSTRACT: BACKGROUND: Sandflies are vectors of Leishmania, the causative agent of leishmaniasis in mammalian hosts, including humans. The protozoan parasite is transmitted by the sandfly bite during salivation that occurs at the moment of blood feeding. The components of vector saliva include anticlotting and vasodilatory factors that facilitate blood flow and immunomodulatory factors that inhibit wound healing and quell the immune response. Not surprisingly, these factors also play important roles in the establishment of Leishmania infection. To date, the majority of knowledge that has been generated regarding the process of Leishmania infection, including L. infantum chagasi transmission has been gathered by using intradermal or subcutaneous inoculation of purified parasites. FINDINGS: This study presents the establishment of a transmission model of Leishmania infantum chagasi by the bite of Lutzomyia longipalpis, the vector of American visceral leishmaniasis. The parasites were successfully transmitted by infected sandfly bites to mice and hamsters, indicating that both animals are good experimental models. The L. infantum chagasi dose that was transmitted in each single bite ranged from 10 to 10, 000 parasites, but 75% of the sandflies transmitted less than 300 parasites. CONCLUSIONS: The strategy for initiating infection by sandfly bite of experimental animals facilitates future investigations into the complex and dynamic mechanisms of visceral leishmaniasis. It is important to elucidate the transmission mechanism of vector bites. This model represents a useful tool to study L. infantum chagasi infection transmitted by the vector.
	PMID: 22260275 [PubMed - as supplied by publisher]

3.	Rev Esp Quimioter. 2011 Sep;24(3):123-6. Side effects of benznidazole treatment in a cohort of patients with Chagas disease in non-endemic country. Carrilero B, Murcia L, Martínez-Lage L, Segovia M. Source Unidad Regional de Medicina Tropical, Servicio de Microbiología, Hospital Universitario Virgen de la Arrixaca, Carretera Madrid-Cartagena, El Palmar Murcia, Spain. Abstract Chagas disease is a disease endemic in Latin America, caused by the parasite Trypanosoma cruzi. Benznidazole is the most commonly used drug for the etiological treatment of the disease although its effectiveness varies according to the phase of the same and toxic side effects are frequent. This prospective study describes the side effects of benznidazole treatment of a cohort of 373 chronic patients. Of these 40.2% presented adverse reactions. The most frequent side effect were dermatological reactions 32.4% (121 of 373) followed by digestive intolerance 9.1% (34 of 373). Surprisingly, three cases of migratory arthritis were observed. Patients treated with benznidazole must be followed up so that the long term incidence of side effects can be studied. Free Article
	PMID: 21947093 [PubMed - indexed for MEDLINE]
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4.	Rev Med Chil. 2011 Feb;139(2):258-66. Epub 2011 Jul 11. [Oral transmission of Chagas' disease]. [Article in Spanish] Toso M A, Vial U F, Galanti N. Source Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de ChileSantiago, Chile. Abstract The traditional transmission pathways of Chagas' disease are vectorial, transfusional, transplacental and organ transplantation. However, oral transmission is gaining importance. The first evidence of oral transmission was reported in Brazil in 1965. Nowadays the oral route is the transmission mode in 50% of cases in the Amazon river zone. Oral infection is produced by the ingestion of infected triatomine bugs or their feces, undercooked meat from infested host animals and food contaminated with urine or anal secretion of infected marsupials. Therefore travelers to those zones should be advised about care to be taken with ingested food. In Chile, this new mode of transmission should be considered in public health policies. Free Article
	PMID: 21773665 [PubMed - indexed for MEDLINE]
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5.	Rev Med Chil. 2011 Feb;139(2):247-57. Epub 2011 Jul 11. [Update on the treatment of Chagas' disease]. [ Article in Spanish] Apt W, Zulantay I. Source Laboratorio de Parasitología Básico-Clínico, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. wapt@med.uchile.cl Abstract Efficient drugs against Chagas' disease must have an effect on the amastigote forms or intracellular reproduction elements of Trypanosoma cruzi (T. cruzi). Trypomastigote and epimastigote forms derive from the former and their response to medications is less marked. The only drugs used in humans are nifurtimox (NF) and benznidazole (BNZ). Other useful medications are allopurinol and itraconazole. NF acts producing free radicals and BNZ inhibits the synthesis of macromolecules. There is consensus that Chagas' disease must be treated in all its periods, since T.cruzi DNA is detected by polymerase chain reaction in chronic cases, even when microscopy is negative. The pharmacological treatment modifies the natural evolution of the disease. It also helps to solve a public health problem, considering that there is a high number of subjects with Chagas' disease. Subjects with chronic chagasic cardiomyopathy with terminal heart failure are the only cases without indication for treatment. Due to the digestive and skin secondary effects of the drugs, treated patients must be controlled clinically and with complete blood counts and hepatic proiles before, during and after the therapy. Approximately 30% of patients will experience secondary effects. Children have a better tolerance to the drugs. Congenital or acquired acute, intermediate and chronic cases should be treated. Free Article
	PMID: 21773664 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-01-20T10:53:00.000-08:00

