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Sent on Saturday, 2012 January 28Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | J Am Soc Nephrol. 2012 Jan 26. [Epub ahead of print]Renal Leishmaniasis as Unusual Cause of Nephrotic Syndrome in an HIV Patient.Amann K, Bogdan C, Harrer T, Rech J.Source*Abt. für Nephropathologie, Pathologisches Institut. AbstractRenal involvement is a rare complication in HIV-1-infected patients leading to various pathologies and clinical symptoms. In addition to the classic HIV-1-associated nephropathy with collapsing-type focal segmental glomerulosclerosis and characteristic tubulocystic changes, which is more common in Afro-American than in Caucasian HIV-1 patients, immune complex GNs such as membranous GN and membranoproliferative GN are particularly common renal manifestations. Besides HIV-1 itself, a number of opportunistic infections may cause renal disease in HIV-1-infected patients. In this study, we report an unusual case of HIV-1 infection with a severe renal manifestation of systemic leishmaniasis that developed years after repeated visits to Mediterranean countries. The case presents several remarkable clinical, pathologic, and therapeutic aspects that may be important for daily clinical practice. |
| 2. | An Bras Dermatol. 2011 Dec;86(6):1141-4.Combining diagnostic procedures for the management of leishmaniasis in areas with high prevalence of Leishmania guyanensis.Benicio Ede A, Nunes Gadelha EP, Talhari A, Silva RM Jr, Ferreira LC, Santos MC, Mira MT, Oliveira CM, Talhari C, Talhari S, Machado PR, Schriefer A.AbstractBACKGROUND:The Amazon region corresponds to approximately 40% of the cases of leishmaniasis in Brazil. We report a prospective study with 180 patients conducted in a health care unit that diagnoses 10% of the cases of leishmaniasis in the Brazilian Amazon. The study addresses how a combination of procedures improves diagnosis in areas with high prevalence of Leishmania guyanensis. OBJECTIVES:to evaluate diagnostic methods in areas with high prevalence of Leishmania guyanensis. METHODS:All subjects were amastigote-positive by direct microscopic examination of lesion scarifications. We conducted skin biopsy and histopathology, polymerase chain reaction and parasite cultivation. RESULTS:Polymerase chain reaction detected almost ninety percent of infections when two amplification protocols were used (mini-exon and HSP-70). HSP-70 specific polymerase chain reaction matched the sensitivity of parasite cultivation plus histopathology. CONCLUSION:The best combination was polymerase chain reaction plus histopathology, which increased diagnostic sensitivity to 94%. Species discrimination by polymerase chain reaction disclosed prevalence of human infections with Leishmania guyanensis of 94% and with Leishmania braziliensis of 6% for this region. |
| 3. | An Bras Dermatol. 2011 Dec;86(6):1092-1101.A randomized clinical trial comparing meglumine antimoniate, pentamidine and amphotericin B for the treatment of cutaneous leishmaniasis by Leishmania guyanensis. [Article in English, Portuguese] Neves LO, Talhari AC, Gadelha EP, Silva Júnior RM, Guerra JA, Ferreira LC, Talhari S.SourcePrograma de Pós-Graduação em Medicina Tropical, Fundação de Medicina Tropical Heitor Vieira Dourado, Universidade do Estado do Amazonas. AbstractFUNDAMENTALS: American tegumentary leishmaniasis (ATL) treatment remains a challenge, since most available drugs are injectable and only a small number of comparative, randomized clinical trials have been performed to support their use. Moreover, treatment outcome may depend on the causative species of Leishmania. OBJECTIVES:To evaluate and compare the efficacy and tolerability of meglumine antimoniate, pentamidine isethionate, and amphotericin B in the treatment of ATL caused by Leishmania (Viannia) guyanensis. METHODS:185 patients were selected according to the eligibility criteria and randomly allocated into three groups - two groups with 74 patients each, and one group with 37 patients, which underwent meglumine, pentamidine and amphotericin B treatment, respectively. Doses, mode of administration and time periods of treatment followed the current recommendations for each drug. Patients were re-examined one, two and six months after completion of