Tuesday, July 3, 2012

What's new for 'Trypanosomatids' in PubMed

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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. Arch Gynecol Obstet. 2012 Apr;285(4):919-23. Epub 2011 Sep 17.

Chagas disease in Latin American pregnant immigrants: experience in a non-endemic country.

Ramos JM, Milla A, Rodríguez JC, López-Chejade P, Flóres M, Rodríguez JM, Gutiérrez F.

Source

Infectious Diseases Unit, Hospital General Universitario de Elche, Elche, Spain. jramosrincon@yahoo.es

Abstract

PURPOSE:

Chagas disease is a systemic chronic parasitic infection by Trypanosoma cruzi endemic in Latin America. Migration of women of childbearing age from Latin America to developed countries may spread the disease to non-endemic areas through vertical transmission.

METHODS:

Prospective study of seroprevalence of T. cruzi infection in immigrant Latin American pregnant women during a 5-year period (from 2006 to 2010) in Spain.

RESULTS:

Seven out of 545 participants were seropositive for T. cruzi [prevalence 1.28%, 95% confidence interval (CI) 0.06-2.56]. Four (57%) were from Bolivia and three (43.%) from Paraguay. The seroprevalence in pregnant women from Bolivia was 10.26% (95% CI 4.06-23.58) and in participants from Paraguay was 6.52% (95% CI 2.24-17.5). No congenital transmission occurred.

CONCLUSIONS:

Seroprevalence of T. cruzi infection in Latin American pregnant women coming from Bolivia and Paraguay is high. Those women should be screened for T. cruzi to control mother-to-child transmission in non-endemic areas.

PMID: 21927962 [PubMed - indexed for MEDLINE]
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2. Braz J Med Biol Res. 2011 Feb;44(2):84-90. Epub 2011 Jan 14.

Evasion of immune responses by Trypanosoma cruzi, the etiological agent of Chagas disease.

DosReis GA.

Source

Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. gdosreis@biof.ufrj.br

Abstract

Infection with the protozoan parasite Trypanosoma cruzi leads to Chagas disease, which affects millions of people in Latin America. Infection with T. cruzi cannot be eliminated by the immune system. A better understanding of immune evasion mechanisms is required in order to develop more effective vaccines. During the acute phase, parasites replicate extensively and release immunomodulatory molecules that delay parasite-specific responses mediated by T cells. This immune evasion allows the parasite to spread in the host. In the chronic phase, parasite evasion relies on its replication strategy of hijacking the TGF-β signaling pathway involved in inflammation and tissue regeneration. In this article, the mechanisms of immune evasion described for T. cruzi are reviewed.

Free Article
PMID: 21243314 [PubMed - indexed for MEDLINE]
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Saturday, June 30, 2012

What's new for 'Trypanosomatids' in PubMed

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Sent on Saturday, 2012 June 30
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 Jun;6(6):e1707. Epub 2012 Jun 26.

Geographical Distribution of Trypanosoma cruzi Genotypes in Venezuela.

Carrasco HJ, Segovia M, Llewellyn MS, Morocoima A, Urdaneta-Morales S, Martínez C, Martínez CE, Garcia C, Rodríguez M, Espinosa R, de Noya BA, Díaz-Bello Z, Herrera L, Fitzpatrick S, Yeo M, Miles MA, Feliciangeli MD.

Source

Laboratorio de Biología Molecular de Protozoarios, Instituto de Medicina Tropical, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela.

Abstract

Chagas disease is an endemic zoonosis native to the Americas and is caused by the kinetoplastid protozoan parasite Trypanosoma cruzi. The parasite is also highly genetically diverse, with six discrete typing units (DTUs) reported TcI - TcVI. These DTUs broadly correlate with several epidemiogical, ecological and pathological features of Chagas disease. In this manuscript we report the most comprehensive evaluation to date of the genetic diversity of T. cruzi in Venezuela. The dataset includes 778 samples collected and genotyped over the last twelve years from multiple hosts and vectors, including nine wild and domestic mammalian host species, and seven species of triatomine bug, as well as from human sources. Most isolates (732) can be assigned to the TcI clade (94.1%); 24 to the TcIV group (3.1%) and 22 to TcIII (2.8%). Importantly, among the 95 isolates genotyped from human disease cases, 79% belonged to TcI - a DTU common in the Americas, however, 21% belonged to TcIV- a little known genotype previously thought to be rare in humans. Furthermore, were able to assign multiple oral Chagas diseases cases to TcI in the area around the capital, Caracas. We discuss our findings in the context of T. cruzi DTU distributions elsewhere in the Americas, and evaluate the impact they have on the future of Chagas disease control in Venezuela.

PMID: 22745843 [PubMed - in process]
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2. PLoS Negl Trop Dis. 2012 Jun;6(6):e1688. Epub 2012 Jun 26.

Monitoring toxicity associated with parenteral sodium stibogluconate in the day-case management of returned travellers with new world cutaneous leishmaniasi.

Wise ES, Armstrong MS, Watson J, Lockwood DN.

Source

Hospital for Tropical Diseases, University College London Hospitals NHS Trust, London, United Kingdom.

Abstract

BACKGROUND:

Patients with New World cutaneous leishmaniasis (NWCL) caused by Leishmania Viannia are treated with parenteral sodium stibogluconate (SbV) to reduce the risk of development of mucocutanous leishmaniasis. Our centre manages patients with NWCL on an outpatient-basis. This study was conducted to assess the safety and efficacy of this approach.

METHODOLOGY:

We reviewed records of 67 consecutive NWCL patients, aged 17-61 years, treated as day-cases with 20 mg/kg/day SbV for up to 28 days at our UK centre. Data had been collected in a standardised format at the time of treatment using a care-record tool. Patients reported adverse-effects daily using a structured questionnaire. Blood tests and electrocardiograms were performed twice weekly to monitor for toxicity.

PRINCIPAL FINDINGS:

Parenteral SbV treatment was associated with an early, significant suppression of mean lymphocyte and platelet counts. By day four of treatment, lymphocytes reduced by 0.53×10(9)/L (CI 0.29×10(9)/L to 0.76×10(9)/L, p<0.001), and platelets by 31,000/µL (CI 16,000/µL to 46,000/µL, p<0.001). SbV was further associated with significant elevation of serum alanine transaminase concentrations, with a mean peak rise of 107 iu/L by day 13 (CI 52 iu/L to 161 iu/L, p<0.001). These disturbances were temporary and did not result in adverse clinical events. Patient-described symptoms were cumulative and at three weeks of treatment, 59.6% of patients experienced myalgia and 29.8% malaise. Treatment adherence and clinical outcomes were comparable to inpatient treatment studies. A total of 1407 individual doses of SbV resulted in only 26 nights' hospital admission, a saving of 1381 bed-days compared to inpatient treatment.

