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Sent on Friday, 2011 December 30Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | PLoS Negl Trop Dis. 2011 Dec;5(12):e1451. Epub 2011 Dec 20.Metabolic Variation during Development in Culture of Leishmania donovani Promastigotes.Silva AM, Cordeiro-da-Silva A, Coombs GH.SourceStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom. AbstractThe genome sequencing of several Leishmania species has provided immense amounts of data and allowed the prediction of the metabolic pathways potentially operating. Subsequent genetic and proteomic studies have identified stage-specific proteins and putative virulence factors but many aspects of the metabolic adaptations of Leishmania remain to be elucidated. In this study, we have used an untargeted metabolomics approach to analyze changes in the metabolite profile as promastigotes of L. donovani develop during in vitro cultures from logarithmic to stationary phase. The results show that the metabolomes of promastigotes on days 3-6 of culture differ significantly from each other, consistent with there being distinct developmental changes. Most notable were the structural changes in glycerophospholipids and increase in the abundance of sphingolipids and glycerolipids as cells progress from logarithmic to stationary phase. |
| 2. | PLoS Negl Trop Dis. 2011 Dec;5(12):e1448. Epub 2011 Dec 20.Multifaceted Population Structure and Reproductive Strategy in Leishmania donovani Complex in One Sudanese Village.Rougeron V, De Meeûs T, Hide M, Le Falher G, Bucheton B, Dereure J, El-Safi SH, Dessein A, Bañuls AL.SourceLaboratoire MIVEGEC (UMR IRD 224-CNRS 5290-Université Montpellier 1), Montpellier, France. AbstractLeishmania species of the subgenus Leishmania and especially L. donovani are responsible for a large proportion of visceral leishmaniasis cases. The debate on the mode of reproduction and population structure of Leishmania parasites remains opened. It has been suggested that Leishmania parasites could alternate different modes of reproduction, more particularly clonality and frequent recombinations either between related individuals (endogamy) or between unrelated individuals (outcrossing) within strongly isolated subpopulations. To determine whether this assumption is generalized to other species, a population genetics analysis within Leishmania donovani complex strains was conducted within a single village. The results suggest that a mixed-mating reproduction system exists, an important heterogeneity of subsamples and the coexistence of several genetic entities in Sudanese L. donovani. Indeed, results showed significant genetic differentiation between the three taxa (L. donovani, L. infantum and L. archibaldi) and between the human or canine strains of such taxa, suggesting that there may be different imbricated transmission cycles involving either dogs or humans. Results also are in agreement with an almost strict specificity of L. donovani stricto sensu to human hosts. This empirical study demonstrates the complexity of population structure in the genus Leishmania and the need to pursue such kind of analyses at the smallest possible spatio-temporal and ecological scales. |
| 3. | PLoS Negl Trop Dis. 2011 Dec;5(12):e1433. Epub 2011 Dec 20.Post-Kala-azar Dermal Leishmaniasis in Nepal: A Retrospective Cohort Study (2000-2010).Uranw S, Ostyn B, Rijal A, Devkota S, Khanal B, Menten J, Boelaert M, Rijal S.SourceDepartment of Internal Medicine, B.P. Koirala Institute of Health Sciences, Ghopa, Dharan, Nepal. AbstractINTRODUCTION:Post-kala-azar dermal leishmaniasis (PKDL) is a cutaneous complication appearing after treatment of visceral leishmaniasis, and PKDL patients are considered infectious to sand flies and may therefore play a role in the transmission of VL. We estimated the risk and risk factors of PKDL in patients with past VL treatment in south-eastern Nepal. METHODS:Between February and May 2010 we traced all patients who had received VL treatment during 2000-2009 in five high-endemic districts and screened them for PKDL-like skin lesions. Suspected cases were referred to a tertiary care hospital for confirmation by parasitology (slit skin smear (SSS)) and/or histopathology. We calculated the risk of PKDL using Kaplan-Meier survival curves and exact logistic regression for risk factors. RESULTS:Out of 680 past-treated