Thursday, March 3, 2011

What's new for 'Trypanosomatids' in PubMed

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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 - 8 of 8

1. Appl Biochem Biotechnol. 2011 Mar 2. [Epub ahead of print]

In Vitro Refolding of Triosephosphate Isomerase from L. donovani.

Kumar K, Bhargava P, Roy U.

Division of Biochemistry, Central Drug Research Institute, Lucknow, 226001, UP, India.

Abstract

The triosephosphate isomerase of Leishmania donovani (LdTIM) was expressed at high level in Escherichia coli. The TIM gene was cloned in expression vector pET-23(a) with C-terminal 6× His tag fused in frame, and expressed as a 27.6-kDa protein in E. coli as inclusion bodies. The recombinant LdTIM from E. coli lysate was solubilized in 6 M guanidine hydrochloride and purified by Ni-NTA chromatography. In the present study, the effect of bovine serum albumin on the reactivation of TIM was investigated. Furthermore, 8-anilino-1-naphthalene sulfonic acid was used to detect the structural changes induced by bovine serum albumin (BSA). Here, we conclude that BSA assists in the refolding and regain of LdTIM enzyme activity by providing framework for structure formation. This study indicates that numerous protein-protein contacts are constantly occurring inside the cell that leads to the formation of native protein.

PMID: 21365180 [PubMed - as supplied by publisher]
2. PLoS Negl Trop Dis. 2011 Feb 22;5(2):e1007.

The human african trypanosomiasis control and surveillance programme of the world health organization 2000-2009: the way forward.

Simar ro PP, Diarra A, Ruiz Postigo JA, Franco JR, Jannin JG.

World Health Organization, Control of Neglected Tropical Diseases, Innovative and Intensified Disease Management, Geneva, Switzerland.

PMID: 21364972 [PubMed - in process]
3. PLoS Negl Trop Dis. 2011 Feb 22;5(2):e972.

Diagnostic Accuracy of PCR in gambiense Sleeping Sickness Diagnosis, Staging and Post-Treatment Follow-Up: A 2-year Longitudinal Study.

Deborggraeve S, Lejon V, Ekangu RA, Mumba Ngoyi D, Pati Pyana P, Ilunga M, Mulunda JP, Büscher P.

Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium.

Abstract

BACKGROUND: The polymerase chain reaction (PCR) has been proposed for diagnosis, staging and post-treatment follow-up of sleeping sickness but no large-scale clinical evaluations of its diagnostic accuracy have taken place yet.

METHODOLOGY/PRINCIPAL FINDINGS: An 18S ribosomal RNA gene targeting PCR was performed on blood and cerebrospinal fluid (CSF) of 360 T. brucei gambiense sleeping sickness patients and on blood of 129 endemic controls from the Democratic Republic of Congo. Sensitivity and specificity (with 95% confidence intervals) of PCR for diagnosis, disease staging and treatment failure over 2 years follow-up post-treatment were determined. Reference standard tests were trypanosome detection for diagnosis and trypanosome detection and/or increased white blood cell concentration in CSF for staging and detection of treatment failure. PCR on blood showed a sensitivity of 88.4% (84.4-92.5%) and a specificity of 99.2% (97.7-100%) for diagnosis, while for disease staging the sensitivity and specificity of PCR on cerebrospinal fluid were 88.4% (84.8-91.9%) and 82.9% (71.2-94.6%), respectively. During follow-up after treatment, PCR on blood had low sensitivity to detect treatment failure. In cerebrospinal fluid, PCR positivity vanished slowly and was observed until the end of the 2 year follow-up in around 20% of successfully treated patients.

CONCLUSIONS/SIGNIFICANCE: For T.b. gambiense sleeping sickness diagnosis and staging, PCR performed better than, or similar to, the current parasite detection techniques but it cannot be used for post-treatment follow-up. Continued PCR positivity in one out of five cured patients points to persistence of living or dead parasites or their DNA after successful treatment and may necessitate the revision of some paradigms about the pathophysiology of sleeping sickness.

PMID: 21364966 [PubMed - in process]
4. Cell Death Dis. 2010 Sep 2;1(9):e71.

Cathepsin B-like and cell death in the unicellular human pathogen Leishmania.

El-Fa dili AK, Zangger H, Desponds C, Gonzalez IJ, Zalila H, Schaff C, Ives A, Masina S, Mottram JC, Fasel N.

Department of Biochemistry, Faculty of Biology and Medicine, University of Lausanne, 155 Chemin des Boveresses, 1066 Epalinges, Switzerland.

Abstract

In several studies reporting cell death (CD) in lower eukaryotes and in the human protozoan parasite Leishmania, proteolytic activity was revealed using pan-caspase substrates or inhibitors such as carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). However, most of the lower eukaryotes do not encode caspase(s) but MCA, which differs from caspase(s) in its substrate specificity and cannot be accountable for the recognition of Z-VAD-FMK. In the present study, we were interested in identifying which enzyme was capturing the Z-VAD substrate. We show that heat shock (HS) induces Leishmania CD and leads to the intracellular binding of Z-VAD-FMK. We excluded binding and inhibition of Z-VAD-FMK to Leishmania major metacaspase (LmjMCA), and identified cysteine proteinase C (LmjCPC), a cathepsin B-like (CPC) enzyme, as the Z-VAD-FMK binding enzyme. We confirmed the specific interaction of Z-VAD-FMK with CPC by showing that Z-VAD binding is absent in a Leishmania mexicana strain in which the cpc gene was deleted. We also show that parasites exposed to various stress conditions release CPC into a soluble fraction. Finally, we confirmed the role of CPC in Leishmania CD by showing that, when exposed to the oxidizing agent hydrogen peroxide (H(2)O(2)), cpc knockout parasites survived better than wild-type parasites (WT). In conclusion, this study identified CPC as the substrate of Z-VAD-FMK in Leishmania and as a potential additional executioner protease in the CD cascade of Leishmania and possibly in other lower eukaryotes.