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Sent on Friday, 2012 January 20
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PubMed Results

Items 1 - 10 of 11

1.	Dermatoendocrinol. 2011 Oct;3(4):220-9. Epub 2011 Oct 1. Antimicrobial implications of vitamin D. Youssef DA, Miller CW, El-Abbassi AM, Cutchins DC, Cutchins C, Grant WB, Peiris AN. Source Mountain Home VAMC Medicine Service; Mountain Home; TN USA. Abstract Evidence exists that vitamin D has a potential antimicrobial activity and its deficiency has deleterious effects on general well-being and longevity. Vitamin D may reduce the risk of infection through multiple mechanisms. Vitamin D boosts innate immunity by modulating production of anti-microbial peptides (AMPs) and cytokine response. Vitamin D and its analogues via these mechanisms are playing an increasing role in the management of atopic dermatitis, psoriasis, vitiligo, acne and rosacea. Vitamin D may reduce susceptibility to infection in patients with atopic dermatitis and the ability to regulate local immune and inflammatory responses offers exciting potential for understanding and treating chronic inflammatory dermatitides. Moreover, B and T cell activation as well as boosting the activity of monocytes and macrophages also contribute to a potent systemic anti-microbial effect. The direct invasion by pathogenic organisms may be minimized at sites such as the respiratory tract by enhancing clearance of invading organisms. A vitamin D replete state appears to benefit most infections, with the possible noteworthy exception of Leishmaniasis. Antibiotics remain an expensive option and misuse of these agents results in significant antibiotic resistance and contributes to escalating health care costs. Vitamin D constitutes an inexpensive prophylactic option and possibly therapeutic product either by itself or as a synergistic agent to traditional antimicrobial agents. This review outlines the specific antimicrobial properties of vitamin D in combating a wide range of organisms. We discuss the possible mechanisms by which vitamin D may have a therapeutic role in managing a variety of infections.
	PMID: 22259647 [PubMed - in process]

2.	J Antimicrob Chemother. 2012 Jan 18. [Epub ahead of print] Asiaticoside induces tumour-necrosis-factor-α-mediated nitric oxide production to cure experimental visceral leishmaniasis caused by antimony-susceptible and -resistant Leishmania donovani strains. Bhaumik SK, Paul J, Naskar K, Karmakar S, De T. Source Division of Infectious Disease and Immunology, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India. Abstract OBJECTIVES: The aim of this study was to investigate and characterize the efficacy of asiaticoside in an experimental model of visceral leishmaniasis caused by antimony-susceptible (AG83) and -resistant (GE1F8R and K39) Leishmania donovani. METHODS: The effect of asiaticoside was evaluated by microscopic counting of intracellular amastigotes in cultured macrophages stained with Giemsa. The antileishmanial effect of the compounds was assessed in infected BALB/c mice by estimation of splenic and liver parasite burdens in Leishman Donovan units. Cytokines were measured by real-time PCR and ELISA. Intracellular tumour necrosis factor-α (TNF-α) was measured by fluorescence-activated cell sorting. Nitric oxide was measured by the Griess reaction. RESULTS: Besides effectively inhibiting in vitro replication of the parasite within macrophages, asiaticoside treatment resulted in almost complete clearance of the liver and splenic parasite burden when administered at a dose of 5 mg/kg × 10 starting on day +30 of challenge with antimony-susceptible (AG83) and -resistant (GE1F8R and K39) L. donovani. Asiaticoside treatment was associated with a switch in the host from a Th2- to a Th1-type immune response accompanied by the induction of TNF-α-mediated nitric oxide production, all of which are important elements for macrophage function in antileishmanial defence mechanisms. CONCLUSIONS: These results suggest that oral therapy with asiaticoside shows promising antileishmanial efficacy in animals infected by antimony-susceptible (AG83) and -resistant (GE1F8R and K39) L. donovani.
	PMID: 22258930 [PubMed - as supplied by publisher]

