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Sent on Saturday, 2011 Jul 09Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Parasitol Res. 2011 Jul 8. [Epub ahead of print]Prevalence of Trypanosoma sp. in cattle from Tanzania estimated by conventional PCR and loop-mediated isothermal amplification (LAMP).Laohasinnarong D, Thekisoe OM, Malele I, Namangala B, Ishii A, Goto Y, Kawazu SI, Sugimoto C, Inoue N.SourceO.I.E. Reference Laboratory on Surra, National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan. AbstractThis study compared the prevalence of trypanosome infections estimated by PFR-loop-mediated isothermal amplification (LAMP) with conventional polymerase chain reaction (PCR) tests. One hundred forty eight cattle blood samples were collected from Robanda village, Mara region, Tanzania in April 2008. In conventional PCR, four sets of primers, specific for the detection of Trypanosoma sp., Trypanosoma brucei rhodesiense, Trypanosoma vivax, and Trypanozoon, as well as a modified LAMP were used. Conventional PCR detected no infection or up to 8, 1, and 3 infections with Trypanosoma congolense savannah, Trypanozoon, and T. vivax, respectively, whereas LAMP detected additional 44 Trypanozoon positive cases. Our results clearly indicate that the prevalence of Trypanozoon spp. in cattle in Robanda village estimated by PFR-LAMP (30.4%) was significantly higher than the estimates by PCR assays (0.6-2%). As such, future studies should target epidemiological surveys of Trypanozoon and T. brucei rhodesiense infections in possible reservoir animals by LAMP to further elucidate the actual prevalence of these parasites. |
| 2. | Mem Inst Oswaldo Cruz. 2011 Jun;106(4):507-9.Miltefosine induces programmed cell death in Leishmania amazonensis promastigotes.Marinho Fde A, Gonçalves KC, Oliveira SS, Oliveira AC, Bellio M, d'Avila-Levy CM, Santos AL, Branquinha MH.SourceDepartamento de Microbiologia Geral, Instituto de Microbiologia Prof. Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil, 21941-902. AbstractIn the current study, we evaluated the mechanism of action of miltefosine, which is the first effective and safe oral treatment for visceral leishmaniasis, in Leishmania amazonensis promastigotes. Miltefosine induced a process of programmed cell death, which was determined by the externalization of phosphatidylserine, the incorporation of propidium iodide, cell-cycle arrest at the sub-G0/G1 phase and DNA fragmentation into oligonucleosome-sized fragments. Despite the intrinsic variation that is detected in Leishmania spp, our results indicate that miltefosine causes apoptosis-like death in L. amazonensis promastigote cells using a similar process that is observed in Leishmania donovani. |
| 3. | Mem Inst Oswaldo Cruz. 2011 Jun;106(4):475-8.The in vitro leishmanicidal activity of hexadecylphosphocholine (miltefosine) against four medically relevant Leishmania species of Brazil.Morais-Teixeira E, Damasceno QS, Galuppo MK, Romanha AJ, Rabello A.SourceLaboratório de Pesquisas ClÃnicas, Centro de Pesquisas René Rachou-Fiocruz, Belo Horizonte, MG, Brasil, 30190-002. AbstractThe in vitro leishmanicidal activity of miltefosine® (Zentaris GmbH) was assessed against four medically relevant Leishmania species of Brazil: Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis and Leishmania (Leishmania) chagasi. The activity of miltefosine against these New World species was compared to its activity against the Old World strain, Leishmania (Leishmania) donovani, which is known to be sensitive to the effects of miltefosine. The IC50 and IC90 results suggested the New World species harboured similar in vitro susceptibilities to miltefosine; however, miltefosine was approximately 20 times more active against the Old World L. (L.) donovani than against the New World L. (L.) chagasi species. The selectivity index varied from 17.2-28.9 for the New World Leishmania species and up to 420.0 for L. (L.) donovani. The differences in susceptibility to miltefosine suggest that future clinical trials with this drug should include a laboratory pre-evaluation and a dose-defining step. |
