Friday, March 16, 2012

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 - 8 of 8

1. Curr Opin HIV AIDS. 2012 Mar 13. [Epub ahead of print]

Mechanisms of interaction between protozoan parasites and HIV.

Andreani G, Lodge R, Richard D, Tremblay MJ.

Source

aCentre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec - CHUL bDépartement de Microbiologie-Infectiologie et Immunologie, Faculté de médecine, Université Laval, Québec, Québec, Canada 1These authors contributed equally to this work.

Abstract

PURPOSE OF REVIEW:

This review summarizes the current knowledge on human immunodeficiency virus type 1 (hereinafter called HIV)/protozoan co-infections in the case of three important, although neglected, tropical diseases: malaria, trypanosomiasis (Chagas disease) and leishmaniasis. The HIV pandemic has modified the immunopathogenic, epidemiological and therapeutic aspects of these human diseases.

RECENT FINDINGS:

In-vitro data suggests that HIV favors Leishmania infection, whereas different parasites have contrasting effects on HIV. However, many of the previous models are a limited representation of the complex interactions within the host; this situation is particularly the case when microbial products are used in place of live parasites.

SUMMARY:

In the host, protozoan parasites generally enhance HIV replication and accelerate AIDS progression. HIV alters parasite pathogenesis, often worsening disease outcome. These aspects bring significant complications for the treatment of co-infected individuals.

PMID: 22418447 [PubMed - as supplied by publisher]
2. Chem Biol Drug Des. 2012 Mar 14. doi: 10.1111/j.1747-0285.2012.01380.x. [Epub ahead of print]

Molecular modeling of T. rangeli, T. brucei gambiense and T. evansi sialidases in complex with the DANA inhibitor.

Lima AH, Souza PR, Alencar N, Lameira J, Govender T, Kruger HG, Maguire GE, Alves CN.

Source

Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, CP 11101, 66075-110, Belém, PA, Brazil. Instituto de Ciências Biológicas, Universidade Federal do Pará, CP 11101, 66075-110, Belém, PA, Brazil. School of Pharmacy and Pharmacology, University of KwaZulu Natal, Durban 4001, South Africa. School of Chemistry, University of KwaZulu Natal, Durban 4001, South Africa.

Abstract

Trypanosomal (trans-) sialidases are enzymes that catalyze the transfer of sialic acid residues between host and parasite glycoconjugates. Herein, we have used homology modeling to construct the 3D structures of sialidases from T. brucei and T. evansi. Hybrid Quantum Mechanical/Molecular Mechanical (QM/MM) Molecular Dynamics simulations were used to determine the interaction energy between the DANA inhibitor and the three sialidases studied here. Our results suggest that the two constructed enzymes share the same basic fold motive of the T. rangeli crystallographic structure. In addition, QM/MM MD simulations show that the DANA inhibitor forms a stronger complex with T. rangeli than with T. brucei and T. evansi sialidase. Finally, the interaction energy by residues shows that the arginine triad plays a decisive role to complex DANA with the enzyme through hydrogen bonding. © 2012 John Wiley & Sons A/S.

Copyright © 2012 John Wiley & Sons A/S.

PMID: 22416952 [PubMed - as supplied by publisher]
3. Parasite Immunol. 2012 Mar 14. doi: 10.1111/j.1365-3024.2012.01361.x. [Epub ahead of print]

Characterization of Leishmania infantum thiol-dependent reductase 1 and evaluation of its potential to induce immune protection.

Sil va AM, Tavares J, Silvestre R, Ouaissi A, Coombs GH, Cordeiro-da-Silva A.

Source

IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal Laboratório de Ciências Biológicas, Faculdade de Farmácia da Universidade do Porto, R. Aníbal Cunha n.º 164, 4050-047 Porto, Portugal Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK INSERM, UMR CNRS 5235, Université de Montpellier 2, Bât 24 - CC 107, Pl. Eugène Bataillon, 34095 Montpellier Cx 5, France.

Abstract

The need to develop an effective vaccine against leishmaniasis to prevent the 2 million new cases each year led to the search for antigens able to elicit protection against infection with Leishmania. In this study we have characterized a parasite-specific protein of Leishmania infantum named Thiol dependent reductase 1 (TDR1). The protein is present in both life cycle stages of L. infantum with a notable higher expression in the amastigote forms, suggesting a role in the interaction between the parasite and the mammalian host. TDR1 is localized in the cytosol, although we were able to detect the protein in the culture medium of both promastigotes and axenic amastigotes and consequently TDR1 is considered an excreted/secreted molecule of the parasite. Therefore we have evaluated the potential of TDR1 recombinant protein to protect against experimental challenge with L. infantum parasites using a murine model. Despite a reduction in spleen parasite load in the chronic phase of disease, TDR1 administration was not effective in the protection of Balb/c mice against visceral leishmaniasis and thus TDR1 do not have a crucial role in the modulation of mammalian host immune response, as observed with its protein counterpart Tc52 of T. cruzi. © 2012 Blackwell Publishing Ltd.

