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Sent on Friday, 2011 Jun 10Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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1. | Mem Inst Oswaldo Cruz. 2011 May;106(3):381-2.Lutzomyia longipalpis in Uruguay: the first report and the potential of visceral leishmaniasis transmission.Salomón OD, Basmajdian Y, Fernández MS, Santini MS.SourceCentro Nacional de Diagnóstico y Investigación en Endemo-Epidemias, Ministerio de Salud de la Nación, Buenos Aires, Argentina. AbstractPhlebotomine captures were performed in February 2010 in Salto (Salto department) and Bella Unión-Cuarein (Artigas department), Uruguay. Bella Unión is located across the Paraná River from Monte Caseros, Argentina, where a focus of canine visceral leishmaniasis (VL) was reported in 2009. No VL cases have ever been recorded in Uruguay and the last reported capture of Phlebotominae was in 1932 (Lutzomyia cortelezzii and Lutzomyia gaminarai). Light traps were placed in peridomestic environments, and Lutzomyia longipalpis, the main vector of visceral leishmaniasis, was found in Salto and Bella Unión. This is a first report of an area of potential VL transmission in Uruguay. Active and coordinated surveillance is required immediately the Uruguay-Argentina-Brazil border area. |
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2. | PLoS Negl Trop Dis. 2011;5(5):e1141. Epub 2011 May 31.Effect of BMAP-28 Antimicrobial Peptides on Leishmania major Promastigote and Amastigote Growth: Role of Leishmanolysin in Parasite Survival.Lynn MA, Kindrachuk J, Marr AK, Jenssen H, Panté N, Elliott MR, Napper S, Hancock RE, McMaster WR.SourceImmunity and Infection Research Centre, Vancouver Coastal Health Research Institute, and the Department of Medical Genetics, Vancouver, Canada. AbstractBACKGROUND:Protozoan parasites, such as Leishmania, still pose an enormous public health problem in many countries throughout the world. Current measures are outdated and have some associated drug resistance, prompting the search into novel therapies. Several innovative approaches are under investigation, including the utilization of host defence peptides (HDPs) as emerging anti-parasitic therapies. HDPs are characterised by their small size, amphipathic nature and cationicity, which induce permeabilization of cell membranes, whilst modulating the immune response of the host. Recently, members of the cathelicidin family of HDPs have demonstrated significant antimicrobial activities against various parasites including Leishmania. The cathelicidin bovine myeloid antimicrobial peptide 28 (BMAP-28) has broad antimicrobial activities and confers protection in animal models of bacterial infection or sepsis. We tested the effectiveness of the use of BMAP-28 and two of its isomers the D-amino acid form (D-BMAP-28) and the retro-inverso form (RI-BMAP-28), as anti-leishmanial agents against the promastigote and amastigote intracellular Leishmania major lifecycle stages. METHODOLOGY/PRINCIPAL FINDINGS:An MTS viability assay was utilized to show the potent antiparasitic activity of BMAP-28 and its protease resistant isomers against L. major promastigotes in vitro. Cell membrane permeability assays, caspase 3/7, Tunel assays and morphologic studies suggested that this was a late stage apoptotic cell death with early osmotic cell lysis caused by the antimicrobial peptides. Furthermore, BMAP-28 and its isomers demonstrated anti-leishmanial activities against intracellular amastigotes within a macrophage infection model. CONCLUSIONS/SIGNIFICANCE:Interestingly, D-BMAP-28 appears to be the most potent antiparasitic of the three isomers against wild type L. major promastigotes and amastigotes. These exciting results suggest that BMAP-28 and its protease resistant isomers have significant therapeutic potential as novel anti-leishmanials. |
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3. | PLoS Negl Trop Dis. 2011;5(5):e1171. Epub 2011 May 31.Foxp3 and IL-10 Expression Correlates with Parasite Burden in Lesional Tissues of Post Kala Azar Dermal Leishmaniasis (PKDL) Patients.Katara GK, Ansari NA, Verma S, Ramesh V, Salotra P.SourceInstitute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, India. AbstractBACKGROUND:Post kala-azar dermal leishmaniasis (PKDL), a sequel to visceral leishamaniasis (VL) in 5-15% cases, constitutes a parasite reservoir important in disease transmission. The precise immunological cause of PKDL outcome remains obscure. However, overlapping counter regulatory responses with elevated IFN-γ and IL-10 are reported. METHODOLOGY/PRINCIPAL FINDINGS:Present study deals with ex-vivo mRNA and protein analysis of natural regulatory T cells (nTreg) markers (Foxp3, CD25 and CTLA-4) and IL-10 levels in lesion tissues of PKDL patients at pre and post treatment stages. In addition, correlation of nTreg markers and IL-10 with parasite load in tissue lesions was investigated. mRNA levels of nTreg markers and IL-10 were found significantly elevated in pre-treatment PKDL cases compared to controls (Foxp3, P = 0.0009; CD25 & CTLA-4, P<0.0001; IL-10, P<0.0001), and were restored after treatment. Analysis of nTreg cell markers and IL-10 in different clinical manifestations of disease revealed elevated levels in nodular lesions compared to macules/papules. Further, Foxp3, CD25 and IL-10 mRNA levels directly correlated with parasite load in lesions tissues. CONCLUSION/SIGNIFICANCE:Data demonstrated accumulation of nTreg cells in infected tissue and a correlation of both IL-10 and nTreg levels with parasite burden suggesting their role in disease severity in PKDL. |
