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Sent on Saturday, 2010 Mar 13Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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1. | PLoS One. 2010 Mar 10;5(3):e9630.A Search for Trypanosoma brucei rhodesiense Diagnostic Antigens by Proteomic Screening and Targeted Cloning.Manful T, Mulindwa J, Frank FM, Clayton CE, Matovu E.Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Heidelberg, Germany. BACKGROUND: The only available diagnostic method for East African trypanosomiasis is light microscopy of blood samples. A simple immunodiagnostic would greatly aid trypanosomiasis control. METHODOLOGY AND PRINCIPAL FINDINGS: To find trypanosome proteins that are specifically recognised by sera from human sleeping sickness patients, we have screened the Trypanosoma brucei brucei proteome by Western blotting. Using cytosolic, cytoskeletal and glycosomal fractions, we found that the vast majority of abundant trypanosome proteins is not specifically recognised by patient sera. We identified phosphoglycerate kinase (PGKC), heat shock protein (HSP70), and histones H2B and H3 as possible candidate diagnostic antigens. These proteins, plus paraflagellar rod protein 1, rhodesain (a cysteine protease), and an extracellular fragment of the Trypanosoma brucei nucleoside transporter TbNT10, were expressed in E. coli and tested for reactivity with patient and control sera. Only TbHSP70 was preferentially recognized by patient sera, but the sensitivity and specificity were insufficient for use of TbHSP70 alone as a diagnostic. Immunoprecipitation using a native protein extract revealed no specifically reacting proteins. CONCLUSIONS: No abundant T. brucei soluble, glycosomal or cytoskeletal protein is likely to be useful in diagnosis. To find useful diagnostic antigens it will therefore be necessary to use more sophisticated proteomic methods, or to test a very large panel of candidate proteins. |
PMID: 20224787 [PubMed - in process] | |
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2. | Actas Dermosifiliogr. 2010 Mar;101(2):164-167.Leishmaniasis and Rheumatoid Nodulosis in a Patient with HIV Infection.[Article in English, Spanish] García-Río I, Daudén E, Ballestero-Díez M, Fraga J, García-Díez A.Departamento de Dermatología, Hospital Universitario de la Princesa, Madrid, España. We describe the case of a 44-year-old homosexual man diagnosed with HIV infection and visceral leishmaniasis. He presented nodules on the dorsum of the hands. Histological study of one of the nodules revealed necrobiotic palisading granulomas with abundant Leishmania amastigotes within the histiocytes and in the adjacent extracellular space. Tissue and peripheral blood cultures were positive for Leishmania infantum, zymodeme MON-24. A biopsy of healthy skin did not reveal the presence of Leishmania. A diagnosis of rheumatoid nodulosis with Leishmania was made and treatment was started with intravenous liposomal amphotericin, leading to slight improvement. We believe that the presence of the parasite within the nodules was the result of its dissemination during visceral leishmaniasis in an immunocompromised patient with HIV infection, and that the Leishmania did not have an etiological role in the appearance of the nodules. We present the first case of the association between Leishmania and rheumatoid nodulosis. |
PMID: 20223159 [PubMed - as supplied by publisher] | |
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3. | Parasit Vectors. 2010 Mar 11;3(1):16. [Epub ahead of print]Synthetic sex pheromone a ttracts the leishmaniasis vector Lutzomyia longipalpis to experimental chicken sheds treated with insecticide.Bray DP, Alves GB, Dorval ME, Brazil RP, Hamilton JG.ABSTRACT: BACKGROUND: Current strategies for controlling American visceral leishmaniasis (AVL) have been unable to prevent the spread of the disease across Brazil. With no effective vaccine and culling of infected dogs an unpopular and unsuccessful alternative, new tools are urgently needed to manage populations of the sand fly vector, Lutzomyia longipalpis Lutz and Neiva (Diptera: Psychodidae). Here, we test two potential strategies for improving L. longipalpis control using the synthetic sand fly pheromone (+/-)-9-methylgermacrene-B: the first in conjunction with spraying of animal houses with insecticide, the second using coloured sticky traps. RESULTS: Addition of synthetic pheromone resulted in greater numbers of male and female sand flies being caught and killed at experimental chicken sheds sprayed with insecticide, compared to pheromone-less controls. Furthermore, a ten-fold increase in the amount of sex pheromone released from test sheds increased the number of females attracted and subsequently killed. Treating sheds with insecticide alone resulted in a significant decrease in numbers of males