CONCLUSIONS/SIGNIFICANCE:

In specialist centres, NWCL patients aged below 65 years and without co-morbidities can be safely and effectively treated without hospital admission. This reduces the cost of treatment, and is much preferred by patients. Twice weekly blood and electrocardiographic monitoring may be surplus to requirement in clinically well, low-risk patients.

PMID: 22745840 [PubMed - in process]
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3. Parasite Immunol. 2012 Jun 28. doi: 10.1111/j.1365-3024.2012.01379.x. [Epub ahead of print]

Decrease in anti-Leishmania IgG3 and IgG1 after cutaneous leishmaniasis lesion healing is correlated with the time of clinical cure.

Fagundes-Silva GA, Vieira-Gonçalves R, Nepomuceno MP, de Souza MA, Junior SF, Oliveira-Neto MP, Da-Cruz AM, Gomes-Silva A.

Source

Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. Instituto de Pesquisa Clínica Evandro Chagas (IPEC), FIOCRUZ, Rio de Janeiro, Brazil. Universidade Estácio de Sá, Faculdade de Medicina, Rio de Janeiro, Brazil. Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil. Allergy and Immunology Division, Feinberg School of Medicine, Northwestern University, Chicago, USA.

Abstract

For better efficiency in the establishment of American tegumentary leishmaniasis clinical cure, the World Health Organization suggests that the clinical criteria are supported by serologic data. The present study aims to investigate the dynamics of IgG subclass production in clinical evolution post-treatment of cutaneous leishmaniasis (CL). Paired sera from 23 subjects with CL resulting from Leishmania braziliensis infection were studied during the active lesion phase (aCL) and after clinical cure post therapy (hCL), which included an alternative protocol with a low dose of antimony. Anti-Leishmania IgG and its subclasses were measured using ELISA, and the immunoglobulin levels were correlated with patients' clinical data. All of the subjects were clinically healed and did not present relapse during follow-up. Serum levels of anti-Leishmania IgG (r=-0.79; p<0.0001), IgG1 (r=-0.64, p<0.001) and IgG3 (r=-0.42, p<0.045) in hCL were negatively correlated with the duration of clinical cure. After 24 months of clinical cure, 73% of samples were negative for IgG1 and 78% were negative for IgG3. In conclusion, the detection of serum anti-Leishmania IgG1 and IgG3 is an improved laboratory strategy to aid in the decision of interruption of the ambulatory follow-up of CL patients. © 2012 Blackwell Publishing Ltd.

© 2012 Blackwell Publishing Ltd.

PMID: 22742527 [PubMed - as supplied by publisher]
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4. J Infect Dis. 2012 May 15;205(10):1617-8; author reply 1618. Epub 2012 Apr 5.

Tryptophan catabolism during intracellular infection.

Schroecksnadel S, Kurz K, Weiss G, Fuchs D.

Comment on

PMID: 22492858 [PubMed - indexed for MEDLINE]
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5. Exp Parasitol. 2012 May;131(1):80-4. Epub 2012 Mar 23.

Influence of Trypanosoma evansi in adenine nucleotides and nucleoside concentration in serum and cerebral cortex of infected rats.

Da Silva AS, Oliveira CB, Rosa LD, Leal CA, Da Cruz RC, Thomé GR, Athayde ML, Schetinger MR, Monteiro SG, Lopes ST.

Source

Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Santa Maria, RS,Brazil. aleksandro_ss@yahoo.com.br

Abstract

This study aimed to evaluate the adenine nucleotides and nucleoside concentration in serum and cerebral cortex of rats infected with Trypanosma evansi. Each rat was intraperitoneally infected with 1 × 10(6) trypomastigotes suspended in cryopreserved blood (Group A; n = 18). Twelve animals were used as controls (Group B). The infected animals were monitored daily by blood smears. At days 4 and 20 post-infection (PI) it was collected serum and cerebral cortex to measure the levels of ATP, ADP, AMP and adenosine by high performance liquid chromatography (HPLC). In serum there was a significant (P < 0.05) increase in the ATP, AMP and adenosine concentrations at days 4 and 20 PI in infected rats when compared to not-infected. Furthermore, in the cerebral cortex it was observed a significant (P < 0.05) increase in the concentrations of ATP, AMP and decreased adenosine levels at day 4 PI. At day 20 PI it was only observed an increase in the AMP and adenosine concentrations in cerebral cortex of infected rats when compared to not-infected. It was not observed any difference in ADP concentration in serum and brain at days 4 and 20 PI. No change was observed histologically in the cerebral cortex of infected animals. The results allow us to conclude that infection with T. evansi in rats causes an increase in the concentrations of ATP, AMP and adenosine in serum and cerebral cortex the time periods evaluated. These alterations occurred as a result of T. evansi infection which involves neurotransmission, neuromodulation and immune response impairment confirm the importance of the purinergic system in this pathology.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID: 22465613 [PubMed - indexed for MEDLINE]
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6. PLoS One. 2012;7(3):e34360. Epub 2012 Mar 26.

TNF-α is involved in the abnormal thymocyte migration during experimental Trypanosoma cruzi infection and favors the export of immature cells.

Pérez AR, Berbert LR, Lepletier A, Revelli S, Bottasso O, Silva-Barbosa SD, Savino W.

Source

Faculty of Medical Sciences, Institute of Immunology, National University of Rosario, Rosario, Argentina. perez.ana@conicet.gov.ar

Abstract

Previous studies revealed a significant production of inflammatory cytokines together with severe thymic atrophy and thymocyte migratory disturbances during experimental Chagas disease. Migratory activity of thymocytes and mature T cells seem to be finely tuned by cytokines, chemokines and extracellular matrix (ECM) components. Systemic TNF-α is enhanced during infection and appears to be crucial in the response against the parasite. However, it also seems to be involved in disease pathology, since it is implicated in the arrival of T cells to effector sites, including the myocardium. Herein, we analyzed the role of TNF-α in the migratory activity of thymocytes in Trypanosoma cruzi (T. cruzi) acutely-infected mice. We found increased expression and deposition of TNF-α in the thymus of infected animals compared to controls, accompanied by increased co-localization of fibronectin, a cell migration-related ECM molecule, whose contents in the thymus of infected mice is also augmented. In-vivo studies showed an enhanced export of thymocytes in T. cruzi-infected mice, as ascertained by intrathymic injection of FITC alone or in combination with TNF-α. The increase of immature CD4(+)CD8(+) T cells in secondary lymphoid organs was even more clear-cut when TNF-α was co-injected with FITC. Ex-vivo transmigration assays also revealed higher number of migrating cells when TNF-α was added onto fibronectin lattices, with higher input of all thymocyte subsets, including immature CD4(+)CD8(+). Infected animals also exhibit enhanced levels of expression of both mRNA TNF-α receptors in the CD4(+)CD8(+) subpopulation. Our findings suggest that in T. cruzi acute infection, when TNF-α is complexed with fibronectin, it favours the altered migration of thymocytes, promoting the release of mature and immature T cells to different compartments of the immune system. Conceptually, this work reinforces the notion that thymocyte migration is a multivectorial biological event in health and disease, and that TNF-α is a further player in the process.

