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Biomedical subjects

S Meydani

Publications and source records attributed to S Meydani.

4 recordsLinked to original sources

Vitamin E and macrophage cyclooxygenase regulation in the aged.

Aging is associated with increased evidence of cardiovascular disease (CVD). Atherosclerosis, a major cause of CVD, is an inflammatory process whose development is influenced by several proinflammatory mediators. Products of arachidonic acid metabolism, in particular, prostaglandin (PG) E(2) and thromboxane (TX) A(2), play an important role in the development of atherosclerosis. We showed previously that the aged have higher PGE(2) production compared with their young counterparts. This age-associated increase in PGE(2) production is mainly a consequence of increased cyclooxygenase (COX) activity. We demonstrated further that increased COX activity in old mice is due to the increased expression of mRNA and protein for the inducible form of COX, COX-2. Vitamin E has been shown to reduce PGE(2) production and risk of CVD. In aged mice, we showed that a vitamin E-induced decrease in PGE(2) production is due to decreased COX activity. However, vitamin E had no effect on COX mRNA and protein levels, indicating a post-translational regulation of COX by vitamin E. Further experiments indicated that vitamin E decreases COX activity through reducing formation of peroxynitrite, a hydroperoxide shown to be involved in the activation of COX-2. Other homologues of tocopherols were also effective in inhibiting COX activity, but their degree of inhibition varied. The varied potency to inhibit COX activity was not explained totally by differences in their antioxidant capacity. Vitamin E-induced inhibition of COX activity might contribute to its effect of reducing CVD risk.

Aged↗

High-performance liquid chromatography with coulometric electrode array detector for the determination of quercetin levels in cells of the immune system.

There is mounting evidence emphasizing the importance of intracellular antioxidant levels for maintenance of the immune function. The flavonoid quercetin, a natural antioxidant, has been shown to modulate enzymes involved in the regulation of the inflammatory response. However, up to now, there have been no studies describing quercetin levels in cells of the immune system. A gradient reversed-phase HPLC technique to identify and quantify intracellular levels of quercetin and its application in mice splenocytes are described. Mobile phases were a 0.01 M sodium phosphate monobasic solution adjusted to pH 2.8 with 85% orthophosphoric acid (buffer, Solvent A) and methanol (Solvent B) with a flow rate of 1 ml/min. An eight-channel coulometric electrode array detector was used. In vitro supplementation with increasing concentration of quercetin (25, 50, and 100 microM) raises intracellular quercetin levels in a dose-dependent manner. The method has the required features of specificity and sensitivity for monitoring quercetin uptake in cells of the immune system.

Animals↗

Prostaglandins and their metabolites in the gastrointestinal tract of Yucatan miniature swine.

Concentration of prostaglandins E1, E2, F2alpha, and 15 keto, 13, 14-dihydro F2alpha (MPF2alpha), were measured in gastric, duodenal, jejunal, and ileal mucosa, and in the luminal contents of these gastrointestinal segments in miniature swine at 30, 60, and 120 min after they ingested a liquid nutrient meal. Large quantities of E1 and F2alpha were present in gastric contents at 30 min with lesser amounts of E2 and MPF2alpha. The concentrations of E1, E2, and F2alpha in the gastric contents decreased progressively with time after feeding. The total quantity and the concentrations of E1 and F2alpha decreased with passage of ingesta through the duodenum and jejunum. Mucosal concentrations of E1 and F2alpha were greatest in the duodenum and proximal jejunum and lowest in gastric mucosa. These results indicate that there is considerable production and metabolism of prostaglandins in the gastrointestinal tract, with major amounts secreted into the luminal contents of the stomach and duodenum after food intake.

Alprostadil↗

Prostaglandins in human duodenal secretions.

Prostaglandins E1, E2 and F2 alpha were measured in duodenal secretions from two healthy, fasting male subjects. Secretions were collected by duodenal intubation prior to, and following, stimulation by secretin and cholecystokinin. Prostaglandins were measured with a radioimmunoassay technique. The ranges of concentrations found were PGE1: 2.4-110 ng/ml, PGE2: 0.004-1.51 ng/ml, and PGG2 alpha: 0.44-14.6 ng/ml.

Adult↗