Friday, April 3, 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 -5 of 5

1: N Engl J Med. 2009 Apr 2;360(14):e20.Click here to read

Lupoid leishmaniasis.

Zaz T, Turki H.

Service de Dermatologie, Sfax 3029, Tunisia, taoufikzaz@gmail.com.

PMID: 19339717 [PubMed - in process]

2: Clin Vaccine Immunol. 2009 Apr 1. [Epub ahead of print]Click here to read

Cellular and humoral responses against Leishmania virulence factors in healed Cutaneous Leishmaniasis and Mediterranean Visceral Leishmaniasis patients.

Lakhal-Naouar I, Boussoffara T, Meddeb-Garnaoui A, Ben Achour-Chenik Y, Louzir H, Chenik M.

Laboratory of Immunopathology Vaccinology and Molecular Genetics (LIVGM), Institut Pasteur de Tunis, 13, Place Pasteur, 1002, Tunis-Belvédère, Tunisia.

Cellular and humoral immune responses of healed cutaneous leishmaniasis and mediterranean visceral leishmaniasis patients were evaluated against Leishmania major virulence proteins LmPDI and MAPKK. Only MAPKK induces significant PBMC proliferation with IFNgamma production as well as antibody responses. Thus, it may constitute an interest in Leishmania vaccination and serodiagnosis.

PMID: 19339488 [PubMed - as supplied by publisher]

3: Clin Vaccine Immunol. 2009 Apr 1. [Epub ahead of print]Click here to read

{inverted question}Recombinant peptide mixtures or multiepitope chimeric proteins as sensitizing antigens for immunodiagnosis? A comparative study using several Trypanosoma cruzi peptides.

Camussone C, Gonzalez V, Belluzo MS, Pujato N, Ribone ME, Lagier CM, Marcipar IS.

Laboratorio de Tecnología Biológica, Universidad Nacional del Litoral, Santa Fe, Argentina; Departamento de Química Analítica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.

The aim of this work was to determine the best strategy to display antigens (Ags) on immunochemical devices, to improve the test selectivity and sensitivity. We evaluated comparatively 5 Trypanosoma cruzi antigenic recombinant peptides, chose the 3 more sensitive, built up chimeras bearing these selected Ags, and systematically compared by enzyme-linked immunosorbent assay the performance of the assortments of those peptides with that of the multiepitope constructions bearing all those peptides lineally fused. The better-performing Ags compared included peptides homologous to the previously described T. cruzi flagelar repetitive antigen (here named RP1), the shed acute-phase antigen (RP2), B13 (RP5), and the chimeric recombinant proteins CP1 and CP2, bearing repetitions of RP1-RP2 and RP1-RP2-RP5, respectively. The diagnostic performance of these Ags was assessed by the discrimination efficiency +OD/cutoff (mean optical density value of the positive serum samples tested over the cutoff value), compared with each other either alone, in mixtures or as peptide-fused chimeras, and with that of total parasite homogenate (TPH). The +OD/cutoff obtained for CP1 and CP2 were 25% and 52% higher than those of their individual-Ags mixtures, respectively. CP2 was the only antigen that showed enhanced discrimination efficiency between Chagas' positive- and negative samples, when compared with TPH. This study highlights the convenience of performing immunochemical assays using hybrid, single-molecule, chimeric Ags instead of peptide mixtures. CP2 preliminary tests rendered 98.6% sensitivity when evaluated with a 141-Chagas' positive serum panel, and 99.4% specificity, as assessed with a 164-Chagas' negative serum panel containing 15 samples from individuals infected with Leishmania ssp.

PMID: 19339486 [PubMed - as supplied by publisher]

4: Brain. 2009 Mar 31. [Epub ahead of print]Click here to read

Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis.

Rodgers J, Stone TW, Barrett MP, Bradley B, Kennedy PG.

1 Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Glasgow, UK.

Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasites Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense, and is a major cause of systemic and neurological disability throughout sub-Saharan Africa. Following early-stage disease, the trypanosomes cross the blood-brain barrier to invade the central nervous system leading to the encephalitic, or late stage, infection. Treatment of human African trypanosomiasis currently relies on a limited number of highly toxic drugs, but untreated, is invariably fatal. Melarsoprol, a trivalent arsenical, is the only drug that can be used to cure both forms of the infection once the central nervous system has become involved, but unfortunately, this drug induces an extremely severe post-treatment reactive encephalopathy (PTRE) in up to 10% of treated patients, half of whom die from this complication. Since it is unlikely that any new and less toxic drug will be developed for treatment of human African trypanosomiasis in the near future, increasing attention is now being focussed on the potential use of existing compounds, either alone or in combination chemotherapy, for improved efficacy and safety. The kynurenine pathway is the major pathway in the metabolism of tryptophan. A number of the catabolites produced along this pathway show neurotoxic or neuroprotective activities, and their role in the generation of central nervous system inflammation is well documented. In the current study, Ro-61-8048, a high affinity kynurenine-3-monooxygenase inhibitor, was used to determine the effect of manipulating the kynurenine pathway in a highly reproducible mouse model of human African trypanosomiasis. It was found that Ro-61-8048 treatment had no significant effect (P = 0.4445) on the severity of the neuroinflammatory pathology in mice during the early central nervous system stage of the disease when only a low level of inflammation was present. However, a significant (P = 0.0284) reduction in the severity of the neuroinflammatory response was detected when the inhibitor was administered in animals exhibiting the more severe, late central nervous system stage, of the infection. In vitro assays showed that Ro-61-8048 had no direct effect on trypanosome proliferation suggesting that the anti-inflammatory action is due to a direct effect of the inhibitor on the host cells and not a secondary response to parasite destruction. These findings demonstrate that kynurenine pathway catabolites are involved in the generation of the more severe inflammatory reaction associated with the late central nervous system stages of the disease and suggest that Ro-61-8048 or a similar drug may prove to be beneficial in preventing or ameliorating the PTRE when administered as an adjunct to conventional trypanocidal chemotherapy.

PMID: 19339256 [PubMed - as supplied by publisher]

5: Bioorg Med Chem Lett. 2009 Mar 16. [Epub ahead of print]Click here to read

Peganine hydrochloride dihydrate an orally active antileishmanial agent.

Khaliq T, Misra P, Gupta S, Reddy KP, Kant R, Maulik PR, Dube A, Narender T.

Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226 001, UP, India.

Protozoic infections caused by genus Leishmania pose an enormous public health threat in developing countries, compounded by the toxicity and resistance to current therapies. Under the aegis of our ongoing program on drug discovery and development on antileishmanial agents from plants, we carried out bioassay guided fractionation on Peganum harmala seeds which resulted in the isolation of 1 as an antileishmanial agent. 2D-NMR spectral data and single crystal X-ray crystallography data indicated 1 as peganine hydrochloride in dihydrated form. The compound 1 exhibited in-vitro activity against both extracellular promastigotes as well as intracellular amastigotes residing within murine macrophages in Leishmania donovani. Furthermore, 1 also exhibited in-vivo activity, 79.6 (+/-8.07)% against established VL in hamsters at a dose of 100mg/kgb.wt.

PMID: 19339182 [PubMed - as supplied by publisher]

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