VL patients, 37(5.4%) presented active skin lesions suspect of PKDL during the survey. Thirty-three of them underwent dermatological assessment, and 16 (2.4%) were ascertained as probable (2) or confirmed (14) PKDL. Survival analysis showed a 1.4% risk of PKDL within 2 years of VL treatment. All 16 had been previously treated with sodium stibogluconate (SSG) for their VL. In 5, treatment had not been completed (≤21 injections). Skin lesions developed after a median time interval of 23 months [interquartile range (IQR) 16-40]. We found a higher PKDL rate (29.4%) in those inadequately treated compared to those who received a full SSG course (2.0%). In the logistic regression model, unsupervised treatment [odds ratio (OR) = 8.58, 95% CI 1.21-374.77], and inadequate SSG treatment for VL in the past (OR = 11.68, 95% CI 2.71-45.47) were significantly associated with PKDL. CONCLUSION:The occurrence of PKDL after VL treatment in Nepal is low compared to neighboring countries. Supervised and adequate treatment of VL seems essential to reduce the risk of PKDL development and active surveillance for PKDL is needed. |
| 4. | PLoS Negl Trop Dis. 2011 Dec;5(12):e1429. Epub 2011 Dec 20.Potentiating Effects of MPL on DSPC Bearing Cationic Liposomes Promote Recombinant GP63 Vaccine Efficacy: High Immunogenicity and Protection.Mazumder S, Maji M, Ali N.SourceInfectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Jadavpur, Kolkata, India. AbstractBACKGROUND:Vaccines that activate strong specific Th1-predominant immune responses are critically needed for many intracellular pathogens, including Leishmania. The requirement for sustained and efficient vaccination against leishmaniasis is to formulate the best combination of immunopotentiating adjuvant with the stable antigen (Ag) delivery system. The aim of the present study is to evaluate the effectiveness of an immunomodulator on liposomal Ag through subcutaneous (s.c.) route of immunization, and its usefulness during prime/boost against visceral leishmaniasis (VL) in BALB/c mice. METHODOLOGY/PRINCIPAL FINDINGS:Towards this goal, we formulated recombinant GP63 (rGP63)-based vaccines either with monophosphoryl lipid A-trehalose dicorynomycolate (MPL-TDM) or entrapped within cationic liposomes or both. Combinatorial administration of liposomes with MPL-TDM during prime confers activation of dendritic cells, and induces an early robust T cell response. To investigate whether the combined formulation is required for optimum immune response during boost as well, we chose to evaluate the vaccine efficacy in mice primed with combined adjuvant system followed by boosting with either rGP63 alone, in association with MPL-TDM, liposomes or both. We provide evidences that the presence of either liposomal rGP63 or combined formulations during boost is necessary for effective Th1 immune responses (IFN-γ, IL-12, NO) before challenge infection. However, boosting with MPL-TDM in conjugation with liposomal rGP63 resulted in a greater number of IFN-γ producing effector T cells, significantly higher levels of splenocyte proliferation, and Th1 responses compared to mice boosted with liposomal rGP63, after virulent Leishmania donovani (L. donovani) challenge. Moreover, combined formulations offered superior protection against intracellular amastigote replication in macrophages in vitro, and hepatic and splenic parasite load in vivo. CONCLUSION:Our results define the immunopotentiating effect of MPL-TDM on protein Ag encapsulated in a controlled release system against experimental VL. |
| 5. | J Clin Microbiol. 2011 Dec 28. [Epub ahead of print]Peripheral blood buffy coat smear: A promising tool for diagnosis of visceral leishmaniasis.Salam MA, Khan MG, Bhaskar KR, Afrad MH, Huda MM, Mondal D.SourceRajshahi Medical College, Rajshahi-6000, Bangladesh. AbstractConfirmative diagnosis of Visceral Leishmaniasis (VL) is still being a challenge at the primary health care facilities in most of the rural endemic areas in the Indian sub-continent. Conventional methods for parasitological confirmation are risky and require skilled personnel hence, unreachable to the poor people in the endemic region. Buffy coat smear microscopy, as a minimally invasive simple alternative, for the parasitological diagnosis of VL was evaluated in this prospective study. One hundred twelve VL patients were enrolled in this