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 - 10 of 17

1.	Am J Trop Med Hyg. 2011 Feb;84(2):261-6. Antileishmania immunological tests for asymptomatic subjects living in a visceral leishmaniasis-endemic area in Brazil. Silva LA, Romero HD, Nogueira Nascentes GA, Costa RT, Rodrigues V, Prata A. Department of Tropical Medicine and Infectology, Federal University of Triângulo Mineiro, Uberaba, Brazil; Laboratory of Leishmaniasis and Vaccines, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. Abstract Abstract. The objective of this study was to evaluate the behavior of different tests used for the diagnosis of visceral leishmaniasis (VL) in asymptomatic subjects living in an endemic area. No gold standard is available for the diagnosis of asymptomatic infection with Leishmania. In continuation of a previous study, 1,017 subjects living in a VL-endemic area were clinically reevaluated. Of these, 576 had at least one positive serological test in a first assessment. About 3 years after the first evaluation, none of the subjects had progressed to clinical VL. Among this group, 246 subjects were selected, and five serological tests (enzyme-linked immunosorbent assay p [ELISAp], ELISArK39, ELISArK26, indirect immunofluorescence test [IIFT] using L. amazonensis promastigote antigen, and an immunochromatographic test using rK39 antigen [TRALd]) and the Montenegro skin test (MST) were repeated. There was a significant increase in the number of subjects who tested positive in the MST, IIFT, ELISAp, and ELISArK39 in the second evaluation. For all tests, there were subjects who tested positive in the first evaluation and negative in the second evaluation. A positive result in the serological tests and MST in subjects from the endemic area studied did not indicate a risk of progression to VL and may only be temporary.
	PMID: 21292896 [PubMed - in process]
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2.	Am J Trop Med Hyg. 2011 Feb;84(2):255-60. Randomized Controlled Clinical Tr ial to Access Efficacy and Safety of Miltefosine in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania (Viannia) guyanensis in Manaus, Brazil. Chrusciak-Talhari A, Dietze R, Chrusciak Talhari C, da Silva RM, Gadelha Yamashita EP, de Oliveira Penna G, Lima Machado PR, Talhari S. Fundação de Medicina Tropical do Amazonas and Universidade Estadual do Amazonas, Manaus, AM, Brasil; Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brasil; Universidade de Brasília, Núcleo de Medicina Tropical, Brasília, DF, Brasil; Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brasil. Abstract Abstract. Miltefosine has been used in the treatment of several new world cutaneous leishmaniasis (CL) species with variable efficacy. Our study is the first evidence on its clinical efficacy in Leishmania (Viannia) guyanensis. In this phase II/III randomized clinical trial, 90 CL patients were randomly allocated (2:1) to oral miltefosine (2.5 mg/kg/day/28 days) (N = 60) or parenteral antimony (15-20 mg/Sb/kg/day/20 days) (N = 30) according to age groups: 2-12 y/o and 13-65 y/o. Patients were human immunodeficiency virus (HIV) noninfected parasitological proven CL without previous treatment. Definitive cure was accessed at 6 months follow-up visit. No severe adverse events occurred. Vomiting was the most frequent adverse event (48.3%) followed by nausea (8.6%) and diarrhea (6.7%). Cure rates were 71.4% (95% confidence interval [CI] = 57.8-82.7) and 53.6% (95% CI = 33.9-72.5) (P = 0.05) for miltefosine and antimonial, respectively. There were no differences in cure rates between age groups within the same treatment arms. Miltefosine was safe and relatively well tolerated and cure rate was higher than antimony.
	PMID: 21292895 [PubMed - in process]
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3.	J Ethnopharmacol. 2011 Jan 31. [Epub ahead of print] Deciphering molecular mechanism underlying antileishmanial activity of Nyctanthes arbortristis , an Indian medicinal plant. Shukla AK, Patra S, Dubey VK. Department of Biotechnology, Indian Institute of Technology Guwahati, Assam, India- 781039. Abstract ETHNOPHARMACOLOGICAL RELEVANCE: : Nyctanthes arbortristis L. (Oleaceae) is widely used in the traditional medicine of India. The plant is shown to have antibacterial and antileishmanial activities. AIM OF THE STUDY: : Evaluation of iridoid glucosides from the plant as inhibitor of trypanothione reductase (TryR), a validated drug target enzyme of the Leishmania parasite. The study contributes towards understanding mechanism of antileishmanial effect of the plant. MATERIALS AND METHODS: : TryR of Leishmania parasite is expressed and purified. Iridoid glucosides are isolated from the plant and tested as inhibitor of TryR enzyme of the parasite. RESULTS: Inhibitory constant (K(i)) of various iridoid glucosides ranges from 3.24±0.05μM to 6.49±0.05μM. Thus, the molecular mechanism underlying antileishmanial activity of these compounds is mediated through inhibition of TryR. CONCLUSION: The current study also points out towards potential application of iridoid glucosides as novel drugs against the disease. Copyright © 2011. Published by Elsevier Ireland Ltd.
