No abstract

Nitric oxide (NO) is a gaseous signaling molecule and effector in various biological processes. In mammalian cells, NO is produced by a family of NO synthases (NOS). Three NOS isoforms have been identified as: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). In addition to NO, NOS also produces superoxide anion. This phenomenon is named NOS uncoupling as superoxide generation mainly occurs when NOS is not coupled with its cofactor or substrate. nNOS was first found to produce superoxide under L-arginine depletion condition. Further studies demonstrated that superoxide production is a general feature of all three NOS isoforms. In particular, superoxide generated from uncoupled eNOS has been found to play critical roles in the process of various cardiovascular diseases. Although NOS was first found to produce superoxide only when uncoupled with its cofactor or substrate, recent studies reveal that oxygen reduction to superoxide is an intrinsic process amid NO synthesis. Tetrahydrobiopterin plays a controlling role in preventing superoxide release from the eNOS oxygenase domain. Besides tetrahydrobiopterin, the regulation of eNOS uncoupling by the interactions with other proteins, protein phosphorylation, S-glutathionylation, and endogenous L-arginine derivatives, will be discussed in this review.

SSc patients are at high risk of developing cancer, especially of the lung, oral cavity and pharynx, and blood.

BackgroundGlycosylated hemoglobin A1C (HbA1c) has been widely recognized as a marker for predicting the severity of diabetes mellitus (DM) and several cardiovascular diseases. However, whether HbA1c could predict the severity and clinical outcomes in patients with stable coronary artery disease (CAD) remains largely unknown. We determine relationship of HbA1c with severity and outcome in patients with stable CAD.MethodsWe enrolled 1433 patients with stable angina who underwent coronary angiography and were followed up for an average 12 months. The patients were classified into three groups by tertiles of baseline HbA1c level (low group <5.7%, n = 483; intermediate group 5.7 - 6.3%, n = 512; high group >6.3%, n = 438). The relationships between the plasma HbA1c and severity of CAD and early clinical outcomes were evaluated.ResultsHigh HbA1c was associated with three-vessel disease. Area under the receivers operating characteristic curve (AUC = 0.67, 95% CI: 0.63-0.71, P < 0.001) and multivariate logistic regression analysis suggested that HbA1C was an independent predictor of severity of CAD (OR = 1.60, 95% CI: 1.29-1.99, P < 0.001) even after adjusting for gender, age, risk factor of CAD, lipid profile and fasting blood glucose. During follow-up, 133 patients underwent pre-specified outcomes. After adjusting for multiple variables in the Cox regression model, HbA1C remained to be an independent predictor of poor prognosis (HR = 1.28, 95% CI: 1.12-1.45, P < 0.001).ConclusionsWe concluded that high level of baseline HbA1c appeared to be an independent predictor for the severity of CAD and poor outcome in patients with stable CAD.