3.	RNA Biol. 2012 Jan 1;9(1). [Epub ahead of print] Pseudogenes are not pseudo any more. Wen YZ, Zheng LL, Qu LH, Ayala FJ, Lun ZR. Source Center for Parasitic Organisms, State Key Laboratory of Biocontrol, School of Life Sciences and Key Laboratory of Tropical Diseases and Control of the Ministry of Education, Zhongshan Medical School, Sun Yat-Sen University; Guangzhou, China. Abstract Recent significant progress towards understanding the function of pseudogenes in protozoa (Trypanosoma brucei), metazoa (mouse) and plants, make it pertinent to provide a brief overview on what has been learned about this fascinating subject. We discuss the regulatory mechanisms of pseudogenes at the post-transcriptional level and advance new ideas towards understanding the evolution of these, sometimes called "garbage genes" or "junk DNA," seeking to stimulate the interest of scientists and additional research on the subject. We hope this mini review can be helpful to scientists working or seeking to work on these and related issues.
	PMID: 22258143 [PubMed - as supplied by publisher]

4.	Emerg Infect Dis. 2012 Jan;18(1):184-6. doi: 10.3201/eid1801.102001. Visceral Leishmaniasis during Italian Renaissance, 1522-1562. Nerlich AG, Bianucci R, Trisciuoglio A, Schönian G, Ball M, Giuffra V, Bachmeier B, Pusch CM, Ferroglio E, Fornaciari G. Abstract TO THE EDITOR: Leishmaniasis, an infectious disease caused by parasites of the genus Leishmania, is transmitted to humans through the bite of a female sandfly. The 3 forms of leishmaniasis are visceral (VL) and cutaneous (CL), which are typical of the Old World, and mucocutaneous leishmaniasis, which occurs primarily in Central and South America. VL (also called kala-azar) is caused by species of the L. donovani complex (including L. infantum), and CL is mainly caused by L. major or L. tropica (1). In Italy, VL and CL are caused by L. infantum. The origin and spread of leishmaniasis are a matter of debate. Widespread in antiquity, visceral leishmaniasis has been identified only in mummies from ancient Egypt and upper Nubia (2). Similarly, only 4 cases of mucocutaneous leishmaniasis have been identified in skulls from northern Chile (3).
	PMID: 22257739 [PubMed - in process]

5.	Emerg Infect Dis. 2012 Jan;18(1):183-4. doi: 10.3201/eid1801.110408. Cutaneous leishmaniasis acquired in jura, france. Faber WR, Hoekzema R, Bart A, Zeegelaar JE, de Vries HJ. Abstract TO THE EDITOR: Cutaneous leishmaniasis is well established in the Mediterranean basin. However, the disease is spreading and new foci have been reported (1-3). Because of climate change, it is feasible that vector-borne diseases such as cutaneous leishmaniasis may spread northward into Europe (4). We report a patient who acquired cutaneous leishmaniasis while on holiday in Jura, France.
	PMID: 22257720 [PubMed - in process]