treatment. RESULTS:No differences were observed among the therapeutic groups in relation to gender, age, number or site of lesions. Intention-to-treat (ITT) analysis showed efficacy of 58.1% for pentamidine and 55.5% for meglumine (p=0.857). The amphotericin B group was analyzed separately, since 28 patients (75.7%) in this group refused to continue participating in the study. Mild or moderate adverse effects were reported by 74 (40%) patients, especially arthralgia (20.3%) in the meglumine group, and pain (35.1%) or induration (10.8%) at the site of injection in the pentamidine group. CONCLUSION:Pentamidine and meglumine show similar efficacy in the treatment of ATL caused by L. guyanensis. Given the low efficacy of both drugs, there is an urgent need for new therapeutical approaches. |
| 4. | Int J Parasitol. 2012 Jan 11. [Epub ahead of print]Acylation-dependent and independent membrane targeting and distinct functions of small myristoylated proteins (SMPs) in Leishmania major.Tull D, Heng J, Gooley PR, Naderer T, McConville MJ.SourceDepartment of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia. AbstractTrypanosomatid parasites express a number of mono- and diacylated proteins that are targeted to distinct regions of the plasma membrane including the cell body, the flagellum and the flagellar pocket. The extent to which the acylation status and other protein motifs regulate the targeting and/or retention of these proteins to the distinct membrane domains is poorly defined. We have previously described a family of small myristoylated proteins (SMPs) that are either monoacylated (myristoylated) or diacylated (myristoylated and palmitoylated) and targeted to distinct plasma membrane domains. Diacylated SMP-1 is a major constituent of the flagellar membrane, whereas monoacylated SMP-2 resides in the flagellar pocket in Leishmania major. Here, we show that a third SMP family member, monoacylated SMP-4, localizes predominantly to the pellicular membrane. Density gradient centrifugation of detergent-insoluble membranes indicated that SMP-4 was associated with detergent-insoluble domains but was not tightly associated with the subpellicular cytoskeleton. Based on the localisation of truncated SMP proteins, we conclude that the flagellum targeting of SMP-1 is primarily dependent on the dual-acylation motif. In contrast, the localisation of SMP-4 to the cell body membrane was dependent on N-terminal myristoylation and a C-terminal peptide subdomain with a predicted α-helical structure. Strikingly, a SMP-1 chimera containing the SMP-4 C-terminal extension was selectively trafficked to the distal tip of the flagellum and failed to complement the loss of native SMP-1 in a Δsmp1/2 double knockout strain. Collectively, these results suggest that dual acylation is sufficient to target some SMP proteins to the flagellum, while the unique C-terminal extensions of these proteins may confer additional membrane targeting signals that are important for both localisation and SMP function. Copyright © 2012. Published by Elsevier Ltd. |
| 5. | Acta Trop. 2012 Jan 18. [Epub ahead of print]Anti-Trypanosoma cruzi activity of nicotinamide.Soares MB, Silva CV, Bastos TM, Guimarães ET, Figueira CP, Smirlis D, Azevedo WF Jr.SourceCentro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão, 121, Candeal 40296-710, Salvador, BA, Brazil; Hospital São Rafael, Av. São Rafael, 2152, São Marcos 41253-190, Salvador, BA, Brazil. AbstractInhibition of Trypanosoma brucei and Leishmania spp. sirtuins has shown promising antiparasitic activity, indicating that these enzymes may be used as targets for drug discovery against trypanosomatid infections. In the present work we carried out a virtual screening focused on the C pocket of Sir2 from Trypanosoma cruzi. Using this approach, the best ligand found was nicotinamide. In vitro tests confirmed the anti-T. cruzi activity of nicotinamide on epimastigote and trypomastigote forms. Moreover, treatment of T. cruzi-infected macrophages with nicotinamide caused a significant reduction in the number of amastigotes. In addition, alterations in the mitochondria and an increase in the vacuolization in the cytoplasm were observed in epimastigotes treated with nicotinamide. Analysis of the complex of Sir2 and nicotinamide revealed the details of the possible ligand-target interaction. Our data reveal a potential use of TcSir2 as a target for anti-T. cruzi drug discovery. Copyright © 2012 Elsevier B.V. All rights reserved. |
