Potent bicyclic lactam inhibitors of thrombin: Part I: P3 modifications

Peptidomimetic inhibitors of general structure 1 have been prepared. Optimization of the binding affinities of these compounds through variation of the P3 hydrophobic residue is described. Selected substituted bicylic lactams displayed interesting pharmacological profiles both in vitro and in vivo.     

Effects of short-term suppression of ovarian hormones on cardiovascular and neuroendocrine reactivity to stress in women

The present study reduced the levels of ovarian hormones to early postmenopausal levels by a GnRH agonist and evaluated the effects of a temporary suppression of ovarian hormones on premenopausal women's cardiovascular and neuroendocrine responses to laboratory challenges. The stress responses of 24 healthy young women were evaluated during three tasks during the early follicular phase and then after three monthly injections of Lupron, which suppressed their levels of estradiol, FSH, and LH. Thereafter, half the group resumed menstrual cycles (labeled Cycle), and half continued having Lupron injections in combination with transdermal estradiol (labeled Patch) and all were reevaluated a third time. A third group (labeled Control) of 12 women had four monthly injections of Lupron first and then were evaluated the first time. After their cycles resumed, they were reevaluated twice 3 months apart. Results showed that the magnitude of the blood pressure and catecholamine changes declined over the three evaluations, suggesting that the women's stress responses habituated. Although the suppression of ovarian hormone levels led to alterations in ovarian hormones for several months, which were accompanied by typical menopausal symptoms, cardiovascular and neuroendocrine responses to stress did not vary. This study did not test the effects of current estrogen exposure or of long term suppression of ovarian hormones upon cardiovascular and neuroendocrine responses.     

The characteristics of exploratory behavior in Wistar rats in a permanent inhomogeneous magnetic field

The influence of weak perturbations (up to 300 microT) in the natural magnetic field (MF) (induced by the introduction of three constant magnets) on the problem task solving in complex maze was studied in two groups of Wistar rats. Under the action of inhomogeneous magnetic field there were no spontaneous change of the orienting for the explorative activity independently of the individual in the presence of the organization of goal-directed behaviour. Instead of the expected explorative activity, the stable and deep locomotor depression developed after orienting in a new environment. Such a phenomenon was manifested only against the background of informational loading. Nevertheless, under these conditions a short external stimulations resulted in even faster rat learning than in the control animals. It is suggested that the MF characteristics play a crucial role in the transformation of the orienting (unconditioned activity) into the explorative (cognitive) activity.     

Preliminary study of the effects of feeding ethyl mercury chloride on four breeds of chickens

Different breeds of chickens namely Single Comb White Leghorn (S.C.W.L.), New Hamsphire (N.H.), Iraqi (IRQ) and a cross (CRS.) S.C.W.L. X N.H. X IRQ. were housed in small pens (20 females and 2 males each) and given, in the diet, 40% wheat treatmed with ethyl mercury chloride, for 88 days. Throughout the whole experiment all birds remained active and showed no symptoms of toxicity. The Iraqi breed was significantly higher than the other breeds with respect to egg production. The results also indicated that mercury in egg white is almost three times as much as that in the yolk, although there was no significant difference between the breeds. The liver and kidney of the four breeds tended to accumulate the highest amount of mercury. Significant differences appeared between sexes according to liver and kidney. White Leghorn and local breeds behaved the same, but N.H. had the highest concentration of mercury in most tissues.     

Growth hormone radiologand assay unresponsive to human prolactin

A specific and sensitive radioligand assay for growth hormone with female rat liver plasma membranes is presented. Growth hormones of different species are able to displace labelled human growth hormone from membrane binding sites with parallel standard curves. Human prolactin V-L-S is not equal to 1 and the international human prolactin standard MRC 71/222 do not affect the assay. Human prolactin preparations with different growth hormone content displace human growth hormone tracer only to the same extent as they contain growth hormone when measured by radioimmunoassay.     

Immediate microscopic detection of an actinomycete in the soil producing a luminescent antibiotic

The effects of 10-day pretreatment with i.p. injections of zinc chloride, 16 mg/kg, on gastric secretion and on gastric ulceration induced by stress or by acid accumulation were examined in pylorus-occluded rats. Zinc chloride pretreatment significantly reduced the volume of gastric secretion and the total acid output as well as the incidence of gastric ulcers induced either by stress or by acid accumulation. The findings support the idea zinc compounds may be useful in the treatment of gastric ulcers.