PMCID: PMC3312912 Free PMC Article
PMID: 22461911 [PubMed - indexed for MEDLINE]
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7. Exp Parasitol. 2012 May;131(1):130-2. Epub 2012 Mar 7.

Anti-Trypanosoma cruzi and cytotoxic activities of Eugenia uniflora L.

Santos KK, Matias EF, Tintino SR, Souza CE, Braga MF, Guedes GM, Rolón M, Vega C, de Arias AR, Costa JG, Menezes IR, Coutinho HD.

Source

Laboratório de Microbiologia e Biologia Molecular, Universidade Regional do Cariri, Crato, CE, Brazil.

Abstract

Chagas disease is caused by Trypanosoma cruzi, being considered a public health problem. An alternative to combat this pathogen is the use of natural products isolated from fruits such as Eugenia uniflora, a plant used by traditional communities as food and medicine due to its antimicrobial and biological activities. Ethanolic extract from E. uniflora was used to evaluate in vitro anti-epimastigote and cytotoxic activity. This is the first record of anti-Trypanosoma activity of E. uniflora, demonstrating that a concentration presenting 50% of activity (EC(50)) was 62.76 μg/mL. Minimum inhibitory concentration (MIC) was ≤ 1024 μg/mL. Our results indicate that E. uniflora could be a source of plant-derived natural products with anti-epimastigote activity with low toxicity.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID: 22426246 [PubMed - indexed for MEDLINE]
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8. Exp Parasitol. 2012 May;131(1):57-62. Epub 2012 Mar 8.

In vitro activity of N-benzenesulfonylbenzotriazole on Trypanosoma cruzi epimastigote and trypomastigote forms.

Becerra MC, Guiñazú N, Hergert LY, Pellegrini A, Mazzieri MR, Gea S, Albesa I.

Source

Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Instituto Multidisciplinario de Biología Vegetal, IMBIV-CONICET, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Córdoba, Argentina. becerra@fcq.unc.edu.ar

Abstract

Chagas disease is still an important health problem in Central and South America. However, the only drugs currently available for specific treatment of this disease may induce toxic side effects in the host. The aim of this work was to determine the activity of N-benzenesulfonylbenzotriazole (BSBZT) against the protozoan parasite Trypanosoma cruzi. The effects of BSBZT and benzotriazole (BZT) were compared to those of benznidazole (BZL) on epimastigote and trypomastigote forms. BSBZT was found to have an in vitro growth inhibitory dose-dependent activity against epimastigotes, with flow cytometry analysis confirming that the treated parasites presented size reduction. BSBZT showed an IC(50) of 21.56 μg/mL (81.07 μM) against epimastigotes at 72 h of incubation, whereas BZT did not affect the growth of this parasite form. Furthermore, the toxic effect of BSBZT, was stronger and appeared earlier (at 24h) in trypomastigotes than in epimastigotes, with the LC(50) of this compound being 28.40 μg/mL (106.79 μM) against trypomastigotes. The concentrations of BSBZT used in this study presented low hemolytic activity and cytotoxicity. Consequently, at concentrations near IC(50) and LC(50) (25μg/mL), BSBZT caused only 2.4% hemolysis and 15% of RAW 264.7 cell cytotoxicity. These results reveal the potential of BSBZT as a prototype in drug design for developing new anti-T. cruzi compounds.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID: 22425748 [PubMed - indexed for MEDLINE]
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Friday, June 29, 2012

What's new for 'Trypanosomatids' in PubMed

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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. Electrophoresis. 2012 Jul;33(12):1901-10. doi: 10.1002/elps.201200007.

CE-ESI-MS metabolic fingerprinting of Leishmania resistance to antimony treatment.

Canuto GA, Castilho-Martins EA, Tavares M, López-Gonzálvez A, Rivas L, Barbas C.

Source

Center for Metabolomics and Bioanalysis (CEMBIO), Faculty of Pharmacy, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, Madrid, Spain; Institute of Chemistry, University of São Paulo (USP), Campus São Paulo, São Paulo, Brazil.

Abstract

Metabolomics has become an invaluable tool to unveil biology of pathogens, with immediate application to chemotherapy. It is currently accepted that there is not one single technique capable of obtaining the whole metabolic fingerprint of a biological system either due to their different physical-chemical properties or concentrations. In this work, we have explored the capability of capillary electrophoresis mass spectrometry with a sheathless interface with electrospray ionization (CE-ESI-TOF-MS) to separate metabolites in order to be used as a complementary technique to LC. As proof of concept, we have compared the metabolome of Leishmania infantum promastigotes BCN 150 (Sb (III) IC(50) = 20.9 μM) and its variation when treated with 120 μM of Sb(III) potassium tartrate for 12 h, as well as with its Sb(III) resistant counterpart obtained by growth of the parasites under increasing Sb(III) in a step-wise manner up to 180 μM. The number of metabolites compared were of 264 for BCN150 Sb(III) treated versus nontreated and of 195 for Sb(III) resistant versus susceptible parasites. After successive data filtering, differences in seven metabolites identified in databases for Leishmania pathways, showed the highest significant differences, corresponding mainly to amino acids or their metabolite surrogates. Most of them were assigned to sulfur containing amino acids and polyamine biosynthetic pathways, of special relevance considering the deterioration of the thiol-dependent redox metabolism in Leishmania by Sb(III). Given the low concentrations typical for most of these metabolites, the assay can be considered a success that should be explored for new biological questions.

© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID: 22740478 [PubMed - in process]
2. J Invest Dermatol. 2012 Jun 28. doi: 10.1038/jid.2012.205. [Epub ahead of print]

Immunity to Sand Fly Salivary Protein LJM11 Modulates Host Response to Vector-Transmitted Leishmania Conferring Ulcer-Free Protection.

Gomes R, Oliveira F, Teixeira C, Meneses C, Gilmore DC, Elnaiem DE, Kamhawi S, Valenzuela JG.

Source

Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.