| 4. | Braz J Otorhinolaryngol. 2011 Jun;77(3):380-4.Mucocutaneous Leishmaniasis: clinical markers in presumptive dia gnosis. [Article in English, Portuguese] Diniz JL, Costa MO, Gonçalves DU.SourceGraduate Studies Program in Health Sciences: Infectology and Tropical Medicine, UFMG. AbstractMucocutaneous Leishmaniasis (ML) can lead to serious sequela; however, early diagnosis can prevent complications. AIM:To evaluate clinical markers for the early diagnosis of ML. MATERIALS AND METHODS:A series study of 21 cases of ML, which were evaluated through clinical interview, nasal endoscopy, biopsy and the Montenegro test. RESULTS:A skin scar and previous diagnosis of cutaneous leishmaniasis (CL) were reported in 8(38%) patients, and 13(62%) of them denied having had previous CL and had no scar. Nasal/oral symptom onset until the ML diagnosis varied from 5 months to 20 years, mean value of 6 years. In the Montenegro test, the average size of the papule was 14.5 mm, which did not correlate with disease duration (p=0.87). The nose was the most often involved site and the extension of the injured mucosa did not correlate with disease duration. The parasite was found in 2 (9.52%) biopsy specimens. CONCLUSIONS:ML diagnosis was late. Finding the parasite in the mucosa, cutaneous scar and/or previous diagnosis of CL were not clinical markers for ML. ML diagnosis must be based on the Montenegro test, chronic nasal and/or oral discharge and histological findings ruling out other granulomatous diseases. |
| 5. | An Bras Dermatol. 2011 Jun;86(3):497-506.Advances in the treatment of cutaneous leishmaniasis in the new world in the last ten years: a systematic literature review. [Article in English, Portuguese] Almeida OL, Santos JB.SourceEscola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brasil. AbstractINTRODUCTION:The therapeutic arsenal against cutaneous leishmaniasis is very limited. Pentavalent antimonial compounds have been the drugs of choice for treatment of this disease for over 50 years. Despite their effectiveness, these drugs require daily injections, have many side effects and present prolonged healing time. OBJECTIVE:To carry out a systematic literature review on the advances in the treatment of cutaneous leishmaniasis in the new world in the last ten years. METHODS:We conducted an electronic search on the Pubmed and LILACS database as well as on the SciELO electronic library in June 2009. The search words in English were: "cutaneous", "leishmaniasis" and "treatment". We included only randomized, double-blind and placebo controlled trials. We used the Jadad scale to assess the quality of the selected studies. RESULTS:According to the inclusion and exclusion criteria, only eight articles were selected. The drugs evaluated in the selected studies were glucantime®, miltefosine, immunotherapy, imiquimod, rhGM-CSF and pentoxifylline, and paromomycin. CONCLUSION:Although cutaneous leishmaniasis is a major public health issue, the published data on the use of new drugs for the treatment of cutaneous leishmaniasis in Brazil are still quite limited. |
| 6. | PLoS Negl Trop Dis. 2011 Jun;5(6):e1216. Epub 2011 Jun 28.Parasitic Loads in Tissues of Mice Infected with Trypanosoma cruzi and Treated with AmBisome.Cencig S, Coltel N, Truyens C, Carlier Y.SourceLaboratoire de Parasitologie, Faculté de Médecine, Université Libre de Bruxelles, Brussels, Belgium. AbstractBACKGROUND:Chagas disease is one of the most important public health problems and a leading cause of cardiac failure in Latin America. The currently available drugs to treat T. cruzi infection (benznidazole and nifurtimox) are effective in humans when administered during months. AmBisome (liposomal amphotericin B), already shown efficient after administration for some days in human and experimental infection with Leishmania, has been scarcely studied in T. cruzi infection. AIMS:This work investigates the effect of AmBisome treatment, administered in 6 intraperitoneal injections at various times during acute and/or chronic phases of mouse T. cruzi infection, comparing survival rates and parasitic loads in several tissues. METHODOLOGY:Quantitative PCR was used to determine parasitic DNA amounts in tissues. Immunosuppressive treatment with cyclophosphamide was used to investigate residual infection in tissues. FINDINGS:Administration of AmBisome during the acute phase of infection prevented mice from fatal issue. Parasitaemias (microscopic examination) were reduced in acute phase and undetectable in chronic infection. Quantitative PCR analyses showed significant parasite