Wednesday, July 29, 2009

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 20

1: Eur J Immunol. 2009 Jul 27. [Epub ahead of print]Click here to read

L-Arginine deprivation impairs Leishmania major-specific T-cell responses.

Munder M, Choi BS, Rogers M, Kropf P.

Department of Hematology, Oncology, and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.

The amino acid L-arginine plays a crucial role in the regulation of immune responses. We have recently shown that uncontrolled replication of Leishmania parasites at the site of pathology correlates with high levels of arginase activity in nonhealing leishmaniasis and that this elevated arginase activity causes local depletion of L-arginine. To further our understanding of the impact of L-arginine deprivation in experimental leishmaniasis, here we characterize in detail the effects of L-arginine deprivation on antigen-specific T cells and MPhi. The results of our study show that decrease of L-arginine levels in the extracellular milieu affects the biological activities of Leishmania major-specific T cells, both at the level of the magnitude and the quality of their responses. L. major-specific CD4(+) T cells rendered hyporesponsive by L-arginine deprivation can be partially rescued by addition of exogenous L-arginine to produce IL-4 and IL-10, but not to produce IFN-gamma. Furthermore, our results show that L-arginine deprivation also greatly impacts parasite growth in activated macrophages. In summary, our results suggest that L-arginine levels affect both Th cell responses and parasite replication.

PMID: 19637195 [PubMed - as supplied by publisher]

2: Biomol NMR Assign. 2008 Jun;2(1):65-8. Epub 2008 Apr 10.

1H, 13C, and 15N assignment of the oxidized and reduced forms of T. brucei glutathione peroxidase-type tryparedoxin peroxidase.

Melchers J, Krauth-Siegel L, Muhle-Goll C.

Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany.

The cysteine-homologues of glutathione peroxidases in Trypanosoma brucei catalyze the trypanothione/tryparedoxin-dependent reduction of hydroperoxides. We report the 1H, 13C, and 15N assignment of the oxidized and reduced form of the enzyme by NMR. Major changes between these two forms were only observed for residues close to the catalytic site.

PMID: 19636927 [PubMed - in process]

3: Biomol NMR Assign. 2008 Jun;2(1):59-60. Epub 2008 Mar 26.

1H, 13C and 15N resonance assignment of Urm1 from Trypanosoma brucei.

Zhang W, Ding H, Zhang J, Tu X.

Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, P.R. China.

Urm1 (ubiquitin-related modifier), involved in diverse biological processes in yeast, is proved to be a "molecular fossil" in ubiquitin superfamily. Here we report the resonance assignment of Urm1 from Trypanosoma brucei.

PMID: 19636925 [PubMed - in process]

4: PLoS Negl Trop Dis. 2009 Jul 28;3(7):e491.Click here to read

First-Line Therapy for Human Cutaneous Leishmaniasis in Peru Using the TLR7 Agonist Imiquimod in Combination with Pentavalent Antimony.

Miranda-Verastegui C, Tulliano G, Gyorkos TW, Calderon W, Rahme E, Ward B, Cruz M, Llanos-Cuentas A, Matlashewski G.

Universidad Peruana Cayetano Heredia, Lima, Peru.

BACKGROUND: Current therapies for cutaneous leishmaniasis are limited by poor efficacy, long-term course of treatment, and the development of resistance. We evaluated if pentavalent antimony (an anti-parasitic drug) combined with imiquimod (an immunomodulator) was more effective than pentavalent antimony alone in patients who had not previously been treated. METHODS: A randomized double-blind clinical trial involving 80 cutaneous leishmaniasis patients was conducted in Peru. The study subjects were recruited in Lima and Cusco (20 experimental and 20 control subjects at each site). Experimental arm: Standard dose of pentavalent antimony plus 5% imiquimod cream applied to each lesion three times per week for 20 days. Control arm: Standard dose of pentavalent antimony plus placebo (vehicle cream) applied as above. The primary outcome was cure defined as complete re-epithelization with no inflammation assessed during the 12 months post-treatment period. RESULTS: Of the 80 subjects enrolled, 75 completed the study. The overall cure rate at the 12-month follow-up for the intention-to-treat analysis was 75% (30/40) in the experimental arm and 58% (23/40) in the control arm (p = 0.098). Subgroup analyses suggested that combination treatment benefits were most often observed at the Cusco site, where L. braziliensis is the prevalent species. Over the study period, only one adverse event (rash) was recorded, in the experimental arm. CONCLUSION: The combination treatment of imiquimod plus pentavalent antimony performed better than placebo plus pentavalent antimony, but the difference was not statistically significant. TRIAL REGISTRATION: Clinical Trials.gov NCT00257530.

PMID: 19636365 [PubMed - in process]

5: Am J Trop Med Hyg. 2009 Aug;81(2):213-8.Click here to read

First report of Leishmania tropica from a classical focus of L. major in North-Sinai, Egypt.