Abstract

Leishmania vaccines that protect against needle challenge fail against the potency of a Leishmania-infected sand fly transmission. Here, we demonstrate that intradermal immunization of mice with 500 ng of the sand fly salivary recombinant protein LJM11 (rLJM11) from Lutzomyia longipalpis, in the absence of adjuvant, induces long-lasting immunity that results in ulcer-free protection against Leishmania major delivered by vector bites. This protection is antibody independent and abrogated by depletion of CD4(+) T cells. Two weeks after challenge, early induction of IFN-γ specifically to rLJM11 correlates to diminished parasite replication in protected animals. At this time point, Leishmania-specific induction of IFN-γ in these mice is low in comparison with its high level in non-protected controls. We hypothesize that early control of parasites in a T-cell helper type 1 environment induced by immunity to LJM11 permits the slow development of Leishmania-specific immunity in the absence of open ulcers. Leishmania-specific immunity observed 5 weeks after infection in rLJM11-immunized mice shows a twofold increase over controls in the percentage of IFN-γ-producing CD4(+) T cells. We propose LJM11 as an immunomodulator that drives an efficient and controlled protective immune response to a sand fly-transmitted Leishmania somewhat mimicking "leishmanization"-induced protective immunity but without its associated lesions.Journal of Investigative Dermatology advance online publication, 28 June 2012; doi:10.1038/jid.2012.205.

PMID: 22739793 [PubMed - as supplied by publisher]
3. Rev Esp Enferm Dig. 2012 Jun;104(6):333.

Visceral leishmaniasis diagnosed by double balloon enteroscopy.

Gómez-Espín R, Fuentes E, López-Espín MI, Bebia P, Esteban P, Chacón S, J L Rodrigo, López-Higueras A, Pérez-Cuadrado E.
PMID: 22738708 [PubMed - as supplied by publisher]
4. Bioorg Med Chem Lett. 2012 Jun 7. [Epub ahead of print]

Discovery of nitroheterocycles active against African trypanosomes. In vitro screening and preliminary SAR studies.

Arán VJ, Kaiser M, Dardonville C.

Source

Instituto de Química Médica, CSIC, Juan de la Cierva 3, E-28006 Madrid, Spain.

Abstract

A selection of 76 nitroheterocycles and related compounds from our in-house compound library was screened in vitro against the parasite Trypanosoma brucei rhodesiense, causative agent of human African trypanosomiasis (HAT). The unspecific cytotoxicity of the compounds was also evaluated against rat myoblast L6-cells to measure the selectivity of the compounds towards the parasite. This screening revealed some preliminary structure-activity relationships (SAR) among the series, and six hit compounds showing interesting activity (IC(50)⩽10μM) and fair selectivity (SI>17). The 7-nitroquinoxalin-2-one and 5-nitroindazole scaffold derivatives 58 and 35, respectively, are particularly interesting because of their established oral bioavailability in mice. These hits represent interesting starting points for a medicinal project aimed at identifying the SAR behind this class of compounds.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22738640 [PubMed - as supplied by publisher]
5. J Vector Borne Dis. 2012 Mar;49(1):54.

Insect vectors of Leishmania: distribution, physiology and their control.

Sharma U, Singh S.
PMID: 22737744 [PubMed - in process]
6. Parasitology. 2012 Apr;139(4):516-21. Epub 2012 Feb 6.

Trypanosoma cruzi discrete typing units in Chagas disease patients from endemic and non-endemic regions of Argentina.

Cura CI, Lucero RH, Bisio M, Oshiro E, Formichelli LB, Burgos JM, Lejona S, Brusés BL, Hernández DO, Severini GV, Velazquez E, Duffy T, Anchart E, Lattes R, Altcheh J, Freilij H, Diez M, Nagel C, Vigliano C, Favaloro L, Favaloro RR, Merino DE, Sosa-Estani S, Schijman AG.

Source

Laboratorio de Biología Molecular de la Enfermedad de Chagas, Instituto de Ingeniería Genética y Biología Molecular, Vuelta de Obligado 2490, 2do piso, 1428, Ciudad de Buenos Aires, Argentina.

Abstract

Genetic diversity of Trypanosoma cruzi may play a role in pathogenesis of Chagas disease forms. Natural populations are classified into 6 Discrete Typing Units (DTUs) Tc I-VI with taxonomical status. This study aimed to identify T. cruzi DTUs in bloodstream and tissue samples of Argentinean patients with Chagas disease. PCR-based strategies allowed DTU identification in 256 clinical samples from 239 Argentinean patients. Tc V prevailed in blood from both asymptomatic and symptomatic cases and Tc I was more frequent in bloodstream, cardiac tissues and chagoma samples from immunosuppressed patients. Tc II and VI were identified in a minority of cases, while Tc III and Tc IV were not detected in the studied population. Interestingly, Tc I and Tc II/VI sequences were amplified from the same skin biopsy slice from a kidney transplant patient suffering Chagas disease reactivation. Further data also revealed the occurrence of mixed DTU populations in the human chronic infection. In conclusion, our findings provide evidence of the complexity of the dynamics of T. cruzi diversity in the natural history of human Chagas disease and allege the pathogenic role of DTUs I, II, V and VI in the studied population.

PMID: 22309735 [PubMed - indexed for MEDLINE]
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7. Placenta. 2012 Apr;33(4):264-70. Epub 2012 Jan 31.

Differential susceptibility of isolated human trophoblasts to infection by Trypanosoma cruzi.

Díaz-Luján C, Triquell MF, Schijman A, Paglini P, Fretes RE.

Source

Placenta and Chagas Laboratory, Cell Biology, Histology and Embryology Department, Medicine Faculty, Universidad Nacional Córdoba, Enrique Barros y Enfermera Gordillo, CP 5000, Córdoba, Argentina. cintiadiaz@yahoo.com

Abstract

The aim of the work was to analyze the susceptibility of the placental syncytiotrophoblast (STB) and cytotrophoblast (CTB) cells to infection by the causal agent of congenital Chagas' disease, Trypanosoma cruzi, and the possible parasite route for placental invasion. Monolayers of CTB and STB and VERO as control cells were used. The infection of STB was significantly lower that of the CTB and Vero cells (p < 0.05) which coincided with a significantly increased mortality of parasite cells in the culture medium and trypanocidal levels of nitric oxide. We conclude that the syncytiotrophoblast, the first placental barrier, is the main barrier of the chorionic villous that limits the infection by T. cruzi. This work opens the possibility of a new mechanism for placental infection when there are discontinuities in the first placental barrier.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22296856 [PubMed - indexed for MEDLINE]
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8. Parasitology. 2012 Apr;139(4):506-15. Epub 2012 Jan 5.

Study of Trypanosoma cruzi epimastigote cell death by NMR-visible mobile lipid analysis.

Benitez D, Pezaroglo H, Martínez V, Casanova G, Cabrera G, Galanti N, González M, Cerecetto H.

