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Sent on Saturday, 2011 May 28Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Biol Trace Elem Res. 2011 May 27. [Epub ahead of print]Reduction of Sb(V) in a Human Macrophage Cell Line Measured by HPLC-ICP-MS.Hansen C, Hansen EW, Hansen HR, Gammelgaard B, Stürup S.SourceDepartment of Pharmaceutics and Analytical Chemistry, University of Copenhagen, Universitetsparken 2, DK, 2100, Copenhagen Ø, Denmark, clha@farma.ku.dk. AbstractDrugs based on pentavalent antimony are first-line treatment of the parasite disease leishmaniasis. It is generally believed that Sb(V) acts as a prodrug, which is activated by reduction to Sb(III); however, the site of reduction is not known. It has been hypothesised that the reduction takes place in the parasites' host cells, the macrophages. In this study, the human macrophage cell line Mono Mac 6 was exposed to Sb(V) in form of the drug sodium stibogluconate (Pentostam™). Cell extracts were analysed for Sb species by high-performance liquid chromatography with inductively coupled plasma-mass spectrometry detection. We found that Sb(V) is actually reduced to Sb(III) in the macrophages; up to 23% of the intracellular Sb was found as Sb(III). Transfer of the cells to Sb-free medium rapidly decreased their Sb(V) and Sb(III) content. Induction of the cell's production of reactive oxygen species did not have any marked effect on the intracellular amounts of Sb(III). |
| 2. | Sci Pharm. 2011 Mar;79(1):137-144. Epub 2011 Feb 7.Antitrypanosomal and Cytotoxic Activities of 22-Hydroxyclerosterol, a New Sterol from Allexis cauliflora (Violaceae).Nganso YO, Ngantchou IE, Nkwenoua E, Nyasse B, Denier C, Hannert V, Schneider B.SourceLaboratory of Medicinal Chemistry & Pharmacognosy, Department of Organic Chemistry, Faculty of Sciences, University of Yaoundé I, Box 812 Yaoundé, Cameroon. AbstractIn the search for new antiparasitic natural compounds from the medicinal plants from Cameroon, the new 22-hydroxyclerosterol, established as such on the basis of detailed chemical and spectroscopic analysis, was isolated from the hexane extract of the stem bark of Allexis cauliflora together with the known clerosterol. 22-Hydroxyclerosterol inhibited the growth of Trypanosoma brucei brucei cells with an ED(50) value of 1.56 μM. The compound was also established as an uncompetitive inhibitor of the glycolytic enzyme PGI of T. brucei (Ki'= 3 ± 1 μM), an uncompetitive inhibitor of mammalian rabbit muscles' enzyme PyK (Ki'= 26 ± 3 μM) and a mixed inhibitor of PyK of Leishmania mexicana (Ki'= 65 ± 10 μM; Ki= 24 ± 5 μM). |
| 3. | Trans R Soc Trop Med Hyg. 2011 May 24. [Epub ahead of print]Direct agglutination test (DAT): improvement of biosafety for laboratory diagnosis of visceral leishmaniasis.Oliveira E, Saliba SW, Andrade CF, Rabello A.SourceClinical Research Laboratory, Centro de Pesquisas René Rachou-FIOCRUZ, Av. Augusto de Lima 1715, 30190-002 Belo Horizonte, Minas Gerais, Brazil. AbstractIn this study, the direct agglutination test (DAT), using 2-mercaptoethanol (2-ME), kaolin or N-acetylcysteine (NAC) as sample diluents, was used to assay 89 samples from visceral leishmaniasis (VL) patients and 130 samples from patients with other diseases and healthy individuals. Maintaining a cut-off of 1:100, the DAT assays with 2-ME, kaolin or NAC presented sensitivities of 94.4%, 95.5% and 100% (P = 0.09) and specificities of 99.2%, 100% and 97.7% (P = 0.17), respectively. Based on these results, we suggest that NAC can be used as a replacement for 2-ME in the DAT, increasing biosafety in the diagnosis of VL. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. |
