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Biomedical subjects

Y C Ng

Publications and source records attributed to Y C Ng.

61 records · Page 4Linked to original sources

Percutaneous absorption, disposition, and excretion of 4,4'-methylenebis(2-chloroaniline) in dogs.

Percutaneous (pc) absorption, disposition, and excretion of 14C-MBOCA (4,4'-methylenebis(2-chloroaniline) ) were investigated in male beagle-type dogs by HPLC and compared to intravenously (iv) administered controls. Following application of 115 muCi MBOCA to a 25 cm2 area of the skin, no measurable radioactivity was detected in blood for the subsequent 24-hr period, but 14C-MBOCA and metabolites were excreted in urine and bile. During the 24-hr collection period, a total of 1.3% of the administered dose was recovered in the urine (0.4% of which was unchanged MBOCA). At 24 hr 0.62% of the dose was recovered in gallbladder bile. Approximately 90% of the administered dose was recovered in skin at the application site. Liver, kidney, and fat were the tissues with highest radioactivity. After a bolus iv injection, MBOCA disappeared rapidly from blood (t 1/2 beta = 0.70 hr). In the 24 hr following iv injection, 46% of the administered dose was excreted in urine (0.54% of which was unchanged MBOCA). At 24 hr 32% of the dose was recovered in gallbladder bile. Tissue radioactivity was 10-20 X higher after iv than pc administration and highest in liver, kidney, fat, and lung. The results demonstrated in a canine model that skin absorption was a viable route of entry for MBOCA and that unmetabolized MBOCA was a small percentage (0.4-0.5%) of the total urinary excretion. MBOCA was rapidly and extensively metabolized and excreted in urine and bile following both iv and pc administration.

Animals↗

Effects of progesterone derivatives on sodium pump activity and force of myocardial contraction in isolated guinea pig heart.

A progesterone derivative, chlormadinone acetate, has been reported to inhibit isolated Na,K-ATPase, to increase intracellular sodium, to decrease the force of myocardial contraction and to antagonize the positive inotropic action of ouabain. Because several inhibitors of isolated Na,K-ATPase fail to interact with the sodium pump in intact cells, two progesterone derivatives, chlormadinone acetate and megestrol acetate were examined for their effects on Na,K-ATPase, sodium pump activity and the force of contraction in isolated guinea pig atria. Both megestrol acetate and chlormadinone acetate inhibited specific (ATP-dependent) 3H-ouabain binding to Na,K-ATPase isolated from guinea pig brain or heart, with a corresponding inhibition of enzyme activity. The effects on Na,K-ATPase obtained from brain were more pronounced than that obtained from heart. The inhibitory effect of megestrol acetate was partially antagonized by K+. In electrically stimulated left atrial muscle preparations, neither compound affected ouabain-sensitive 42K+ uptake. Additionally, these compounds failed to affect the force of myocardial contraction or to influence the positive inotropic action of ouabain. These data fail to support the contention that inhibition of the sarcolemmal sodium pump is unrelated to the ouabain-induced increase in the force of myocardial contraction.

Animals↗

Lipid-tail group dependent structure of the fd gene 8 protein.

Using circular dichroism several laboratories have shown that the fd coat protein can assume three distinct conformations depending on the conditions. We have reinvestigated these three conformations using laser Raman spectroscopy and the quantitative estimates of alpha-helix by Raman agree fairly well with the earlier estimates obtained by CD. In addition, we have studied in more detail the conditions governing the 3 conformations. To our surprise, the nature f the lipid tail group seems to be the determining factor for two of the conformations. A lipid tail group dependence of protein structure is without precedent and has potential consequences for the assembly of filamentous phages as well as for the structure and function of cell membranes.

Circular Dichroism↗

Effects of metabolic inhibitors on the assembly of fd phage.

Treatment of E. coli cells that are actively producing fd phage with KCN, arsenate, DNP or CCCP inhibits production of infectious phage. These results are consistent with (but do not prove) an energy dependence for the assembly of fd phage. The major difficulty is to distinguish between a direct dependence on the proton motive force and an indirect one. Very preliminary experiments with valinomycin, which can be used to manipulate the voltage gradient of the cell membrane, and nigericin, which can be used to alter the pH gradient, suggest that a voltage gradient is not required for phage assembly but that pH gradient is required.

Arsenates↗

Cardiac actions of phencyclidine in isolated guinea pig and rat heart: possible involvement of slow channels.

The mechanisms responsible for the positive inotropic effect of phencyclidine were studied in isolated preparations of guinea pig and rat heart. In electrically paced left atrial muscle preparations, phencyclidine increased the force of contraction; rat heart muscle preparations were more sensitive than guinea pig heart muscle preparations. The positive inotropic effect of phencyclidine was not significantly reduced by a combination of phentolamine and nadolol; however, the effect was competitively blocked by verapamil in the presence of phentolamine and nadolol. Inhibition of the outward K+ current by tetraethylammonium chloride also produced a positive inotropic effect; however, the effect of tetraethylammonium was reduced by phentolamine and nadolol, and was almost insensitive to verapamil. The inotropic effect of phencyclidine was associated with a marked prolongation of the action potential duration and a decrease in maximal upstroke velocity of the action potential, with no change in the resting membrane potential. In partially depolarized atrial muscle preparations, which were reactivated by elevation of the extracellular Ca2+ level and stimulation at a high voltage, phencyclidine markedly increased the amplitude and the duration of the slow action potentials. Rat heart muscle preparations had higher sensitivity to these effects of phencyclidine. The specific [3H]phencyclidine binding observed with membrane preparations from guinea pig ventricular muscle was saturable with a single class of high-affinity binding site. This binding was inhibited by verapamil, diltiazem, or nitrendipine, but not by ryanodine or tetrodotoxin. These results suggest that the positive inotropic effect of phencyclidine results from enhanced Ca2+ influx via slow channels, either by stimulation of the channels or secondary to inhibition of outward K+ currents.

Animals↗