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Sent on Friday, 2012 February 03Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | PLoS One. 2012;7(1):e31059. Epub 2012 Jan 27.Developmentally Regulated Sphingolipid Degradation in Leishmania major.Zhang O, Xu W, Balakrishna Pillai A, Zhang K.SourceDepartment of Biological Sciences, Texas Tech University, Lubbock, Texas, United States of America. AbstractLeishmania parasites alternate between extracellular promastigotes in sandflies and intracellular amastigotes in mammals. These protozoans acquire sphingolipids (SLs) through de novo synthesis (to produce inositol phosphorylceramide) and salvage (to obtain sphingomyelin from the host). A single ISCL (Inositol phosphoSphingolipid phospholipase C-Like) enzyme is responsible for the degradation of both inositol phosphorylceramide (the IPC hydrolase or IPCase activity) and sphingomyelin (the SMase activity). Recent studies of a L. major ISCL-null mutant (iscl(-)) indicate that SL degradation is required for promastigote survival in stationary phase, especially under acidic pH. ISCL is also essential for L. major proliferation in mammals. To further understand the role of ISCL in Leishmania growth and virulence, we introduced a sole IPCase or a sole SMase into the iscl(-) mutant. Results showed that restoration of IPCase only complemented the acid resistance defect in iscl(-) promastigotes and improved their survival in macrophages, but failed to recover virulence in mice. In contrast, a sole SMase fully restored parasite infectivity in mice but was unable to reverse the promastigote defects in iscl(-). These findings suggest that SL degradation in Leishmania possesses separate roles in different stages: while the IPCase activity is important for promastigote survival and acid tolerance, the SMase activity is required for amastigote proliferation in mammals. Consistent with these findings, ISCL was preferentially expressed in stationary phase promastigotes and amastigotes. Together, our results indicate that SL degradation by Leishmania is critical for parasites to establish and sustain infection in the mammalian host. |
| 2. | Ceylon Med J. 2011 Dec;56(4):179-80. doi: 10.4038/cmj.v56i4.3904.First successful in vitro culture of Leishmania sp. causing autochthonous visceral leishmaniasis in Sri Lanka.Ranasinghe PH, Abeygunasekera PH, Athauda SB, Chandrasekharan NV, Mendis AS, Hulangamuwa CS, Wickremasinghe DR.SourceDepartment of Parasitology, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka. ishalindra@yahoo.com. |
| 3. | Parasitol Res. 2012 Feb 2. [Epub ahead of print]Antileishmanial activity of cryptolepine analogues and apoptotic effects of 2,7-dibromocryptolepine against Leishmania donovani promastigotes.Hazra S, Ghosh S, Debnath S, Seville S, Prajapati VK, Wright CW, Sundar S, Hazra B.SourceDepartment of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India. AbstractCryptolepine (5-methyl-10H-indolo [3, 2-b] quinoline), an indoloquinoline alkaloid (1) isolated from a medicinal plant traditionally used in Western Africa for treatment of malaria, has been shown to possess broad spectrum biological activity in addition to its antiplasmodial effect. Here, the antileishmanial properties of 11 synthetic derivatives of cryptolepine against Leishmania donovani parasites have been evaluated for the first time. 2,7-Dibromocryptolepine (8; IC(50) 0.5 ± 0.1 μM) was found to be the most active analogue against the promastigote form of a classical L. donovani strain (AG83) in comparison to the natural alkaloid, cryptolepine (1; IC(50) 1.6 ± 0.1 μM). Further, 8 was found to substantially inhibit the intracellular amastigote forms of two clinical isolates, one of them being an SbV-resistant strain of L. donovani. Moreover, the toxicity of 8 against normal mouse peritoneal macrophage cells was markedly lower than that of 1 (IC(50) values: 9.0 ± 1.2 and 1.1 ± 0.3 μM, respectively), indicating 8 to be a prospective "lead" towards novel antileishmanial therapy. This was supported by studies on the mechanism of cytotoxicity induced by 8 in L. donovani promastigotes (AG83), which revealed the cytoplasmic and nuclear features of metazoan apoptosis. Light microscopic observation demonstrated a gradual decline in the motility, cell volume, and survival of the treated parasites with increasing incubation time. Flow cytometric analysis of phosphatidylserine externalization and distribution of cells in different phases of cell cycle confirmed the presence of a substantial percentage of cells in early apoptotic stage. Disruption of mitochondrial membrane integrity in terms of depolarization of membrane potential, and finally degradation of chromosomal DNA into oligonucleosomal fragments-the hallmark event of apoptosis-characterized the mode of cell death in L. donovani promastigotes. |
