Tuesday, June 2, 2009

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: Mol Divers. 2009 May 30. [Epub ahead of print]Click here to read

Parallel synthesis of a series of non-functional ATP/NAD analogs with activity against trypanosomatid parasites.

Link A, Heidler P, Kaiser M, Brun R.

Institute of Pharmacy, Ernst-Moritz-Arndt-University, Friedrich-Ludwig-Jahn-Strasse 17, 17487, Greifswald, Germany, link@uni-greifswald.de.

Non-functional analogs of the cofactors ATP and NAD are putative inhibitors of ATP- or NAD-dependant enzymes. Since pathogenic protozoa rely heavily on the salvage of purine nucleosides from the bloodstream of their host, such compounds are of interest as antiplasmodial and antitrypanosomal agents with a multitude of molecular targets. By replacing the negatively charged phosphate residues with a constrained unsaturated amide spacer and the nicotinamide moiety of NAD with various lipophilic substituents, 15 new ATP/NAD analogs were obtained in screening quantities. In these compounds, a 5'-desoxyadenosine moiety was conserved as key molecular recognition motif. The inhibition of P. falciparum and T. brucei ssp. in a whole parasite in vitro assay is reported.

PMID: 19484371 [PubMed - as supplied by publisher]

2: Internist (Berl). 2009 May 31. [Epub ahead of print]Click here to read

[Travel medicine.]

[Article in German]

Schubert S, Grimm M.

Klinik und Poliklinik für Gastroenterologie & Rheumatologie, Fachbereich Infektions- und Tropenmedizin, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland, Stefan.Schubert@medizin.uni-leipzig.de.

Travel medicine deals with travellers' diseases. The target group is therefore distinct from tropical medicine. It has gained in significance due to the increase in tourism and professional work abroad in the last 50 years. Dangerous and widespread diseases in tropical countries, in particular tropical malaria, have come into focus in industrialized countries because of their appearance in travellers. Travel medicine deals not only with infectious or transmittable diseases, but also with the ability of patients with chronic diseases to travel, the medical aspects of flying, as well as the health hazards of professional work or high-risk sports abroad. The risk of disease as a result of travelling can be minimized by advice and prophylactic measures, such as vaccinations and drug prophylaxis against malaria, if indicated. On return, medical symptoms should be investigated promptly to ensure early detection of life-threatening disease courses, particularly tropical malaria, as well as to prevent the occurrence of small-scale epidemics. A small number of diseases can also emerge after several years, such as benign types of malaria, amoebic liver abscess and visceral leishmaniasis (kala-azar). Aids also belongs to these diseases. Therefore, in this era of HIV pandemic travellers concerned should be made aware of the risks.

PMID: 19484193 [PubMed - as supplied by publisher]

3: Acta Trop. 2009 May 28. [Epub ahead of print]Click here to read

A new focus of cutaneous leishmaniasis in the central area of Paraná State, southern Brazil.

Soccol VT, Castro EA, Schühli GS, de Carvalho Y, Marques E, Pereira ED, Alcantara FD, Machado AM, Kowalthuk W, Membrive N, Luz E.

Laboratório de Parasitologia Molecular. Departamento de Patologia Básica, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico - Jardim das Américas. Zip code: 81531-990 - Curitiba, PR - Brazil.

We report a new endemic zone of cutaneous leishmaniasis (CL) in the central area of the State of Paraná (Municipality of Prudentópolis), in southern Brazil. This region was not previously considered endemic for CL, and this work constitutes the first report of CL endemicity there. Leishmaniasis was confirmed by smear, culture, and ELISA. Parasites were isolated and identified by random amplification of polymorphic DNA (PCR-RAPD). Phylogeographical analysis, based on two different criteria, was able to distinguish between RAPD profiles from different geographical regions. In total, 100 patients were diagnosed with leishmaniasis by culture and serology methods. The reported incidence rate was 4.32%. Of the 100 patients, 92% of the patients had single lesions, and 79.98% of these lesions were located on their limbs. The fact that 61% of patients were male rural workers points to an extradomiciliar type of transmission. In houses where human leishmaniasis was diagnosed, 29% of the dogs presented anti-Leishmania antibodies. A total of 1,663 phlebotomines, representing 5 species, were captured in the studied area with CDC-like light minitraps. Lutzomyia intermedia sl was the most prevalent species (94.40%). The isolated parasites were grouped with L. (V.) braziliensis. The epidemiological implications are discussed in the present article.

PMID: 19482000 [PubMed - as supplied by publisher]

4: Trans R Soc Trop Med Hyg. 2009 May 27. [Epub ahead of print]Click here to read

Atypical manifestations of tegumentary leishmaniasis in a transmission area of Leishmania braziliensis in the state of Bahia, Brazil.

Guimarães LH, Machado PR, Lago EL, Morgan DJ, Schriefer A, Bacellar O, Carvalho EM.

Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, R. João das Botas S/N, Canela 40110-160, Salvador, Bahia, Brazil.

American tegumentary leishmaniasis (ATL) can occur in different forms, classically categorised as cutaneous leishmaniasis, mucosal leishmaniasis, diffuse cutaneous leishmaniasis and disseminated leishmaniasis. We analysed the presence of atypical manifestations (vegetative, verrucous, crusted and lupoid) among a cohort of patients presenting to the Health Post of Corte de Pedra, Bahia, Brazil. Among 1396 patients diagnosed with ATL in 2005-2006, 35 patients (2.5%) presented with atypical manifestations of the disease. Of these patients, 14 were pregnant women, 2 were co-infected with HIV and 19 had no co-morbidity or other apparent risk factors for the development of atypical ATL. The latter 19 patients were the focus of this study. They were predominantly adult males, frequently presenting with facial lesions [P<0.001; odds ratio (OR)=17.5, 95% CI 6.1-52.4] and had higher rates of treatment failure with antimonial therapy (P<0.001; OR=327, 95% CI 45-6668) compared with patients with classic ATL attending in the same period. Thirteen cases healed with amphotericin B, introduced after failure of three or more courses of antimony, suggesting that amphotericin B should be considered as the drug of choice for all patients diagnosed with atypical ATL.