Source

Grupo de Química Medicinal, Laboratorio de Química Orgánica, Universidad de la República, Montevideo, Uruguay.

Abstract

Cell death mechanisms in Trypanosoma cruzi have not been disclosed in detail though different conventional techniques have been used in the classification of parasite-cell death type. Nuclear magnetic resonance (NMR) has successfully been used as a tool to evaluate the onset of apoptosis in a number of higher eukaryote-cell models analysing the ratio of CH(2)/CH(3) integration from the visible mobile lipids (VML). Surprisingly, this versatile non-invasive spectroscopy technique has never been employed with this purpose in T. cruzi. In the present study it is shown that under different parasite death-conditions the ratio CH(2)/CH(3) varied drastically. Thus, T. cruzi epimastigotes in apoptotic conditions increase significantly this ratio while in necrotic as well as in autophagic situations the parasites maintain the VML, CH(2)/CH(3) ratio, in normal values. Additionally, other VML markers commonly used in these studies, such as the change in the region of methyl-choline moiety, -N(+)(CH(3))(3), exhibited different particular patterns according to the type of cell death. Our results suggest that the (1)H NMR-VML technique is an adequate tool to discriminate different T. cruzi death pathways.

PMID: 22216891 [PubMed - indexed for MEDLINE]
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Thursday, June 28, 2012

What's new for 'Trypanosomatids' in PubMed

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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 - 5 of 5

1. Iran Red Crescent Med J. 2011 May;13(5):348-51. Epub 2011 May 1.

Intestinal leishmaniasis in acquired immunodeficiency syndrome.

Molaei M, Minakari M, Pejhan Sh, Mashayekhi R, Modaress Fatthi AR, Zali MR.

Source

Department of Pathology, Research Center of Gastroenterology and Liver Disease, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

In endemic regions, visceral leishmaniasis is one of the most common opportunistic infections in HIV positive patients. Simultaneous infection with Leishmania and HIV has been reported in some countries but this is the first report of such a case in Iran. Our patient was a 27 years old man with intermittent night fever, abdominal pain, loss of appetite, vomiting, watery diarrhea and severe weight loss for 6 months. He had low socio-economic status with an imprisonment history. The patient was quite cachectic and had low grade fever. Physical exam and upper GI endoscopy revealed oropharyngeal candidiasis. Microscopic evaluation of duodenal biopsy material showed Leishmania amastigotes in macrophages of lamina propria. Leishman bodies were also observed in bone marrow aspiration specimen. Serologic tests were positive for Leishmania infantum. HIV antibody was also positive with a CD4+cell count of 80/μl. The diagnosis was acquired immunodeficiency syndrome with simultaneous visceral leishmaniasis involving intestinal mucosa.

PMID: 22737493 [PubMed - in process]
2. Iran Red Crescent Med J. 2011 Dec;13(12):863-7. Epub 2011 Dec 1.

Detection of drug resistance gene in cutaneous leishmaniasis by PCR in some endemic areas of iran.

Alizadeh R, Hooshyar H, Bandehpor M, Arbabi M, Kazemi F, Talari A, Kazemi B.

Source

Department of Parasitology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.

Abstract

BACKGROUND:

Cutaneous leishmaniasis is still a health problem in many rural and urban regions of Iran and drug resistance has emerged as a major impediment in the treatment of leishmaniasis. This study aims to determine the drug resistance gene in cutaneous leishmaniasis by PCR in some endemic areas of Iran.

METHODS:

Ninety seven samples were collected from ulcers of leishmaniasis patients from some endemic areas of Iran. The Giemsa stained samples were examined microscopically and cultured in NNN and RPMI 1640 mediums for parasite detection. After DNA extraction, PCR was done by a pair of specific primers. For detection of mutation in DNA, first PCR products were electrophoresed on CSGE gel. The suspected samples were compared by sequencing and RFLP results were demonstrated. Comparison of DNA derived from a wild type cell and mutant cell was undertaken by CSGE and sequencing methods.

RESULTS:

Among 90 isolates (92.8%) examined for detection of mutation in gene with CSGE and RFLP, 10 (11.1%) revealed a disorder in sequencing selection for unresponsive to drug.

CONCLUSION:

Drug resistance in cutaneous leishmaniasis to sodium stiboglocanat is probably due to a mutation in a genome. A field study is needed to determine the distribution of drug resistance and other gene mutations involved in unresponsiveness to drugs in leishmaniasis endemic areas of Iran.

PMID: 22737430 [PubMed - in process]
3. Exp Parasitol. 2012 Jun 23. [Epub ahead of print]

Mitochondrial damage contribute to Epigallocatechin-3-gallate induced death in Leishmania amazonensis.

F Inacio JD, Canto-Cavalheiro MM, S Menna-Barreto RF, Almeida-Amaral EE.

Source

Laboratório de Bioquímica de Tripanosomatideos, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract

Epigallocatechin-3-gallate (EGCG), the most abundant flavonoid in green tea, has been reported to have antiproliferative effects on Trypanosoma cruzi however, the mechanism of protozoan action of EGCG has not been studied. In the present study, we demonstrate the mechanism for the antileishmanial activity of EGCG against Leishmania amazonensis promastigotes. Incubation with EGCG significantly inhibited L. amazonensis promastigote proliferation in a time- and dose-dependent manner. The IC(50) for EGCG at 120 hours was 0.063 mM. Ultrastructural alterations of the mitochondria were observed in promastigote treated with EGCG, being the organelle injury reinforced by the decrease in rhodamine 123 fluorescence. The effects of several drugs that interfere directly with mitochondrial physiology in parasites such as Leishmania have been described. The unique mitochondrial features of Leishmania make this organelle an ideal drug target while minimizing toxicity. These data suggest mitochondrial collapse as a part of the EGCG mechanism of action and demonstrate the leishmanicidal effect of EGCG.

Copyright © 2012. Published by Elsevier Inc.

PMID: 22735546 [PubMed - as supplied by publisher]
4. Curr Comput Aided Drug Des. 2012 Jun 25. [Epub ahead of print]

Structure- and Ligand-Based Structure-Activity Relationships for a Series of Inhibitors of Aldolase.

Ferreira LG, Andricopulo AD.

Source

Laboratório de Química Medicinal e Computacional, Instituto de Física de São Carlos, Universidade de São Paulo, Av. Trabalhador São-Carlense 400, 13560-970, São Carlos-SP, Brazil. aandrico@if.sc.usp.br.

