The effects of carbon monoxide on respiratory chemoreflexes in humans

As protection against low-oxygen and high-carbon-dioxide environments, the respiratory chemoreceptors reflexly increase breathing. Since CO is also frequently present in such environments, it is important to know whether CO affects the respiratory chemoreflexes responsiveness. Although the peripheral chemoreceptors fail to detect hypoxia produced by CO poisoning, whether CO affects the respiratory chemoreflex responsiveness to carbon dioxide is unknown. The responsiveness of 10 healthy male volunteers were assessed before and after inhalation of approximately 1200 ppm CO in air using two iso-oxic rebreathing tests; hypoxic, to emphasize the peripheral chemoreflex, and hyperoxic, to emphasize the central chemoreflex. Although mean (SEM) COHb values of 10.2 (0.2)% were achieved, no statistically significant effects of CO were observed. The average differences between pre- and post-CO values for ventilation response threshold and sensitivity were -0.5 (0.9) mmHg and 0.8 (0.3) L/min/mmHg, respectively, for hyperoxia, and 0.7 (1.1) mmHg and 1.2 (0.8) L/min/mmHg, respectively, for hypoxia. The 95% confidence intervals for the effect of CO were small. We conclude that environments with low levels of CO do not have a clinically significant effect acutely on either the central or the peripheral chemoreflex responsiveness to carbon dioxide.     

Synthesis and structure-activity relationships of a novel series of tricyclic dihydropyridine-based KATP openers that potently inhibit bladder contractions in vitro

Structure-activity relationships were investigated on a novel series of tricyclic dihydropyridine-containing K(ATP) openers. This diverse group of analogues, comprising a variety of heterocyclic rings fused to the dihydropyridine nucleus, was designed to determine the influence on activity of hydrogen-bond-donating and -accepting groups and their stereochemical disposition. Compounds were evaluated for K(ATP) activity in guinea pig bladder cells using a fluorescence-based membrane potential assay and in a pig bladder strip assay. The inhibition of spontaneous bladder contractions in vitro was also examined for a subset of compounds. All compounds studied showed greater potency to inhibit spontaneous bladder contractions relative to their potencies to inhibit contractions elicited by electrical stimulation.     

Participation of pregnant women in clinical trials: will they participate and why?

The objective of this study is to investigate the willingness of pregnant women to participate in a randomized placebo-controlled clinical trial, and to explore the determinants of their decision making. Cross-sectional survey with semistructured interview and thematic content analysis of pregnant women in a tiertiary care obstetric outpatient clinic. Among the 50 women surveyed, 37 (74%; 95% confidence interval, 60-85%) indicated that they would be willing to participate in a randomized placebo-controlled trial of an injectable medicine given throughout pregnancy, while 5/50 (10%; 95% confidence interval, 3-22%) would decline to participate. Potential benefit to the health of the fetus was ranked as the most important determinant for willingness to participate (68%), followed by benefit to personal health (27%), and altruism (5%). A majority of pregnant women would be willing to participate in a randomized placebo-controlled clinical trial. Pregnant women appear to be willing to accept risks to themselves, if there is a chance that participation in a clinical trial would help their pregnancy and improve their baby's health.