Epigenetic perturbations in the pathogenesis of mustard toxicity; hypothesis and preliminary results

Among the most readily available chemical warfare agents, sulfur mustard (SM), also known as mustard gas, has been the most widely used chemical weapon. SM causes debilitating effects that can leave an exposed individual incapacitated for days to months; therefore delayed SM toxicity is of much greater importance than its ability to cause lethality. Although not fully understood, acute toxicity of SM is related to reactive oxygen and nitrogen species, oxidative stress, DNA damage, poly(ADP-ribose) polymerase (PARP) activation and energy depletion within the affected cell. Therefore several antioxidants and PARP inhibitors show beneficial effects against acute SM toxicity. The delayed toxicity of SM however, currently has no clear mechanistic explanation. One third of the 100,000 Iranian casualties are still suffering from the detrimental effects of SM in spite of the extensive treatment. We, therefore, made an attempt whether epigenetic aberrations may contribute to pathogenesis of mustard poisoning. Preliminary evidence reveals that mechlorethamine (a nitrogen mustard derivative) exposure may not only cause oxidative stress, DNA damage, but epigenetic perturbations as well. Epigenetic refers to the study of changes that influence the phenotype without causing alteration of the genotype. It involves changes in the properties of a cell that are inherited but do not involve a change in DNA sequence. It is now known that in addition to mutations, epimutations contribute to a variety of human diseases. Under light of preliminary results, the current hypothesis will focus on epigenetic regulations to clarify mustard toxicity and the use of drugs to correct possible epigenetic defects

Molecular detection of Bacillus anthracis: evaluation of the efficiency of DNA extraction and a novel dry PCR

Background: Due to recent increase in mailings of anthrax spores, the detection of bioweapons has gained a great deal of interest. This study aimed to investigate the yield and purity of DNA obtained from spores and vegetative forms of Bacillus anthracis for detection by conventional (wet) and dry (lyophilized) PCR methods

Effect of nitrogen mustard, a vesicant agent, on lymphocyte energy metabolism

SERDAR, Muhittin A./0000-0002-3014-748XWOS: 000241193900013PubMed: 17032138Background: The vesicant agents sulfur and nitrogen mustards, which contain chloroethyl groups, are potent inhibitors of DNA synthesis and cell growth, likely changing the utilization of anaerobic glycolysis for energy generation. Methods: To investigate the effect of nitrogen mustard on cellular energy metabolism, lymphocytes treated with increasing doses of mechlorethamine (HN2), a nitrogen mustard and an analogue of sulfur mustard, were incubated with radiolabeled glucose. The rates of aerobic and anaerobic glycolysis were then determined. Results: Glycogen consumption was significantly higher in cells treated with HN2 in a dose-dependent manner compared to untreated cells. Similarly, the amount of end-product lactate was increased, but CO2 was reduced in HN2-treated cells. Conclusions: Lymphocytes normally use aerobic glycolysis under aerobic conditions, but energy metabolism predominantly involved anaerobic glycolysis after severe intoxication with mustard agent

Antimicrobial susceptibility and molecular subtyping of 55 Turkish Bacillus anthracis strains using 25-loci multiple-locus VNTR analysis

Anthrax, which is caused by the bacterium Bacillus anthracis, is one of the oldest documented infectious diseases in both livestock and humans. The differentiation of B. anthracis strains is difficult because of their highly homogeneous genomes

Spectrophotometric methods for the determination of fluoride ion using indole-3-acetic acid interaction with iron(III)

This study is related to the determination of fluoride ion by the conversion of pink-colored Fe(III) and indole-3-acetic acid (IAA) into a colorless hexafluoride ferrite complex with the addition of fluoride. The optimum conditions of the complex formation were found to be pH 1.7 and a temperature of 60 degrees C. The maximum absorption wavelength of the complex and the detection limit of the method were 525 nm and 0.26 mg/L, respectively. The interfering effects of the different cations (Ag+, Al3+, Ba2+, Ca2+, Cd2+, Co2+, Cu2+, K+, Mg2+, Na+, Ni2+, Pb2+) and anions (SO42-, SO32-, NO2-, I-, Br-, Cl-, SCN-, CH3COO-, H2PO4-, ClO4-) were also investigated. The method was applied to standard and real samples and the resulting data were statistically compared at a confidence level of 95\% with those obtained with the use of a fluoride-selective electrode

Crystal Structure Of {Bis[N-(2-Hydroxyethylamino)Ethylsalicylaldiminato]-Iron(Iii)} Chloride

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