Cardiovascular action of" peritoneal dialysate-depressor-I" (PD. D-I), a short-acting hypotensive phospholipid occurring in dog peritoneal dialysate, was investigated. With an intravenous injection of PD. D-I into an anaesthetized rat, a sharp fall of arterial blood pressure was observed and the effects were dose dependent. The maximum hypotensive effect was about 60 mmHg and the minimum effective dose was approximately 35 μg/kg. Neither tachyphylaxis nor sensitization was observed. Even in conscious rats PD. D-I elicited hypotensive responses, though the effect was much weaker than that produced in anaesthetized rats. In spinal rats the hypotensive effects were also observed. In the tests on rats reserpinized or pretreated with antimuscarinic, antihistaminic, β-adrenergic-blocking and ganglionic-blocking agents, the depressor effect of PD. D-I was not affected. PD. D-I elicited also hypotensive responses in anaesthetized cats, rabbits and guinea pigs in the same degree as those in anaesthetized rats. The relaxation of the peripheral blood vessels was observed in the test on perfused rabbit ear. The depressor factor showed no smooth muscle stimulating activity in isolated guinea pig ileum preparations. Judging from these findings, the hypotensive effect of PD. D-I is not ascribable to the central, sympathetic or parasympathetic nervous system but possibly to direct action on the peripheral vascular system.

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The mechanism of antitumor activity of 5-fluorouracil (FU) was studied in mouse leukemia L5178Y cells in vitro. FU increased labeled-thymidine incorporation into acidinsoluble fraction and inhibited labeled-deoxycytidine incorporation as did 5-fluorouridine (FUR) and 5-fluoro-2'-deoxyuridine (FUdR). FU and FUR inhibited labeled-uridine incorporation but FUdR did not. For reversal method at the equieffective concentration of FU, FUR or FUdR, antiproliferating effects of FU and FUR were partially reversed by thymidine and deoxyuridine though FUdR toxicity was completely abolished by both compounds. These results demonstrate that FU and FUR affect not only thymidylate synthesis as a consequence of the conversion to deoxymononucleotide, but also the site concerning functioning RNA synthesis in L5178Y cells, and the FUdR is a specific inhibitor of thymidylate synthesis.

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The influence of Ca²⁺ on the antioxytocin actions of papaverine, deoxycholate and 1, 1-diphenyl-3-piperidinobutanol hydrochloride (Aspaminol) was investigated in the ovariectomized and the estradiol-treated rat uteri, and Ca exchangeability and Ca content in both uteri were compared. No qualitative difference in the responses to deoxycholate and Aspaminol at normal and higher Ca²⁺ concentrations in the estradiol-treated rat uterus was seen as compared to those obtained from the ovariectomized one. The antioxytocin action of papaverine in the estrogenized uterus was antagonized by excess external Ca²⁺, but not in the ovariectomized one. There were no significant differences either in the total Ca content or the non-displaceable Ca by La between the ovariectomized and the estrogenized rat uterine longitudinal muscle layers, while Ca exchangeability in the estrogenized specimen was much greater than that in the ovariectomized one. These results suggest that the antagonism of papaverine against excess exogenous Ca²⁺ may be related to the more increased Ca exchangeability in the estradiol-treated rat myometrium.

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5-Fluorouracil-resistant cell line designated as L5178Y/FU was established in this experiment. This is one of the colonies derived from the subculture which acquired resistance to 5-fluorouracil by passaging the L5178Y cells through ten successive episodes of culture in Fischer's medium containing 5-fluorouracil, in which each 5-fluorouracil treatment was followed by recovery intervals. The resistance of this line is about 80-fold that of the IC₉₉ of 5-fluorouracil, and also shows a cross resistance to both 5-fluorouridine and 5-fluoro-2'-deoxyuridine. 5-Fluoro-2'-deoxyuridine resistant subline designated as L5178Y/FUdR was also isolated from the subculture which acquired resistance to 5-fluoro-2'-deoxyuridine by using the same selection procedure. The resistance of this line is about 650-fold that of the IC₉₉ of 5-fluoro-2'-deoxyuridine, and shows a partial cross-resistance to 5-fluorouridine, but not to 5-fluorouracil.