load reductions in heart, liver, spleen, skeletal muscle and adipose tissues in acute as well as in chronic infection. An earlier administration of AmBisome (one day after parasite inoculation) had a better effect in reducing parasite loads in spleen and liver, whereas repetition of treatment in chronic phase enhanced the parasite load reduction in heart and liver. However, whatever the treatment schedule, cyclophosphamide injections boosted infection to parasite amounts comparable to those observed in acutely infected and untreated mice. CONCLUSIONS:Though AmBisome treatment fails to completely cure mice from T. cruzi infection, it impedes mortality and reduces significantly the parasitic loads in most tissues. Such a beneficial effect, obtained by administrating it over a short time, should stimulate studies on using AmBisome in association with other drugs in order to shorten recovery from T. cruzi infection. |
| 7. | PLoS Negl Trop Dis. 2011 Jun;5(6):e1151. Epub 2011 Jun 28.SCYX-7158, an Orally-Active Benzoxaborole for the Treatment of Stage 2 Human African Trypanosomiasis.Jacobs RT, Nare B, Wring SA, Orr MD, Chen D, Sligar JM, Jenks MX, Noe RA, Bowling TS, Mercer LT, Rewerts C, Gaukel E, Owens J, Parham R, Randolph R, Beaudet B, Bacchi CJ, Yarlett N, Plattner JJ, Freund Y, Ding C, Akama T, Zhang YK, Brun R, Kaiser M, Scandale I, Don R.SourceSCYNEXIS, Inc., Research Triangle Park, North Carolina, United States of America. AbstractBACKGROUND:Human African trypanosomiasis (HAT) is an important public health problem in sub-Saharan Africa, affecting hundreds of thousands of individuals. An urgent need exists for the discovery and development of new, safe, and effective drugs to treat HAT, as existing therapies suffer from poor safety profiles, difficult treatment regimens, limited effectiveness, and a high cost of goods. We have discovered and optimized a novel class of small-molecule boron-containing compounds, benzoxaboroles, to identify SCYX-7158 as an effective, safe and orally active treatment for HAT. METHODOLOGY/PRINCIPAL FINDINGS:A drug discovery project employing integrated biological screening, medicinal chemistry and pharmacokinetic characterization identified SCYX-7158 as an optimized analog, as it is active in vitro against relevant strains of Trypanosoma brucei, including T. b. rhodesiense and T. b. gambiense, is efficacious in both stage 1 and stage 2 murine HAT models and has physicochemical and in vitro absorption, distribution, metabolism, elimination and toxicology (ADMET) properties consistent with the compound being orally available, metabolically stable and CNS permeable. In a murine stage 2 study, SCYX-7158 is effective orally at doses as low as 12.5 mg/kg (QD×7 days). In vivo pharmacokinetic characterization of SCYX-7158 demonstrates that the compound is highly bioavailable in rodents and non-human primates, has low intravenous plasma clearance and has a 24-h elimination half-life and a volume of distribution that indicate good tissue distribution. Most importantly, in rodents brain exposure of SCYX-7158 is high, with C(max) >10 µg/mL and AUC(0-24 hr) >100 µg*h/mL following a 25 mg/kg oral dose. Furthermore, SCYX-7158 readily distributes into cerebrospinal fluid to achieve therapeutically relevant concentrations in this compartment. CONCLUSIONS/SIGNIFICANCE:The biological and pharmacokinetic properties of SCYX-7158 suggest that this compound will be efficacious and safe to treat stage 2 HAT. SCYX-7158 has been selected to enter preclinical studies, with expected progression to phase 1 clinical trials in 2011. |
| 8. | PLoS Pathog. 2011 Jun;7(6):e1002089. Epub 2011 Jun 30.T. brucei Infection Reduces B Lymphopoiesis in Bone Marrow and Truncates Compensatory Splenic Lymphopoiesis through Transitional B-Cell Apoptosis.Bockstal V, Guirnalda P, Caljon G, Goenka R, Telfer JC, Frenkel D, Radwanska M, Magez S, Black SJ.SourceDepartment of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts, United States of America. AbstractAfrican trypanosomes of the Trypanosoma brucei species are extracellular protozoan parasites that cause the deadly disease African trypanosomiasis in humans and contribute to the animal counterpart, Nagana. Trypanosome clearance from the bloodstream is mediated by antibodies specific for their Variant Surface Glycoprotein (VSG) coat antigens. However, T. brucei