PMID: 21364675 [PubMed - in process]
5. Am J Trop Med Hyg. 2011 Mar;84(3):508.

Visceral Leishmaniasis in Far Western Nepal: Another Case and Concerns about a New Area of Endemicity.

Schwarz D, Andrews J, Gauchan B.

Nyaya Health.

PMID: 21363996 [PubMed - in process]
6. Am J Trop Med Hyg. 2011 Mar;84(3):406-10.

Comparison of major immunoglobulins intrathecal synthesis patterns in ecuadorian and cuban patients with angiostrongyliasis.

Padilla-Docal B, Dorta-Contreras AJ, Moreira JM, Martini-Robles L, Muzzio-Aroca J, Alarcón F, Magraner-Tarrau ME, Bu-Coifiu-Fanego R.

Laboratorio Central de Líquido Cefalorraquídeo (LABCEL), Facultad de Ciencias Médicas Dr. Miguel Enríquez, Universidad de Ciencias Médicas de La Habana, Cuba; Dirección de Control y Mejoramiento de la Salud Pública, Ministerio de Salud Pública, Quito, Ecuador; Departamento de Parasitología, Instituto Nacional de Higiene Dr. Leopoldo Izquieta Perez, Guayaquil, Ecuador; Servicio de Neurología, Hospital Eugenio Espejo, Quito, Ecuador.

Abstract

Abstract. Angiostrongylus cantonensis meningitis was first reported in Cuba in 1981, and it was recently reported in South America. The aim of this paper is to evaluate the intrathecal immunoglobulin synthesis patterns from Cuba's and Ecuador's patients with angiostrongyliasis; 8 Ecuadorian patients from two different outbreaks and 28 Cuban patients were studied. Simultaneous blood and cerebrospinal fluid simples were taken. Immunoglobulin (Ig) A, IgM, IgG, and albumin were quantified by radial immunodiffusion. Corresponding Reibergrams were applied. A three-Ig pattern was the most frequent in the two groups, but IgM was presented in all Ecuadorian young mature patients; however, in the Cuban children, only 12 of 28 patients had intrathecal IgM, but about 90% had an IgA and IgG synthesis at time of later puncture. This indicates that, with a larger amount of parasites ingested, clinical symptoms are more severe, and a higher frequency of intrathecal IgM synthesis could be observed. This is discussed as a similarity with the intrathecal IgM synthesis in African trypanosomiasis.

PMID: 21363978 [PubMed - in process]
7. Genome Res. 2011 Mar 1. [Epub ahead of print]

High throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome.

Alsford S, Turner D, Obado S, Sanchez-Flores A, Glover L, Berriman M, Hertz-Fowler C, Horn D.

LSHTM;

Abstract

African trypanosomes are major pathogens of humans and livestock and represent a model for studies of unusual protozoal biology. We describe a high throughput phenotyping approach termed RNA interference (RNAi) target sequencing, or RIT-seq that, using Illumina sequencing, maps fitness-costs associated with RNAi. We scored the abundance of >90,000 integrated RNAi targets recovered from trypanosome libraries before and after induction of RNAi. Data are presented for 7,435 protein coding sequences, >99% of a non-redundant set in the Trypanosoma brucei genome. Analysis of bloodstream and insect life -cycle stages and differentiated libraries revealed genome-scale knockdown profiles of growth and development, linking thousands of previously uncharacterised and "hypothetical" genes to essential functions. Genes underlying prominent features of trypanosome biology are highlighted, including the constitutive emphasis on post-transcriptional gene expression control, the importance of flagellar motility and glycolysis in the bloodstream, and of carboxylic acid metabolism and phosphorylation during differentiation from the bloodstream to the insect-stage. The current data-set also provides much needed genetic validation to identify new drug-targets. RIT-seq represents a versatile new tool for genome-scale functional analyses and for the exploitation of genome sequence data.

PMID: 21363968 [PubMed - as supplied by publisher]
8. Biomed Pharmacother. 2010 Nov;64(9):624-6. Epub 2010 Jul 21.

Trypanocidal activity of lipophilic diamines and amino alcohols.

Júnior CO, Alves RO, Rezende CA, da Costa CF, Silva H, Le Hyaric M, Fontes AP, Alves RJ, Romanha AJ, de Almeida MV.

Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, Cidade Universitária, 36036-900 Juiz de Fora, MG, Brazil.

Abstract

Trypanocidal activity of a number of lipophilic diamines and amino alcohols was evaluated in vitro against Trypanosoma cruzi blood stream forms. Several of the studied compounds showed inhibition of T. cruzi growth. The most active ones were compounds 3, 4 and 5 with a IC₅₀ of 31.2 μg/mL, activity similar to the reference drug crystal violet.

Copyright © 2010 Elsevier Masson SAS. All rights reserved.
PMID: 20888176 [PubMed - indexed for MEDLINE]
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