What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2011 Mar 01
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

Items 1 - 7 of 7

1.	Mol Biochem Parasitol. 2011 Feb 24. [Epub ahead of print] The Trypanosoma brucei zinc finger protein ZC3H18 is involved in differentiation. Benz C, Mulindwa J, Ouna B, Clayton C. Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, 120 University Place, Glasgow G12 8TA. Abstract In mammalian cells, the degradation of mRNAs that have AU-rich elements in their 3'-untranslated regions is accelerated by the binding of proteins that contain two CCCH-zinc-finger-domains. Three CCCH zinc-finger proteins, TbZFP1, TbZFP2, and TbZFP3, have been shown to have roles in trypanosome differentiation. We here studied another protein, ZC3H18, which has two CCCH zinc finger domains. The ZC3H18 gene is not essential in bloodstream forms, but in an in vitro model of differentiation, depletion of ZC3H18 delayed the transformation of bloodstream-form trypanosomes to the procyclic form that grows in the Tsetse fly. Copyright © 2011. Published by Elsevier B.V.
	PMID: 21354218 [PubMed - as supplied by publisher]

2.	Exp Parasitol. 2011 Feb 24. [Epub ahead of print] Trypanosoma brucei gambiense: HMI-9 Medium Containing Methylcellulose and Human Serum Supports the Continuous Axenic in Vitro Propagation of the Bloodstream Form. Van Reet N, Pyana PP, Deborggraeve S, Büscher P, Claes F. Institute of Tropical Medicine, Department of Parasitology, Nationalestraat 155, 2000 Antwerp, Belgium; University of Antwerp, Laboratory of Pathology, Universiteitsplein 1, 2610 Wilrijk, Belgium. Abstract Trypanosoma brucei (T.b.) gambiense causes the chronic form of human African trypanosomiasis or sleeping sickness. One of the major problems with studying T.b. gambiense is the difficulty to isolate it from its original host and the difficult adaptation to in vivo and in vitro mass propagation. The objective of this study was to evaluate if an established method for axenic culture of pleomorphic bloodstream form T.b. brucei strains, based on methylcellulose containing HMI-9 medium, also facilitated the continuous in vitro propagation of other bloodstream form Trypanozoon strains, in particular of T.b. gambiense. Bloodstream form trypanosomes from one T.b. brucei, two T.b. rhodesiense, one T. evansi and seven T.b. gambiense strains were isolated from mouse blood and each was concurrently cultivated in liquid and methylcellulose-containing HMI-9 based medium, either with or without additional human serum supplementation, for over 10 consecutive sub passages. Although HMI-9 based medium supplemented with 1.1% (w/v) methylcellulose supported the continuous cultivation of all non gambiense strains better than liquid media could, the in vitro cultivation of all gambiense strains was only achieved in HMI-9 based medium containing 1.1% (w/v) methylcellulose, 15% (v/v) foetal calf serum and 5% (v/v) heat-inactivated human serum. Copyright © 2011. Published by Elsevier Inc.
	PMID: 21354143 [PubMed - as supplied by publisher]

3.	Exp Parasitol. 2011 Feb 24. [Epub ahead of print] Generating Knock-in Parasites: Integration of an Ornithine Decarboxylase Transgene into its Chromosomal Locus in Leishmaniadonovani. Roberts SC, Kline C, Liu W, Ullman B. Pacific University School of Pharmacy, 222 Se 8[th] Ave., Hillsboro, OR, 97123-4216 USA. Abstract Leishmania null mutants created by targeted gene replacement are typically complemented with chimeric episomes harboring the replaced gene in order to validate that the observed phenotype is due to the specific gene deletion. However, the current inventory of available episomes for complementation of genetic lesions in Leishmania is unstable in the absence of drug selection, and levels of gene expression cannot be controlled, especially in vivo. To circumvent this impediment, a strategy to re-introduce the targeted gene into the original chromosomal locus to generate "knock-in" parasites within selectable null backgrounds has been developed. A genomic fragment encompassing the ornithine decarboxylase locus and lacking heterologous DNA sequences was transfected into ornithine decarboxylase-deficient L. donovani. The construct randomly integrated into either chromosomal allele by homologous recombination restoring polyamine prototrophy and revealing that LdODC was functionally expressed in the knock-in clones. This strategy offers a mechanism for complementing a genetic lesion amenable to positive selection in a manner that facilitates stable gene expression from its original locus in the absence of continuous drug pressure. Copyright © 2011. Published by Elsevier Inc.
	PMID: 21354142 [PubMed - as supplied by publisher]

4.	Exp Parasitol. 2011 Feb 24. [Epub ahead of print] In vitro and experimental therapeutic studies of the calcium channel blocker bepridil: detection of viable Leishmania (L.) chagasi by real-time PCR. Reimão JQ, Colombo FA, Pereira-Chioccola VL, Tempone AG. Laboratory of Applied Toxinology on Anti-parasitic Drugs, Department of Parasitology, Instituto Adolfo Lutz Avenida Dr. Arnaldo, 351, 8° andar. Cerqueira César, CEP 01246-902 - São Paulo/SP, Brazil. Abstract The need for novel and efficacious drugs against neglected parasitic diseases, such as Leishmaniasis and American Trypanosomiasis, is certainly apparent. In this work, we evaluated the in vitro potential of the calcium channel blocker bepridil against Leishmania spp. and Trypanosoma cruzi parasites and exploited an experimental assay using a hamster model with Leishmania (L.) chagasi, with a real-time PCR method for therapeutic evaluation. Bepridil was in vitro effective against promastigotes and intracellular amastigotes of L.(L.)chagasi, with 50% inhibitory concentration (IC(50)) values of 3.81 and 21.55 μM, respectively. Leishmania(L.)amazonensis, L. (L.)major and L. (V.)braziliensis promastigotes and Trypanosomacruzi trypomastigotes were also susceptible to bepridil, with in vitro selectivity toward parasites and IC(50) values in the range of 3 to 7 μM. The mammalian cytotoxicity using LLC-MK2 cells resulted in an IC(50) value of 62.67 μM. However, bepridil showed lack of activity at 12 mg/kg in the experimental hamster model infected with L. (L.) chagasi parasites. However, the real-time PCR was a promising tool for the accurate and fast quantification of RNA of living parasites in the liver and spleen of infected hamsters after treatment, eliminating time-consuming light microscopy evaluations. Copyright © 2011. Published by Elsevier Inc.
	PMID: 21354141 [PubMed - as supplied by publisher]

