Thursday, August 20, 2009

What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2009 Aug 20
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 -4 of 4

1: Parasitol Res. 2009 Aug 19. [Epub ahead of print]Click here to read

Apoptosis caused by Hsp90 inhibitor geldanamycin in Leishmania donovani during promastigote-to-amastigote transformation stage.

Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, China.

The role of heat shock protein 90 inhibitor geldanamycin (GA) during Leishmania donovani promastigote-to-amastigote transformation in axenic conditions was investigated. Promastigotes exhibited apoptotic morphologic changes after GA treatment at a high temperature, and the effect is in a dose- and time-dependant manner. Meanwhile, cell cycle analysis showed a significant increase at the expense of cells in the G0/G1 phase and a decrease in the S and G2/M phases after GA treatment. In addition, cellular glutathione level was reduced and reactive oxygen species content was increased afterwards. Pretreatment with antioxidants reduced the percentage of GA-induced cell apoptosis. After treatment, cultures in pH 5.5 showed a lower percentage of apoptosis than those in pH 7.4. The present study showed that GA could cause apoptosis in L. donovani but could not cause stage differentiation in high temperature and that acidic conditions were likely to be crucial for the transformation and survival of the parasite within its human host.

PMID: 19690889 [PubMed - as supplied by publisher]

2: Med Chem. 2009 Jul;5(4):392-7.Click here to read

Leishmanicidal activity of new megazol derivatives.

FioCruz-Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos - Far Manguinhos Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil.

A series of thirteen new megazol derivatives, designed exploring the molecular hybridization approach between megazol (3) and heterocombretastatins (2), was synthesized. These new compounds were tested for in vitro antiparasitic activity upon axenic amastigotes of Leishmania donovani. Biological results led us to identify a new potent megazol derivative (4g), which presents an IC(50) = 0.081microg/mL, more active tham the reference drug miltefosine (IC(50) = 0.131microg/mL).

PMID: 19689398 [PubMed - in process]

3: Immunol Lett. 2009 Mar 24;123(1):38-45. Epub 2009 Feb 14.Click here to read LinkOut

5-Lipoxygenase plays a role in the control of parasite burden and contributes to oxidative damage of erythrocytes in murine Chagas' disease.

Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina, Paraná, Brazil.

Chagas' disease is accompanied by severe anemia and oxidative stress, which may contribute to mortality. In this study, we investigated the role of 5-lipoxygenase (5-LO) in the control of parasitism and anemia associated with oxidative damage of erythrocytes in experimental Trypanosoma cruzi infection. Wild-type C57BL/6, 129Sv mice treated or not with nordihydroguaiaretic acid (NDGA, 5-LO inhibitor), mice lacking the 5-LO enzyme gene (5-LO(-/-)) and inducible nitric oxide synthase gene (iNOS(-/-)) were infected with the Y strain of T. cruzi. Impairment of 5-LO resulted in increased numbers of trypomastigote forms in the blood and amastigote forms in the heart of infected mice. We assessed oxidative stress in erythrocytes by measuring oxygen uptake, induction time and chemiluminescence following treatment with tert-butyl hydroperoxide (TBH). Our results show that 5-LO metabolites increased lipid peroxidation levels in erythrocytes during the early phase of murine T. cruzi infection. NDGA treatment reduced oxidative damage of erythrocytes in C57BL/6 T. cruzi-infected mice but not in C57BL/6 iNOS(-/-) infected mice, showing that the action of NDGA is dependent on endogenous nitric oxide (NO). In addition, our results show that 5-LO metabolites do not participate directly in the development of anemia in infected mice. We conclude that 5-LO products may not only play a major role in controlling heart tissue parasitism, i.e., host resistance to acute infection with T. cruziin vivo, but in the event of an infection also play an important part in erythrocyte oxidative stress, an NO-dependent effect.

PMID: 19428550 [PubMed - indexed for MEDLINE]

4: Parasitol Res. 2008 Feb;102(3):523-6. Epub 2007 Dec 29.Click here to read LinkOut

Genotyping of Panamanian Trypanosoma cruzi stocks using the calmodulin 3'UTR polymorphisms.

Oswaldo Cruz Institute, Fiocruz, Rio de Janiero, Brazil.

Mutations in the 3' untranslated region of calmodulin gene have recently been reported to be specific to different Trypanosoma cruzi lineages. In the present report, this molecular marker was used to genotype 24 T. cruzi isolates from humans and vectors from different endemic areas in Panama. The finding of solely T. cruzi I genotype might explain the low morbidity of Chagas' disease in the region when compared to other countries in Latin America.

PMID: 18165887 [PubMed - indexed for MEDLINE]

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