6.	BMC Genomics. 2012 Jan 18;13(1):29. [Epub ahead of print] Centromere-associated repeat arrays on Trypanosoma brucei chromosomes are much more extensive than predicted. Echeverry MC, Bot C, Obado SO, Taylor MC, Kelly JM. Abstract ABSTRACT: BACKGROUND: African trypanosomes belong to a eukaryotic lineage which displays many unusual genetic features. The mechanisms of chromosome segregation in these diploid protozoan parasites are poorly understood. Centromeres in Trypanosoma brucei have been localised to chromosomal regions that contain an array of ~147 bp AT-rich tandem repeats. Initial estimates from the genome sequencing project suggested that these arrays ranged from 2 - 8 kb. In this paper, we show that the centromeric repeat regions are much more extensive. RESULTS: We used a long-range restriction endonuclease mapping approach to more accurately define the sizes of the centromeric repeat arrays on the 8 T. brucei chromosomes where unambiguous assembly data were available. The results indicate that the sizes of the arrays on different chromosomes vary from 20 to 120 kb. In addition, we found instances of length heterogeneity between chromosome homologues. For example, values of 20 and 65 kb were obtained for the arrays on chromosome 1, and 50 and 75 kb for chromosome 5. CONCLUSIONS: Our results show that centromeric repeat arrays on T. brucei chromosomes are more similar in size to those of higher eukaryotes than previously suspected. This information provides a firmer framework for investigating aspects of chromosome segregation and will allow epigenetic features associated with the process to be more accurately mapped.
	PMID: 22257693 [PubMed - as supplied by publisher]

7.	Cell Microbiol. 2012 Jan 19. doi: 10.1111/j.1462-5822.2012.01756.x. [Epub ahead of print] Trafficking and release of the metacyclic HASPB protein in the kinetoplastid parasite Leishmania. Maclean LM, O'Toole PJ, Stark M, Marrison J, Seelenmeyer C, Nickel W, Smith DF. Source Centre for Immunology and Infection, Department of Biology/Hull York Medical School, University of York, York YO10 5YW, UK Technology Facility, Department of Biology, University of York, Heslington, York YO10 5YW, UK Heidelberg University Biochemistry Center, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany. Abstract Proteins of the Leishmania HASPB family are only expressed in infective parasites (both extra- and intracellular stages) and, together with the peripheral membrane protein SHERP, are essential for parasite differentiation (metacyclogenesis) in the sand fly vector. HASPB is a "non-classically" secreted protein, requiring N-terminal acylation for trafficking to and exposure on the plasma membrane. Here, we use live cell imaging methods to further explore this pathway to the membrane and flagellum. Unlike HASPB trafficking in transfected mammalian cells, we find no evidence for a phosphorylation-regulated recycling pathway in metacyclic parasites. Once at the plasma membrane, HASPB18-GFP can undergo bidirectional movement within the inner leaflet of the membrane and on the flagellum. Transfer of fluorescent protein between the flagellum and the plasma membrane is compromised, however, suggesting the presence of a diffusion barrier at the base of the Leishmania flagellum. Full-length HASPB is released from the metacyclic parasite surface on to macrophages during phagocytosis but while expression is maintained in intracellular amastigotes, HASPB cannot be detected on the external surface in these cells. Thus HASPB may be a dual function protein that is shed by the infective metacyclic but retained internally once Leishmania are taken up by macrophages. © 2012 Blackwell Publishing Ltd. © 2012 Blackwell Publishing Ltd.
	PMID: 22256896 [PubMed - as supplied by publisher]