PMID: 19481233 [PubMed - as supplied by publisher]

5: Hum Immunol. 2009 Jun;70(6):383-390. Epub 2009 Jan 20.Click here to read

Th1/Th2 immune responses are associated with active cutaneous leishmaniasis and clinical cure is associated with strong interferon-gamma production.

Castellano LR, Filho DC, Argiro L, Dessein H, Prata A, Dessein A, Rodrigues V.

Laboratory of Immunology, Universidade Federal do Triângulo Mineiro, Minas Gerais, Brazil.

In leishmaniasis, Th1-related cytokines production seems to be crucial for host control of parasite burden and clinical cure. Visceral and diffuse cutaneous leishmaniasis are characterized by negative skin test for parasite antigens and failure to produce Th1 cytokines, whereas tegumentary leishmaniasis is characterized by positive skin test and the ability of peripheral blood mononuclear cells (PBMCs) to produce Th1 cytokines. In this study, specific antibody plasma levels and cytokine production in PBMC culture supernatants were evaluated by enzyme-linked immunoabsorbent assay in patients with active or cured cutaneous leishmanial lesions and in subjects without disease history living in the same endemic area. Higher tumor necrosis factor-alpha, interferon (IFN)-gamma, interleukin (IL)-12, IL-4, and IL-10 levels were observed in patients with active lesions, whereas cured subjects produced only IFN-gamma at elevated levels. Analysis of specific antibody isotypes correlate with cellular immune response observed in vitro, as the production of IgG1 and IgG3 was higher in patients with active lesions. Our results suggest the presence of a mixed Th1/Th2 response during active disease and that clinical cure is associated with a sustained Th1 response characterized by elevated IFN-gamma levels and down-modulation of IL-4 and IL-10 production.

PMID: 19480861 [PubMed - as supplied by publisher]

6: Indian J Med Res. 2009 Jan;129(1):102-4.Click here to read LinkOut

Newer strategies for the kala-azar elimination programme in India.

Thakur CP, Meenakshi Thakur AK, Thakur S.

PMID: 19287067 [PubMed - indexed for MEDLINE]

7: Xenobiotica. 2009 Mar;39(3):236-48.Click here to read LinkOut

o-Nitroanilines as major metabolic products of anti-Trypanosoma cruzi 5-phenylethenylbenzofuroxans in microsomal and cytosolic fractions of rat hepatocytes and in whole parasitic cells.

Boiani M, Merlino A, Gerpe A, Porcal W, Croce F, Depaula S, Rodríguez MA, Cerecetto H, González M.

Departamento de Química Orgánica, Facultad de Química-Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.

The metabolism of six anti-Trypanosoma cruzi 5-phenylethenylbenzofuroxans (PhEBfx) was studied in vitro using rat hepatic microsomal and cytosolic fractions as a mammalian model and whole cells of T. cruzi as a parasitic model. Some of the expected metabolites were synthesized to provide authentic chromatographic standards. The metabolites were identified using high-performance liquid chromatography (HPLC) in comparison with the authentic standards and their proportions were determined. Their structures were confirmed using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. The behaviour of the six PhEBfx in the three different systems was similar. The main metabolites, formed by reductive processes, were the corresponding o-nitroanilines. Two of the test compounds were studied for extended time periods in the rat liver preparations and their terminal metabolites were identified as o-phenylendiamine derivatives.

PMID: 19280522 [PubMed - indexed for MEDLINE]

8: Immunol Cell Biol. 2008 Nov-Dec;86(8):688-99. Epub 2008 Sep 9. LinkOut

A novel nervous system-induced factor inducing immune responses in the spleen.

Bakhiet M, Taha S.

Department of Molecular Medicine, HH Princess Al-Jawhara Center for Genetics and Inherited Diseases - College of Medicine and Medical Sciences, AGU, Manama, Kingdom of Bahrain. moiz@agu.edu.bh

This study relates to a novel mediator signaling between the nervous system and the spleen following an immune challenge. Using enzyme-linked immunospot and cell proliferation assays, we found that supernatants of cultured splenocytes prepared from subcutaneously trypanosome-inoculated rats and mice spleens obtained immediately after inoculation and added to naive cells significantly stimulate interferon-gamma production and cell proliferation compared to phosphate-buffered saline-inoculated animals. This action was abrogated by surgical denervation of the spleen. Using the fluorescent differential display technology, the gene involved in this process was identified and further cloned and its sequence was mapped to chromosome 14 (GenBank accession number: EU552928). Protein expression revealed approximately 15 kDa molecule with biological activities similar to the cultured supernatants of splenocytes obtained directly from parasite-inoculated animals. Antibodies raised against the protein blocked the activities of both the protein and the supernatant and also recognized a band in the active supernatant with the same molecular mass as the protein. Furthermore, the protein was able to reactivate experimentally immunosuppressed cells by regaining their ability to proliferate, suggesting that such a nervous system-induced immune system-released activating agent (ISRAA) may have a potential therapeutic benefit in immunocompromised situations and in further understanding the mechanism for innate immunity commencement and action.

PMID: 18779837 [PubMed - indexed for MEDLINE]

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