Tuesday, August 31, 2010

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 13

1. Rev Soc Bras Med Trop. 2010 Aug;43(4):481.

An atypical presentation of cutaneous leishmaniasis.

Amato VS, Tonacio AC, Alves Mdo M.

Division of Infectious and Parasitic Diseases at the Hospital of Clinics, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.

PMID: 20802961 [PubMed - in process]
2. Rev Soc Bras Med Trop. 2010 Aug;43(4):478-9.

[Visceral leishmaniasis and malnutrition: a relation much neglected.]

[Article in Portuguese]

Malafaia G.

Departamento de Areas Acadêmicas, Campus Anápolis, Instituto Federal de Educação, Ciência e Tecnologia de Goiás, GO.

PMID: 20802959 [PubMed - in process]
3. Rev Soc Bras Med Trop. 2010 Aug;43(4):400-4.

Seroprevalence and risk factors for canine visceral leishmaniasis in the endemic area of Dias D'Avila, State of Bahia, Brazil.

Oliveira LC, Araújo RR, Alves CR, Mouta-Confort E, López JA, Mendonça-Lima FW.

School of Veterinary Medicine, Federal University of Bahia, Salvador, BA, Brazil.

Abstract

INTRODUCTION: Visceral leishmaniasis (VL) is an important zoonosis in relation to public health systems. Dogs are the main domestic reservoir. This study aimed to investigate occurrences of canine VL in Dias D'Avila, State of Bahia, Brazil.

METHODS: The prevalence was evaluated by means of clinical and laboratory tests on a population of 312 domestic dogs from 23 localities in this municipality, using indirect immunofluorescence and immunoenzymatic assays.

RESULTS: Among the animals examined, 3.2% and 6.7% showed signs of VL, confirmed by indirect immunofluorescence and immunoenzymatic assays, respectively, with a distribution of 29.9% (24 dogs) in the rural zone and 4.9% (288 dogs) in the urban zone (p = 0.001). The clinical evaluation on seropositive dogs showed both asymptomatic animals (2.4%) and symptomatic animals (47.6%), along with other abnormalities (e.g. normocytic and normochromic anemia, with leukocytosis and thrombocytopenia). Observations relating to phenotypic characteristics (e.g. sex, age, breed and hair) did not present statistical significance, although high seropositivity among male, short-haired and mixed-breed dogs was observed.

CONCLUSIONS: The findings showed that VL was a predominantly rural zoonosis and that close contact between poultry and domestic dogs significantly increased the risk of canine infection in this region.

PMID: 20802939 [PubMed - in process]
4. Rev Soc Bras Med Trop. 2010 Aug;43(4):396-9.

Autochthonous visceral leishmaniasis in Brasília, Federal District, Brazil.

Carranza-Tamayo CO, Carvalho Mdo S, Bredt A, Bofil MI, Rodrigues RM, Silva AD, Cortez SM, Romero GA.

Tropical Medicine Unit, University of Brasilia, Brasília, DF, Brazil.

Abstract

INTRODUCTION: Visceral leishmaniasis is a public health threat in Brazil considering the high lethality rates and increasing geographical dispersion to large urban conglomerates over the past 25 years. This study aimed to confirm suspected autochthonous cases of visceral leishmaniasis reported from 2005 to 2009 among individuals living in Brasilia, Federal District.

METHODS: A retrospective review of the surveillance data obtained on a regular basis and clinical records of the reported cases were performed in 2009.

RESULTS: Data from entomological and canine surveys revealed the presence of both Lutzomyia longipalpis and positive serology for Leishmania in dogs within 19 of the 21 neighborhoods where human cases occurred since 2005. The review of surveillance data and medical records, together with the entomological and canine survey data, permitted confirmation of 21 autochthonous human cases in the Federal District. The disease predominantly affected children (12/21) and those from the Sobradinho region (16/21); the typical presentation of fever, hepatosplenomegaly and pancytopenia was observed in 67% of cases. Three deaths occurred during the study period. Leishmania (Leishmania) chagasi was successfully isolated from one human case and twelve canine cases.