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4. | PLoS Negl Trop Dis. 2011;5(5):e1169. Epub 2011 May 31.Lutzomyia longipalpis Saliva or Salivary Protein LJM19 Protects against Leishmania braziliensis and the Saliva of Its Vector, Lutzomyia intermedia.Tavares NM, Silva RA, Costa DJ, Pitombo MA, Fukutani KF, Miranda JC, Valenzuela JG, Barral A, de Oliveira CI, Barral-Netto M, Brodskyn C.SourceCentro de Pesquisa Gonçalo Moniz, FIOCRUZ, Salvador, Bahia, Brazil. AbstractBACKGROUND:Leishmania transmission occurs in the presence of insect saliva. Immunity to Phlebotomus papatasi or Lutzomyia longipalpis saliva or salivary components confers protection against an infection by Leishmania in the presence of the homologous saliva. However, immunization with Lutzomyia intermedia saliva did not protect mice against Leishmania braziliensis plus Lu. intermedia saliva. In the present study, we have studied whether the immunization with Lu. longipalpis saliva or a DNA plasmid coding for LJM19 salivary protein would be protective against L. braziliensis infection in the presence of Lu. intermedia saliva, the natural vector for L. braziliensis. METHODOLOGY/PRINCIPAL FINDINGS:Immunization with Lu. longipalpis saliva or with LJM19 DNA plasmid induced a Delayed-Type Hypersensitivity (DTH) response against Lu. longipalpis as well as against a Lu. intermedia saliva challenge. Immunized and unimmunized control hamsters were then intradermally infected in the ears with L. braziliensis in the presence of Lu. longipalpis or Lu. intermedia saliva. Animals immunized with Lu. longipalpis saliva exhibited smaller lesion sizes as well as reduced disease burdens both at lesion site and in the draining lymph nodes. These alterations were associated with a significant decrease in the expression levels of IL-10 and TGF-β. Animals immunized with LJM19 DNA plasmid presented similar findings in protection and immune response and additionally increased IFN-γ expression. CONCLUSIONS/SIGNIFICANCE:Immunization with Lu. longipalpis saliva or with a DNA plasmid coding LJM19 salivary protein induced protection in hamsters challenged with L. braziliensis plus Lu. intermedia saliva. These findings point out an important role of immune response against saliva components, suggesting the possibility to develop a vaccine using a single component of Lu. longipalpis saliva to generate protection against different species of Leishmania, even those transmitted by a different vector. |
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5. | Acta Trop. 2011 May 30. [Epub ahead of print]Serological evidence of Histoplasma capsulatum infection among dogs with leishmaniasis in Brazil.Cordeiro RA, Coelho CG, Brilhante RS, Sidrim JJ, Castelo-Branco DS, Moura FB, Rocha MF.SourceDepartment of Pathology and Legal Medicine, School of Medicine, Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, CE, Brazil. AbstractHistoplasmosis is a systemic infection caused by the fungus Histoplasma capsulatum. Environmental sources of infection for humans and animals in certain regions and the prevalence of infection in animals are frequently unknown. Because of the clinical and epidemiological similarities between histoplasmosis and leishmaniasis in northeastern Brazil, we decided to investigate the serologic evidence of H. capsulatum in dogs, considering that these animals can act as sentinels for histoplasmosis. A total of 224 serum samples from dogs were tested for antibodies against H. capsulatum through immunodiffusion. A total of 128 (57.14%) samples were positive for leishmaniasis by indirect immunofluorescence assay and four (1.78%) samples were positive for antibodies against H. capsulatum. Immunological evidence of the co-existence of histoplasmosis and leishmaniasis in dogs living in urban areas was observed. Diagnosis and clinical management of these diseases in endemic areas should be improved by veterinarians. Copyright © 2011. Published by Elsevier B.V. |
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6. | BMC Vet Res. 2011 Jun 8;7(1):27. [Epub ahead of print]Survey of domestic cattle for anti-Leishmania antibodies and Leishmania DNA in a visceral leishmaniasis endemic area of Bangladesh.Alam MS, Ghosh D, Khan MG, Islam MF, Mondal D, Itoh M, Islam MN, Haque R.AbstractABSTRACT: BACKGROUND:Visceral leishmaniasis (VL), caused by an intracellular parasite Leishmania donovani in the Indian subcontinent, is considered to be anthroponotic. The role of domestic animals in its transmission is still unclear. Although cattle are the preferred blood host for Phlebotomus argentipes, the sandfly vector of VL in the Indian subcontinent, very little information is available for their role in the disease transmission. In this study, we examined domestic cattle for serological and molecular evidence of Leishmania infection in a