	PMID: 21291983 [PubMed - as supplied by publisher]
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4.	Mol Biochem Parasitol. 2011 Jan 31. [Epub ahead of print] The Hus1 homologue of Leishmania major encodes a nuclear protein that participates in DNA damage response. Nunes VS, Damasceno JD, Freire R, Tosi LR. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo; Av Bandeirantes, 3900; 14049-900, Ribeirão Preto, SP, Brasil. Abstract The protozoan parasite Leishmania presents a dynamic and plastic genome in which gene amplification and chromosome translocations are common phenomena. Such plasticity hints at the necessity of dependable genome maintenance pathways. Eukaryotic cells have evolved checkpoint control systems that recognize altered DNA structures and halt cell cycle progression allowing DNA repair to take place. In these cells, the PCNA-related heterotrimeric complex formed by the proteins Hus1, Rad9, and Rad1 is known to participate in the early steps of replicative stress sensing and signaling. Here we show that the Hus1 homolog of Leishmania major is a nuclear protein that improves the cell capability to cope with replicative stress. Overexpression of LmHus1 confers resistance to the genotoxic drugs hydroxyurea (HU) and methyl methanesulfonate (MMS) and resistance to HU correlates to reduced net DNA damage upon LmHus1 expression. Copyright © 2011. Published by Elsevier B.V.
	PMID: 21291918 [PubMed - as supplied by publisher]
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5.	Mol Biochem Parasitol. 2011 Jan 31. [Epub ahead of print] Functional characterization of NADP-dependent isocitrate dehydrogenase isozymes from Trypanosoma cruzi. Leroux AE, Maugeri DA, Cazzulo JJ, Nowicki C. Instituto de Química y Fisicoquímica Biológica IQUIFIB-CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires. Abstract Trypanosoma cruzi exhibits two putative isocitrate dehydrogenases (IDHs). Both idh genes were cloned and the recombinant enzymes expressed in E. coli. Our results showed that T. cruzi IDHs are strictly dependent on NADP(+) and display apparent affinities towards isocitrate and the coenzyme in the low micromolar range. In T. cruzi, IDHs are cytosolic and mitochondrial enzymes, and there is no evidence for the typical Krebs cycle-related NAD-dependent IDH. Hence, like in T. brucei, the Krebs cycle is not a canonical route in T. cruzi. However, the citrate produced in the mitochondrion could be isomerized into isocitrate in the cytosol and the mitochondrion by means of the putative aconitase, which would provide the substrate for both IDHs. The cytosolic IDH is significantly more abundant in amastigotes, cell-derived and metacyclic trypomastigotes than in epimastigotes. This observation fits in well with the expected oxidative burst this pathogen has to face when infecting the mammalian host. Copyright © 2011. Published by Elsevier B.V.
	PMID: 21291916 [PubMed - as supplied by publisher]
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6.	Emerg Infect Dis. 2011 Feb;17(2):326-7. Dogs as Reservoirs for Leishmania braziliensis.< /h1>Dantas-Torres F. Universita degli Studi di Bari, Bari, Italy. Abstract To the Editor: I have read the review by Sousa and Pearson (1), which provides a fascinating historical account of the Great Drought and the smallpox epidemic of the 1870s and their association with the emergence of cutaneous leishmaniasis in Ceara, Brazil. In their review, the authors went back to the 19th century, remembering the hard years experienced by those who faced the Great Drought, which prompted the immigration of thousands of persons from Ceara to the Amazon region, and a devastating smallpox epidemic, which resulted in the death of >100,000 persons. Later, they returned to the present situation of cutaneous leishmaniasis in Brazil.
	PMID: 21291626 [PubMed - in process]
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7.	Adv Exp Med Biol. 2011;704:359-71. TRP Channels in Parasites. Wolstenholme AJ, Williamson SM, Reaves BJ. Department of Infectious Diseases, University of Georgia, Athens, GA, 30602, USA, adrianw@uga.edu. Abstract A wide range of single- and multi-cellular parasites infect humans and other animals, causing some of the most prevalent and debilitating diseases on the planet. There have been virtually no published studies on the TRP channels of this diverse group of organisms. However, since many parasite genomes have been sequenced, it is simple to demonstrate that they are present in all parasitic metazoans and that sequences related to the yeast trp are present in many protozoans, including all the kinetoplastids. We compared the TRP genes of three species of animal and plant parasitic nematode to those of C. elegans and found that the parasitic species all had fewer such genes. These differences may reflect the phylogenetic distance between the species studied, or may be due to loss of specific gene functions following the evolution of the parasitic lifestyle. Other helminth groups, the trematodes and cestodes, seem to possess many TRPC and TRPM genes, but lack TRPV and TRPN. Most ectoparasites are insects or arachnids. We compared the TRP genes of a plant parasitic aphid and an animal parasite louse and tick with those of Drosophila. Again, all the parasitic species seemed to have fewer types of TRP channel, though the difference was less marked than for the nematodes. The aphid lacks TRPP and TRPML channel genes, whereas the tick lacked those encoding TRPVs. Again, these differences may reflect adaptation to parasitism, and could enable TRP channels to be targeted in the development of novel antiparasitic drugs.