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The effect of hydralazine on the alteration of blood sugar, tissue glycogen and blood cAMP levels in rats were investigated. Hydralazine was found to increase blood sugar level in intact rats when administered i. p. On the other hand, this hyperglycemia was partially blocked either by the treatment of intact rats with propranolol, β-adrenergic blocker, or by adrenalectomy. Hydralazine treatment increased blood cAMP level, leading to the hyperglycemia, because pretreatment with phentolamine partially blocked the hydralazine-induced hyperglycemia.

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Antibody to aprotinin was easily produced in rabbits by injecting an emulsion of Trasylol and adjuvant, and its specificity was confirmed by double diffusion, immunoelectrophoresis in gel, passive hemagglutination and affinity chromatography of Trasylol. The location of aprotinin in bovine lung and pancreas was determined by an indirect fluorescent antibody technique. The fluorescence observed in the connective tissues was found to be due to the mononuclear cells in these tissues.

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The preparation and antigenic properties of two different types of dehydroepiandrosterone sulfate-bovine serum albumin (BSA) conjugates in which the hapten is linked to the carrier protein through the C-17 or C-15 position have been described. Antibodies raised against these antigens in rabbits possessed the high affinity (K_a=1.43×10⁹-2.20×10⁹M^-1) to dehydroepiandrosterone sulfate. Antiserum elicited by immunization with the hapten-15β-BSA conjugate was specific to dehydroepiandrosterone sulfate, exhibiting no significant cross-reactivities for other sulfated steroids and no cross-reactions for free steroids and their glucuronides with an exception of 16α-hydroxydehydroepiandrosterone 3-sulfate (16.8%).

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Effects of a new minor tranquilizer, CS-386 and diazepam were studied upon the gastric contraction and excitation of lumbar gamma-motoneurons following stimulation of some of the brain structures as well as upon the spontaneous gastric motility in the cat. CS-386 inhibited the hypothalamus-induced gastric contraction with little changes in spontaneous motility at doses of 5 and 10 mg/kg (i. d.). Diazepam inhibited both the hypothalamus-induced contraction and spontaneous motility at these doses. The vagal nerve-induced gastric contraction was suppressed by diazepam (5 mg/kg, i. d.) but not by the same dose of CS-386. Bemegride (5 mg/kg, i. v.) antagonized almost completely the depression caused by 5 mg/kg of CS-386, but not that by a dose of 10mg/kg or 5 as well as 10mg/kg of diazepam. Excitation of the lumbar gamma-motoneuron following stimulation of the posterior hypothalamus or the mesencephalic reticular formation was depressed by CS-386 or diazepam (10mg/kg, p. o.), but not by lower doses. Based on these evidences, it was suggested that CS-386 could be effective in stress-induced gastric lesions with lower side effects in digestive organs than diazepam.

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In the experiment on continuous perfusion of rat stomach in vivo, genipin inhibited only the gastric acid secretion induced by carbachol, but not by tetragastrin, or histamine. In the experiment on isolated organs, genipin showed a weak competitive anti-acetylcholine action on the intestinal contraction. Based on these facts and results reported previously, it is conceivable that anti-cholinergic action at least partly contributes to the genipin-induced inhibitory effect on gastric functions. Erythritol clearance was increased with the increase in bile flow by administration of genipin. Genipin showed a significant choleretic action, and just then the concentration of biliary bile acid was decreased inversely. In the relationship between bile flow and biliary bile acid excretion rate, the slope of regression line obtained from genipin-treated group was not significantly different from that of control, and these lines were approximately parallel to each other. Genipin did not affect the concentration of sodium, potassium, chloride, or bicarbonate in the bile collected during the initial stage, in which bile flow was increased, after administration. It is concluded from these results that genipin-induced choleretic action proceeds by a mechanism wherein water is driven along osmotic gradient which originates in the transport of bile acid-independent fraction from hepatocytes into canaliculi, mainly through active Na⁺ transport.

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