| 4. | Int Immunopharmacol. 2011 May 23. [Epub ahead of print]Vaccine candidates for leishmaniasis: A review.Nagill R, Kaur S.AbstractLeishmaniasis is a diverse group of clinical syndromes caused by protozoan parasites of the genus Leishmania. The clinical manifestation of the disease varies from self-limiting cutaneous lesions to progressive visceral disease. It is estimated that 350million people are at risk in 88 countries, with a global incidence of 1-1.5million cases of cutaneous and 500,000 cases of visceral leishmaniasis. The key control measures mainly rely on early case detection and chemotherapy which has been hampered by the toxicity of drugs, side-effects and by the emergence of drug resistance in parasites. Control of reservoir host and vector is difficult due to operational difficulties and frequent relapses in the host. Therefore, the development of effective and affordable vaccine against leishmaniasis is highly desirable. Although considerable progress has been made over the last decade in understanding immune mechanisms underlying potential candidate antigens, including killed, live attenuated parasites, crude parasites, pure or recombinant Leishmania proteins or DNA encoding leishmanial proteins, as well as immunomodulators from sand fly saliva, very few candidate vaccines have progressed beyond the experimental stage. As such there is no vaccine against any form of human leishmaniasis. In recent years, however, much interest has been stimulated towards vaccination against leishmaniasis focused mainly on cutaneous leishmaniasis with fewer attempts against visceral leishmaniasis. Copyright © 2011. Published by Elsevier B.V. |
| 5. | Exp Parasitol. 2011 May 15. [Epub ahead of print]Leishmania aethiopica: Development of specific and sensitive PCR diagnostic test.Kuru T, Janusz N, Gadisa E, Gedamu L, Aseffa A.SourceDepartment of Biological Sciences, University of Calgary, Calgary, Alberta, Canada T2N 1N4. AbstractPCR has proved useful for rapid diagnosis and typing of Leishmania. Lack of specificity to discriminate between species and/or sensitivity to detect from clinical samples has always been an issue. Previously developed primers either require PCR-RFLP analysis for Leishmania aethiopica discrimination or lack sensitivity to detect L. aethiopica from clinical samples. Here we report the development and validation of L. aethiopica specific PCR primers (V5F/V10R) based on cysteine protease B (cpb), a multicopy and polymorphic gene of Leishmania. V5F/V10R primers differentiate L. aethiopica from Leishmania tropica, Leishmania major, Leishmania donovani and Leishmania infantum by direct PCR. In addition, they are sensitive enough to detect L. aethiopica from biopsy samples. The primers can be very useful for epidemiological studies, species typing and diagnosis of L. aethiopica directly from clinical samples. Implementation of these primers in routine L. aethiopica diagnosis can improve detection rate, save time, money and labor required for culturing Leishmania. Copyright © 2011. Published by Elsevier Inc. |
| 6. | Confl Health. 2011 May 26;5(1):7. [Epub ahead of print]Challenges of controlling sleeping sickness in areas of violent conflict: experience in the Democratic Republic of Congo.Tong J, Valverde O, Mahoudeau C, Yun O, Chappuis F.AbstractABSTRACT: BACKGROUND:Human African trypanosomiasis (HAT), or sleeping sickness, is a fatal neglected tropical disease if left untreated. HAT primarily affects people living in rural sub-Saharan Africa, often in regions afflicted by violent conflict. Screening and treatment of HAT is complex and resource-intensive, and especially difficult in insecure, resource-constrained settings. The country with the highest endemicity of HAT is the Democratic Republic of Congo (DRC), which has a number of foci of high disease prevalence. We present here the challenges of carrying out HAT control programmes in general and in a conflict-affected region of DRC. We discuss the difficulties of measuring disease burden, medical care complexities, waning international support, and research and development barriers for HAT. DISCUSSION:In 2007, Medecins Sans Frontieres (MSF) began screening for HAT in the Haut-Uele and Bas-Uele districts of Orientale Province in northeastern DRC, an area of high prevalence affected by armed conflict. Through early 2009, HAT prevalence rate of 3.4% was found, reaching 10% in some villages. More than 46,000 patients were screened and 1,570 treated for HAT during this time. In March 2009, two treatment centres were forced to close due to insecurity, disrupting patient treatment, follow-up, and transmission-control efforts. One project was reopened in December 2009 when the security situation improved, and another in late 2010 based on concerns that population displacement might reactivate historic foci. In all of 2010, 770 patients were treated at these