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Sent on Tuesday, 2010 May 11Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Parasitol Res. 2010 May 8. [Epub ahead of print]Erratum to: A new experimental culture medium for cultivation of Leishmania amazonensis: its efficacy for the continuous in vitro growth and differentiation of infective promastigote forms.de Almeida Rodrigues I, Alcântara da Silva B, Souza Dos Santos AL, Vermelho AB, Alviano CS, Lourenço Dutra PM, do Socorro Santos Rosa M.Departamento de Microbiologia Geral, Instituto de Microbiologia Prof. Paulo de Góes (IMPPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Bloco I, Ilha do Fundão, Rio de Janeiro, RJ 21941-902, Brazil. |
| PMID: 20454803 [PubMed - as supplied by publisher] | |
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| 2. | PLoS Negl Trop Dis. 2010 May 4;4(5):e678.Diverse effects on mitochondrial and nuclear functions elicited by drugs and genetic knockdowns in bloodstream stage Trypanosoma brucei.Worthen C, Jensen BC, Parsons M.Seattle Biomedical Research Institute, Seattle, Washington, USA. AbstractBACKGROUND: The options for treating the fatal disease human African trypanosomiasis are limited to a few drugs that are toxic or facing increasing resistance. New drugs that kill the causative agents, subspecies of Trypanosoma brucei, are therefore urgently needed. Little is known about the cellular mechanisms that lead to death of the pathogenic bloodstream stage. METHODOLOGY/PRINCIPAL FINDINGS: We therefore conducted the first side by side comparison of the cellular effects of multiple death inducers that target different systems in bloodstream form parasites, including six drugs (pentamidine, prostaglandin D(2), quercetin, etoposide, camptothecin, and a tetrahydroquinoline) and six RNAi knockdowns that target distinct cellular functions. All compounds tested were static at low concentrations and killed at high concentrations. Dead parasites were rapidly quantified by forward and side scatter during flow cytometry, as confirmed by ethidium homodimer and esterase staining, making these assays convenient for quantitating parasite death. The various treatments yielded different combinations of defects in mitochondrial potential, reactive oxygen species, cell cycle, and genome segregation. No evidence was seen for phosphatidylserine exposure, a marker of apoptosis. Reduction in ATP levels lagged behind decreases in live cell number. Even when the impact on growth was similar at 24 hours, drug-treated cells showed dramatic differences in their ability to further proliferate, demonstrating differences in the reversibility of effects induced by the diverse compounds. CONCLUSIONS/SIGNIFICANCE: Parasites showed different phenotypes depending on the treatment, but none of them were clear predictors of whether apparently live cells could go on to proliferate after drugs were removed. We therefore suggest that clonal proliferation assays may be a useful step in selecting anti-trypanosomal compounds for further development. Elucidating the genetic or biochemical events initiated by the compounds with the most profound effects on subsequent proliferation may identify new means to activate death pathways. |
| PMID: 20454560 [PubMed - in process] | |
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| 3. | PLoS Negl Trop Dis. 2010 May 4;4(5):e675.Antileishmanial high-throughput drug screening reveals drug candidates with new scaffolds.Siqueira-Neto JL, Song OR, Oh H, Sohn JH, Yang G, Nam J, Jang J, Cechetto J, Lee CB, Moon S, Genovesio A, Chatelain E, Christophe T, Freitas-Junior LH.Center for Neglected Diseases Drug Discovery (CND3), Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, South Korea. AbstractDrugs currently available for leishmaniasis treatment often show parasite resistance, highly toxic side effects and prohibitive costs commonly incompatible with patients from the tropical endemic countries. In this sense, there is an urgent need for new drugs as a treatment solution for this neglected disease. Here we show the development and implementation of an automated high-throughput viability screening assay for the discovery of new drugs against Leishmania. Assay validation was done with Leishmania promastigote forms, including the screening of 4,000 compounds with known pharmacological