8.	PLoS Negl Trop Dis. 2011 Aug;5(8):e1272. Epub 2011 Aug 2. Analyses of 32 loci clarify phylogenetic relationships among Trypanosoma cruzi lineages and support a single hybridization prior to human contact. Flores-López CA, Machado CA. Source Department of Biology, University of Maryland, College Park, MD, USA. Abstract BACKGROUND: The genetic diversity of Trypanosoma cruzi, the etiological agent of Chagas disease, has been traditionally divided in two major groups, T. cruzi I and II, corresponding to discrete typing units TcI and TcII-VI under a recently proposed nomenclature. The two major groups of T. cruzi seem to differ in important biological characteristics, and are thus thought to represent a natural division relevant for epidemiological studies and development of prophylaxis. To understand the potential connection between the different manifestations of Chagas disease and variability of T. cruzi strains, it is essential to have a correct reconstruction of the evolutionary history of T. cruzi. METHODOLOGY/PRINCIPAL FINDINGS: Nucleotide sequences from 32 unlinked loci (>26 Kilobases of aligned sequence) were used to reconstruct the evolutionary history of strains representing the known genetic variability of T. cruzi. Thorough phylogenetic analyses show that the original classification of T. cruzi in two major lineages does not reflect its evolutionary history and that there is only strong evidence for one major and recent hybridization event in the history of this species. Furthermore, estimates of divergence times using Bayesian methods show that current extant lineages of T. cruzi diverged very recently, within the last 3 million years, and that the major hybridization event leading to hybrid lineages TcV and TcVI occurred less than 1 million years ago, well before the contact of T. cruzi with humans in South America. CONCLUSIONS/SIGNIFICANCE: The described phylogenetic relationships among the six major genetic subdivisions of T. cruzi should serve as guidelines for targeted epidemiological and prophylaxis studies. We suggest that it is important to reconsider conclusions from previous studies that have attempted to uncover important biological differences between the two originally defined major lineages of T. cruzi especially if those conclusions were obtained from single or few strains. PMCID: PMC3149036 Free PMC Article
	PMID: 21829751 [PubMed - indexed for MEDLINE]
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9.	PLoS Negl Trop Dis. 2011 Aug;5(8):e1226. Epub 2011 Aug 2. How do tsetse recognise their hosts? The role of shape in the responses of tsetse (Glossina fuscipes and G. palpalis) to artificial hosts. Tirados I, Esterhuizen J, Rayaisse JB, Diarrassouba A, Kaba D, Mpiana S, Vale GA, Solano P, Lehane MJ, Torr SJ. Source Natural Resource Institute, University of Greenwich, Chatham, Kent, United Kingdom. Abstract Palpalis-group tsetse, particularly the subspecies of Glossina palpalis and G. fuscipes, are the most important transmitters of human African trypanomiasis (HAT), transmitting >95% of cases. Traps and insecticide-treated targets are used to control tsetse but more cost-effective baits might be developed through a better understanding of the fly's host-seeking behaviour. Electrocuting grids were used to assess the numbers of G. palpalis palpalis and G. fuscipes quanzensis attracted to and landing on square or oblong targets of black cloth varying in size from 0.01 m(2) to 1.0 m(2). For both species, increasing the size of a square target from 0.01 m(2) (dimensions=0.1 × 0.1 m) to 1.0 m(2) (1.0 × 1.0 m) increased the catch ~4x however the numbers of tsetse killed per unit area of target declined with target size suggesting that the most cost efficient targets are not the largest. For G. f. quanzensis, horizontal oblongs, (1 m wide × 0.5 m high) caught ~1.8x more tsetse than vertical ones (0.5 m wide × 1.0 m high) but the opposite applied for G. p. palpalis. Shape preference was consistent over the range of target sizes. For G. p. palpalis square targets caught as many tsetse as the oblong; while the evidence is less strong the same appears to apply to G. f. quanzensis. The results suggest that targets used to control G. p. palpalis and G. f. quanzensis should be square, and that the most cost-effective designs, as judged by the numbers of tsetse caught per area of target, are likely to be in the region of 0.25 × 0.25 m(2). The preference of G. p. palpalis for vertical oblongs is unique amongst tsetse species, and it is suggested that this response might be related to its anthropophagic behaviour and hence importance as a vector of HAT. PMCID: PMC3149008 Free PMC Article
	PMID: 21829734 [PubMed - indexed for MEDLINE]
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10.	Protist. 2011 Jul;162(3):503-24. Epub 2011 Mar 21. Phylogenetic validation of the genera Angomonas and Strigomonas of trypanosomatids harboring bacterial endosymbionts with the description of new species of trypanosomatids and of proteobacterial symbionts. Teixeir a MM, Borghesan TC, Ferreira RC, Santos MA, Takata CS, Campaner M, Nunes VL, Milder RV, de Souza W, Camargo EP. Source Department of Parasitology, ICB, University of São Paulo (USP), São Paulo, 05508-000, SP, Brazil. mmgteix@icb.usp.br Abstract We comparatively examined the nutritional, molecular and optical and electron microscopical characteristics of reference species and new isolates of trypanosomatids harboring bacterial endosymbionts. Sequencing of the V7V8 region of the small subunit of the ribosomal RNA (SSU rRNA) gene distinguished six major genotypes among the 13 isolates examined. The entire sequences of the SSU rRNA and glycosomal glyceraldehyde phosphate dehydrogenase (gGAPDH) genes were obtained for phylogenetic analyses. In the resulting phylogenetic trees, the symbiont-harboring species clustered as a major clade comprising two subclades that corresponded to the proposed genera Angomonas and Strigomonas. The genus Angomonas comprised 10 flagellates including former Crithidia deanei and C. desouzai plus a new species. The genus Strigomonas included former Crithidia oncopelti and Blastocrithidia culicis plus a new species. Sequences from the internal transcribed spacer of ribosomal DNA (ITS rDNA) and size polymorphism of kinetoplast DNA (kDNA) minicircles revealed considerable genetic heterogeneity within the genera Angomonas and Strigomonas. Phylogenetic analyses based on 16S rDNA and ITS rDNA sequences demonstrated that all of the endosymbionts belonged to the Betaproteobacteria and revealed three new species. The congruence of the phylogenetic trees of trypanosomatids and their symbionts support a co-divergent host-symbiont evolutionary history. Copyright © 2011 Elsevier GmbH. All rights reserved.
	PMID: 21420905 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-01-20T08:57:00.000-08:00