© 2012 Blackwell Publishing Ltd.

PMID: 22416787 [PubMed - as supplied by publisher]
4. Parazitologiia. 2011 Nov-Dec;45(6):409-24.

[Investigation of causes of the conflict between taxonomy and molecular phylogeny of trypanosomatids by the example of Leptomonas nabiculae podlipaev, 1987].

[Article in Russian]
Kostygov AIu, Malysheva MN, Frolov AO.

Abstract

Results of study of Leptomonas nabiculae using various molecular markers and different material (cultures D2 et Nfm2) contradicted each other and taxonomic position of this species. We investigated morphology of the cells in these cultures as well as in hapantotype of L. nabiculae and those of L. peterhoffi and L. occidentalis that had been described from the same host species. We also reconstructed 18S rRNA gene phylogeny using sequences from both cultures. The D2 culture according to its morphology and phylogenetic position revealed to be a Crithidia that had accompanied L. nabiculae in a mixed infection. We named it Crithidia dedva. The cells in the hapantotypes of the three Leptomonas species and those of the Nfm2 culture represent a single species that is a Herpetomonas (H. nabiculae) judging by morphology and molecular phylogeny. We also showed that the sequence of 18S rRNA gene that had been formerly determined represents a chimaera. This had resulted in the wrong position of this species on the phylogenetic tree that had contradicted results of the analysis of 5s rRNA gene.

PMID: 22384679 [PubMed - indexed for MEDLINE]
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5. PLoS One. 2011;6(10):e27133. Epub 2011 Oct 31.

Benznidazole therapy modulates interferon-γ and M2 muscarinic receptor autoantibody responses in Trypanosoma cruzi-infected children.

Cutrullis RA, Moscatelli GF, Moroni S, Volta BJ, Cardoni RL, Altcheh JM, Corral RS, Freilij HL, Petray PB.

Source

Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.

Abstract

OBJECTIVE:

The presence of autoantibodies with adrenergic and cholinergic activity, capable of triggering neurotransmitter receptor-mediated effects, has been associated with pathogenesis in T. cruzi-infected hosts. The goal of this study was to investigate the production of anti-M2 muscarinic receptor autoantibodies (Anti-M2R AAbs) as well as the IFN-γ profile in children at the early stage of Chagas disease, and to examine whether trypanocidal chemotherapy with benznidazole (BZ) could modify both response patterns.

METHODS:

This study comprised 30 T. cruzi-infected children (mean age: 13.8 years) and 19 uninfected controls (mean age: 12.7 years). Infected patients were treated with BZ and followed-up. Blood samples collected at diagnosis-T0, end of treatment-T1, and six months later-T2 were analysed by ELISA for detection of Anti-M2R AAbs and circulating levels of IFN-γ.

RESULTS:

At T0, anti-M2R AAbs were demonstrated in 56.7% of T. cruzi-infected patients, whereas uninfected controls were 100% negative. The average age of Anti-M2R AAbs(+) patients was higher than that from negative population. Infected children also displayed significantly stronger serum IFN-γ responses than controls. Upon BZ treatment, a significant linear decreasing trend in Anti-M2R AAb reactivity was recorded throughout the follow-up, with 29.7-88.1% decrease at T2. IFN-γ circulating levels also declined by T2.

CONCLUSION:

Anti-M2R AAbs and IFN-γ raise early during chagasic infection in children and are downmodulated by BZ therapy. These findings reinforce the usefulness of early BZ treatment not only to eliminate the parasite but also to reduce potentially pathogenic immune responses.

PMCID: PMC3205037 Free PMC Article
PMID: 22066031 [PubMed - indexed for MEDLINE]
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6. Cytokine. 2011 Dec;56(3):627-32. Epub 2011 Sep 23.

Melatonin and zinc treatment: distinctive modulation of cytokine production in chronic experimental Trypanosoma cruzi infection.

Brazão V, Del Vecchio Filipin M, Santello FH, Caetano LC, Abrahão AA, Toldo MP, do Prado JC Jr.