properties. In an attempt to find new compounds with leishmanicidal properties, 26,500 structurally diverse chemical compounds were screened. A cut-off of 70% growth inhibition in the primary screening led to the identification of 567 active compounds. Cellular toxicity and selectivity were responsible for the exclusion of 78% of the pre-selected compounds. The activity of the remaining 124 compounds was confirmed against the intramacrophagic amastigote form of the parasite. In vitro microsomal stability and cytochrome P450 (CYP) inhibition of the two most active compounds from this screening effort were assessed to obtain preliminary information on their metabolism in the host. The HTS approach employed here resulted in the discovery of two new antileishmanial compounds, bringing promising candidates to the leishmaniasis drug discovery pipeline. |
| PMID: 20454559 [PubMed - in process] | |
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| 4. | Indian Pediatr. 2010 Mar 15. pii: S09747559090059-2. [Epub ahead of print]Portal Hypertension with Visceral Leishmaniasis.Prasad R, Singh UK, Mishra OP, Jaiswal BP, Muthusami S.Department of Pediatrics, Nalanda Medical College, Patna, Bihar; and *Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi; India. Correspondence to: Dr Utpal Kant Singh, 8, Rajendra Nagar, Patna 800 013, Bihar, India. utpalkant.singh@yahoo.co.in. AbstractWe conducted this study to observe evidence of portal hypertension in children with visceral leishmaniasis (VL). Eighty-eight consecutive cases (50 male) of VL were subjected to ultrasonography. Those with evidence of portal hypertension also underwent upper gastrointestinal endoscopy and liver biopsy. Eight patients had portal hypertension as evidenced by dilated caliber of portal and splenic veins. Two patients had periportal, splenic and peripancreatic collaterals and one patient had cavernous transformation of portal vein. Out of eight patients, four patients had esophageal and gastric varices. Liver biopsy was done in four patients and revealed hepatic sinusoidal dilations without any evidence of fibrosis. Portal hypertension may be an independent manifestation of VL and remain undiagnosed unless a physician maintains a high index of suspicion. |
| PMID: 20453266 [PubMed - as supplied by publisher] | |
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| 5. | Nucleic Acids Res. 2010 May 7. [Epub ahead of print]Rapid decay of unstable Leishmania mRNAs bearing a conserved retroposon signature 3'-UTR motif is initiated by a site-specific endonucleolytic cleavage without prior deadenylation.Müller M, Padmanabhan PK, Rochette A, Mukherjee D, Smith M, Dumas C, Papadopoulou B.Infectious Disease Research Centre, CHUL Research Centre and Department of Microbiology and Immunology, Faculty of Medicine, Laval University, Quebec, Canada. AbstractWe have previously shown that the Leishmania genome possess two widespread families of extinct retroposons termed Short Interspersed DEgenerated Retroposons (SIDER1/2) that play a role in post-transcriptional regulation. Moreover, we have demonstrated that SIDER2 retroposons promote mRNA degradation. Here we provide new insights into the mechanism by which unstable Leishmania mRNAs harboring a SIDER2 retroposon in their 3'-untranslated region are degraded. We show that, unlike most eukaryotic transcripts, SIDER2-bearing mRNAs do not undergo poly(A) tail shortening prior to rapid turnover, but instead, they are targeted for degradation by a site-specific endonucleolytic cleavage. The main cleavage site was mapped in two randomly selected SIDER2-containing mRNAs in vivo between an AU dinucleotide at the 5'-end of the second 79-nt signature (signature II), which represents the most conserved sequence amongst SIDER2 retroposons. Deletion of signature II abolished endonucleolytic cleavage and deadenylation-independent decay and increased mRNA stability. Interestingly, we show that overexpression of SIDER2 anti-sense RNA can increase sense transcript abundance and stability, and that complementarity to the cleavage region is required for protecting SIDER2-containing transcripts from degradation. These results establish a new paradigm for how unstable mRNAs are degraded in Leishmania and could serve as the basis for a better understanding of mRNA decay pathways in general. |