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Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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Items 1 - 6 of 6

1.	PLoS Negl Trop Dis. 2012 Jan;6(1):e1438. Epub 2012 Jan 10. Diagnostic accuracy of molecular amplification tests for human african trypanosomiasis-systematic review. Mugasa CM, Adams ER, Boer KR, Dyserinck HC, Büscher P, Schallig HD, Leeflang MM. Source Royal Tropical Institute, KIT Biomedical Research, Amsterdam, The Netherlands. Abstract BACKGROUND: A range of molecular amplification techniques have been developed for the diagnosis of Human African Trypanosomiasis (HAT); however, careful evaluation of these tests must precede implementation to ensure their high clinical accuracy. Here, we investigated the diagnostic accuracy of molecular amplification tests for HAT, the quality of articles and reasons for variation in accuracy. METHODOLOGY: Data from studies assessing diagnostic molecular amplification tests were extracted and pooled to calculate accuracy. Articles were included if they reported sensitivity and specificity or data whereby values could be calculated. Study quality was assessed using QUADAS and selected studies were analysed using the bivariate random effects model. RESULTS: 16 articles evaluating molecular amplification tests fulfilled the inclusion criteria: PCR (n = 12), NASBA (n = 2), LAMP (n = 1) and a study comparing PCR and NASBA (n = 1). Fourteen articles, including 19 different studies were included in the meta-analysis. Summary sensitivity for PCR on blood was 99.0% (95% CI 92.8 to 99.9) and the specificity was 97.7% (95% CI 93.0 to 99.3). Differences in study design and readout method did not significantly change estimates although use of satellite DNA as a target significantly lowers specificity. Sensitivity and specificity of PCR on CSF for staging varied from 87.6% to 100%, and 55.6% to 82.9% respectively. CONCLUSION: Here, PCR seems to have sufficient accuracy to replace microscopy where facilities allow, although this conclusion is based on multiple reference standards and a patient population that was not always representative. Future studies should, therefore, include patients for which PCR may become the test of choice and consider well designed diagnostic accuracy studies to provide extra evidence on the value of PCR in practice. Another use of PCR for control of disease could be to screen samples collected from rural areas and test in reference laboratories, to spot epidemics quickly and direct resources appropriately.
	PMID: 22253934 [PubMed - in process]

2.	PLoS One. 2012;7(1):e30029. Epub 2012 Jan 12. Characterization of a Novel Association between Two Trypanosome-Specific Proteins and 5S rRNA. Ciganda M, Williams N. Source Department of Microbiology and Immunology & Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, Buffalo, New York, United States of America. Abstract P34 and P37 are two previously identified RNA binding proteins in the flagellate protozoan Trypanosoma brucei. RNA interference studies have determined that the proteins are essential and are involved in ribosome biogenesis. Here, we show that these proteins interact in vitro with the 5S rRNA with nearly identical binding characteristics in the absence of other cellular factors. The T. brucei 5S rRNA has a complex secondary structure and presents four accessible loops (A to D) for interactions with RNA-binding proteins. In other eukaryotes, loop C is bound by the L5 ribosomal protein and loop A mainly by TFIIIA. The binding of P34 and P37 to T. brucei 5S rRNA involves the LoopA region of the RNA, but these proteins also protect the L5 binding site located on LoopC.
	PMID: 22253864 [PubMed - in process]