CONCLUSIONS: Visceral leishmaniasis should be considered endemic in Brasilia based on the documented epidemiological behavior herein described and the confirmed autochthony of human cases.

PMID: 20802938 [PubMed - in process]
5. Rev Soc Bras Med Trop. 2010 Aug;43(4):393-5.

Cytokine expression in the duodenal mucosa o f patients with visceral leishmaniasis.

Luz KG, Tuon FF, Duarte MI, Maia GM, Matos P, Ramos AM, Nicodemo AC.

Department of Infectious Diseases, Federal University of Rio Grande do Norte, Natal, RN, Brazil.

Abstract

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL.

METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-gamma, TNF-alpha and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed.

RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-alpha, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-gamma was lower in the VL patients (p < 0.05).

CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.

PMID: 20802937 [PubMed - in process]
6. Rev Soc Bras Med Trop. 2010 Aug;43(4):386-92.

Is severe visceral leishmaniasis a systemic inflammatory response syndrome? A case control study.

Costa CH, Werneck GL, Costa DL, Holanda TA, Aguiar GB, Carvalho AS, Cavalcanti JC, Santos LS.

Laboratory of Leishmaniasis, Tropical Diseases Institute Natan Portella, Teresina, PI, Brazil.

Abstract

INTRODUCTION: The objective of the study is to identify the main risk factors for death by New World visceral leishmaniasis and establish a coherent pathogenic substrate of severe disease based on clinical findings.

METHODS: Seventy-six deceased inpatients and 320 successfully treated inpatients with VL were studied in a case control study.

RESULTS: Bacterial infection and bleeding were mutually exclusive events leading to death. Five risk factors were unique for death by bacterial infection (malnutrition, pulmonary rales, severe anemia, severe absolute neutropenia and higher neutrophil count), while another six were unique for death by bleeding (jaundice, severe relative neutropenia, severe thrombocytopenia, liver injury, kidney failure, higher bone marrow parasite load). Bacterial infection, bleeding, severe anemia, diarrhea, dyspnea, edema, jaundice and bone marrow parasite load were the main syndromes of visceral leishmaniasis among successfully treated patients.

CONCLUSIONS: The data support the idea that bacterial infections are due to immune paralysis. Broad organ and system involvement is plausibly due to the high production of proinflammatory cytokines, whose actions fit well with visceral leishmaniasis. The syndromes and causative mediators are typical of a slowly developing systemic inflammatory response syndrome.

PMID: 20802936 [PubMed - in process]
7. J Biol Chem. 2010 Aug 26. [Epub ahead of print]

Selective fusion of azurophilic granules with Leishmania-containing phagosomes in human neutrophils.

Mollinedo F, Janssen H, de la Iglesia-Vicente J, Villa-Pulgarin JA, Calafat J.

CSIC - Universidad de Salamanca, Spain;

Abstract

Leishmania parasites use polymorphonuclear neutrophils as intermediate hosts before their ultimate delivery to macrophages following engulfment of parasite-infected neutrophils. This leads to a silent and unrecognized entry of Leishmania into the macrophage host cell. Neutrophil function depends on its cytoplasmic granules, but their mobilization and role in how Leishmania parasites evade intracellular killing in neutrophils remain undetermined. Here, we have found by ultrastructural approaches that neutrophils ingested L. major promastigotes, and azurophilic granules fused in a preferential way with parasite-containing phagosomes, without promoting parasite killing. Azurophilic granules, identified by the granule marker myeloperoxidase, also fused with L. donovani-engulfed vacuoles in human neutrophils. In addition, the azurophilic membrane marker CD63 was also detected in the vacuole surrounding the parasite, and in the fusion of azurophilic granules with the parasite-engulfed phagosome. Tertiary and specific granules, involved in vacuole acidification and superoxide anion generation, hardly fused with Leishmania-containing phagosomes. L. major interaction with neutrophils did not elicit production of reactive oxygen species or mobilization of tertiary and specific granules. By using immunogold electron microscopy approaches in the engulfment of L. major and L. donovani by human neutrophils, we did not find a significant contribution of endoplasmic reticulum to the formation of Leishmania-containing vacuoles. Live Leishmania parasites were required to be optimally internalized by neutrophils. Our data suggest that Leishmania promastigotes modulate their uptake by neutrophils, and regulate granule fusion processes in a rather selective way to favor parasite survival in human neutrophils.