| PMID: 20453029 [PubMed - as supplied by publisher] | |
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| 6. | Int J Parasitol. 2010 May 5. [Epub ahead of print]Genetic structure of Phlebotomus (Larroussius) ariasi populations, the vector of Leishmania infantum in the western Mediterranean: Epidemiological implications.Franco FA, Morillas-Márquez F, Barón SD, Morales-Yuste M, Gálvez R, Díaz V, Pesson B, Alves-Pires C, Depaquit J, Molina R, Afonso MO, Gállego M, Guernaoui S, Bounamous A, Martín-Sánchez J.Departamento de Parasitología, Facultad de Farmacia, Universidad de Granada, Spain. AbstractIn recent years there has been growing interest in analyzing the geographical variations between populations of different Phlebotomus spp. by comparing the sequences of various genes. However, little is known about the genetic structure of Phlebotomus ariasi. In this study, we were able to sequence a fragment of the mitochondrial Cyt b gene in 133 sandflies morphologically identified as P. ariasi and proceeding from a wide geographical range covering 35 locations in 11 different regions from five countries. The intraspecific diversity of P. ariasi is high, with 45 haplotypes differing from each other by one to 26 bases and they are distributed in two mitochondrial lineages, one limited geographically to Algeria and the other widely dispersed across Mediterranean countries. The Algerian lineage is characterized by having 13 fixed polymorphisms and is made up of one sole haplotype. The European/Moroccan P. ariasi lineage is characterized by being made up of a great diversity of haplotypes (44) which display some geographical structuring. This could be one of the multiple factors involved in the epidemiological heterogeneity of the foci of leishmaniasis. Phlebotomus chadlii is the sister group of European/Moroccan P. ariasi. The separation of the Algerian haplotype, H45, from the rest of the specimens, European/Moroccan P. ariasi and P. chadlii, is well supported by the bootstrap analysis. Copyright © 2010. Published by Elsevier Ltd. |
| PMID: 20451525 [PubMed - as supplied by publisher] | |
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| 7. | Trans R Soc Trop Med Hyg. 2010 May 5. [Epub ahead of print]Insulin-like growth factor-I induced and constitutive arginase activity differs among isolates of Leishmania deriv ed from patients with diverse clinical forms of Leishmania braziliensis infection.Vendrame CM, Souza LD, Carvalho MD, Salgado K, Carvalho EM, Goto H.Laboratório de Soroepidemiologia e Imunobiologia, Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, Avenida Dr. Enéas de Carvalho Aguiar n degrees 470, prédio II, 4 degrees andar, CEP 05403-000, São Paulo, SP, Brazil; Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil. AbstractArginase activity has been related to leishmaniasis development, thus we studied the constitutive and insulin-like growth factor (IGF) I-induced arginase activity of Leishmania (Viannia) braziliensis isolates from patients with different clinical forms of American tegumentary leishmaniasis (ATL). Isolates from mucosal leishmaniasis presented higher basal levels of arginase activity than isolates from other clinical forms of ATL. Isolates from disseminated leishmaniasis that present mucosal lesion in some cases reached the arginase activity similar to that of isolates from mucosal leishmaniasis upon IGF-I stimulation. Differences in arginase activity may influence disease outcomes such as evolution to mucosal lesion in patients with L. (V.) braziliensis infection. Copyright © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. |
| PMID: 20451229 [PubMed - as supplied by publisher] | |
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| 8. | Expert Rev Cardiovasc Ther. 2010 May;8(5):717-28.Trypanosomiasis, cardiomyopathy and the risk of ischemic stroke.Carod-Artal FJ.Neurology Department, Hospital Vírgen de la Luz, Av. Hermandad Donantes de sangre s/n, 16002, Cuenca, Spain. fjcarod-artal@hotmail.com AbstractAmerican (Chagas disease) and African (sleeping sickness) trypanosomiasis are neglected tropical diseases and are a heavy burden in Latin America and Africa, respectively. Chagas disease is an independent risk factor for stroke. Apical aneurysm, heart failure and cardiac arrhythmias are associated with ischemic stroke in chagasic cardiomyopathy. Not all chagasic patients who suffer an ischemic stroke have a severe cardiomyopathy, and stroke may be the first manifestation of Chagas disease. Cardioembolism affecting the middle cerebral artery is the most common stroke subtype. Risk of recurrence is high and careful evaluation of recurrence risk should be addressed. Repolarization changes, low voltage and prolonged QT interval are common electrocardiography alterations in human African trypanosomiasis, and can be found in more than 70% of patients. Epidemiological studies are needed to asses the risk of stroke in African trypanosomiasis perimyocarditis. |
