Wednesday, August 5, 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: Lasers Med Sci. 2009 Aug 5. [Epub ahead of print]

Photodynamic therapy in dermatology: a review.

Choudhary S, Nouri K, Elsaie ML.

Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, FL, USA.

Photodynamic therapy (PDT) is used for the prevention and treatment of non-melanoma skin cancer. Until recently, clinically approved indications have been restricted to actinic keratoses, nodular and superficial basal cell carcinoma, and, since 2006, Bowen disease. However, the range of indications has been expanding continuously. PDT is also used for the treatment of non-malignant conditions such as acne vulgaris and leishmaniasis, as well as for treating premature skin aging due to sun exposure. The production of reactive oxygen intermediates like singlet oxygen depends on the light dose applied as well as the concentration and localization of the photosensitizer in the diseased tissue. Either cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving inflammatory skin conditions are induced. Treating superficial non-melanoma skin cancer, PDT has been shown to be highly efficient, despite the low level of invasiveness. The excellent cosmetic results after treatment are beneficial, too.

PMID: 19653060 [PubMed - as supplied by publisher]

2: PLoS Negl Trop Dis. 2009 Aug 4;3(8):e495.

Preclinical Assessment of the Treatment of Second-Stage African Trypanosomiasis with Cordycepin and Deoxycoformycin.

Vodnala SK, Ferella M, Lundén-Miguel H, Betha E, van Reet N, Amin DN, Oberg B, Andersson B, Kristensson K, Wigzell H, Rottenberg ME.

Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.

BACKGROUND: There is an urgent need to substitute the highly toxic compounds still in use for treatment of the encephalitic stage of human African trypanosomiasis (HAT). We here assessed the treatment with the doublet cordycepin and the deaminase inhibitor deoxycoformycin for this stage of infection with Trypanosoma brucei (T.b.). METHODOLOGY/PRINCIPAL FINDINGS: Cordycepin was selected as the most efficient drug from a direct parasite viability screening of a compound library of nucleoside analogues. The minimal number of doses and concentrations of the drugs effective for treatment of T.b. brucei infections in mice were determined. Oral, intraperitoneal or subcutaneous administrations of the compounds were successful for treatment. The doublet was effective for treatment of late stage experimental infections with human pathogenic T.b. rhodesiense and T.b. gambiense isolates. Late stage infection treatment diminished the levels of inflammatory cytokines in brains of infected mice. Incubation with cordycepin resulted in programmed cell death followed by secondary necrosis of the parasites. T.b. brucei strains developed resistance to cordycepin after culture with increasing concentrations of the compound. However, cordycepin-resistant parasites showed diminished virulence and were not cross-resistant to other drugs used for treatment of HAT, i.e. pentamidine, suramin and melarsoprol. Although resistant parasites were mutated in the gene coding for P2 nucleoside adenosine transporter, P2 knockout trypanosomes showed no altered resistance to cordycepin, indicating that absence of the P2 transporter is not sufficient to render the trypanosomes resistant to the drug. CONCLUSIONS/SIGNIFICANCE: Altogether, our data strongly support testing of treatment with a combination of cordycepin and deoxycoformycin as an alternative for treatment of second-stage and/or melarsoprol-resistant HAT.

PMID: 19652702 [PubMed - as supplied by publisher]

3: RNA Biol. 2009 Oct 17;6(4). [Epub ahead of print]

Families of H/ACA ncRNA molecules in trypanosomatids.

Doniger T, Michaeli S, Unger R.

The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Israel.

H/ACA molecules are small nucleolar RNAs (snoRNAs) that guide the conversion of a uridine into a pseudouridine. This modification is crucial for ribosomal RNA (rRNA) function. In addition, H/ACA RNA also function in ribosomal RNA processing. Unlike the double hairpin structure of H/ACA molecules in other organisms, H/ACA molecules in Trypanosomes have a single hairpin structure. Here we describe the repertoireof the 46 published H/ACA molecules in Trypanosoma brucei, as well as identify the orthologous counterparts in other Trypanosomatids enlarging the H/ACA collection in this family to over 300.

PMID: 19652533 [PubMed - as supplied by publisher]

4: J Vet Med Sci. 2009;71(7):951-956.

Quantitative Differences in Immune Responses in Mouse Strains that Differ in their Susceptibility to Trypanosoma brucei brucei Infection.

Namangala B, DE Baetselier P, Beschin A.

The University of Zambia, Faculty of Veterinary Medicine, Department of Paraclinical Studies.

We compared the relative resistance and soluble variant surface glycoprotein (VSG)-specific responses in (C57BL/6 x BALB/c)-F1 (B6B-F1) and C3H mice during infection with Trypanosoma brucei brucei, the hemoprotozoan parasite causing a debilitating disease in man and livestock. We demonstrated that C3H mice are relatively more trypanosusceptible, as evidenced by their reduced ability to control parasitemia and shorter survival time, than B6B-F1 mice. Quantitative differences in the pattern of cytokine and antibody (Ab) production were observed between the 2 mouse strains following infection with T. b. brucei. Thus, although both mouse strains recorded detectable levels of IFN-gamma, TNF-alpha, NO and IL-10 in plasma and lymph nodes, as well as plasma IgM, IgG1, IgG2a, IgG2b and IgG3 Abs against VSG, the susceptible C3H mice only exhibited trace levels of Abs of all isotypes and yet produced elevated levels of IFN-gamma, TNF-alpha and NO, compared to the relatively trypanotolerant B6B-F1 mice. In aggregate, these data strongly suggest that trypanosome-infected C3H mice have an immunological defect, manifested not only by suppression at the B cell clonal level, but also at the level of protective T cell and macrophage phenotypes.

PMID: 19652484 [PubMed - as supplied by publisher]

5: J Insect Physiol. 2009 Jul 31. [Epub ahead of print]

Functional characterization of a salivary apyrase from the sand fly, Phlebotomus duboscqi, a vector of Leishmania major.

Hamasaki R, Kato H, Terayama Y, Iwata H, Valenzuela JG.

Department of Veterinary Hygiene, Faculty of Agriculture, Yamaguchi University, Yamaguchi, Japan.

Two transcripts coding for proteins homologous to apyrases were identified by massive sequencing of a Phlebotomus (P.) duboscqi salivary gland cDNA library. The sequence analysis revealed that the amino acids important for enzymatic activity including nucleotidase activity and the binding of calcium and nucleotides were well conserved in these molecules. A recombinant P. duboscqi salivary apyrase was expressed in Escherichia coli and purified. The resulting protein efficiently hydrolyzed ADP and ATP, but not AMP, GDP, CDP or UDP, in a calcium-dependent manner. Further, the recombinant protein inhibited ADP- and collagen-induced platelet aggregation. The results indicated that this salivary protein plays an important role in the blood-feeding process in P. duboscqi. Its unique enzymatic activity makes the salivary apyrase an attractive candidate as a therapeutic agent for the treatment of thrombotic pathologies as well as a reagent for a wide variety of research purposes.

PMID: 19651132 [PubMed - as supplied by publisher]

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