Tuesday, September 29, 2009

What's new for 'Trypanosomatids' in PubMed

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
Do not reply directly to this message.

Sender's message:

Sent on Tuesday, 2009 Sep 29
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
Click here to view complete results in PubMed. (Results may change over time.)
To unsubscribe from these e-mail updates click here.



PubMed Results
Items 1 -10 of 12

1: Med Mal Infect. 2009 Sep 22. [Epub ahead of print]

[Liposomal amphotericin B as treatment for visceral leishmaniasis in Europe, 2009.]

[Article in French]

Rosenthal E, Delaunay P, Jeandel PY, Haas H, Pomares-Estran C, Marty P.

Service de médecine interne, centre hospitalier universitaire de Nice et université de Nice Sophia-Antipolis, France.

Visceral leishmaniasis (VL) causes an estimated 500,000 new cases of disease and more than 50,000 deaths a year. For more than 60 years, pentavalent antimonies were considered the standard therapy for VL. The emergence of Leishmania strains resistant to antimonials led to the evaluation of other treatments including amphotericin B and its lipidic derivatives. Clinical trials with liposomal amphotericin B demonstrated that total doses of 10 to 20mg/kg, administered according to various regimens, had a 90-98% efficacy in non-immunocompromised patients. Compared to antimonials, liposomal amphotericin B provides favorable efficacy/tolerance and cost efficacy ratios. The WHO recently produced consensus recommendations for the use of liposomal amphotericin B in VL. In Europe, liposomal amphotericin B has progressively become the reference treatment of VL in clinical practice, and it is recommended as the first line therapy.

PMID: 19783391 [PubMed - as supplied by publisher]

Related articles

2: Int J Antimicrob Agents. 2009 Sep 25. [Epub ahead of print]

Apoptosis-like death in Leishmania donovani promastigotes induced by diospyrin and its ethanolamine derivative.

Mukherjee P, Majee SB, Ghosh S, Hazra B.

Department of Microbiology, Bose Institute, Calcutta 700054, India.

Previous studies have demonstrated that diospyrin (1), a quinonoid plant product, can inhibit the growth of Leishmania donovani parasites. Here, several derivatives of 1 were evaluated by the MTT assay and it was observed that the ethanolamine analogue (10) exhibited maximum cytotoxicity [50% inhibitory concentration (IC(50))=2.9muM] against L. donovani promastigotes. Subsequently, the mode of cell death in promastigotes was investigated through externalisation of membrane-associated phosphatidylserine, mitochondrial membrane depolarisation, DNA laddering and in situ labelling of DNA fragmentation by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) methods. Whilst both 1 and 10 were found to induce apoptosis-like death in promastigotes, the effect of 10 was evidently stronger even at a lower concentration. Hence, the ethanolamine derivative (10) of diospyrin (1) may be a prospective 'lead' for the development of novel cytotoxic agents inducing apoptosis in L. donovani parasites.

PMID: 19783125 [PubMed - as supplied by publisher]

Related articles

3: Acta Trop. 2009 Sep 24. [Epub ahead of print]

Characterization of Leishmania (Leishmania) tropica axenic amastigotes.

Nasereddin A, Schweynoch C, Schonian G, Jaffe CL.

Kuvin Centre for the Study of Tropical and Infectious Diseases, IMRIC, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel; Institute of Microbiology and Hygiene, Charite University Medicine, Berlin, Dorotheenstr. 96, 10117 Berlin, Germany.

