MODES OF INACTIVATION OF NEUROHYPOPHYSIAL HORMONES: SIGNIFICANCE OF PLASMA DISAPPEARANCE RATE FOR THEIR PHYSIOLOGICAL RESPONSES

Analogues of oxytocin and deaminooxytocin with 4-glutamine replaced by 4-glutamic acid methyl ester readily lose their uterotonic activity when incubated with rat serum, presumably by hydrolysis to the much less active 4-glutamic acid derivatives. On the other hand, inactivation of the deaminooxytocin analogue in the rat uterus, as demonstrated by the 'oil-bath'technique, is only slightly more rapid than that of deaminooxytocin and distinctly slower than that of oxytocin. Its in situ/in vitro ratio of uterotonic activity is less than 0.1 whereas that for deaminooxytocin is about 3 and also the persistence of the uterotonic effect in situ is slightly less than that of deaminooxytocin. The results with these 'rapidly inactivated'analogues can be used as proof of some predictions of the three-compartment model for tissue distribution of neurohypophysial hormones and its influence upon the time course of a biological response published earlier. The potential use of analogues of neurohypophysial hormones as probes for inactivation mechanisms and the results thus far obtained are discussed.     

Rescue of menotrophin cycles prone to develop ovarian hyperstimulation

Summary. In an attempt to prevent the loss of'overstimulated cycles' associated with human menopausal gonadotrophin (hMG)-induced ovulation, oestradiol levels and ovarian follicular state were monitored in 12 women with'overstimulated cycles' after withholding hMG for several days. Human chorionic gonadotrophin (hCG) was administered when oestradiol levels were 1700 pg/ml and the leading follicles between 17 and 22 mm in diameter. During the withholding period follicular growth continued in all patients, while oestradiol levels declined in all but three. These three patients conceived. Ovulation was observed in six additional women. Ovarian hyperstimulation did not occur in any of the 12 patients. We conclude that a rescue of'overstimulated cycles' is sometimes possible. Conception seems to depend on a continuing rise of E2 levels and early detection of'overstimulation'.     

Stridor is not a scientifically valid outcome measure for assessing airway injury

Since about a decade cuffed intubation is becoming more popular in pediatric anesthesia. Studies supporting cuffed intubation compared cuffed and uncuffed intubation by using stridor as main outcome measure after extubation. No differentiations were made between benign (oedema) and severe (ulceration of mucosa) lesions. Stridor was considered to represent all relevant injuries. Far reaching conclusions for daily practice were drawn from these studies. Pediatric endoscopists and – ENT-surgeons with extensive experience in this field have warned against this opinion because significant injury of the airway is not always accompanied by stridor! The symptom of stridor might develop weeks and months after injury when silent ulcerations of the mucosa retract to significant stenosis. Only endoscopy can evidently detect all airway injuries. Studies describing airway injury by endoscopic control are urgently needed to find the best way of preventing airway injury by intubation.     

Restitution of Ca2+ Release and Vulnerability to Arrhythmias

New information has recently been obtained along two essentially parallel lines of research: investigations into the fundamental mechanisms of Ca²⁺-induced Ca²⁺ release (CICR) in heart cells, and analyses of the factors that control the development of unstable rhythms such as repolarization alternans. These lines of research are starting to converge such that we can begin to understand unstable and potentially arrhythmogenic cardiac dynamics in terms of the underlying mechanisms governing not only membrane depolarization and repolarization but also the complex bidirectional interactions between electrical and Ca²⁺ signaling in heart cells. In this brief review, we discuss the progress that has recently been made in understanding the factors that control the beat-to-beat regulation of cardiac Ca²⁺ release and attempt to place these results within a larger context. In particular, we discuss factors that may contribute to unstable Ca²⁺ release and speculate about how instability in CICR may contribute to the development of arrhythmias under pathological conditions.