Abstract

Aldolase has emerged as a promising molecular target for the treatment of human African trypanosomiasis. Over the last years, due to the increasing number of patients infected with Trypanosoma brucei, there is an urgent need for new drugs to treat this neglected disease. In the present study, two-dimensional fragment-based quantitative-structure activity relationship (QSAR) models were generated for a series of inhibitors of aldolase. Through the application of leave-one-out and leave-many-out cross-validation procedures, significant correlation coefficients were obtained (r2 = 0.98 and q2 = 0.77) as an indication of the statistical internal and external consistency of the models. The best model was employed to predict pKi values for a series of test set compounds, and the predicted values were in good agreement with the experimental results, showing the power of the model for untested compounds. Moreover, structure-based molecular modeling studies were performed to investigate the binding mode of the inhibitors in the active site of the parasitic target enzyme. The structural and QSAR results provided useful molecular information for the design of new aldolase inhibitors within this structural class.

PMID: 22734708 [PubMed - as supplied by publisher]
5. Clin Vaccine Immunol. 2012 Feb;19(2):167-73. Epub 2011 Dec 7.

Characterization of an immunodominant antigenic epitope from Trypanosoma cruzi as a biomarker of chronic Chagas' disease pathology.

Thomas MC, Fernández-Villegas A, Carrilero B, Marañón C, Saura D, Noya O, Segovia M, Alarcón de Noya B, Alonso C, López MC.

Source

Instituto de Parasitología y Biomedicina López Neyra, CSIC, Parque Tecnológico de Ciencias de la Salud, Granada, Spain.

Abstract

Nowadays, the techniques available for chronic Chagas' disease diagnosis are very sensitive; however, they do not allow discrimination of the patient's clinical stages of the disease. The present paper describes that three out of the five different repeats contained in the Trypanosoma cruzi TcCA-2 membrane protein (3972-FGQAAAGDKPPP, 6303-FGQAAAGDKPAP, and 3973-FGQAAAGDKPSL) are recognized with high sensitivity (>90%) by sera from chronic Chagas' disease patients and that they are not recognized by sera from patients in the acute phase of the disease. A total of 133 serum samples from chagasic patients and 50 serum samples from healthy donors were tested. In addition, sera from 15 patients with different autoimmune diseases, 43 serum samples from patients suffering an infectious disease other than Chagas' disease, and 38 serum samples from patients with nonchagasic cardiac disorders were also included in this study. The residue 3973 peptide shows a specificity of >98%, as it is not recognized by individuals with autoimmune and inflammatory processes or by patients with a nonchagasic cardiomyopathy. Remarkably, the levels of antibody against the 3973 epitope detected by the sera from Chagas' disease patients in the symptomatic chronic phase, involving cardiac or digestive alterations, are higher than those detected by the sera from Chagas' disease patients in the indeterminate phase of the disease. It is suggested that the diagnostic technique described could also be used to indicate the degree of pathology. The amino acids F, Q, and DKP located in the peptide at positions 1, 3, and 8 to 10, respectively, are essential to conform to the immunodominant antigenic epitope.

PMCID: PMC3272920 [Available on 2012/8/1]
PMID: 22155766 [PubMed - indexed for MEDLINE]
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Wednesday, June 27, 2012

What's new for 'Trypanosomatids' in PubMed

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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. Trop Anim Health Prod. 2012 Apr;44(4):873-9. Epub 2011 Sep 21.

Economic burden of bovine trypanosomosis in three villages of Metekel zone, northwest Ethiopia.

Tesfaye D, Speybroeck N, De Deken R, Thys E.

Source

School of Veterinary Medicine, Hawassa University, P.O. Box 5, Hawassa, Ethiopia. dawit89@yahoo.com

Abstract

The study was carried out to assess the economic burden of trypanosomosis in three villages of the Metekel zone in 2009. The disease was found to cause substantial economic losses through cattle mortality, drug purchase, and draft power loss of infected oxen. The farmers in the area were spending a significantly (p < 0.05) higher amount of money for the treatment of trypanosomosis than all other diseases combined. The overall mortality rate of cattle due to trypanosomosis was 4.4%. The mortality was significantly higher (p < 0.05) in an area where trypanosomosis prevalence was also higher. Many of the farmers prioritized losses of draft power as the most important impact of the disease. The overall prevalence of the disease was 12.1%. The disease burden was significantly (p < 0.05) higher in the rainy season than at other times of the year. In general, farmers had good knowledge on the signs and seasonality of trypanosomosis. Thus, tsetse suppression activities that involve the local community can be an important tool towards minimizing the economic burden of the disease in the area.

PMID: 21935660 [PubMed - indexed for MEDLINE]
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2. Recent Pat Antiinfect Drug Discov. 2011 Sep 1;6(3):216-59.

A decade of targets and patented drugs for chemotherapy of Chagas disease.

Duschak VG.

Source

Instituto Nacional de Parasitología Dr. Mario Fatala Chaben, ANLIS-Malbrán, Ministerio de Salud de la nación. Av. Paseo Colon 568 (1063), Buenos Aires, Argentina. vduschak@conicet.gov.ar

Abstract

Chagas disease, a parasitic infection typically spread by triatomine bugs, affects millions of people throughout Latin America. Current chemotherapy based on the nitroaromatic compounds, benzonidazole and nifurtimox provides unsatisfactory results and suffers from considerable side effects. Therefore, there is still an urgent need for new drugs to treat this neglected disease. During the last decade, the advances and understanding in the biology and biochemistry of Trypanosoma cruzi have allowed the identification of multiple new targets for Chagas' disease chemotherapy. Among the most promising targets for antiparasitic drugs are: cruzipain, the main cysteine protease of T. cruzi, essential for parasite survival and proliferation in mammalian host; ergosterol biosynthesis pathway; trypanothione synthesis and thiol-dependant redox metabolism. Specific enzymes of the glycolytic, pentose phosphate, polyisoprenoid (farnesylpyrophosphate synthase) and other particular biosynthetic pathways as well as enzymes from purine salvage (hypoxanthine-guanine phosphoribosyl-transferase, dihydrofolate reductase) have also been intensively studied in T. cruzi. In particular, trypanocidal agents that target the validated biochemical pathways of the parasite including cysteine proteinase inhibitors and inhibitors capable to block ergosterol biosynthesis are currently in the pipeline. Among the latter, posaconazole and ravuconazole, are planned to enter in clinical trials for trypanocidal chemotherapy in the near future. This review will summarize advances on antichagasic agents directed to specific parasite targets such as metabolic pathways or specific enzymes. Related patents filed and issued from 2000 to 2010 claiming inhibitors for specific parasite targets will be also discussed. Among them, the most represented were those related with cysteine proteinase inhibitors.

PMID: 21824073 [PubMed - indexed for MEDLINE]
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Tuesday, June 26, 2012

What's new for 'Trypanosomatids' in PubMed

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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. Int J Biochem Cell Biol. 2012 Jun 20. [Epub ahead of print]

Trypanosomes lacking uracil-DNA glycosylase are hypersensitive to antifolates and present a mutator phenotype.