Shehata MG, Samy AM, Doha SA, Fahmy AR, Kaldas RM, Furman BD, Villinski JT.

Entomology Department, Faculty of Science, Ain Shams University, Cairo, Egypt. mgdshehata@yahoo.com

Cutaneous leishmaniasis (CL) is prevalent in the Egyptian Sinai Peninsula and previous research has consistently documented the etiologic agent to be Leishmania major. We report the first isolation of Leishmania tropica from human cases of CL in a Northern Sinai community bordering Palestine. Parasite culturing, real-time polymerase chain reaction (PCR), gene sequencing, and restriction fragment length polymorphism (RFLP) analyses indicate CL cases in this community were caused by either L. major or L. tropica (three cases each). Two wild-caught rodents (Gerbillus pyramidum floweri) were infected with L. tropica. Phlebotomus papatasi sand flies were found harboring L. major, however only non-infected individuals of Phlebotomus sergenti, a vector for L. tropica, were caught. Patients with L. tropica had not traveled from the region in over a year, suggesting these cases are autochthonous. This scenario is consistent with an incursion of L. tropica from bordering countries and raises concerns about expansion of this parasite further into Egypt.

PMID: 19635872 [PubMed - in process]

6: Am J Trop Med Hyg. 2009 Aug;81(2):209-12.Click here to read

AA-amyloidosis caused by visceral leishmaniasis in a human immunodeficiency virus-infected patient.

de Vallière S, Mary C, Joneberg JE, Rotman S, Bullani R, Greub G, Gillmore JD, Buffet PA, Tarr PE.

Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

AA-amyloidosis in the setting of chronic visceral leishmaniasis (VL) has been reported in animal models but documentation in humans is unavailable. Here, we report on a Portuguese man who in 1996 was diagnosed with both human immunodeficiency virus (HIV)-infection and VL. Antiretroviral treatment led to sustained suppression of HIV viremia but CD4+ lymphocytes rose from 8 to only 160 cells/mL. Several courses of antimony treatment did not prevent VL relapses. Renal failure developed in 2006 and renal biopsy revealed AA-amyloidosis. The patient had cryoglobulinemia and serum immune complexes containing antibodies directed against seven leishmanial antigens. Antimony plus amphotericin B, followed by oral miltefosine resulted in a sustained VL treatment response with elimination of circulating Leishmania infantum DNA and CD4+ recovery. The concomitant reduction of serum AA levels and disappearance of circulating leishmanial immune complexes suggests that prolonged VL may lead to AA-amyloidosis in immunocompromised humans.

PMID: 19635871 [PubMed - in process]

7: Am J Trop Med Hyg. 2009 Aug;81(2):202-8.Click here to read

Evaluation of Leishmania species reactivity in human serologic diagnosis of leishmaniasis.

Silvestre R, Santarém N, Teixeira L, Cunha J, Schallig H, Cordeiro-da-Silva A.

Parasite Disease Group, IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal. rleal@ibmc.up.pt

The sensitivities and specificities of IgG-ELISA and IgG flow cytometry based techniques using different Leishmania species were determined using sera collected from 40 cutaneous or visceral leishmaniasis patients. The flow cytometry technique, using promastigote parasite forms, performed better than total soluble extract IgG-ELISA. At the species level, the use of Leishmania amazonensis and Leishmania major as antigens in enzyme linked immunosorbent assay (ELISA) decreased the overall sensitivity. To assess the specificity of these tests, sera from malaria, toxoplasmosis, amoebiasis, schistosomiasis, and leprosy patients were used. We also included sera from Leishmania non-infected endemic individuals. The cutaneous species displayed a decreased specificity in both assays. Although more sensitive, flow cytometry using promastigote parasite forms generally presented lower levels of specificity when compared with total extract of IgG-ELISA. Overall, the results of the study show the potential of IgG flow cytometry for the diagnosis of leishmaniasis. Although highly sensitive, a refinement of the flow cytometry method should be performed to improve the overall specificity.

PMID: 19635870 [PubMed - in process]

8: Am J Trop Med Hyg. 2009 Aug;81(2):195-201.Click here to read

Sociodemographic and environmental risk factors for American cutaneous leishmaniasis (ACL) in the State of Alagoas, Brazil.

Pedrosa Fde A, Ximenes RA.

Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Alagoas, Prado, Maceió-AL, Brasil. fernandopedrosa@uol.com.br

The multiplicity of factors involved in the transmission of the American cutaneous leishmaniasis (ACL) constitutes a challenge to its control. Thus, knowledge of such factors may contribute extremely toward redefining the control strategies. The aim of this study was to identify sociodemographic and environmental factors relating to ACL transmission in the State of Alagoas, Brazil. A case-control study with incident cases was conducted. Diagnostic criteria were the presence of compatible skin lesions, laboratory confirmation, and clinical cure after treatment. Two control groups were matched to cases by sex and age: one comprising neighbors and the other from a community-based draw; controls were individuals with no lesion and a negative Montenegro intradermal reaction. Between July 1, 2004 and February 1, 2007, 98 cases and the same number of controls per group were selected. In the multivariate analysis, for both control groups, ACL was associated with absence of a gas stove and forest less than 200 m away; for neighborhood controls with schooling of 4 years or less, family income greater than one minimum salary, birds inside the home, forest-related leisure activities, and rural work or school activities; and for community controls with non-durable wall material in the house, per capita income greater than US$ 28.31, animals inside the house, and absence of dogs and cats around the house. Specific control measures are recommended for areas with similar characteristics: protection for individuals undertaking forest-related leisure activities; distancing houses from forests by more than 200 m; and elimination of bird or other animal-rearing inside homes. General measures of improved housing and living conditions are also recommended.

PMID: 19635869 [PubMed - in process]

9: J Cell Biol. 2009 Jul 27;186(2):243-54.Click here to read

Cohesin regulates VSG monoallelic expression in trypanosomes.

Landeira D, Bart JM, Van Tyne D, Navarro M.

Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Cientificas, 18100 Granada, Spain.

Antigenic variation allows Trypanosoma brucei to evade the host immune response by switching the expression of 1 out of approximately 15 telomeric variant surface glycoprotein (VSG) expression sites (ESs). VSG ES transcription is mediated by RNA polymerase I in a discrete nuclear site named the ES body (ESB). However, nothing is known about how the monoallelic VSG ES transcriptional state is maintained over generations. In this study, we show that during S and G2 phases and early mitosis, the active VSG ES locus remains associated with the single ESB and exhibits a delay in the separation of sister chromatids relative to control loci. This delay is dependent on the cohesin complex, as partial knockdown of cohesin subunits resulted in premature separation of sister chromatids of the active VSG ES. Cohesin depletion also prompted transcriptional switching from the active to previously inactive VSG ESs. Thus, in addition to maintaining sister chromatid cohesion during mitosis, the cohesin complex plays an essential role in the correct epigenetic inheritance of the active transcriptional VSG ES state.

PMID: 19635842 [PubMed - in process]

10: J Immunol Methods. 2009 Jul 24. [Epub ahead of print]Click here to read

Anti-fixed Leishmania chagasi Promastigotes IgG Antibodies Detected by Flow Cytometry (FC-AFPA-IgG) as a Tool for Serodiagnosis and for Post-therapeutic Cure Assessment in American Visceral Leishmaniasis.

Garcia LM, Coelho-Dos-Reis JG, Peruhype-Magalhães V, Teixeira-Carvalho A, Rocha RD, Araújo MS, Gomes IT, Carvalho SF, Dietze R, Lemos EM, Andrade MC, Martins-Filho OA.

Centro de Pesquisas René Rachou, Laboratório de Biomarcadores de Diagnóstico e Monitoração, Avenida Augusto de Lima 1715, 30190-002, Belo Horizonte, Minas Gerais, Brasil; Universidade Estadual de Montes Claros, Campus Universitário Professor Darcy Ribeiro, Vilar Mauricéia, 39401-084, Montes Claros, Minas Gerais, Brasil.

Visceral leishmaniasis (VL) is a systemic infection, caused by an intracellular protozoan parasite belonging to the Leishmania donovani complex. The diagnosis of VL is complex because most clinical features are shared with other commonly occurring febrile hepatosplenic diseases that can be endemic along with VL. A number of serological devices are available but still require improvement mainly due to residual post-therapeutic serology and the cross-reactivity with other Trypanosomatidae protozooses. This study intended to describe and evaluate the performance of an indirect immunofluorescence assay referred as flow cytometry anti-Fixed Leishmania chagasi promastigote IgG antibodies (FC-AFPA-IgG) for serodiagnosis of VL and assessment of post-therapeutic cure. The sera reactivity is reported as the percentage of positive fluorescent parasite (PPFP) along the titration curve. The analysis of sera titration curve indicated the sera dilution 1:32,000 and the PPFP=25% as the cut-off to segregate positive and negative results. Using these parameters, the FC-AFPA-IgG displayed outstanding sensitivity and specificity for diagnosis and post-therapeutic cure assessment purposes. The inter-test reproducibility of FC-AFPA-IgG was also verified, considering two independent Analysts and validated the results obtained by FC-AFPA-IgG. Moreover, the comparison between FC-AFPA-IgG and the conventional serologic test (ELISA) showed that besides the statistically analogous results with strong positive strong correlation the FC-AFPA-IgG displayed higher performance indexes. Further analysis demonstrated that while cross-reactivity was observed in 8% of samples tested by ELISA, no cross-reactivity was detected by FC-AFPA-IgG. Together, the findings presented in this study showed the potential of FC-AFPA-IgG in both diagnoses and post-therapeutic cure assessment of VL.

PMID: 19635482 [PubMed - as supplied by publisher]

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