| 4. | Res Vet Sci. 2012 Jan 30. [Epub ahead of print]Monitoring the reverse to normal of clinico-pathological findings and the disease free interval time using four different treatment protocols for canine leishmaniosis in an endemic area.Paradies P, Sasanelli M, Amato ME, Greco B, De Palo P, Lubas G.SourceDepartment of Public Health and Animal Sciences, Faculty of Veterinary Medicine, University of Bari, Italy. AbstractTwenty-four dogs naturally infected by Leishmania spp. were treated with four different protocols using meglumine antimoniate (aNm) and allopurinol in combination or in monotherapy. Aiming to compare the efficacy of the different treatments the reverse to normal of clinico-pathological findings and the disease free interval time (DFIT) were evaluated. Treated dogs were monitored for 1year and, in absence of relapses, the DFIT was postponed to the last available follow-up. Seven dogs treated with aNm alone showed relapses during the year of observation. In the group of dogs treated with the combination of aNm (50mg/kg/SC 12 hourly up to clinico-pathological recovery) and allopurinol (15mg/kg/PO 12 hourly administered for 6months) no relapses were registered in the year of monitoring and the DFIT reached up to 65months. Our results showed that this combination represents the best choice to treat canine leishmaniosis compared to other protocols. Copyright © 2012 Elsevier Ltd. All rights reserved. |
| 5. | Chem Biol Drug Des. 2012 Feb 1. doi: 10.1111/j.1747-0285.2012.01329.x. [Epub ahead of print]Comparative Analysis of Different DNA Binding Drugs for Leishmaniasis Cure: A Pharmacoinformatics Approach.Chauhan N, Vidyarthi AS, Poddar R.SourceDepartment of Biotechnology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835215 (INDIA). AbstractSeveral experiments have been performed to test DNA binding drugs to cure Leishmania infection. However, there are no details of pharmacoinformatics study. Herein, we have selected a good number of compounds from experimentally verified studies and performed a comparative analysis based on Pharmacoinformatics techniques. In silico docking study were performed to observe the molecular level interactions of these known ligands with the DNA receptor by automated computational docking using Glide. A comparison between the calculated interaction energies and in silico ADME/T study was made. In agreement of drug likeness rules, our study suggests that, Seco-hydroxy-aza-CBI-TMI (compound 4b; GScore: -12.058) is a potential molecule for targeting the DNA to cure Leishmaniasis. © 2012 John Wiley & Sons A/S. © 2012 John Wiley & Sons A/S. |
| 6. | Mol Microbiol. 2012 Feb 2. doi: 10.1111/j.1365-2958.2012.07988.x. [Epub ahead of print]Expression of the RNA Recognition Motif protein RBP10 promotes a bloodstream-form transcript pattern in Trypanosoma brucei.Wurst M, Seliger B, Jha BA, Klein C, Queiroz R, Clayton C.SourceZentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, D69120 Heidelberg. AbstractWhen Trypanosoma brucei differentiates from the bloodstream form to the procyclic form, there are decreases in the levels of many mRNAs encoding proteins required for the glycolytic pathway, and the mRNA encoding the RNA Recognition Motif protein RBP10 decreases in parallel. We show that RBP10 is a cytoplasmic protein that is specific to bloodstream-form trypanosomes, where it is essential. Depletion of RBP10 caused decreases in many bloodstream-form-specific mRNAs, with increases in mRNAs associated with the early stages of differentiation. The changes were similar to, but more extensive than, those caused by glucose deprivation. Conversely, forced RBP10 expression in procyclics induced a switch towards bloodstream-form mRNA expression patterns, with concomitant growth inhibition. Forced expression of RBP10 prevented differentiation of bloodstream forms in response to cis-aconitate, but did not prevent expression of key differentiation markers in response to glucose deprivation. RBP10 was not associated with heavy polysomes, showed no detectable in vivo binding to RNA, and was not stably associated with other proteins. Tethering of RBP10 to a reporter mRNA inhibited translation, and halved the abundance of the bound mRNA. We suggest that RBP10 may prevent the expression of regulatory proteins that are specific to the procyclic form. © 2012 Blackwell Publishing Ltd. © 2012 Blackwell Publishing Ltd. |