	PMID: 21290306 [PubMed - in process]
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8.	Eur J Immunol. 2011 Jan 4. doi: 10.1002/eji.201040985. [Epub ahead of print] PKCδ regulates IL-12p40/p70 production by macrophages and dendritic cells, driving a type 1 healer phenotype in cutaneous leishmaniasis. Guler R, Afshar M, Arendse B, Parihar SP, Revaz-Breton M, Leitges M, Schwegmann A, Brombacher F. International Centre for Genetic Engineering and Biotechnology (ICGEB) and Institute of Infectious Diseases and Molecular Medicine (IIDMM), Division of Immunology, Health Science Faculty, University of Cape Town, Cape Town, South Africa. Abstract The protein kinase C (PKC) family is involved in the regulation of many intracellular signalling pathways. Here, we report that the PKCδ isoform regulates IL-12p40/p70 production in macrophages and DC and that PKCδ deficiency in mice transforms the 129/Sv healer to a non-healer strain during cutaneous leishmaniasis. Leishmania major-infected PKCδ(-/-) 129/Sv mice developed a rapid increase in footpad swelling and parasite burden with disease progression, leading to necrosis and ulceration similar to non-healer BALB/c mice. Moreover, PKCδ(-/-) mice failed to develop delayed-type hypersensitivity responses against Leishmania antigen. PKCδ(-/-) macrophages were fully functional with normal MHC class II surface expression and GM-CSF production, recruitment to the draining lymph node and killing effector functions by NO production. In contrast, macrophages and DC produced significantly reduced IL-12p40 and IL-12p70 compared to the WT cells. Decreased IL-12 production resulted in diminished Th1 differentiation, as determined by a striking reduction in IFN-γ by antigen-specific stimulated CD4(+) T cells isolated from popliteal lymph nodes of L. major-infected PKCδ(-/-) mice, explaining the "non-healer" phenotype. We conclude from these data that PKCδ is a regulator of IL-12p40/p70 production by DC and macrophages, driving the healer phenotype during cutaneous leishmaniasis. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
	PMID: 21287553 [PubMed - as supplied by publisher]
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9.	Parasitol Res. 2011 Feb 2. [Epub ahead of print] The typing of Trypanosoma evansi isolates using mobile genetic element (MGE) PCR. Njiru ZK, Gitonga PK, Ndungu K. School of Veterinary Sciences, University of Queensland, Inner Ring Road, Gatton, 4343, Australia, z.njiru@uq.edu.au. Abstract The mobile genetic element PCR (MGE-PCR) is a simple and sensitive technique that can be used to detect genetic variability in Trypanosoma brucei ssp. To investigate the reliability of MGE-PCR in genotyping Trypanosoma evansi, stocks that were isolated directly from camels and after their respective passage in mice were analyzed. Construction of a dendrogram using the MGE-PCR banding profiles revealed a clear distinction between T. evansi and T. brucei, as well as discriminating the T. evansi strains (T. evansi with minicircle types B and A). A minor host-dependent clustering shows a genetic difference of <15%. Changes in the banding profiles were observed after serial passage of T. evansi type B in mice, while those of T. evansi type A were identical. It is apparent that significant random insertion mobile element positional variation occurs when T. evansi isolates are introduced into a new host, a factor that needs to be considered when MGE-PCR is used to determine genetic variation in T. evansi isolates that have different host origins.
	PMID: 21287202 [PubMed - as supplied by publisher]
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10.	Molecules. 2010 Oct 21;15(10):7363-77. Chemometric studies on natural products as potential inhibitors of the NADH oxidase from Trypanosoma cruzi using the VolSurf approach. < a href="http://www.ncbi.nlm.nih.gov/pubmed?term=%22Scotti%20L%22%5BAuthor%5D">Scotti L, Ferreira EI, Silva MS, Scotti MT. LTF, University Federal of Paraíba, Campus I, João Pessoa-PB, Brazil. Abstract Natural products have widespread biological activities, including inhibition of mitochondrial enzyme systems. Some of these activities, for example cytotoxicity, may be the result of alteration of cellular bioenergetics. Based on previous computer-aided drug design (CADD) studies and considering reported data on structure-activity relationships (SAR), an assumption regarding the mechanism of action of natural products against parasitic infections involves the NADH-oxidase inhibition. In this study, chemometric tools, such as: Principal Component Analysis (PCA), Consensus PCA (CPCA), and partial least squares regression (PLS), were applied to a set of forty natural compounds, acting as NADH-oxidase inhibitors. The calculations were performed using the VolSurf+ program. The formalisms employed generated good exploratory and predictive results. The independent variables or descriptors having a hydrophobic profile were strongly correlated to the biological data.
	PMID: 20966878 [PubMed - indexed for MEDLINE]
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