| 6. | Exp Parasitol. 2012 Jan 20. [Epub ahead of print]Effectiveness of liposomal buparvaquone in an experimental hamster model of Leishmani a (L.) infantum chagasi.Reimão JQ, Colombo FA, Pereira-Chioccola VL, Tempone AG.SourceDepartment of Parasitology, Instituto Adolfo Lutz, Avenida Dr. Arnaldo, 351, 8° Andar. Cerqueira César, CEP 01246-902 São Paulo, SP, Brazil. AbstractThe objective of this study was to develop a novel liposomal formulation, containing phosphatidylserine (PS), of buparvaquone (BPQ) and to evaluate its in vivo effectiveness in Leishmania (L.) infantum chagasi-infected hamsters. The activity of BPQ was evaluated against both the promastigote forms of different Leishmania species and the intracellular amastigotes of L. (L.) infantum chagasi. Buparvaquone was entrapped in PS-liposomes (BPQ-PS-LP), and the drug was quantified by ultra-high-performance liquid chromatography. The treatment was quantified by detecting the RNA of the living amastigotes in the spleen and the liver by real-time PCR. In vitro assays with L. (L.) infantum chagasi intracellular amastigotes were performed in peritoneal macrophages for the evaluation of the 50% inhibitory concentration (IC(50)). BPQ-PS-LP at 0.33mg/kg/day for eight consecutive days reduced the number of amastigotes by 89.4% (P<0.05) in the spleen and by 67.2% (P>0.05) in the liver, compared to 84.3% (P<0.05) and 99.7% (P<0.05), respectively, following Glucantime® treatment at 50mg/kg/day. Free BPQ at 20mg/kg/day failed to treat the hamsters when compared to the untreated group. BPQ was significantly (P<0.05) selective against L. (L.) infantum chagasi intracellular amastigotes, with an IC(50) value of 1.5μM; no in vitro mammalian cytotoxicity could be detected. Other cutaneous species were also susceptible to BPQ, with IC(50) values in the range 1-4μM. BPQ-PS-LP caused a significant reduction in the parasite burden at a 60-fold lower dose than did the free BPQ. These results show the potential of PS-liposome formulations for the successful targeted delivery of BPQ in visceral leishmaniasis. Copyright © 2012. Published by Elsevier Inc. |
| 7. | Braz J Biol. 2011 May;71(2):491-500.Prevalence and intensity of infection, metacyclogenesis and nuclear phenotypes in Panstrongylus megistus (Burmeister, 1835) after ingestion of Trypanosoma cruzi (Chagas, 1909) II and subjection to heat shock.Garcia SL, Rodrigues VL, Garcia NL, Mello ML.SourceDepartamento de Anatomia, Biologia Celular e Fisiologia e Biofísica, Universidade Estadual de Campinas, Campinas, SP, Brazil, 13083-863. AbstractThis study aimed to contribute to our knowledge of the parasite-vector interaction associated with Trypanosoma cruzi (Chagas, 1909) infection in Panstrongylus megistus (Burmeister, 1835), an important vector of Chagas' disease in Brazil. The prevalence and intensity of T. cruzi infection, the incidence of metacyclogenesis and the frequency of nuclear phenotypes in Malpighian tubules were investigated in nymphs of P. megistus, reared at 28 °C and subjected to heat shock (40 °C, 1 hour) two days after infection with T. cruzi II (Y strain). Following the 45-day post-infection period, the frequency of epimastigotes was much higher than that of trypomastigotes in both heat-shocked and non-shocked insects, and the prevalence of infection was not altered by heat shock. Fewer epimastigotes and trypomastigotes were found in the infected insects subjected to the heat shock, indicating that the multiplication and metacyclogenesis of the parasites were affected by the stress. In infected specimens heat shock promoted an increased frequency of cell nuclei with heterochromatin decondensation, a cell survival response to stress, and did not affect insect survival. The effects of infection and heat shock, especially on the multiplication and metacyclogenesis of T. cruzi, and the observed resistance to heat shock developed by P. megistus nymphs are suggestive that they should be considered when adequate conditions for rearing these infected insects in the laboratory are pursued. |
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