study. Buffy coat was separated from peripheral blood of all enrolled subjects using the Histopaque-1119 solution. Leishman-stained buffy coat smear was examined for Leishmania Donovani (LD) body and buffy coat was also utilized for detection of parasite DNA by Leishmania-nested polymerase chain reaction (Ln-PCR) for all cases. Concomitant splenic smears could be examined for LD body in 66 cases and parasite load was graded in a scale of 1+ to 6+ for LD-positive smears. All splenic smear-positive cases were also found positive by Ln-PCR. Of 112 enrolled VL cases, 103 were found positive (92%) for LD bodies in buffy coat smear microscopy which is promising as a confirmative diagnosis tool. We have also found a significant association in the buffy coat smear positivity with parasitic burden in the spleen smear. In this preliminary observation in Bangladesh, buffy coat smear microscopy has been found to be very simple, minimally invasive and risk-free method of parasitological diagnosis for VL with a good diagnostic accuracy for its potentiality in field use. |
| 6. | Hum Vaccin. 2011 Nov;7(11):1225-33.Vaccination against trypanosomiasis: Can it be done or is the trypanosome truly the ultimate immune destroyer and escape artist?La Greca F, Magez S.SourceLaboratory for Cellular and Molecular Immunology, Vrije Universiteit Brussel; Brussels, Belgium. AbstractTo date, human African trypanosomiasis (HAT) still threatens millions of people throughout sub-Sahara Africa, and new approaches to disease prevention and treatment remain a priority. It is commonly accepted that HAT is fatal unless treatment is provided. However, despite the well-described general symptoms of disease progression during distinct stages of the infection, leading to encephalitic complications, coma and death, a substantial body of evidence has been reported suggesting that natural acquired immunity could occur. Hence, if under favorable conditions natural infections can lead to correct immune activation and immune protection against HAT, the development of an effective anti-HAT vaccine should remain a central goal in the fight against this disease. In this review, we will (1) discuss the vaccine candidates that have been proposed over the past years, (2) highlight the main obstacles that an efficient anti-trypanosomiasis vaccine needs to overcome and (3) critically reflect on the validity of the widely used murine model for HAT. |
| 7. | J Immunol. 2011 Dec 28. [Epub ahead of print]Lymph Node Hypertrophy following Leishmania major Infection Is Dependent on TLR9.Carvalho LP, Petritus PM, Trochtenberg AL, Zaph C, Hill DA, Artis D, Scott P.SourceDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104. AbstractControl of the protozoan parasite Leishmania major is dependent on establishing a robust T cell response. An early event in the development of an effective T cell response is the expansion (or hypertrophy) of the lymph node draining the site of infection, although the mechanisms involved in this response are not completely understood. In this study, we show that lymph node hypertrophy following L. major infection in mice is associated with increased recruitment of lymphocytes to the lymph node from the blood, and that CD62L-deficient mice, which are unable to recruit cells to the lymph node, develop a chronic infection with L. major. Injection of L. major-activated dendritic cells promoted lymph node hypertrophy, and this correlated with an increase in the expression of CCR7 on dendritic cells, although the upregulation of CCR7 occurred on the bystander (uninfected) dendritic cells rather than those containing parasites. We found that increased CCR7 expression was TLR9-dependent, that TLR9(-/-) dendritic cells migrated less efficiently to the draining lymph node, and that TLR9(-/-) mice exhibited a deficit in lymph node expansion following L. major infection, as well as increased susceptibility. Taken together, to our knowledge, these results are the first to demonstrate that activation of dendritic cells via TLR9 is essential for the induction of lymph node hypertrophy in leishmaniasis. |