5.	Exp Parasitol. 2011 Feb 24. [Epub ahead of print] Leishmania infantum and Toxoplasma gondii: Mixed infection of macrophages in vitro and in vivo. Christodoulou V, Messaritakis I, Svirinaki E, Tsatsanis C, Antoniou M. Laboratory of Clinical Bacteriology, Parasitology, Zoonoses, and Geographical Medicine, Faculty of Medicine, University of Crete, Crete, Greece. Abstract Although macrophages have a microbicidal role in the immune system they themselves can be infected by pathogens. Often a simultaneous infection by more than one microbe may occur in a single cell. This is the first report of coinfection of macrophages with Toxoplasma gondii and Leishmania infantum, in vitro and in vivo. L. infantum does not cause severe disease in mice but T. gondii, RH strain, is lethal. Cell culture studies using THP-1 macrophages dually infected in vitro revealed that 4.3% harbored both parasites 24hrs after infection. When mice were infected with both parasites on the same day 7.3% of the infected cells carried both parasites 7 days later. Yet, if mice were first infected with L. infantum and then with Toxoplasma (5 days post infection) 18.7% of the macrophages hosted either parasite but concomitant infection could not be found and mice, already harboring L. infantum, survived Toxoplasma's lethal effect. Copyright © 2011. Published by Elsevier Inc.
	PMID: 21354140 [PubMed - as supplied by publisher]

6.	Eur J Med Chem. 2011 Feb 24. [Epub ahead of print] 1-Aryl-4-nitro-1H-imidazoles, a new promising series for the treatment of human African trypanosomiasis. Trunz BB, Jędrysiak R, Tweats D, Brun R, Kaiser M, Suwiński J, Torreele E. Drugs for Neglected Diseases initiative, 15 Chemin Louis-Dunant, 1202 Geneva, Switzerland. Abstract Nitroimidazoles are a well-known class of antibacterial and antiprotozoal drugs but in spite of the widespread clinical and veterinary use of these drugs, this family has been stigmatized in part due to associated genotoxicity problems. Here we report the synthesis, the anti-trypanosomal activity and a structure-activity relationship (SAR) study of a series of about fifty 1-aryl-4-nitro-1H-imidazoles, with an emphasis on selected in vivo active molecules. Compounds 4-nitro-1-{4-(trifluoromethoxy)phenyl}-1H-imidazole and 1-(3,4-dichlorophenyl)-4-nitro-1H-imidazole are curative in mouse models of both acute and chronic African trypanosomiasis when given orally at doses of 25-50 mg/kg for 4 days for the acute infection, and 50-100 mg/kg (bid) for 5 days in the chronic model. While both compounds are bacterial mutagens, activity is lost in strains lacking bacterial specific nitro-reductases. Mammalian nitro-reductases do not reduce nitroaromatic compounds with low redox potentials with same avidity as their bacterial counterparts and these compounds were shown to be devoid of genotoxicity in mammalian cells. Both compounds are promising leads for the treatment of human African trypanosomiasis (HAT or sleeping sickness), including the fatal stage 2 of the disease, for which new treatments are urgently needed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
	PMID: 21353728 [PubMed - as supplied by publisher]

7.	Trans R Soc Trop Med Hyg. 2011 Feb 23. [Epub ahead of print] Urine antigen detection by latex agglutination test for diagnosis and assessment of initial cure of visceral leishmaniasis. Salam MA, Khan MG, Mondal D. Department of Microbiology, Rajshahi Medical College, Rajshahi, Bangladesh. Abstract This prospective study evaluated the usefulness of the kala-azar latex agglutination test (KAtex) for the diagnosis and laboratory assessment of initial cure of visceral leishmaniasis (VL) (or kala-azar) patients following 30 days of sodium antimony gluconate treatment at Rajshahi Medical College Hospital (Bangladesh). KAtex detects a low molecular weight, heat-stable, carbohydrate antigen in the urine of VL patients. KAtex was performed using freshly voided urine samples obtained from 36 parasitologically confirmed cases of VL before and after treatment as well as from 40 healthy controls (20 each from kala-azar-endemic and non-endemic zones). KAtex was found to be positive in 27 (75%) of the 36 patients at diagnosis and was negative in all the controls. The diagnostic sensitivity and specificity of KAtex were 75% (95% CI 57-87%) and 100% (95% CI 89-100%), respectively. Following treatment, all 36 VL cases were negative for Leishman-Donovan bodies by splenic smear microscopy and 34 (94.4%) were negative by KAtex. This limited study suggests that KAtex is a satisfactorily sensitive, highly specific, rapid and completely non-invasive urine-based antigen detection test for the diagnosis of VL. Currently, this is the only non-invasive laboratory tool useful for the assessment of initial cure in VL patients. Copyright © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
	PMID: 21353275 [PubMed - as supplied by publisher]