sites, despite a limited geographical range of action for the mobile teams. SUMMARY:In conflict settings where HAT is prevalent, targeted medical interventions are needed to provide care to the patients caught in these areas. Strategies of integrating care into existing health systems may be unfeasible since such infrastructure is often absent in resource-poor contexts. HAT care in conflict areas must balance logistical and medical capacity with security considerations, and community networks and international-response coordination should be maintained. Research and development for less complicated, field-adapted tools for diagnosis and treatment, and international support for funding and program implementation, are urgently needed to facilitate HAT control in these remote and insecure areas. |
| 7. | Mol Microbiol. 2011 May 26. doi: 10.1111/j.1365-2958.2011.07703.x. [Epub ahead of print]Interactions among Trypanosoma brucei RAD51 paralogues in DNA repair and antigenic variation.Dobson R, Stockdale C, Lapsley C, Wilkes J, McCulloch R.SourceUniversity of Glasgow, College of Medical Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, The Wellcome Trust Centre for Molecular Parasitology, Sir Graeme Davis Building, 120 University Place, Glasgow G12 8TA, UK. AbstractHomologous recombination in Trypanosoma brucei is used for moving variant surface glycoprotein (VSG) genes into expression sites during immune evasion by antigenic variation. A major route for such VSG switching is gene conversion reactions in which RAD51, a universally conserved recombinase, catalyses homology-directed strand exchange. In any eukaryote, RAD51-directed strand exchange in vivo is mediated by further factors, including RAD51-related proteins termed Rad51 paralogues. These appear to be ubiquitously conserved, although their detailed roles in recombination remain unclear. In T. brucei, four putative RAD51 paralogue genes have been identified by sequence homology. Here we show that all four RAD51 paralogues act in DNA repair, recombination and RAD51 subnuclear dynamics, though not equivalently, while mutation of only one RAD51 paralogue gene significantly impedes VSG switching. We also show that the T. brucei RAD51 paralogues interact, and that the complexes they form may explain the distinct phenotypes of the mutants as well as observed expression interdependency. Finally, we document the Rad51 paralogues that are encoded by a wide range of protists, demonstrating that the Rad51 paralogue repertoire in T. brucei is unusually large among microbial eukaryotes and that one member of the protein family corresponds with a key, conserved eukaryotic Rad51 paralogue. © 2011 Blackwell Publishing Ltd. |
| 8. | Nat Prod Commun. 2011 May;6(5):689-94.Antiprotozoal, antitubercular and cytotoxic potential of cyanobacterial (blue-green algal) extracts from Ireland.Broniatowska B, Allmendinger A, Kaiser M, Montamat-Sicotte D, Hingley-Wilson S, Lalvani A, Guiry M, Blunden G, Tasdemir D.SourceDepartment of Pharmaceutical and Biological Chemistry, Centre for Pharmacognosy and Phytotherapy, School of Pharmacy, University of London, London WC1N 1AX, UK. AbstractCyanobacteria (= blue-green algae) are prolific producers of structurally distinct and biologically active metabolites. In the continuation of our search for new sources of anti-infective natural products, we have assessed the in vitro antiprotozoal (Plasmodium falciparum, Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani) and antitubercular (Mycobacterium tuberculosis) potential of samples of two terrestrial cyanobacteria, Nostoc commune (collected when desiccated and wet) and Rivularia biasolettiana. The cytotoxic potential of the extracts was also evaluated against primary L6 cells. Except for T. cruzi and M. tuberculosis, the crude extracts were active against all the organisms tested and showed no toxicity. The crude extracts were then partitioned between n-hexane, chloroform and aqueous methanol and retested against the same panel of pathogens. The chloroform sub-extracts of both N. commune samples showed significant activity against T. b. rhodesiense (IC50 values 2.0 and 3.5 microg/mL) and P. falciparum (IC50s 7.4 and 5.8 microg/mL), with low toxicity. This trend was also true for R. biasolettiana