Reduction in oxidatively generated DNA damage following smoking cessation

<p>Abstract</p> <p>Background</p> <p>Cigarette smoking is a known cause of cancer, and cancer may be in part due to effects of oxidative stress. However, whether smoking cessation reverses oxidatively induced DNA damage unclear. The current study sought to examine the extent to which three DNA lesions showed significant reductions after participants quit smoking.</p> <p>Methods</p> <p>Participants (n = 19) in this study were recruited from an ongoing 16-week smoking cessation clinical trial and provided blood samples from which leukocyte DNA was extracted and assessed for 3 DNA lesions (thymine glycol modification [d(T^gpA)]; formamide breakdown of pyrimidine bases [d(T^gpA)]; 8-oxo-7,8-dihydroguanine [d(G^h)]) via liquid chromatography tandem mass spectrometry (LC-MS/MS). Change in lesions over time was assessed using generalized estimating equations, controlling for gender, age, and treatment condition.</p> <p>Results</p> <p>Overall time effects for the d(T^gpA) (χ²(3) = 8.068, p < 0.045), d(P^fpA) (χ²(3) = 8.477, p < 0.037), and d(G^h) (χ²(3) = 37.599, p < 0.001) lesions were seen, indicating levels of each decreased significantly after CO-confirmed smoking cessation. The d(T^gpA) and d(P^fpA) lesions show relatively greater rebound at Week 16 compared to the d(G^h) lesion (88% of baseline for d(T^gpA), 64% of baseline for d(P^fpA), vs 46% of baseline for d(G^h)).</p> <p>Conclusions</p> <p>Overall, results from this analysis suggest that cigarette smoking contributes to oxidatively induced DNA damage, and that smoking cessation appears to reduce levels of specific damage markers between 30-50 percent in the short term. Future research may shed light on the broader array of oxidative damage influenced by smoking and over longer durations of abstinence, to provide further insights into mechanisms underlying carcinogenesis.</p

Potential Relevance of α1-Adrenergic Receptor Autoantibodies in Refractory Hypertension

-AAB might have a mechanistic role and could represent a therapeutic target. in cardiomyocytes and induce mesentery artery segment contraction.-AAB in hypertensive patients, and the notion of immunity as a possible cause of hypertension

A new arylating agent, 2-carboxy-4,6-dinitrochlorobenzene: reaction with model compounds and bovine pancreatic ribonuclease

The reagent 2-carboxy-4,6-dinitrochlorobenzene (CDNCB) reacts with the imino, amino and sulfhydryl groups of model compounds. At pH 8.2, sulfhydryl groups react much faster than do amines. Nα-Acetylhistidine, Nα-acetyltyrosine and Nα-acetyltryptophan do not react. Poly (L-Lysine) and poly (DL-lysine) react about 50 times as fast as does Nα-acetyllysine. A dichloroanalog, 6-carboxy-2,4-dinitro-1,3-dichlorobenzene, shows stepwise reactivity with amines. With bovine pancreatic ribonuclease, which contains no sulfhydryl, CDNCB reacts preferentially with the e-amino of Lys-41 at 450 times the rate with the E-amino of Nα-acetyllysine. The preferential reactivity at Lys-41 is discussed in relation to the pK of Lys-41, the cationic character of the active site cleft, and the mechanism of RNAase action on substrates