| 7. | Cad Saude Publica. 2011 Oct;27(10):1917-29.[Seroprevalence for Trypanosoma cruzi infection and associated factors in an endemic area of Venezuela]. [Article in Spanish] Bonfante-Cabarca s R, Rodríguez-Bonfante C, Vielma BO, García D, Saldivia AM, Aldana E, Curvelo JL.SourceDecanato de Ciencias de la Salud, Universidad Centroccidental Lisandro Alvarado, Venezuela. rcabarca@ucla.edu.ve AbstractThis study investigated risk factors associated with positive serological status for Trypanosoma cruzi antibodies in 26 rural communities including 905 households, 2,156 humans, and 333 dogs in Lara State, Venezuela. Serology was performed with ELISA and MABA. Data were obtained from entomological, demographic, and clinical surveys. Risk factors were determined through binary logistic regression. Seroprevalence was 7.24% in humans and 6.9% in canines. Positive serological status was positively associated with the Rhodnius prolixus vector, age, maternal history of Chagas disease, tobacco chewing, presence of mammals and birds in the household, household disarray, mud-and-wattle outbuildings, and animal nests and burrows in the peridomicile, and negatively associated with tobacco and alcohol consumption, history of cancer, and storage deposits in the peridomile. In conclusion, Chagas disease in this rural area is an old phenomenon transmitted by R. prolixus or by the transplacental route, associated with socio-cultural habits related to poverty, sylvatic surroundings, and the host's medical history. |
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| 8. | J Bioenerg Biomembr. 2011 Aug;43(4):419-24. Epub 2011 Jul 6.Role of Trypanosoma cruzi peroxiredoxins in mitoc hondrial bioenergetics.Peloso Ede F, Vitor SC, Ribeiro LH, Piñeyro MD, Robello C, Gadelha FR.SourceUniversidade Estadual de Campinas, Instituto de Biologia, Departamento de Bioquímica, IB, UNICAMP, Campinas, São Paulo, Brazil. AbstractTrypanosoma cruzi cytosolic (TcCPx) and mitochondrial tryparedoxin peroxidase (TcMPx) play a fundamental role in H(2)O(2) detoxification. Herein, mitochondrial bioenergetics was evaluated in cells that overexpressed TcCPx (CPx) and TcMPx (MPx) and in pTEX. In MPx, a higher expression was observed for TcCPx, and the same correlation was true for CPx. Differences in H(2)O(2) release among the overexpressing cells were detected when the mitochondrial respiratory chain was inhibited using antimycin A or thenoyltrifluoroacetone. MPx had higher O(2) consumption rates than pTEX and CPx, especially in the presence of oligomycin. In all of the cells, the mitochondrial membrane potential and the ATP levels were similar. Because of the mild uncoupling that was observed in MPx, the presence or induction of a proton transporter in the mitochondrial membrane is suggested when TcMPx is expressed at higher levels. Our results show a possible interplay between the cytosolic and mitochondrial antioxidant systems in a trypanosomatid. |
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| 9. | J Bioenerg Biomembr. 2011 Aug;43(4):409-17. Epub 2011 Jul 6.O2 consumption rates along the growth curve: new insights into Trypanosoma cruzi mitochond rial respiratory chain.Silva TM, Peloso EF, Vitor SC, Ribeiro LH, Gadelha FR.SourceDepartamento de Bioquímica, Universidade Estadual de Campinas, Instituto de Biologia, Campinas, São Paulo, Brazil. AbstractUnderstanding the energy-transduction pathways employed by Trypanosoma cruzi, the etiological agent of Chagas disease, may lead to the identification of new targets for development of a more effective therapy. Herein, the contribution of different substrates for O(2) consumption rates along T. cruzi epimastigotes (Tulahuen 2 and Y strains) growth curve was evaluated. O(2) consumption rates were higher at the late stationary phase not due to an increase on succinate-dehydrogenase activity. Antimycin A and cyanide did not totally inhibit the mitochondrial respiratory chain (MRC). Malonate at 10 or 25 mM was not a potent inhibitor of complex II. Comparing complex II and III, the former appears to be the primary site of H(2)O(2) release. An update on T. cruzi MRC is presented that together with our results bring important data towards the understanding of the parasite's MRC. The findings mainly at the stationary phase could be relevant for epimastigotes transformation into the metacyclic form, and in this sense deserves further attention. |
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