A comparison of the inhibitory effects of melatonin and indomethacin on platelet aggregation and thromboxane release

Collagen-induced platelet aggregation and thromboxane release is inhibited, in a concentration response relationship, by preincubation of gel-filtered platelets with melatonin in the concentration range 430 nM - 4.3 mM. Inhibition of platelet aggregation and thromboxane release also occurs in the presence of indomethacin (4.3 nM - 4.3 mM), a known potent inhibitor of prostaglandin synthesis. Arachidonic acid-induced platelet aggregation and thromboxane release was inhibited in the presence of 4.0 mM melatonin. We therefore propose that inhibition of prostaglandin synthesis maybe the mechanism by which melatonin expresses its activity. Its antigonadotropic activity may result from inhibition of PGE synthesis in the hypothalamus and median eminence

Progesterone binding protein in the bovine corpus luteum

A high-affinity binding protein for progesterone in the bovine corpus luteum is described. The steroid-binding characteristics of the cytosolic fraction of mid-luteal tissue was investigated using sucrose density gradients and equilibrium dialysis. Added progesterone, R5020 and danazol (17α-pregn-4-en-20-yno[2,3-d]isoxazol-17-ol) were taken into 5-20% w/w sucrose gradients whereas added cortisol was not. The progesterone-binding component of the cytosolic supernatant sedimented as a single species (4.1S) in the presence of 0.4 M KCl. The equilibrium association constants at 4°C for progesterone were 3.94 × 10 ± 0.73 × 10 (SEM) 1/mol (n = 11) for the cytosolic supernatant and 7.67 × 10 ± 0.94 × 10 1/mol (n = 2) for a fraction of binding protein prepared from the cytosolic supernatant by hydroxylapatite chromatography. Cross reaction studies using the cytosolic supernatant showed that pregnenolone, 5α-pregnanedione and deoxycorticosterone were effective competitors of progesterone binding (67%, 62% and 55%, respectively, relative to progesterone at 100%). Cortisol, estradiol-17β, estrone and cholesterol showed less than 5% cross reaction. The function of the progesterone-binding protein is presently unknown, but it may serve as a unidirectional carrier of progesterone during luteal steroidogenesis and/or secretion

Tight glycemic control in critical care - The leading role of insulin sensitivity and patient variability: A review and model-based analysis.

Tight glycemic control (TGC) has emerged as a major research focus in critical care due to its potential to simultaneously reduce both mortality and costs. However, repeating initial successful TGC trials that reduced mortality and other outcomes has proven difficult with more failures than successes. Hence, there has been growing debate over the necessity of TGC, its goals, the risk of severe hypoglycemia, and target cohorts. This paper provides a review of TGC via new analyses of data from several clinical trials, including SPRINT, Glucontrol and a recent NICU study. It thus provides both a review of the problem and major background factors driving it, as well as a novel model-based analysis designed to examine these dynamics from a new perspective. Using these clinical results and analysis, the goal is to develop new insights that shed greater light on the leading factors that make TGC difficult and inconsistent, as well as the requirements they thus impose on the design and implementation of TGC protocols. A model-based analysis of insulin sensitivity using data from three different critical care units, comprising over 75,000h of clinical data, is used to analyse variability in metabolic dynamics using a clinically validated model-based insulin sensitivity metric (S(I)). Variation in S(I) provides a new interpretation and explanation for the variable results seen (across cohorts and studies) in applying TGC. In particular, significant intra- and inter-patient variability in insulin resistance (1/S(I)) is seen be a major confounder that makes TGC difficult over diverse cohorts, yielding variable results over many published studies and protocols. Further factors that exacerbate this variability in glycemic outcome are found to include measurement frequency and whether a protocol is blind to carbohydrate administration

Optimizing carbon sequestration in commercial forests by integrating carbon management objectives in wood supply modeling

Carbon sequestration, Forest management planning, Goal programming, Growth and yield, Harvesting, Linear programming, Operational emissions, Optimization, Silviculture, Wood products,