Optimum conditions for generating Leishmania (Leishmania) tropica axenic amastigotes (AxA) in culture were determined, pH 5.5/36(o)C, and the parasites characterized by different techniques, including light microscopy, macrophage infection, stage-specific antigen expression and differential display. AxA were morphologically similar to amastigotes and 15.5-fold more infective than stationary phase promastigotes for mouse peritoneal macrophages. Western blotting with promastigote stage specific monoclonal antibodies to either lipophosphoglycan (T2) or a 60 kDa flagella antigen (F3) showed a dramatic decrease in antigen expression when AxA were compared to promastigotes. Similarly F3 gave strong immune fluorescent staining of the promastigote flagellum, but no fluorescence was detected when AxA were examined. Conversely, western blotting with the amastigote specific monoclonal antibody (T16) showed that this antigen is more highly expressed in AxA than promastigotes. Differential display - PCR was used to identify several parasite genes showing stage specific expression. One gene selectively expressed by AxA was partially sequenced and identified as Leishmania (L.) tropicaamastin. Amastigote specific expression of this gene was further confirmed by reverse transcriptase - PCR (RT-PCR) using AxA and infected macrophages. No amastin expression was observed with promastigotes. Expression of the cysteine protease B (cpb) and protein kinase A catalytic isoform 1 subunit (pkac1) in promastigotes and AxA was also examined by RT-PCR. Pkac1 was strongly expressed by promastigotes, while cpb expression was only seen with AxA or infected macrophages. L. (L.) tropica AxA will prove useful for further studies on parasite differentiation and gene regulation, as well as for drug screening.

PMID: 19782652 [PubMed - as supplied by publisher]

Related articles

4: Diagn Microbiol Infect Dis. 2009 Sep 24. [Epub ahead of print]

Leishmania spp. identification by polymerase chain reaction-restriction fragment length polymorphism analysis and its applications in French Guiana.

Simon S, Veron V, Carme B.

Equipe EA 3593, Faculté de Médecine, Université des Antilles et de la Guyane, Cayenne, French Guiana.

Leishmania (Viannia) guyanensis was for many years the only species commonly identified in French Guiana, but precise species identifications were quite rare. We describe a new restriction fragment length polymorphism-polymerase chain reaction technique using a 615-bp fragment of the RNA polymerase II gene and 2 restriction enzymes, TspRI and HgaI. Seven reference strains (Leishmania (Leishmania) amazonensis, Leishmania (Viannia) lainsoni, Leishmania (Viannia) braziliensis, L. (V.) guyanensis, Leishmania (Viannia) naiffi, Leishmania (Leishmania) major, Leishmania (Leishmania) infantum) and 112 clinical samples from positive lesions were used for the development of the technique. The rates of positive species identification were 85.7% for punch skin biopsy specimens, 93.1% for positive Giemsa-stained smears, and 100% for positive culture supernatants. In the framework of cutaneous leishmaniasis species surveillance for the 2006 to 2008 period, parasite identification was carried out for 199 samples from different patients. The prevalence of the various Leishmania spp. was 84.4% for L. (V.) guyanensis, 8.0% for L. (V.) braziliensis, 5.0% for L. (L.) amazonensis, and 2.6% for L. (V.) lainsoni. L. (V.) braziliensis seems to be locally an emerging pathogen.

PMID: 19782495 [PubMed - as supplied by publisher]

Related articles

5: Semin Arthritis Rheum. 2009 Sep 24. [Epub ahead of print]

Leishmaniasis and Biologic Therapies for Rheumatologic Diseases.

Cascio A, Iaria M, Iaria C.

Tropical and Parasitological Diseases Unit, Department of Human Pathology, University of Messina, Messina, Italy.

PMID: 19782386 [PubMed - as supplied by publisher]

Related articles

6: Biochim Biophys Acta. 2009 Sep 23. [Epub ahead of print]

A new topology of ACBP from Moniliophthora perniciosa.

Monzani PS, Pereira HM, Melo FA, Meirelles FV, Oliva G, Cascardo JC.

Departamento de Ciências Biológicas, Laboratório de Proteômica, Centro de Biotecnologia e Genética, Universidade Estadual de Santa Cruz, Ilhéus - BA, CEP 45662-900. Brazil.