attracted to sheds (compared to pre-spraying levels), and a near significant decrease in numbers of females. However, this effect was reversed through addition of synthetic pheromone at the time of insecticide spraying, leading to an increase in number of flies attracted post-treatment. In field trials of commercially available different coloured sticky traps, yellow traps caught more males than blue traps when placed in chicken sheds. In addition, yellow traps fitted with 10 pheromone lures caught significantly more males than pheromone-less controls. However, while female sand flies showed a preference for both blue and yellow pheromone traps sticky traps over white traps in the laboratory, neither colour caught significant numbers of females in chicken sheds, either with or without pheromone. CONCLUSIONS: We conclude that synthetic pheromone could currently be most effectively deployed for sand fly control through combination with existing insecticide spraying regimes. Development of a standalone pheromone trap remains a possibility, but such devices may require an additional attractive host odour component to be fully effective. |
PMID: 20222954 [PubMed - as supplied by publisher] | |
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4. | J Immunol. 2010 Feb 1;184(3):1148-52. Epub 2009 Dec 30.Cutting edge: nucleotide-binding oligomerization domain 1-dependent responses account for murine resistance aga inst Trypanosoma cruzi infection.Silva GK, Gutierrez FR, Guedes PM, Horta CV, Cunha LD, Mineo TW, Santiago-Silva J, Kobayashi KS, Flavell RA, Silva JS, Zamboni DS.Department of Cell Biology, University of São Paulo, School of Medicine Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil. An effective innate immune recognition of the intracellular protozoan parasite Trypanosoma cruzi is critical for host resistance against Chagas disease, a severe and chronic illness that affects millions of people in Latin America. In this study, we evaluated the participation of nucleotide-binding oligomerization domain (Nod)-like receptor proteins in host response to T. cruzi infection and found that Nod1-dependent, but not Nod2-dependent, responses are required for host resistance against infection. Bone marrow-derived macrophages from Nod1(-/-) mice showed an impaired induction of NF-kappaB-dependent products in response to infection and failed to restrict T. cruzi infection in presence of IFN-gamma. Despite normal cytokine production in the sera, Nod1(-/-) mice were highly susceptible to T. cruzi infection, in a similar manner to MyD88(-/-) and NO synthase 2(-/-) mice. These studies indicate that Nod1-dependent responses account for host resistance against T. cruzi infection by mechanisms independent of cytokine production. |
PMID: 20042586 [PubMed - indexed for MEDLINE] | |
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5. | Proteins. 2010 Mar;78(4):888-99.Binding of nitrogen-containing bisphosphonates (N-BPs) to the Trypanosoma cruzi farnesyl diphosphate synthase homodimer.Huang CH, Gabelli SB, Oldfield E, Amzel LM.Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. Bisphosphonates (BPs) are a class of compounds that have been used extensively in the treatment of osteoporosis and malignancy-related hypercalcemia. Some of these compounds act through inhibition of farnesyl diphosphate synthase (FPPS), a key enzyme in the synthesis of isoprenoids. Recently, nitrogen-containing bisphosphonates (N-BPs) used in bone resorption therapy have been shown to be active against Trypanosoma cruzi, the parasite that causes American trypanosomiasis (Chagas disease), suggesting that they may be used as anti-trypanosomal agents. The crystal structures of TcFPPS in complex with substrate (isopentenyl diphosphate, IPP) and five N-BP inhibitors show that the C-1 hydroxyl and the nitrogen-containing groups of the inhibitors alter the binding of IPP and the conformation of two TcFPPS residues, Tyr94 and Gln167. Isothermal titration calorimetry experiments suggest that binding of the first N-BPs to the homodimeric TcFPPS changes the binding properties of the second site. This mechanism of binding of N-BPs to TcFPPS is different to that reported for the binding of the same compounds to human FPPS. Proteins 2010. (c) 2009 Wiley-Liss, Inc. |
PMID: 19876942 [PubMed - indexed for MEDLINE] | |