3.	J Trop Med. 2012;2012:780809. Epub 2011 Dec 28. Immunity to visceral leishmaniasis. Ali N, Mekuria AH, Requena JM, Engwerda C. Source Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, 4 Raja, S. C. Mullick Road, Kolkata-32, West Bengal Kolkata 700032, India.
	PMID: 22253634 [PubMed - in process]

4.	Analyst. 2012 Jan 18. [Epub ahead of print] Characterization and identification of suspected counterfeit miltefosine capsules. Dorlo TP, Eggelte TA, de Vries PJ, Beijnen JH. Source Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. t.p.dorlo@amc.uva.nl. Abstract Recently, it was revealed that generic miltefosine capsules for the treatment of visceral leishmaniasis, a fatal parasitic disease, were possibly counterfeit products. Here we report on the methods to characterize and identify miltefosine in pharmaceutical products and the procedures that were used to assess the quality of these suspected counterfeit products. Characterization and identification of miltefosine were done with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), Fourier transform infrared (FT-IR) spectroscopy and near-infrared (NIR) spectroscopy. Moreover, a simple, rapid and inexpensive colorimetric test was developed and evaluated for the detection of miltefosine in pharmaceutical products that can be used in the field. The complementary analytical techniques presented here were able to determine qualitatively or (semi-)quantitatively the presence or absence of miltefosine in pharmaceutical preparations and could identify suspected counterfeit miltefosine capsules. This finding of a suspected counterfeit drug intended to treat a neglected disease in a resource-poor country emphasizes the urgent need to develop more simple inexpensive assays to evaluate drug quality for use in the field.
	PMID: 22251969 [PubMed - as supplied by publisher]

5.	Environ Health Perspect. 2012 Jan 17. [Epub ahead of print] Global Trends in the Use of Insecticides for Vector-borne Disease Control. van den Berg H, Zaim M, Yadav RS, Soares A, Ameneshewa B, Mnzava A, Hii J, Dash AP, Ejov M. Source Wageningen University. Abstract BACKGROUND: Data on insecticide use for vector control are essential for guiding pesticide management systems on judicious and appropriate use, resistance management, and reduction of risks to human health and the environment. OBJECTIVE: To study global use and trends in the use of insecticides for control of vector-borne diseases for the period 2000-2009. METHODS: A survey was distributed to countries with vector control programs to request national data on vector control insecticide use, excluding the use of long-lasting insecticidal nets (LNs). Data were received from 125 countries representing 97% of the human populations of 143 targeted countries. RESULTS: The main disease targeted with insecticides was malaria, followed by dengue, leishmaniasis and Chagas disease. The use of vector control insecticides was dominated by organochlorines (e.g. DDT) in terms of quantity applied (71% of total), and by pyrethroids in terms of the surface or area covered (81% of total). Global use of DDT for vector control, the majority of which was in India alone, was fairly constant during 2000-2009. In Africa, pyrethroid use increased in countries that also achieved high coverage for LNs, and DDT increased sharply until 2008 but dropped in 2009. CONCLUSIONS: The global use of DDT has not changed substantially since the Stockholm Convention entered into force. The dominance of pyrethroid use has major implications due to the spread of insecticide resistance with potential to reduce the efficacy of LNs. Insecticide resistance management should be coordinated between disease-specific programs and sectors within the context of an integrated vector management approach.
	PMID: 22251458 [PubMed - as supplied by publisher]

6.	Nucleus. 2011 Mar-Apr;2(2):136-45. Tryp anosoma cruzi DNA replication includes the sequential recruitment of pre-replication and replication machineries close to nuclear periphery. Calderano SG, de Melo Godoy PD, Motta MC, Mortara RA, Schenkman S, Elias MC. Source Laboratório de Parasitologia, Instituto Butantan, Universidade Federal de São Paulo, São Paulo, Brazil. Abstract In eukaryotes, many nuclear processes are spatially compartmentalized. Previously, we have shown that in Trypanosoma cruzi, an early-divergent eukaryote, DNA replication occurs at the nuclear periphery where chromosomes remain constrained during the S phase of the cell cycle. We followed Orc1/Cdc6, a pre-replication machinery component and the proliferating cell nuclear antigen (PCNA), a component of replication machinery, during the cell cycle of this protozoon. We found that, at the G(1) stage, TcOrc1/Cdc6 and TcPCNA are dispersed throughout the nuclear space. During the G(1)/S transition, TcOrc1/Cdc6 migrates to a region close to nuclear periphery. At the onset of S phase, TcPCNA is loaded onto the DNA and remains constrained close to nuclear periphery. Finally, in G(2), mitosis and cytokinesis, TcOrc1/Cdc6 and TcPCNA are dispersed throughout the nuclear space. Based on these findings, we propose that DNA replication in T. cruzi is accomplished by the organization of functional machineries in a spatial-temporal manner. PMCID: PMC3127095 Free PMC Article
	PMID: 21738836 [PubMed - indexed for MEDLINE]
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What's new for 'Trypanosomatids' in PubMed