Acyl-CoA binding protein (ACBP) is a housekeeping protein and is an essential protein in human cell lines and in Trypanosoma brucei. The ACBP of Moniliophthora perniciosa is composed of 104 amino acids and is possibly a non-classic isoform exclusively from Basidiomycetes. The M. perniciosa acbp gene was cloned, and the protein was expressed and purified. Acyl-CoA ester binding was analyzed by isoelectric focusing, native gel electrophoresis and isothermal titration calorimetry. Our results suggest an increasing affinity of ACBP for longer acyl-CoA esters, such as myristoyl-CoA to arachidoyl-CoA, and best fit modeling indicates two binding sites. ACBP undergoes a shift from a monomeric to a dimeric state, as shown by dynamic light scattering, fluorescence anisotropy and native gel electrophoresis in the absence and presence of the ligand. The protein's structure was determined at 1.6 A resolution and revealed a new topology for ACBP, containing five alpha-helices instead four. alpha-helices 1, 2, 3 and 4 adopted a bundled arrangement that is unique from the previously determined four-helix folds of ACBP, while alpha-helices 1, 2, 4 and 5 formed a classical four-helix bundle. A MES molecule was found in the CoA binding site, suggesting that the CoA site could be a target for small compound screening.

PMID: 19782157 [PubMed - as supplied by publisher]

Related articles

7: Mol Biochem Parasitol. 2009 Sep 23. [Epub ahead of print]

Myristoyl-CoA:protein N-myristoyltransferase depletion in trypanosomes causes avirulence and endocytic defects.

Price HP, Güther ML, Ferguson MA, Smith DF.

Centre for Immunology and Infection, Department of Biology/Hull York Medical School, University of York, York YO10 5YW, UK.

The enzyme myristoyl-CoA:protein N-myristoyltransferase (NMT) catalyses the co-translational covalent attachment of the fatty acid myristate to the N-terminus of target proteins. NMT is known to be essential for viability in Trypanosoma brucei and Leishmania major. Here we describe phenotypic analysis of T. brucei bloodstream form cells following knockdown of NMT expression by tetracycline-inducible RNA interference. Cell death occurs from 72h post-induction, with approximately 50% of cells displaying a defect in endocytic uptake by this time. The majority of these induced cells do not have an enlarged flagellar pocket typical of a block in endocytosis but vesicle accumulation around the flagellar pocket indicates a defect in vesicular progression following endocytic fusion. Induced parasites have a wild-type or slightly enlarged Golgi apparatus, unlike the phenotype of cells with reduced expression of a major N-myristoylated protein, ARL1. Critically we show that following NMT knockdown, T.brucei bloodstream form cells are unable to establish an infection in a mouse model, therefore providing further validation of this enzyme as a target for drug development.

PMID: 19782106 [PubMed - as supplied by publisher]

Related articles

Patient Drug Information

8: J Mol Biol. 2009 Sep 22. [Epub ahead of print]

Crystal structures of Leishmania mexicana phosphoglycerate mutase suggest a one-metal mechanism and a new enzyme subclass.

Nowicki MW, Kuaprasert B, McNae IW, Morgan HP, Harding MM, Michels PA, Fothergill-Gilmore LA, Walkinshaw MD.

Structural Biochemistry Group, Institute of Structural and Molecular Biology, University of Edinburgh, King's Buildings, Mayfield Road, Edinburgh EH9 3JR, Scotland.

The structures of Leishmania mexicana cofactor-independent phosphoglycerate mutase (Lm iPGAM) crystallised with the substrate 3-phosphoglycerate at high and low cobalt concentrations have been solved at 2.00 and 1.90 A resolution. Both structures are very similar and the active site contains both 3- and 2-phosphoglycerate at equal occupancies (50%). Lm iPGAM co-crystallised with the product 2-phosphoglycerate yields the same structure. Two Co(2+) ions are coordinated within the active site with different geometries and affinities. The cobalt at the M1 site has a distorted octahedral geometry and is present at 100% occupancy. The M2 site Co(2+) ion binds with distorted tetrahedral geometry, with only partial occupancy, and coordinates with Ser75, the residue involved in phospho transfer. When the M2 site is occupied, the side chain of Ser75 adopts a position which is unfavourable for catalysis, indicating that this site may not be occupied under physiological conditions and that catalysis may occur via a one metal mechanism. The geometry of the M2 site suggests that it is possible for Ser75 to be activated for phospho transfer by H-bonding to nearby residues rather than by metal coordination. The 16 active-site residues of Lm iPGAM are conserved in the Mn-dependent iPGAM from Bacillus stearothermophilus (33% overall sequence identity). However, Lm iPGAM has an inserted tyrosine (Tyr210) that causes the M2 site to diminish in size, consistent with its reduced metal affinity. Tyr210 is present in trypanosomatid and plant iPGAMs, but not in the enzymes from other organisms, indicating that there are two subclasses of iPGAMs.