Castillo-Acosta VM, Aguilar-Pereyra F, Vidal AE, Navarro M, Ruiz-Pérez LM, González-Pacanowska D.

Source

Instituto de Parasitología y Biomedicina "López-Neyra". Consejo Superior de Investigaciones Científicas. Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, s/n 18100-Armilla (Granada), Spain.

Abstract

Cells contain low amounts of uracil in DNA which can be the result of dUTP misincorporation during replication or cytosine deamination. Elimination of uracil in the base excision repair pathway yields an abasic site, which is potentially mutagenic unless repaired. The Trypanosoma brucei genome presents a single uracil-DNA glycosylase responsible for removal of uracil from DNA. Here we establish that no excision activity is detected on U:G, U:A pairs or single-strand uracil-containing DNA in uracil-DNA glycosylase null mutant cell extracts, indicating the absence of back-up uracil excision activities. While procyclic forms can survive with moderate amounts of uracil in DNA, an analysis of the mutation rate and spectra in mutant cells revealed a hypermutator phenotype where the predominant events were GC to AT transitions and insertions. Defective elimination of uracil via the base excision repair pathway gives rise to hypersensitivity to antifolates and oxidative stress and an increased number of DNA strand breaks, suggesting the activation of alternative DNA repair pathways. Finally, we show that uracil-DNA glycosylase defective cells exhibit reduced infectivity in vivo demonstrating that efficient uracil elimination is important for survival within the mammalian host.

Copyright © 2012. Published by Elsevier Ltd.

PMID: 22728162 [PubMed - as supplied by publisher]
2. Exp Parasitol. 2012 Jun 21. [Epub ahead of print]

Improvements in obtaining New World Leishmania sp from mucosal lesions: notes on isolating and stocking parasites.

Dorta ML, Oliveira MA, Fleuri AK, Duarte FB, Pinto SA, Pereira LI, Ribeiro-Dias F.

Source

Institute of Tropical Pathology and Public Health, Universidade Federal de Goiás, Rua 235 S/N - Setor Universitário, 74605-050, Goiânia, Goiás, Brazil.

Abstract

Tegumentary leishmaniasis is an endemic protozoan disease that, in Brazil, is caused by parasites from Viannia or Leishmania complex. The clinical forms of cutaneous disease comprise localized, disseminated, mucosal or mucocutaneous, and diffuse leishmaniasis. Viannia complex parasites are not easy to isolate from patient lesions, especially from mucosal lesions, and they are difficult to culture. The aim of the present study was to compare the efficiency of ex vivo (culture) and in vivo (IFNγ-deficient mice) parasite isolation methods to improve the isolation rate and storage of stocks of New World Leishmania species that cause cutaneous leishmaniasis (CL) or mucosal leishmaniasis (ML). Biopsy fragments from cutaneous or mucosal lesions were inoculated into culture medium or mouse footpads. We evaluated 114 samples (86 CL, 28 ML) using both methods independently. Samples from CL patients had a higher isolation rate in ex vivo cultures than in mice (34.1% vs. 18.7%, P < 0.05). Nevertheless, almost twice the number of isolates from ML lesions was isolated using the mouse model compared to ex vivo cultures (mouse, 6/25; culture, 3/27). The overall rates of isolation were 40.2% for CL samples and 29.6% for ML samples. Of the 43 isolations, we successfully stocked 35 isolates (81.4%; 27 CL, 8 ML). Contaminations were more frequently detected in cultures of ML than CL lesions. For comparison, the use of both methods simultaneously was performed in 74 samples of CL and 25 samples of ML, and similar results were obtained. Of the eight ML isolates, five were isolated only in mice, indicating the advantage of using the in vivo method to obtain ML parasites. All parasites obtained from in vivo isolation were cryopreserved, whereas only 68% of ex vivo isolations from CL lesions were stocked. In conclusion, the use of genetically modified mice can improve the isolation of parasites from ML. Isolation and stocking of New World Leishmania parasites, especially those from ML that are almost absent in laboratory stocks, are critical for evaluating parasite genetic diversity as well as studying host-parasite interactions to identify biological markers of Leishmania. In this paper, we also discuss some of the difficulties associated with isolating and stocking parasites.

Copyright © 2012. Published by Elsevier Inc.

PMID: 22728105 [PubMed - as supplied by publisher]
3. Aten Primaria. 2012 Jun 20. [Epub ahead of print]

[Community outbreak of leishmaniasis in the southern area of the community of Madrid.]

[Article in Spanish]
Noguerol Álvarez M, San Martín López JV, Aguado Lobo M, Aparicio Azcárraga P .

Source

Medicina de Familia y Comunitaria, Centro de Salud Cuzco, Fuenlabrada, Madrid, España.

PMID: 22727435 [PubMed - as supplied by publisher]
4. Trends Parasitol. 2012 Jun 20. [Epub ahead of print]

Receptor-mediated phagocytosis of Leishmania: implications for intracellular survival.

Ueno N, Wilson ME.

Source

Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.

Abstract

The extracellular promastigote stage of Leishmania spp. is transmitted to mammals by a sand fly vector. Leishmania promastigotes ligate host macrophage receptors, triggering phagocytosis and subsequent internalization, a crucial step for survival. Parasites transform intracellularly to the amastigote stage. Many studies document different receptors detecting promastigotes and amastigotes, but the relative importance of each interaction is ill-defined. Recent studies suggest that the macrophage receptors utilized during phagocytosis impact the intracellular fate of the parasite. This review summarizes the receptors implicated in Leishmania phagocytosis over the past 30 years. It then proceeds to weigh the evidence for or against their potential roles in intracellular parasite trafficking.

Published by Elsevier Ltd.

PMID: 22726697 [PubMed - as supplied by publisher]
5. Trends Parasitol. 2012 Jun 20. [Epub ahead of print]

Purine salvage in Leishmania: complex or simple by design?

Boitz JM, Ullman B, Jardim A, Carter NS.

Source

Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97239, USA.

Abstract

Purine nucleotides function in a variety of vital cellular and metabolic processes including energy production, cell signaling, synthesis of vitamin-derived cofactors and nucleic acids, and as determinants of cell fate. Unlike their mammalian and insect hosts, Leishmania cannot synthesize the purine ring de novo and are absolutely dependent upon them to meet their purine requirements. The obligatory nature of purine salvage in these parasites, therefore, offers an attractive paradigm for drug targeting and, consequently, the delineation of the pathway has been under scientific investigation for over 30 years. Here, we review recent developments that reveal how purines flux in Leishmania and offer a potential 'Achilles' heel' for future validation.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22726696 [PubMed - as supplied by publisher]
6. Adv Parasitol. 2012;79:299-337.

