Plasma concentrations of 9-deoxo-16,16-dimethyl-9-methylene-PGE2 in Rhesus monkeys after administration by various routes

A method is described for the estimation of 9-deoxo-16,16-dimethyl-9-methylene-PGE₂ by double antibody radioimmunoassay. Plasma samples obtained from animals treated with 9-methylene-16,16-dimethyl-PGE₂,1-adamantanamine salt were extracted with diethyl ether to recover the prostaglandin. The validation of sample preparation and assay procedure are presented. Rhesus females were treated by several routes of administration and the samples assayed for drug content. Maximum blood levels were probably reached 30 minutes following subcutaneous injection and within 30 seconds of an intravenous injection. Results of the acute intravenous injection indicate an initial half-life of approximately one minute in peripheral circulation. Continuous intravenous infusion at 3 increasing doses of this compound resulted in a stepwise increase in plasma drug concentrations. Vaginal administration of 9-methylene-16,16-dimethyl-PGE₂,1-adamantanamine salt in suppositories produced a dose dependent increase in plasma drug concentration. Higher plasma drug concentrations were produced when the prostaglandin was delivered in H-15 base suppositories than in E-76 base suppositories.     

The Brompton mixture versus morphine solution given orally: effects on pain.

The Brompton mixture is widely used as an effective method for controlling pain in cancer patients. In a double-blind crossover trial a standard Brompton mixture containing morphine, cocaine, ethyl alcohol, syrup BP and chloroform water was compared with morphine alone in a flavoured aqueous solution; both were administered orally. Pain was measured by means of the pain intensity index of the McGill Pain Questionnaire. Ratings of confusion, nausea and drowsiness were obtained from both the patients and their nurses and relatives. The data showed that there was no significant difference between the Brompton mixture and morphine administered orally for any of the variables. Both relieved pain effectively in about 85% of the patients.     

The role of displacement of the mitral annulus in left atrial filling and emptying in the intact dog

The variations in ventricular-atrial mitral annular position during the cardiac cycle and the simultaneous changes in left atrial silhouette area (obtained by angiography after injections of contrast material into the main pulmonary artery) were investigated in six experiments on intact dogs with chronically implanted intracardiac markers. Frame-by-frame measurements of the angiograms (120 frames/s) were used to determine, under various hemodynamic conditions, the duration, magnitude, and average rate of the mitral annular motion and of the simultaneous changes in left atrial area during atrial filling (ventricular systole) and atrial emptying (early in ventricular diastole). The mitral annulus was seen to move towards the ventricular apex during systole and towards the atrium early in diastole with the duration, average rate, and magnitude of displacement (although varying widely) showing good statistical correlations (P less than 0.0005-0.005) with the changes in projected left atrial area. These findings suggest that the duration, rate, and magnitude of atrial filling and emptying may be, in the intact heart, determined by the movements of the atrioventricular junction.     

Observations on electrocardiogram and plasma catecholamines during dental procedures: the forgotten vagus.

Emotional stress is conventionally considered to be associated with tachycardia and enhanced sympathetic activity. The electrocardiogram and plasma catecholamine and lipid concentrations were observed in 21 young healthy women undergoing dental procedures. Ten of these received premedication with the beta-blocking agent oxprenolol and 11 with a placebo, administered on a double-blind randomised basis. Mild tachycardia occurred in the placebo group a few minutes before and a few minutes after dentistry, but there was a reduction in heart rate immediately before and during the procedure. The pattern was similar in the group who received oxprenolol, though the heart rates at each stage were lower. Plasma adrenaline concentrations were much higher in the samples taken during the procedure than in those taken shortly before and after it. Plasma noradrenaline and lipid concentrations remained unchanged. A decrease in heart rate in the face of intense emotional arousal and an increased plasma adrenaline concentration suggest that the expectation or experience of pain may be associated with parasympathetic dominance despite greatly enhanced sympathetic activity.     

Physical and chemical properties of beta-glucuronidase from the preputial gland of the female rat.

In order to obtain sufficient quantities of beta-glucuronidase for use in structural studies, the enzyme was purified from its richest known source, the female rat preputial gland, by a method similar to that of Ohtsuka and Wakabayashi (1969) (Enzymologia 12, 109). The purified enzyme has an S-o20, w of 12.5 S and a D-o20, w of 4.3 times 10- minus 7 cm-2 S-minus 1. Sedimentation diffusion and sedimentation equilibrium yielded molecular weights of 267,000 and 283,000, respectively. The limiting viscosity (3.6 ml/g) and the f/fo (1.08 at sigma equals to 0.2 g of H2O/g of protein) indicate that the enzyme is a typical globular protein possessing little asymmetry. The circular dichroism spectrum indicates approximately 14% alpha-helix and a far greater amount of random coli than beta structure. The enzyme is acidic, having an isoelectric point of 6.15. In electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate the enzyme exhibits a single band at molecular weight 72,000, a result indicating that the enzyme consists of four subunits of similar molecular weight. Tryptic peptide mapping suggests that the subunits are identical.     

Global biogeography of warning coloration in the butterfly Danaus chrysippus

Warning coloration provides a textbook example of natural selection, but the frequent observation of polymorphism in aposematic species presents an evolutionary puzzle. We investigated biogeography and polymorphism of warning patterns in the widespread butterfly Danaus chrysippus using records from citizen science (n = 5467), museums (n = 8864) and fieldwork (n = 2586). We find that polymorphism in three traits controlled by known mendelian loci is extensive. Broad allele frequency clines, hundreds of kilometres wide, suggest a balance between long-range dispersal and predation of unfamiliar morphs. Mismatched clines for the white hindwing and forewing tip in East Africa are consistent with a previous finding that the black wingtip allele has spread recently in the region through hitchhiking with a heritable endosymbiont. Light/dark background coloration shows more extensive polymorphism. The darker genotype is more common in cooler regions, possibly reflecting a trade-off between thermoregulation and predator warning. Overall, our findings show how studying local adaptation at the global scale provides a more complete picture of the evolutionary forces involved.