In order to examine to what extent adrenergic mechanism contributes to the urethral pressure in patients with benign prostatic hypertrophy, changes in the intraurethral pressure in the prostatic zone were measured in vivo by both the urethral pressure profile technique and the balloon method before and after administration of alpha-adrenergic stimulants and an alpha-adrenergic blocker. The effect of spinal anesthesia on the urethral pressure was also investigated. It is suggested that 40 per cent of the total urethral pressure in patients with benign prostatic hypertrophy is due to alpha-adrenergic tone, and the remaining 53 per cent is due to static pressure resulting from the hypertrophied prostatic bulk. The in vitro study indicates that the increase in urethral pressure and contraction of the prostate, prostatic capsule and prostatic urethra.

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SummaryEffect of Ticlopidine, 5-(2-chlorobenzyl)-4, 5, 6, 7-tetrahydro[3,2-C]pyridine hydrochloride, on platelet aggregation was studied in the rat. Ticlopidine was found to be a potent, long-lasting inhibitor of platelet aggregation. It inhibited the aggregation induced by any of ADP, collagen, thrombin, arachidonic acid and prostaglandin endoperoxides and/or thromboxane A2-like substance. Ticlopidine was effective at doses as low as 30 mg/kg when orally given to rats, and the effect lasted as long as the life span of the circulating platelets (half time: about 48 hours).Ticlopidine inhibited also nucleotide release from and prostaglandin synthesis in the platelets, but did not significantly affect platelet adhesiveness to glass, platelet factor 3 availability and clot retraction.

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There is a considerable interest in developing potent and safe hypolipidemic drugs for the prevention and management of coronary heart disease in man. In rodents, many of these hypolipidemic compounds induce hepatomegaly, proliferation of peroxisomes and a polypeptide with an approximate mol. wt. of 80000 in liver cells. In the present study, we have examined 10 hypolipidemic compounds for the induction of peroxisome proliferation associated 80000 mol. wt. polypeptide (polypeptide PPA-80), peroxisomal enzymes and peroxisome proliferation in rat liver, in view of the emerging evidence that hepatic peroxisome proliferators as a class are carcinogenic in rats and mice. All ten compounds, fenofibrate (isopropyl-[4-( p-chlorobenzoyl)2-phenoxy-2-methyl] propionate; LS 2265 (taurine derivative of fenofibrate); bezafibrate (2-{4-(2-[4-chlorobenzamido)ethyl] phenoxy}-methyl propionic acid; gemfibrozil (5-2[2,5-dimethylphenoxy]2-2-dimethylpentanoic acid); methyl clofenapate (methyl-2-[4-( p-chlorophenyl)phenoxy]-2-methyl propionate); DG 5685 (5-[4-phenoxybenzyl] trans-2-(3-pyridyl)1,3-dioxane), DH6463 (5-[4-phenoxybenzyl] trans-2-(3-pyrimidinyl)-1,3-dioxane); tiadenol(bis[hydroxyethylthio]-7, 10-decane); ciprofibrate (2,-[4-{2,2-dichlorocyclopropyl}-phenoxy]2-methyl propionic acid) and RMI-14,514 ([5-tetradecycloxyl-2-furancarboxylic acid), produced a marked but variable increase in the activities of peroxisomal enzymes catalase, carnitine acetyltransferase, heat-labile enoyl-CoA hydratase and the fatty acid β-oxidation system and in the amount of polypeptide PPA-80 as demonstrated by SDS-polyacrylamide gel electrophoresis. The peptide map patterns of polypeptide PPA-80 in liver induced by these compounds were strikingly similar. The ultrastructural studies demonstrate that fenofibrate, ciprofibrate, LS 2265, DG 5685 and DH 6463 can induce proliferation of peroxisomes in liver cells of rats, and further confirm the previous reports of hepatic peroxisome proliferative activity of methyl clofenapate, tiadenol, bezafibrate, gemfibrozil and RMI-14514, as shown morphologically. Whether these structurally unrelated chemicals or their metabolite(s) directly activate the peroxisome specific genes to induce this multi-enzyme system or they exert their action on peroxisomes indirectly by causing fatty acid overload in hepatocytes remains to be elucidated. These chemicals offer a simple and reproducible means of stimulating peroxisomal enzymes in liver and should serve as useful tools, for evaluating the implications of hepatic peroxisome proliferation and in elucidating the mechanism of peroxisome proliferator-induced carcinogenesis.

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Whole cell, patch-clamp studies were performed to examine the effect of lysophosphatidylcholine (LPC) on the membrane current in guinea-pig ventricular myocytes. The addition of 10 microM LPC to the external solution induced a membrane current which had a reversal potential of 0 mV. When Na+, the main cation in the external solution, was replaced by either K+, N-methyl-D-glucamine (NMG) or 90 mM Ca2+, LPC induced a current with the reversal potential near 0 mV, indicating that the current passed through a Ca2+-permeable non-selective cation channel. The order of the cationic permeability calculated from the reversal potential of the current was Cs+ > K+ > NMG > Na+ > Ca2+. Cl- did not pass through the LPC-induced channel. The LPC-induced current was not blocked by Gd3+ in the external solution, nor by the absence of Ca2+ in the pipette solution. In conclusion, LPC induces a Ca2+-permeable non-selective cation channel in guinea-pig ventricular myocytes.