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6. | Parasitol Res. 2009 Dec;106(1):157-61. Epub 2009 Sep 30.Lipid peroxidation in cats experimentally infected with Trypanosoma evansi.da Silva AS, Wolkmer P, Machado Costa M, Paim F, Belmonte Oliveira C, Adriel Zanette R, Morais Santurio J, Dos Anjos Lopes ST, Gonzalez Monteiro S.Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Santa Maria, Brazil. aleksandro_ss@yahoo.com.br The objective of this study was to evaluate the lipid peroxidation and the susceptibility of erythrocytes to in vitro peroxidation as indicators of oxidative damage in erythrocytes and their roles in the pathogenesis of anemia during experimental Trypanosoma evansi infection in cats. Animals were divided into two groups: control and infected with T. evansi. Seven cats were infected with 10(8) trypomastigotes each, and parasitemia was estimated daily for 49 days by microscopic examination of smears. Hematological and biochemical parameters were evaluated for monitoring of the disease. Plasma lipid peroxidation (Thiobarbituric Acid Reactive Substances (TBARS)) and the susceptibility of erythrocytes to in vitro peroxidation were evaluated. Blood samples for analysis were collected at days 21 and 49 post-inoculation. TBARS level, indicated by MDA concentration, was higher in the infected group than in the control group in both analyzed periods, as well as the in vitro erythrocyte peroxidation (P < 0.001). The infected cats had variable degrees of regenerative anemia, which could be explained by the damage in erythrocyte membrane caused by lipid peroxidation. |
PMID: 19789894 [PubMed - indexed for MEDLINE] | |
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7. | Parasitol Res. 2009 Dec;106(1):111-20. Epub 2009 Sep 26.Acute Trypanosoma cruzi experimental infection induced renal ischemic/reperfusion lesion in mice.de Oliveira GM, da Silva TM, Batista WS, Franco M, Schor N.Laboratório de Biologia Celular, Instituto Oswaldo Cruz/FIOCRUZ, Manguinhos, Rio de Janeiro, Rio de Janeiro, Brazil. gmoliveira@ioc.fiocruz.br Experimental acute infection with Trypanosoma cruzi in mice promotes an intense myocarditis and other systemic changes. However, the network of pathophysiological disorders and renal injury caused by the infection has not been elucidated. Our previous results with a murine model observed a discrete acute myocarditis and high mortality with significant inflammatory kidney injury with T. cruzi infection. The aim of this study was to investigate the mechanisms of kidney injury caused by the parasite in mice during the experimental acute phase. Results employing BALB/c mice infected with T. cruzi of Y strain showed renal injury on the 6th day postinfection (dpi) caused by a transitory decrease of renal blood flow. Acute kidney injury (AKI) was also observed similar to the model of ischemia/reperfusion lesion in these infected mice. The injury was not related to the presence (or multiplication) of parasites. Only rare nests were microscopically detected, and the presence of scattered parasites in renal parenchyma was seen on the 15th dpi. Thus, it was observed that during the acute phase of the disease, AKI in infected mice is linked to early cardiovascular effects, including heart failure, caused by striking inflammatory lesions in the myocardium, which lead to the high mortality rate of animals. |
PMID: 19784671 [PubMed - indexed for MEDLINE] | |
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8. | Parasitol Res. 2009 Dec;106(1):85-93. Epub 2009 Sep 16.In vitro and in vivo documentation of quantum dots labeled Trypanosoma cruzi--Rhodnius prolixus interaction using confocal microscopy.Feder D, Gomes SA, de Thomaz AA, Almeida DB, Faustino WM, Fontes A, Stahl CV, Santos-Mallet JR, Cesar CL.Laboratório de Biologia de Insetos, GBG, Universidade Federal Fluminense (UFF), Niterói, Rio de Janeiro, Brazil. dfeder@vm.uff.br Semiconductor quantum dots (QDs) are highly fluorescent nanocrystals markers that allow long photobleaching and do not destroy the parasites. In this paper, we used fluorescent core shell quantum dots to perform studies of live parasite-vector interaction processes without any observable effect on the vitality of parasites. These nanocrystals were synthesized in aqueous medium and physiological pH, which is very important for monitoring live cells activities, and conjugated with molecules such as lectins to label specific carbohydrates involved on the parasite-vector interaction. These QDs were successfully used for the study of in vitro and in vivo interaction of Trypanosoma cruzi and the triatomine Rhodnius prolixus. These QDs allowed us to acquire real time confocal images sequences of live T. cruzi-R. prolixus interactions for an extended period, causing no damage to the cells. By zooming to the region of interest, we have been able to acquire confocal images at the three to four frames per second rate. Our results show that QDs are physiological fluorescent markers capable to label living parasites and insect vector cells. QDs can be functionalized with lectins to specifically mark surface carbohydrates on perimicrovillar membrane of R. prolixus to follow, visualize, and understand interaction between vectors and its parasites in real-time. |
PMID: 19756738 [PubMed - indexed for MEDLINE] | |
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