VL-endemic area in Bangladesh. Blood samples from 138 domestic cattle were collected from houses with active or recently-treated VL and post-kala-azar dermal leishmaniasis patients. The presence of anti-leishmanial antibodies in serum was investigated using enzyme-linked immunosorbent assay (ELISA) and then with direct agglutination tests (DAT). Nested PCR (Ln PCR) was performed to amplify the ssu-rRNA gene using the DNA extracted from Buffy coat. Recently-developed molecular assay loop-mediated isothermal amplification (LAMP) was also performed for further sensitive detection of parasite DNA. RESULTS:In this study, 9.4% (n=13) of the cattle were found to be positive by ELISA. Of the 13 ELISA-positive cattle, only four (30.8%) were positive in DAT. Parasite DNA was not detected in either of the molecular assays (Ln PCR and LAMP). CONCLUSIONS:The study confirmed the presence of antibodies against Leishmania parasite in cattle. However, the absence of Leishmania DNA in the cattle indicates clearly that the cattle do not play a role as reservoir host. Similar study needs to be undertaken in the Indian subcontinent to determine the role of other domestic animals on which sandflies feed. |
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7. | ACS Chem Biol. 2011 Jun 8. [Epub ahead of print]Trypanos omal dihydrofolate reductase reveals natural antifolate resistance.Vanichtanankul J, Taweechai S, Yuvaniyama J, Vilaivan T, Chitnumsub P, Kamchonwongpaisan S, Yuthavong Y.AbstractDihydrofolate reductase (DHFR) is a potential drug target for Trypanosoma brucei, a human parasite, which is the causative agent for African sleeping sickness. No drug is available against this target, since none of the classical antifolates such as pyrimethamine (PYR), cycloguanil or trimethoprim are effective as selective inhibitors of T. brucei DHFR (TbDHFR). In order to design effective drugs that target TbDHFR, co-crystal structures with bound antifolates were studied. On comparison with malarial Plasmodium falciparum DHFR (PfDHFR), the co-crystal structures of wild-type TbDHFR reveal greater structural similarities to a mutant PfDHFR causing antifolate resistance than the wild-type enzyme. TbDHFR imposes steric hindrance for rigid inhibitors like PYR around Thr86, which is equivalent to Ser108Asn of the malarial enzymes. In addition, a missing residue on TbDHFR active-site loop together with the presence of Ile51 widens its active site even further than the structural effect of Asn51Ile, which is observed in PfDHFR structures. The structural similarities are paralleled by the similarly poor affinities of the trypanosomal enzyme for rigid inhibitors. Mutations of TbDHFR at Thr86 resulted in ten-fold enhancement or seven-fold reduction in the rigid inhibitors affinities for Thr86Ser or Thr86Asn, respectively. The co-crystal structure of TbDHFR with a flexible antifolate WR99210 suggests that its greater affinity result from its ability to avoid such Thr86 clash and occupy the widened binding space similarly to what observed in the PfDHFR structures. Natural resistance to antifolates of TbDHFR can therefore be explained, and potential antifolate chemotherapy of trypanosomiasis should be possible taking this into account. |
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8. | Proc Biol Sci. 2011 Apr 7;278(1708):1025-33. Epub 2010 Sep 29.Spatially explicit predictions of blood parasites in a widely distributed African rainforest bird.Sehgal RN, Buermann W, Harrigan RJ, Bonneaud C, Loiseau C, Chasar A, Sepil I, Valkiūnas G, Iezhova T, Saatchi S, Smith TB.SourceDepartment of Biology, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USA. sehgal@sfsu.edu AbstractCritical to the mitigation of parasitic vector-borne diseases is the development of accurate spatial predictions that integrate environmental conditions conducive to pathogen proliferation. Species of Plasmodium and Trypanosoma readily infect humans, and are also common in birds. Here, we develop predictive spatial models for the prevalence of these blood parasites in the olive sunbird (Cyanomitra olivacea). Since this species exhibits high natural parasite prevalence and occupies diverse habitats in tropical Africa, it represents a distinctive ecological model system for studying vector-borne pathogens. We used PCR and microscopy to screen for haematozoa from 28 sites in Central and West Africa. Species distribution models were constructed to associate ground-based and remotely sensed environmental variables with parasite presence. We then used machine-learning algorithm models to identify relationships between parasite prevalence and environmental predictors. Finally, predictive maps were generated by projecting model outputs to geographically unsampled areas. Results indicate that for Plasmodium spp., the maximum temperature of the warmest month was most important in predicting prevalence. For Trypanosoma spp., seasonal canopy moisture variability was the most important predictor. The models presented here visualize gradients of disease prevalence, identify pathogen hotspots and will be instrumental in studying the effects of ecological change on these and other pathogens. |
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