In vitro assessment of the selectivities of various beta-adrenergic blocking agents

Intrinsic sympathomimetic- and membrane activities of beta-adrenoceptor blocking agents are of little or no clinical significance. A selective blockade of cardiac receptors has important therapeutic consequences, especially in the treatment of patients with obstructive airways diseases. Profound depression of miocardial contractility can be deleterious in patients with cardiac muscle damage and the use of beta-adrenergic blockers with a quantitative selectivity towards chronotropism may become an important consideration. The effects of a number of beta-sympatholytics have been determined on isolated cardiac preparations (beta₁-adrenergic receptors) and tracheal preparations (beta₂-adrenergic receptors) of guinea-pigs. Results indicate that prindolol is the most selective blocker of the beta₁ chronotropic receptors whilst atenolol could be classified as being the most cardioselective beta-adrenergic blocker investigated. Butoxamine, on the other hand, proved to be the most beta₂-selective one.     

Impact of disease frequency and host density on pollination and transmission of an African anther-smut fungus

The vast majority of flowering plants rely solely on insects for pollination. A number of pathogens have evolved mechanisms to exploit these close associations and use pollinators as vectors of infective propagules. Factors that affect pollinator movements and successful pollination may in turn also influence successful transmission of fungal spores. Here we investigate the effect of host density and the frequency of diseased Oxalis lanata individuals infected by the anther-smut fungus, Thecaphora capensis, on the likelihood of receiving pollen and fungal spores. Specifically, we determined the numbers of spores and pollen grains deposited on stigmatic surfaces of selected flowers under natural and standardized conditions where host density and disease frequency varied. The effect of host flower density and diseased flower frequency on pollen and spore transfer was variable under natural conditions and these factors interacted significantly. However, an increase in host density and disease frequency significantly influenced pollen and spore deposits under standardized conditions. The effect of host density was, however, not linear and an optimal flower density for pollen and fungal spore transmission was found. Similar to other systems of vector-borne disease, the transmission of anther-smut of Oxalis lanata is more frequency-dependent than density-dependent. This study represents a first step towards understanding the disease transmission process of T. capensis on Oxalis and lays the foundation for future comparative studies between this and other systems to develop and test general hypotheses of disease dynamics in vector-borne disease transmission systems.     

Immobilization of wild dogs (Lycaon pictus) with a tiletamine hydrochloride/zolazepam hydrochloride combination and subsequent evaluation of selected blood chemistry parameters

A tiletamine hydrochloride/zolazepam hydrochloride combination was used successfully to immobilize captive untamed wild dogs (Lycaon pictus) (n = 16) at dosage rates ranging from 2.3 to 32.3 mg/kg. Animals remained immobilized for periods ranging from 35 min to 24 hr 14 min. There was a significant positive correlation (r = 0.85, P less than 0.01) between dosage rate and the time immobilized. Profuse salivation and intermittent mild myoclonal contractions were observed in some wild dogs. Mildly reduced partial oxygen and carbon dioxide pressures as well as reduced concentrations of bicarbonate were observed in arterial blood at 10 and 20 min after administration of the drug. Serum concentrations of sodium, potassium, chloride, phosphorus, calcium, magnesium, urea, creatinine, glucose, proteins, albumin, gammaglutamyltransferase, creatinine kinase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, insulin, cortisol and thyroxine are presented. These concentrations were found to be in agreement with values previously reported for wild dogs.     

Prolonged plasma half-life of insulin in patients with a genetic defect of high affinity binding sites

Plasma clearance of endogenous and intravenously administered insulin was studied in three sibs with severe insulin resistance secondary to an affinity defect of their insulin receptors, and in five healthy controls. Intravenous infusion of somatostatin was used to inhibit the insulin secretion. 0.3 U of insulin/kg body weight was administered as an intravenous bolus. Plasma glucose, immunoreactive insulin and C-peptide were determined subsequently at constant intervals. We found a prolonged plasma half-life of insulin in the three patients, being 33.5 +/- 11.8 min vs 8.2 +/- 2.2 min in controls, P less than 0.002, but a normal half-life of C-peptide. The result indicates, that the plasma insulin clearance is predominantly mediated by intact insulin receptors. We conclude, that insulin has a prolonged half-life in all patients with insulin resistance secondary to an impaired receptor function.     

Location of ligand-binding sites on the nicotinic acetylcholine receptor alpha-subunit

The portions of the Torpedo californica nicotinic acetylcholine receptor (AChR) alpha-subunit that contribute to the allosteric antagonist-binding site and to the agonist-binding site have been localized by affinity labeling and proteolytic mapping. [3H]Meproadifen mustard was employed as an affinity label for the allosteric antagonist-binding site and [3H]tubocurare as a photoaffinity label for the agonist-binding site. Both labels were found in a 20-kDa proteolytic fragment generated from the AChR alpha-subunit by Staphylococcus aureus V8 protease. This 20-kDa peptide also contains the 3H-labeled 4-(N-maleimido)-alpha-benzyltrimethylammonium iodide-reactive site and binds 125I-alpha-bungarotoxin. N-terminal sequencing established that the 20-kDa fragment began at Ser-173 of the alpha-subunit. Fluorescein isothiocyanate-conjugated concanavalin A could be bound to the second of the two major V8 cleavage products, an 18-kDa peptide. This peptide was also sensitive to treatment with endo-beta-N-acetyl-glucosaminidase H, consistent with the presence of N-linked carbohydrate on this fragment. The N terminus of this peptide was found to be Val-46 of the alpha-subunit sequence. Experiments designed to map disulfide bonds within the AChR alpha-subunit indicate that no bonds exist between the 18-kDa fragment (containing Cys-128 and Cys-142) and the 20-kDa fragment (containing Cys-192, Cys-193, and Cys-222). These results establish that the 20-kDa fragment contributes to both the acetylcholine and the allosteric antagonist-binding sites, whereas there is no evidence that the 18-kDa fragment is part of either site.     

The selectivity of action of the aspartic-proteinase inhibitor IA3 from yeast (Saccharomyces cerevisiae).

The ability of the aspartic-proteinase inhibitor IA3 from yeast (Saccharomyces cerevisiae) to affect the activities of a range of mammalian and microbial aspartic proteinases was examined. The inhibitor appeared to be completely selective in that only the aspartic proteinase A from yeast was inhibited to any significant extent. IA3 thus represents the first example of a totally specific, naturally occurring, aspartic-proteinase inhibitor.