| PMID: 20450304 [PubMed - in process] | |
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| 9. | Rev Soc Bras Med Trop. 2010 Feb;43(1):15-8.Comparative biology of the two sister species of Triatominae (Hemiptera: Reduviid ae).Carbajal de la Fuente AL, Cunha V, Rocha N, Lopes CM, Noireau F.Laboratory, Leishmaniasis Transmitters, Medical and Forensic Entomology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil. carbajal@ioc.fiocruz.br AbstractINTRODUCTION: Triatoma pseudomaculata and T. wygodzinskyi (Hemiptera: Reduviidae: Triatominae) are two Brazilian vectors of Chagas disease. The first is an arboricolous species in sylvatic environment and considered a vector of T. cruzi in peridomestic structures; the second, a rupicolous species in the wild environment of no epidemiological importance. In order to test the assumption that sister species share biological traits, comparative studies of their development cycle and blood ingestion were conducted. METHODS: Eggs laid by five field females of each species were randomly selected. The nymphs were observed daily and fed on mice weekly. The time required to pass through the different stages to adulthood was recorded in days. The triatomines were weighed individually before and after feeding. The mortality rate according to each nymphal stage was calculated. RESULTS AND CONCLUSIONS: Analysis of the results shows that they display only minor biological differences even though they exhibit a distinct ecology. This suggests that the biological traits are important criteria to determine the relationship between species. |
| PMID: 20305961 [PubMed - indexed for MEDLINE] | |
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| 10. | Rev Soc Bras Med Trop. 2010 Feb;43(1):9-14.Occurrence of positivity for Trypanosoma cruzi in triatomine from municipalities in Southeastern Brazil, from 2002 to 2004.Paula MB, Costa IN, Freitas Pde A, Limongi JE, Pajuaba Neto Ade A, Pinto Rde M, Gonçalves AL, Costa-Cruz JM.Regional Center of Zoonotic Diseases of Uberlândia, Department of Health of Uberlândia, Uberlândia, MG. AbstractINTRODUCTION: from an epidemiological point of view, more than 120 species of triatomine (Hemiptera, Reduviidae) are known. The occurrence and positivity for Trypanosoma cruzi in triatomines in 16 municipalities of the Triângulo Mineiro and Alto Paranaíba were evaluated from January 2002 to December 2004. METHODS: the triatomines were captured basically according to the classic norms of the National Health Foundation. The parasitological exams of the triatomines were conducted according to the technique described by the Ministry of Health. During the study period, 990 specimens of triatomines were captured and of these, 771 could be examined. RESULTS: five species were identified: Triatoma sordida, Panstrongylus diasi, Panstrongylus megistus, Panstrongylus geniculatus and Rhodnius neglectus. Triatoma sordida represented 71.5% of all the triatomines captured, followed by Panstrongylus megistus (18%), Rhodnius neglectus (9.3%), Panstrongylus diasi (0.8%) and Panstrongylus geniculatus (0.4%). Of the total number of triatomines examined, 2.7% were positive for Trypanosoma cruzi. Panstrongylus megistus was the species that presented the highest rates of infection by Trypanosoma cruzi (8.3%), followed by Rhodnius neglectus (2.9%) and Triatoma sordida (1.4%). CONCLUSIONS: there is a need to adapt to new circumstances in epidemiology, with greater emphasis on entomological surveillance, since the potential for adaptation of secondary species of triatomines exists, especially where Chagas' disease is already under control. |
| PMID: 20305960 [PubMed - indexed for MEDLINE] | |
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