2012-01-18T04:20:00.000-08:00

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Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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1.	Bioorg Med Chem. 2011 Dec 30. [Epub ahead of print] Identification of Trypanosoma brucei leucyl-tRNA synthetase inhibitors by pharmacophore- and docking-based virtual screening and synthesis. Zhao Y, Wang Q, Meng Q, Ding D, Yang H, Gao G, Li D, Zhu W, Zhou H. Source School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Abstract Human African trypanosomiasis (HAT), caused by the protozoan parasite Trypanosoma brucei, is a neglected fatal disease. Leucyl-tRNA synthetase (LeuRS), which has been successfully applied in the development of antifungal agent, represents a potential antiprotozoal drug target. In this study, a 3D model of T. brucei LeuRS (TbLeuRS) synthetic active site was constructed and subjected to virtual screening using a combination of pharmacophore- and docking-based methods. A new 2-pyrrolinone scaffold was discovered and the structure-activity relationship (SAR) studies aided by the docking model and organic synthesis were carried out. Compounds with various substituents on R(1), R(2) and R(3) were synthesized and their SAR was discussed. Copyright © 2012. Published by Elsevier Ltd.
	PMID: 22249121 [PubMed - as supplied by publisher]
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2.	Curr Opin Infect Dis. 2012 Jan 13. [Epub ahead of print] Miltefosine and cutaneous leishmaniasis. Machado PR, Penna G. Source aServiço de Imunologia, Complexo Hospitalar Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia bTropical Medicine Centre, University of Brasilia, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Rio de Janeiro, Brazil. Abstract PURPOSE OF REVIEW: Miltefosine is a new oral treatment against leishmaniasis. The evidence about its use in New and Old World cutaneous leishmaniasis is presented and discussed. RECENT FINDINGS: Miltefosine is being tested with small clinical trials mainly in endemic cutaneous leishmaniasis regions of South America and Iran. Severe cutaneous leishmaniasis forms successfully treated with miltefosine are reported. SUMMARY: The use of miltefosine in cutaneous leishmaniasis has been addressed in a few clinical trials. An important advantage of this drug is its oral administration when compared with the standard parenteral drugs in the context of a large-scale use in the inner regions of the endemic countries. Miltefosine also shows activity in severe or refractory cases. However, this review points out the need for further investment on clinical research into cutaneous leishmaniasis treatment.
	PMID: 22248979 [PubMed - as supplied by publisher]
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3.	Bioorg Med Chem Lett. 2011 Dec 28. [Epub ahead of print] Synthesis and antikinetoplastid activity of a series of N,N'-substituted diamines. Caminos AP, Panozzo-Zenere EA, Wilkinson SR, Tekwani BL, Labadie GR. Source Instituto de Química Rosario (IQUIR-CONICET-UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK, Rosario, Argentina. Abstract A series of 25 N,N'-substituted diamines were prepared by controlled reductive amination of free aliphatic diamines with different substituted benzaldehydes. The library was screened in vitro for antiparasitic activity on the causative agents of human African trypanosomiasis, Chagas' disease and visceral leishmaniasis. The most potent compounds were derived from a subset of diamines that contained a 4-OBn substitution, having a 50% parasite growth inhibition in the submicromolar (against Trypanosoma cruzi) or nanomolar (against Trypanosoma brucei and Leishmania donovani) range. We conclude that members of this series of N,N'-substituted diamines provide new lead structures that have potential to treat trypanosomal and leishmanial infections. Copyright © 2011 Elsevier Ltd. All rights reserved.
	PMID: 22248858 [PubMed - as supplied by publisher]
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