Identification and characterisation of mutations associated with von Willebrand disease in a Turkish patient cohort

Several cohort studies have investigated the molecular basis of von Willebrand disease (VWD); however, these have mostly focused on European and North American populations. This study aimed to investigate mutation spectrum in 26 index cases (IC) from Turkey diagnosed with all three VWD types, the majority (73%) with parents who were knowingly related. IC were screened for mutations using multiplex ligation-dependent probe amplification and analysis of all von Willebrand factor gene (VWF) exons and exon/intron boundaries. Selected missense mutations were expressed in vitro. Candidate VWF mutations were identified in 25 of 26 IC and included propeptide missense mutations in four IC (two resulting in type 1 and two in recessive 2A), all influencing VWF expression in vitro. Four missense mutations, a nonsense mutation and a small in-frame insertion resulting in type 2A were also identified. Of 15 type 3 VWD IC, 13 were homozygous and two compound heterozygous for 14 candidate mutations predicted to result in lack of expression and two propeptide missense changes. Identification of intronic breakpoints of an exon 17–18 deletion suggested that the mutation resulted from non-homologous end joining. This study provides further insight into the pathogenesis of VWD in a population with a high degree of consanguineous partnerships

Tenofovir Disoproxsil Fumarate in the Treatment of AIDS

Tenofovir disoproxil fumarate is an antiviral drug used against HIV (Human Immunodeficiency Virus) and hepatitis B (HBV) viruses in adults. It is an acyclic nucleoside phosphonate diester analogue of adenosine monophosphate. Tenofovir is a nucleotide reverse transcriptase inhibitor and it shows activity by preventing enzymes (reverse transcriptase of HIV, DNA polymerase of hepatitis B) required for viruses in reproducing themselves. Following the oral administration, tenofovir disoproxil fumarate is rapidly absorbed and converted to tenofovir. It reaches a maximum concentration within two hours. Tenofovir disoproxil fumarate has an intracellular half-life of approximately 17 hours and it is eliminated by a combination of glomerular filtration and active tubular secretion. Due to low rate of genotypic resistance and high antiviral activity, tenofovir disoproxil fumarate has become a preferred drug for both monotherapy and combinationed therapy

The genotoxic risk of underground coal miners from Turkey

PubMedID: 16337427A cytogenetic monitoring study was carried out on a group of workers from a bituminous coal mine in Zonguldak province of Turkey, to investigate the genotoxic risk of occupational exposure to coal mine dust. Cytogenetic analysis, namely sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and micronucleus (MN) tests were performed on a strictly selected group of 39 workers and compared to 34 controls matched for gender, age, and habit. Smoking and age were considered as modulating factors. Both SCE and CA frequencies in coal miners appeared significantly higher than in controls. Similarly, there was a significant increase in the frequency of total micronuclei in exposed group as compared to control group. The effect of smoking on the level of SCE and MN was significant in the control group. A positive correlation between the age and the level of SCE was also found in controls. The frequencies of both SCE and CA were significantly enhanced with the years of exposure. The results of this study demonstrated that occupational exposure to coal mine dust leads to a significant induction of cytogenetic damage in peripheral lymphocytes of workers engaged in underground coal mining. © 2005 Elsevier B.V. All rights reserved.2003/7-47We are grateful to Osman Balamir, manager of the Armutçuk Coal Mining Institution, for his contribution to the study. The authors would like to thank health technicians of the Armutçuk Coal Mining Institution for collecting blood samples. This research was financially supported by the Research Fund of Kahramanmaras Sutcu Imam University (Grant 2003/7-47)

Genotoxic potential of cyfluthrin

PubMedID: 18692594Cyfluthrin (CAS no. 68359-37-5), a synthetic fluorinated pyrethroid insecticide, is widely used in the home environment and in agriculture because of its high activity against a broad spectrum of insect pests and its low animal toxicity. There are no adequate data on genotoxic effects of cyfluthrin. The aim of this study was to analyze the potential genotoxic effects of cyfluthrin. The genotoxicity of cyfluthrin was evaluated, in vitro, by assessing the ability of the insecticide to induce gene mutation (evaluated using the Ames/microsome test), chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronucleus (MN) formation in cultured human peripheral blood lymphocytes. Additionally, CAs and cytotoxicity induced by cyfluthrin were investigated in rat (Rattus norvegicus var. Albinos) bone-marrow cells to assess in vivo genotoxicity of cyfluthrin. The counts of reverse mutations in Salmonella typhimurium were not significantly increased (P > 0.05). The frequency of CAs in human lymphocytes, treated with any concentration of cyfluthrin (500, 1000 or 2000 µg/ml) for a 24-h period, was not significantly increased (P > 0.05). In contrast, CA was significantly increased for the highest two concentrations (1000 and 2000 µg/ml) in the 48-h treatment group compared with the control group (dimethyl sulfoxide, DMSO). Micronucleus formation was significantly (P 0.05). Mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) decreased significantly (P < 0.05) due to the potential cytotoxicity of cyfluthrin, especially after the 48-h treatment period. The frequency of chromosome aberrations in bone-marrow cells of rats treated with the test substance increased significantly (P < 0.05) for all doses (250, 500 and 1000 mg/kg body weight) for the two treatment periods (12 and 24 h) and the two administration routes, viz. intraperitoneal injection (i.p.) and oral gavage (gvg). In vivo cytotoxicity of cyfluthrin was detected only after administration by gavage for the 24-h treatment period. All these findings were not dose-dependent. © 2008 Elsevier B.V. All rights reserved