infection induces polyclonal B cell activation, B cell clonal exhaustion, sustained depletion of mature splenic Marginal Zone B (MZB) and Follicular B (FoB) cells, and destruction of the B-cell memory compartment. To determine how trypanosome infection compromises the humoral immune defense system we used a C57BL/6 T. brucei AnTat 1.1 mouse model and multicolor flow cytometry to document B cell development and maturation during infection. Our results show a more than 95% reduction in B cell precursor numbers from the CLP, pre-pro-B, pro-B, pre-B and immature B cell stages in the bone marrow. In the spleen, T. brucei induces extramedullary B lymphopoiesis as evidenced by significant increases in HSC-LMPP, CLP, pre-pro-B, pro-B and pre-B cell populations. However, final B cell maturation is abrogated by infection-induced apoptosis of transitional B cells of both the T1 and T2 populations which is not uniquely dependent on TNF-, Fas-, or prostaglandin-dependent death pathways. Results obtained from ex vivo co-cultures of living bloodstream form trypanosomes and splenocytes demonstrate that trypanosome surface coat-dependent contact with T1/2 B cells triggers their deletion. We conclude that infection-induced and possibly parasite-contact dependent deletion of transitional B cells prevents replenishment of mature B cell compartments during infection thus contributing to a loss of the host's capacity to sustain antibody responses against recurring parasitemic waves. |
| 9. | Microbiology. 2011 Jul 7. [Epub ahead of print]An optimized in vitro blood-brain barrier model reveals bidirectional transmigration of African trypanosome strains.Untucht C, Rasch J, Fuchs E, Rohde M, Bergmann S, Steinert M.SourceTechnische Universitat Braunschweig, Institute for Microbiology; AbstractThe transmigration of African trypanosomes across the human blood-brain barrier (BBB) is the critical step during the course of the Human African Trypanosomiasis (HAT). The parasites Trypanosoma brucei gambiense and T. b. rhodesiense are transmitted to humans during a bite of Tsetse flies. Trypanosomes multiply within the blood stream and finally invade the central nervous system (CNS), which leads to the death of untreated patients. In order to establish an adequate in vitro BBB model for parasite transmigration, different human cell lines were used including ECV304, HBMEC, and HUVEC as well as C6 rat astrocytes. Validation of the BBB models with E. coli HB101 and E. coli K1 revealed that a combination of ECV304 cells seeded on matrigel as a semi-synthetical basement membrane and C6 astrocytes resulted in an optimal BBB model system. The BBB model showed selective permeability for the pathogenic E. coli K1 strain and African trypanosomes were able to traverse the optimized ECV304-C6 BBB efficiently. Furthermore coincubation indicated that paracellular macrophage transmigration does not facilitate trypanosomal BBB traversal. An inverse assembly of the BBB model demonstrated that trypanosomes were also able to transmigrate the optimized ECV304-C6 BBB backwards, indicating the relevance of the CNS as a possible reservoir of a relapsing parasitemia. |
| 10. | Trends Parasitol. 2011 Jul 5. [Epub ahead of print]Gene expression in Trypanosoma brucei: lessons from high-throughput RNA sequencing.Siegel TN, Gunasekera K, Cross GA, Ochsenreiter T.SourceBiology of Host-Parasite Interactions, Parasitology, Institut Pasteur, 75724 Paris, France; CNRS, URA2581, Institut Pasteur, 75724 Paris, France. AbstractTrypanosoma brucei undergoes major biochemical and morphological changes during its development from the bloodstream form in the mammalian host to the procyclic form in the midgut of its insect host. The underlying regulation of gene expression, however, is poorly understood. More than 60% of the predicted genes remain annotated as hypothetical, and the 5' and 3' untranslated regions important for regulation of gene expression are unknown for >90% of the genes. In this review, we compare the data from four recently published high-throughput RNA sequencing studies in light of the different experimental setups and discuss how these data can enhance genome annotation and give insights into the regulation of gene expression in T. brucei. Copyright © 2011 Elsevier Ltd. All rights reserved. |
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