Orally administered glucagon-like peptide-1 affects glucose homeostasis following an oral glucose tolerance test in healthy male subjects.

Glucagon-like peptide-1 (GLP-1) exerts several effects on glucose homeostasis and reduces food intake. After its release from intestinal L cells, GLP-1 is subject to (i) rapid breakdown by dipeptidyl peptidase IV and (ii) high liver extraction. The highest concentrations of GLP-1 are found in the splanchnic blood rather than in the systemic circulation. An oral delivery system would mimic endogenous secretion. Here we investigated the pharmacokinetic/pharmacodynamic (PK/PD) effects of a single dose (2 mg) of oral GLP-1 administered prior to an oral glucose tolerance test (OGTT) in 16 healthy males. GLP-1 was rapidly absorbed from the gut, leading to tenfold higher plasma concentrations compared with controls. The PD profile was consistent with reported pharmacology; GLP-1 significantly stimulated basal insulin release (P < 0.027), with marked effects on glucose levels. The postprandial glucose peak was delayed with GLP-1, suggesting an effect on gastric emptying.

Cocaine and salicylate: documentation of hydroxyl radical formation in hearts and brains of 18-day-old chick embryos and unexpected interactive toxicity.

RATIONALE: Multiple low doses of cocaine (COC) may cause intermittent vasoconstriction and reperfusion, leading to elevations in damaging reactive oxygen species, such as hydroxyl free radicals (*OH). Salicylate may offer protection because it reacts with *OH and/or because of its anti-inflammatory actions. OBJECTIVE: To measure *OH concentrations in hearts and brains of chicken embryos exposed to multiple, small doses of COC, and to determine if otherwise non-toxic doses of sodium salicylate (NaSal) protected against the marginal but significant reduction in hatchability caused by a model of "binge" COC exposure. METHODS: Three experiments were carried out. In the first, 67.5 mg COC/kg egg was administered as five doses of 13.5 mg/kg egg or 0.675 mg/egg every 1.5 h, injected just beneath the shell, on day 18 of development (E18), 1 h after NaSal (25 or 100 mg/kg egg) was injected as a bolus. Hearts and brains taken shortly afterward were analyzed for *OH. In experiment 2, the dose of COC was reduced to 56.5 mg/kg egg so as to achieve a small but significant reduction in hatchability in order to determine if NaSal protected against or enhanced COC's toxicity, manifest as an increase or decrease in hatchability. The doses of NaSal for this experiment were 50, 100 or 200 mg/kg egg, all devoid of effects upon hatchability when injected alone. Experiment 3 was done to confirm the presence of vascular disruptions/hemorrhages observed on COC-exposed embryos while harvesting hearts and brains for chemical analyses and to quantify what appeared to be enhanced COC-related vascular accidents associated with NaSal pretreatment. The dose of NaSal used in experiment 3 was 200 mg/kg egg and COC was injected again at 5x13.5 mg/kg egg. RESULTS: COC increased *OH in hearts and brains of chicken embryos on E18, and non-toxic doses of NaSal (i.e. 100 or 200 mg/kg egg) enhanced COC's toxicity in a dose-related manner. The lowest NaSal dose (50 mg/kg egg) may have offered some protection against the effects of COC, as the reduction in hatchability caused by 56.5 mg COC/kg egg was no longer significant. Vascular disruptions/hemorrhages were associated with and most likely responsible for the interactive toxicity. CONCLUSIONS: Our unexpected findings may be of clinical relevance because of the use of aspirin for treatment of misdiagnosed "preeclamptic" COC-abusing pregnant women and its possible use for COC abusers at risk for reduced cerebral blood flow and stroke.

In vitro effects of histamine on human pregnant myometrium contractility.

The effects of histamine on pregnant human myometrium was examined by means of an in vitro technique. Samples of myometrium were taken from women delivered by elective caesarean section at various stages of gestation. Histamine (1 x 10(-6) to 1 x 10(-4) M) had good stimulant activity on all the strips examined. This contractile action was unaffected by H2 blockers but was competitively antagonised by H1-blockers. The H2-selective agonist, impromidine, was ineffective at molar concentrations between 1 x 10(-8) and 1 x 10(-3) while a specific full agonist of the H1 receptors, thiazole in the range of molar concentrations from 1 x 10(-6) to 3 x 10(-4), had an activity identical to that of histamine. The data obtained suggest that in the pregnant human myometrium the activation of H1-receptors is responsible for the contractile effect of histamine; a possible involvement of histamine in the pathophysiology of labour is discussed.

La consanguinidad en la parroquia de Los Teques, Venezuela, desde 1790 a 1869. / Consaguinity in the parish of Los Teques, Venezuela, from 1790 to 1869

Utilizando registros eclesiaticos de una parroquia rural venezuelana, Los Teques, se estudio su consanguinidad desde 1970 a 1869.Los valores encontrados son mas altos que los de otras zonas de Venezuela, pero similares a los de otras regiones del mundo; ademas, no muestran variaciones temporales y concuerdan con las caracteristicas demograficas de la poblacion. La frecuencia alta de matrimonio de consanguinidad multiple (tipo M) y de primos hermanos (tipo 22) influye notoriamente en el coeficiente de consaguinidad promedio (alfa) y sugiere la existencia de una red de parantesco compleja y estable y de un patron sociocultural que favorece esos tipos de matrimonios. El efecto sobre la consaguinidad de un patron migratorio masculino tambien es demostrado