Cardiovascular thromboembolic adverse effects associated with cyclooxygenase-2 selective inhibitors and nonselective antiinflammatory drugs.

Background: Concerns of increased cardiovascular (CV) thromboembolic adverse effects from nonsteroidal antiinflammatory drugs (NSAIDs, both nonselective [NS]-NSAIDs and cyclooxygenase [COX]-2 selective inhibitors) have prevented their use despite numerous benefits.

Methods: In this descriptive review, we critically examine the randomized, active- and placebo-controlled studies, observational trials, and meta-analyses evaluating the CV adverse effects associated with long-term and short-term use of COX-2 selective inhibitors and NS-NSAIDs. The potential mechanisms for these CV effects are also presented.

Modulation of endothelial and smooth muscle function by bed rest and hypoenergetic, low-fat nutrition.

Prolonged microgravity alters the regulation of the peripheral vasculature. The influence of reduced food intake, as often observed in astronauts, on vascular function is unclear. In a randomized, four-phase, crossover study, the effect of simulated microgravity (13 days of bed rest), energetic restriction (-25%, fat reduced), and their combination on endothelium-dependent and -independent vasodilation was compared with ambulatory control conditions.

Endothelial venodilator response in carriers of genetic polymorphisms involved in NO synthesis and degradation.

Aims: Polymorphisms of the NOSIII gene and of the CYBA gene have been associated with a number of pathological conditions such as arterial hypertension, coronary artery disease, and myocardial infarction. Because endothelium-dependent vasodilation is impaired in these disorders, we hypothesized that polymorphisms of NOSIII or CYBA might modulate endothelial function of venous capacitance vessels already before cardiovascular disease becomes overt.

Methods: Endothelium-dependent and -independent venodilation was assessed by measuring local vascular responses to bradykinin and sodium nitroprusside in the dorsal hand vein after preconstriction with phenylephrine in 72 healthy male Caucasians after careful exclusion of cardiovascular risk factors.

Rapid detection of polymorphisms of the nitric oxide cascade.

NOS3 (endothelial nitric oxide (NO) synthase) and p22phox (subunit of NAD(P)H oxidase) are two genes whose products are involved in formation and degradation of NO, a ubiquitous signaling molecule largely responsible for the maintenance of normal endothelial function. The G894T polymorphism of NOS3 and the C242T polymorphism of p22phox are reportedly associated with numerous cardiovascular diseases. For each polymorphism we developed a rapid and reliable method with the hybridization probes format on the LightCycler and compared it with conventional PCR-restriction fragment length polymorphism (PCR-RFLP) analysis with regard to reliability, duration and cost.

Dose-dependent increase of saquinavir bioavailability by the pharmaceutic aid cremophor EL.

Aims: Bioavailability of orally administered drugs depends on several factors including active excretion, e.g. by P-glycoprotein (PGP), and presystemic metabolism, e.