Priorities for the elimination of sleeping sickness.

Welburn SC, Maudlin I.

Abstract

Sleeping sickness describes two diseases, both fatal if left untreated: (i) Gambian sleeping sickness caused by Trypanosoma brucei gambiense, a chronic disease with average infection lasting around 3 years, and (ii) Rhodesian sleeping sickness caused by T. b. rhodesiense, an acute disease with death occurring within weeks of infection. Control of Gambian sleeping sickness is based on case detection and treatment involving serological screening, followed by diagnostic confirmation and staging. In stage I, patients can remain asymptomatic as trypanosomes multiply in tissues and body fluids; in stage II, trypanosomes cross the blood-brain barrier, enter the central nervous system and, if left untreated, death follows. Staging is crucial as it defines the treatment that is prescribed; for both forms of disease, stage II involves the use of the highly toxic drug melarsoprol or, in the case of Gambian sleeping sickness, the use of complex and very expensive drug regimes. Case detection of T. b. gambiense sleeping sickness is known to be inefficient but could be improved by the identification of parasites using molecular tools that are, as yet, rarely used in the field. Diagnostics are not such a problem in relation to T. b. rhodesiense sleeping sickness, but the high level of under-reporting of this disease suggests that current strategies, reliant on self-reporting, are inefficient. Sleeping sickness is one of the 'neglected tropical diseases' that attracts little attention from donors or policymakers. Proper quantification of the burden of sleeping sickness matters, as the primary reason for its 'neglect' is that the true impact of the disease is unknown, largely as a result of under-reporting. Certainly, elimination will not be achieved without vast improvements in field diagnostics for both forms of sleeping sickness especially if there is a hidden reservoir of 'chronic carriers'. Mass screening would be a desirable aim for Gambian sleeping sickness and could be handled on a national scale in the endemic countries - perhaps by piggybacking on programmes committed to other diseases. As well as improved diagnostics, the search for non-toxic drugs for stage II treatment should remain a research priority. There is good evidence that thorough active case finding is sufficient to control T. b. gambiense sleeping sickness, as there is no significant animal reservoir. Trypanosoma brucei rhodesiense sleeping sickness is a zoonosis and control involves interrupting the fly-animal-human cycle, so some form of tsetse control and chemotherapy of the animal reservoir must be involved. The restricted application of insecticide to cattle is the most promising, affordable and sustainable technique to have emerged for tsetse control. Animal health providers can aid disease control by treating cattle and, when allied with innovative methods of funding (e.g. public-private partnerships) not reliant on the public purse, this approach may prove more sustainable. Sleeping sickness incidence for the 36 endemic countries has shown a steady decline in recent years and we should take advantage of the apparent lull in incidence and aim for elimination. This is feasible in some sleeping sickness foci but must be planned and paid for increasingly by the endemic countries themselves. The control and elimination of T. b. gambiense sleeping sickness may be seen as a public good, as appropriate strategies depend on local health services for surveillance and treatment, but public-private funding mechanisms should not be excluded. It is timely to take up the tools available and invest in new tools - including novel financial instruments - to eliminate this disease from Africa.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22726645 [PubMed - in process]
7. An Pediatr (Barc). 2012 Jun 20. [Epub ahead of print]

[Pericardial effusion in a case of hemophagocytic lymphohistiocytosis secondary to leishmaniasis.]

[Article in Spanish]
Cerdán Vera MT, Bernal Ferrer AM, Sequi Canet JM, Sifre Aranda M.

Source

Servicio de Pediatría, Hospital Francesc de Borja, Gandía, Valencia, España.

PMID: 22726300 [PubMed - as supplied by publisher]
8. Expert Opin Drug Deliv. 2012 Jun 24. [Epub ahead of print]

Drug delivery systems for the topical treatment of cutaneous leishmaniasis.

Carneiro G, Aguiar MG, Fernandes AP, Ferreira LA.

Source

Federal University of Minas Gerais, Faculty of Pharmacy , Belo Horizonte, Minas Gerais , Brazil.

Abstract

Introduction: The parenteral administration of pentavalent antimonials for the treatment of all forms of leishmaniasis, including cutaneous leishamniasis (CL), has several limitations. Therapy is long, requiring repeated doses and the adverse reactions are frequent. Topical treatment is an attractive alternative for CL, offering significant advantages over systemic therapy: fewer adverse effects, ease of administration, and lower costs. Areas covered: This review covers, from 1984 to the present, the progress achieved for the development of topical treatment for CL, using different drugs such as paromomycin (PA), imiquimod, amphotericin B (AmB), miltefosine, and buparvaquone. PA is the most commonly studied drug, followed by AmB and Imiquimod. These drugs were incorporated in conventional dosage forms or loaded in lipid nanocarries, which have been used mainly for improved skin delivery and antileishmanial activity. Expert opinion: Developing an effective topical treatment for CL using these antileishmanial drugs still remains a great challenge. Insights into the most promising delivery strategies to improve treatment of CL with PA and AmB using conventional dosage forms, lipid nanocarriers, and combined therapy are presented and discussed. The results obtained with combined therapy and alternative delivery systems are promising perspectives for improving topical treatment of CL.

PMID: 22724539 [PubMed - as supplied by publisher]
9. J Proteome Res. 2012 Jun 22. [Epub ahead of print]

Metabolic characterization of Leishmania major infection in activated and non-activated macrophages.

Lamour SD, Choi BS, Keun HC, Muller I, Saric J.

Abstract

Infection with Leishmania spp. can lead to a range of symptoms in the affected individual, depending on underlying immune-metabolic processes. The macrophage activation state plays a key role hereby. Whereas the L-arginine pathway has been described in detail as the main biochemical process responsible for either nitric oxide mediated parasite killing (classical activation) or amplification of parasite replication (alternative activation), we were interested in a wider characterisation of metabolic events in vitro. We therefore assessed cell growth medium, parasite extract, and intra- and extracellular metabolome of activated and non-activated macrophages, in presence and absence of Leishmania major. A metabolic profiling approach was applied combining (1)H NMR spectroscopy with multi- and univariate data treatment. Metabolic changes were observed along both conditional axes i.e. infection state and macrophage activation, whereby significantly higher levels of potential parasite end products were found in parasite exposed samples including succinate, acetate and alanine, compared to uninfected macrophages. The different macrophage activation states were mainly discriminated by varying glucose consumption. The presented profiling approach allowed us to obtain a metabolic snapshot of the individual biological compartments in the assessed macrophage culture experiments and will be a valuable read out system for further multiple component in vitro studies.

PMID: 22724526 [PubMed - as supplied by publisher]