PMID: 20801889 [PubMed - as supplied by publisher]
8. Mol Biochem Parasitol. 2010 Aug 26. [Epub ahead of print]

Crystal structure of Leishmania major ADP ribosylation factor-like 1 and a classification of related GTPase family members in this Kinetoplastid.

Fleming JR, Dawson A, Hunter WN.

Abstract

ADP ribosylation factor-like (ARL) proteins are small GTPases that undergo conformational changes upon nucleotide binding, and which regulate the affinity of ARLs for binding other proteins, lipids or membranes. There is a paucity of structural data on this family of proteins in the Kinetoplastida, despite studies implicating them in key events related to vesicular transport and regulation of microtubule dependent processes. The crystal structure of Leishmania major ARL1 in complex with GDP has been determined to 2.1A resolution and reveals a high degree of structural conservation with human ADP ribosylation factor 1 (ARF1). Putative L. major and Trypanosoma brucei ARF/ARL family members have been classified based on structural considerations, amino acid sequence conservation combined with functional data on Kinetoplastid and human orthologues. This classification may guide future studies designed to elucidate the function of specific family members.

PMID: 20801163 [PubMed - as supplied by publisher]
9. Int J Antimicrob Agents. 2010 Aug 26. [Epub ahead of print]

Leishmaniasis vaccines: past, present and future.

Modabber F.

Drugs for Neglected Diseases Initiative (DNDi), 15 Chemin Louis-Dunant, Geneva 1202, Switzerland.

Abstract

No vaccine exists against any form of leishmaniasis. Because recovery from infection is usually accompanied by a strong immunity and because it is possible to protect experimental animals against live challenge, hope for the development of a vaccine for humans has been high. However, leishmaniasis is a disease of the poor and the market for a vaccine is very limited. Until a few years ago, with minimal resources, only a pragmatic approach was possible for testing the first-generation vaccines (i.e. killed whole parasites). Recently, funding has become available for developing defined second-generation vaccines, including recombinant proteins and DNA constructs. With new adjuvants also being developed there is new hope, and several new vaccines are in development against leishmaniasis.

PMID: 20801000 [PubMed - as supplied by publisher]
10. J Immunol Methods. 2010 Aug 25. [Epub ahead of print]

Using T.brucei as a biological epitope-display platform to elicit specific antibody responses.

Stavropoulos P, Papavasiliou FN.

Abstract

The African trypanosome (Trypanosoma brucei) is transmitted by the bite of the tsetse vector to the mammalian bloodstream where it exists as a completely extracellular parasite. As a result of this exposure, the parasite elicits a robust immune response that is almost exclusively antibody mediated, and is extremely specific to the trypanosome coat displayed on the surface. This coat is comprised of ~11 million copies of a single gpi-linked molecule (the variable surface glycoprotein or VSG) and can therefore be used as a powerful platform for the immunogenic display of antigenic determinants. Here we describe a method to display repetitive, ordered arrays of linear epitopes on the surface of T.brucei and to then use the engineered organisms to generate specific anti-epitope antibody responses, upon injection into mice. This method offers an alternative approach to generating anti-peptide antibodies, and could be a useful option in cases where more traditional methods have failed.

PMID: 20800596 [PubMed - as supplied by publisher]

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