| 8. | J Nat Prod. 2011 Dec 28. [Epub ahead of print]Drug-like Properties: Guiding Principles for the Design of Natural Product Libraries.Camp D, Davis RA, Campitelli M, Ebdon J, Quinn RJ.SourceEskitis Institute, Griffith University , Brisbane, QLD 4111, Australia. AbstractWhile natural products or their derivatives and mimics have contributed around 50% of current drugs, there has been no approach allowing front-loading of chemical space compliant with lead- and drug-like properties. The importance of physicochemical properties of molecules in the development of orally bioavailable drugs has been recognized. Classical natural product drug discovery has only been able to undertake this analysis retrospectively after compounds are isolated and structures elucidated. The present approach addresses front-loading of both extracts and subsequent fractions with desired physicochemical properties prior to screening for drug discovery. The physicochemical profiles of natural products active against two neglected disease targets, malaria and African trypanosomiasis, are presented based on this strategy. This approach can ensure timely development of natural product leads at a hitherto unachievable rate. |
| 9. | J Zoo Wildl Med. 2011 Dec;42(4):608-16.Visceral leishmaniasis in a captive crab-eating fox Cerdocyon thous.Tenório Mda S, Oliveira e Sousa L, Paixão Mdos S, Alves MF, Paulan Sde C, Lima FL, Jusi MM, Tasca KI, Machado RZ, Starke-Buzetti WA.SourceDepartamento de Biologia e Zootecnia, Faculdade de Engenharia de Ilha Solteira FEIS/ UNESP, Avenida Brasil, 56, 15385-000 Ilha Solteira, São Paulo, Brazil. AbstractVisceral leishmaniasis (VL) is a zoonotic disease with worldwide distribution. The crab-eating fox (Cerdocyon thous) is considered a wild reservoir of many zoonotical diseases, particularly VL. This study reported the presence of Leishmania infantum amastigotes in different organs of one captive C. thous found dead in a zoo. This animal was positive by the indirect fluorescence antibody test and had many clinical signs of VL. Intracellular amastigote forms of L. infantum were seen in neutrophils and macrophages in sample tissues from skin, lymph nodes (popliteal, submandibular, prescapular, and mesenteric), spleen, and liver. The numbers of positive cells and intracellular parasites were higher in macrophages than in neutrophils. In addition, polymerase chain reaction demonstrated extensive distribution of Leishmania DNA in C. thous tissues from multiple organs. The presence of intracellular amastigotes in neutrophils and macrophages as well as DNA of the parasite in tissues, specifically skin demonstrate that this crab-eating fox is an adequate host for L. infantum and reinforce the importance of VL for symptomatic wild canids kept in captivity in endemic areas. |
| 10. | BMC Biochem. 2011 Aug 23;12:46.The major leucyl aminopeptidase of Trypanosoma cruzi (LAPTc) assembles into a homohexamer and belongs to the M17 family of metallopeptidases.Cadavid-Restrepo G, Gastardelo TS, Faudry E, de Almeida H, Bastos IM, Negreiros RS, Lima MM, Assumpção TC, Almeida KC, Ragno M, Ebel C, Ribeiro BM, Felix CR, Santana JM.SourceDepartment of Cell Biology, The University of Brasília, Brasília, 70910-900, Brazil. AbstractBACKGROUND:Pathogens depend on peptidase activities to accomplish many physiological processes, including interaction with their hosts, highlighting parasitic peptidases as potential drug targets. In this study, a major leucyl aminopeptidolytic activity was identified in Trypanosoma cruzi, the aetiological agent of Chagas disease. RESULTS:The enzyme was isolated from epimastigote forms of the parasite by a two-step chromatographic procedure and associated with a single 330-kDa homohexameric protein as determined by sedimentation velocity and light scattering experiments. Peptide mass fingerprinting identified the enzyme as the predicted T. cruzi aminopeptidase EAN97960. Molecular and enzymatic analysis indicated that this leucyl aminopeptidase of T. cruzi (LAPTc) belongs to the peptidase family M17 or leucyl aminopeptidase family. LAPTc has a strong dependence on neutral pH, is mesophilic and retains its oligomeric form up to 80°C. Conversely, its recombinant form is thermophilic and requires alkaline pH. CONCLUSIONS:LAPTc is a 330-kDa homohexameric metalloaminopeptidase expressed by all T. cruzi forms and mediates the major parasite leucyl aminopeptidolytic activity. Since biosynthetic pathways for essential amino acids, including leucine, are lacking in T. cruzi, LAPTc could have a function in nutritional supply. |
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