Source

College of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo, Ribeirão Preto, São Paulo, Brazil. vbrazao@fcfrp.usp.br

Abstract

Melatonin by exhibiting antioxidant, anti-aging, and immunomodulatory properties favorably modulate the immune function, protecting the hosts from several infectious diseases. Zinc is an essential trace element important for the efficiency of the immune system in reason of its widespread role in the activity of enzymes, transcription factors and cytokines. The etiology of Chagas' disease, caused by a protozoan parasite Trypanosoma cruzi, has been the focus of considerable discussion, although chronic phase still remains not fully understood. This study showed that zinc and melatonin treatment did not affect the percentage of both CD4+ and CD8+ T lymphocytes subsets in chronically infected animals. Increased levels of IL-2 and IL-10, as well as, enhanced thymocyte proliferation in T. cruzi infected groups under zinc and melatonin therapy was observed as compared to untreated group. Conversely, during the chronic phase of infection, macrophages counts were reduced in melatonin and zinc-melatonin treated animals. The combined actions of zinc and melatonin have beneficial effects in counteracting parasite-induced immune dysregulation, protecting animals against the harmful actions of chronic T. cruzi infection. Furthermore, our results provide an experimental basis for further studies on the role of immunomodulatory therapies.

Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID: 21944888 [PubMed - indexed for MEDLINE]
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7. Vet Parasitol. 2011 Dec 15;182(2-4):359-63. Epub 2011 May 19.

High mortality and lesions of the central nervous system in trypanosomosis by Trypanosoma vivax in Brazilian hair sheep.

Galiza GJ, Garcia HA, Assis AC, Oliveira DM, Pimentel LA, Dantas AF, Simões SV, Teixeira MM, Riet-Correa F.

Source

Veterinary Hospital,, CSTR, Federal University of Campina Grande, Patos, Paraíba 58700-000, Brazil.

Abstract

Here, we report an outbreak of Trypanosoma vivax-induced trypanosomosis in Brazilian hair sheep on a farm in Paraíba state, a non-endemic region in northeastern Brazilian. Of 306 total sheep, 240 showed clinical signs and 216 died. Clinical signs included anorexia, lethargy, anemia, rough hair coat, weight loss, submandibular edema, abortion, and in some cases, neurological signs such as head pressing, lateral recumbence, paddling movements and muscle tremors. T. vivax was identified by blood smear analysis and polymerase chain reaction (PCR). At necropsy, animals exhibited watery blood, pale tissue coloring, and the presence of liquid in the peritoneal cavity and pericardial sac. Histologically, nonsuppurative myocarditis and meningoencephalitis with areas of malacia were observed. After treatment, no parasites were detected by blood smear analysis or PCR. Cattle and buffalo that remained in the same pasture were also infected but presented with asymptomatic infections. Epidemiological data suggest that T. vivax was introduced to the farm and the susceptible flock by buffalos that were asymptomatic carriers of the infection; T. vivax was most likely transmitted by Tabanus spp. bites and also iatrogenically.

Copyright © 2011 Elsevier B.V. All rights reserved.

PMID: 21664764 [PubMed - indexed for MEDLINE]
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8. Cell Cycle. 2011 May 1;10(9):1448-55. Epub 2011 May 1.

Reversion of gene expression alterations in hearts of mice with chronic chagasic card iomyopathy after transplantation of bone marrow cells.

Soares MB, Lima RS, Souza BS, Vasconcelos JF, Rocha LL, Dos Santos RR, Iacobas S, Goldenberg RC, Lisanti MP, Iacobas DA, Tanowitz HB, Spray DC, Campos de Carvalho AC.

Source

Fundação Oswaldo Cruz; Salvador, Bahia, Brazil.

Abstract

Chronic chagasic cardiomyopathy is a leading cause of heart failure in Latin American countries, being associated with intense inflammatory response and fibrosis. We have previously shown that bone marrow mononuclear cell (BMC) transplantation improves inflammation, fibrosis, and ventricular diameter in hearts of mice with chronic Chagas disease. Here we investigated the transcriptomic recovery induced by BMC therapy by comparing the heart transcriptomes of control, chagasic, and BMC transplanted mice. Out of the 9390 unique genes quantified in all samples, 1702 had their expression altered in chronic chagasic hearts compared to those of normal mice. Major categories of significantly upregulated genes were related to inflammation, fibrosis and immune responses, while genes involved in mitochondrion function were downregulated. When BMC-treated chagasic hearts were compared to infected mice, 96% of the alterations detected in infected hearts were restored to normal levels, although an additional 109 genes were altered by treatment. Transcriptomic recovery, a new measure that considers both resotrative and side effects of treatment, was remarkably high (84%). Immunofluorescence and morphometric analyses confirmed the effects of BMC therapy in the pattern of inflammatory-immune response and expression of adhesion molecules. In conclusion, by using large-scale gene profiling for unbiased assessment of therapeutic efficacy we demonstrate immunomodulatory effects of BMC therapy in chronic chagasic cardiomyopathy and identify potentially relevant factors involved in the pathogenesis of the disease that may provide new therapeutic targets.

PMCID: PMC3117044 [Available on 2012/5/1]
PMID: 21467843 [PubMed - indexed for MEDLINE]
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