PMID: 19781556 [PubMed - as supplied by publisher]

Related articles

9: Malawi Med J. 2009 Mar;21(1):22-7.

The epidemiology of trypanosomiasis in Rumphi district, Malawi: a ten year retrospective study.

Madanitsa M, Chisi J, Ngwira B.

College of Medicine, Malawi. mmadanitsa2004@yahoo.com

BACKGROUND: Human African Trypanosomiasis (HAT) is caused by two species of the tsetse fly vectored protozoan hemoflagellates belonging to Trypanosma brucei, namely T.b gambiense which predominates in Western Africa and follows a chronic disease course and T.b rhodensiense which is more prevalent in Southern and Eastern Africa, Malawi included, and follows a more acute and aggressive disease course. Previous studies in the Democratic Republic of Congo, Angola, Uganda and Sudan have demonstrated that the prevalence rates of T.b rhodensiense infection have reached epidemic proportions. OBJECTIVES: To describe the epidemiology of Trypanosomiasis in Rumphi District over the past ten years. METHODOLOGY: A total of 163 records from January 2000 to December 2006 were retrospectively studied. RESULTS: There were more males than females (121 vs. 40) with the 20 - 29 years age bracket having the highest number of cases (26.3%, n = 160). Stage 2 HAT was the commonest stage at presentation (58.2%, n = 158) with the patients in the same being 3.5 times more likely to die than those with stage 1 HAT. Case fatality rates for late and early stage disease were 21.5% (n = 92) and 7.2% (n = 66) respectively with 84.6% having been cured (n = 162). Convulsions were associated with fatal disease outcome and the majority of cases (97.2%, n = 103) lived within 5 kilometres of the Vwaza game reserve boundary. CONCLUSION: More men have been infected than women, with a high involvement in the 20 - 29 age brackets. A dramatic increase with active case finding indicates a high under-detection of the disease with late stage HAT being predominant at presentation. Though it has been found that cases with late stage disease have an increased likelihood of dying compared to those in early stage HAT, the high proportion of successful treatment indicates that the disease still carries a high degree of favourable outcome with treatment. It has also been demonstrated in this study that more than 95% of trypanosomiasis cases live within 5 km of game reserve boundary. Disease interventions should be implemented in areas within 5 km of marshland game reserve boundary as priority areas.

PMID: 19780474 [PubMed - in process]

Related articles

10: Mil Med. 2009 Sep;174(9):904-20.

Use of vector diagnostics during military deployments: recent experience in Iraq and Afghanistan.

Coleman RE, Hochberg LP, Putnam JL, Swanson KI, Lee JS, McAvin JC, Chan AS, Oguinn ML, Ryan JR, Wirtz RA, Moulton JK, Dave K, Faulde MK.

Department of Entomology, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Vector-borne diseases such as malaria, dengue, and leishmaniasis are a threat to military forces deployed outside of the United States. The availability of specific information on the vector-borne disease threat (e.g., presence or absence of a specific disease agent, temporal and geographic distribution of competent vectors, and vector infection rates) allows for effective implementation of appropriate measures to protect our deployed military forces. Vector diagnostics can provide critical, real-time information crucial to establishing effective vector prevention/control programs. In this article we provide an overview of current vector diagnostic capabilities, evaluate the use of vector diagnostics in Operation Enduring Freedom and Operation Iraqi Freedom, and discuss the concept of operations under which vector diagnostics are employed.

PMID: 19780365 [PubMed - in process]

Related articles

Posted by at

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)