extracts, and its chloroform sub-extract showed notable activity against all parasitic protozoa. There were differences in the biological activity profiles of extracts derived from desiccated and hydrated forms of N. commune. To our knowledge, this is the first study assessing the anti-infective activity of desiccated and hydrated forms of N. commune, as well as R. biasolettiana. Furthermore, the present work reports such biological activity in terrestrial cyanobacteria from Ireland for the first time. These results warrant the further study of Irish terrestrial cyanobacteria as a valuable source of new natural product leads for the treatment of parasitic protozoal infections. |
| 9. | Immunology. 2011 May;133(1):29-40. doi: 10.1111/j.1365-2567.2011.03406.x. Epub 2011 Feb 8.Programmed death ligand 2 regulates arginase induction and modifies Trypanosoma cruzi survival in macrophages during murine experimental infection.Dulgerian LR, Garrido VV, Stempin CC, Cerbán FM.SourceCIBICI-CONICET, Departamento Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina. AbstractThe programmed death ligands 1 (PD-L1) and 2 (PD-L2) that bind to programmed death 1 (PD-1) have been involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. However, there are no reports about the role of these molecules during Trypanosoma cruzi infection. We have studied the role of PD-L1 and PD-L2 in T. cruzi infection and their importance in arginase/inducible nitric oxide synthase (iNOS) balance in the immunomodulatory properties of macrophages (Mφ). In this work, we have demonstrated that expression of the PD-1/PD-L pathway is modified during T. cruzi infection on Mφs obtained from peritoneal cavity. The Mφs from T. cruzi-infected mice suppressed T-cell proliferation and this was restored when anti-PD-1 and anti-PD-L1 antibodies were added. Nevertheless, anti-PD-L2 antibody treatment did not re-establish T-cell proliferation. PD-L2 blockade on peritoneal cells from infected mice showed an increase in arginase expression and activity and a decrease in iNOS expression and in nitric oxide (NO) production. Additionally, interleukin-10 production increased whereas interferon-γ production was reduced. As a result, this microenvironment enhanced parasite proliferation. In contrast, PD-1 and PD-L1 blockage increased iNOS expression and NO production on peritoneal Mφs from T. cruzi-infected mice. Besides, PD-L2 knockout infected mice showed an increased in parasitaemia as well as in arginase activity, and a reduction in NO production. Taken together, our results demonstrate that PD-L2 is involved in the arginase/iNOS balance during T. cruzi infection having a protective role in the immune response against the parasite. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd. |
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| 10. | Math Biosci Eng. 2010 Jul;7(3):657-73. doi: 10.3934/mbe.2010.7.657.Alternative transmission modes for Trypa nosoma cruzi.Kribs-Zaleta CM.SourceMathematics Department, University of Texas at Arlington, Box 19408, Arlington, TX 76019-0408, USA. kribs@uta.edu AbstractThe parasite Trypanosoma cruzi, which causes Chagas' disease, is typically transmitted through a cycle in which vectors become infected through bloodmeals on infected hosts and then infect other hosts through defecation at the sites of subsequent feedings. The vectors native to the southeastern United States, however, are inefficient at transmitting T. cruzi in this way, which suggests that alternative transmission modes may be responsible for maintaining the established sylvatic infection cycle. Vertical and oral transmission of sylvatic hosts, as well as differential behavior of infected vectors, have been observed anecdotally. This study develops a model which accounts for these alternative modes of transmission, and applies it to transmission between raccoons and the vector Triatoma sanguisuga. Analysis of the system of nonlinear differential equations focuses on endemic prevalence levels and on the infection's basic reproductive number, whose form may account for how a combination of traditionally secondary infection routes can maintain the transmission cycle when the usual primary route becomes ineffective. |
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