Effect of i.v. and i.d. cinnamaldehyde on plasma catecholamine concentration along with intestinal absorption of the drug was studied in anesthetized dogs. Cinnamaldehyde increased plasma catecholamine concentration, the effect produced through i.d. route (50-100 mg/kg) being dose-dependent and more lasting compared with that through i.v. route (20mg/kg). In the case of 200 mg/kg of i.d. cinnamaldehyde, an exceeding increase in this parameter was obtained during the later period of time course. Intestinal absorption of cinnamaldehyde i.d administered, which was investigated through measurement of cinnamaldehyde concentration in the portal venous blood and in blood of the postcava, occurred very early and was long-lasting. Increase in plasma catecholamine concentration produced by i.v. cinnamaldehyde disappeared after blood circulation through the adrenal glands was stopped, and was not influenced with pretreatment of hexamethonium plus atropine. Almost all the increased portion of plasma catecholamines by i.v. or i.d. cinnamaldehyde was epinephrine. It was concluded that cinnamaldehyde, entering the circulatory system, reaches the adrenals and releases catecholamines from the organ through a mechanism(s) independent of affecting the cholinergic system. i.v. DMPP which was used as a referential drug also increased plasma catecholamine concentration.

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DPG-3-2, a component of ginseng radix, which lowers the blood glucose level and stimulates insulin release in diabetic animals, was studied for its effects on insulin biosynthesis in different preparations of pancreas from animals with normoglycemia and with hyperglycemia (alloxan diabetic rats and genetically diabetic mice, KK-CA^y). We measured incorporation of radioactive leucine into insulin and other protein fractions during a 2-h perfusion of rat pancreas, and into insulin during a 3-h incubation of mouse islets. Biosynthesis of insulin during a long-term culture of islets from KK-CA^y mice was also measured. DPG-3-2 was found practically not to increase the incorporation into insulin in the pancreatic preparations from animals with normoglycemia, but in such preparations from animals with hyperglycemia DPG-3-2 (0.2-1.0 mg/ml caused 1.5-1.8-fold incorporation into insulin. In addition, a long-term treatment of DPG-3-2 (0.5 mg/ml) was shown to stimulate insulin biosyntesis in islets from KK-CA^y mice. Ginsenoside-Rb₁ and -Rg₁ decreased the insulin content of islet to the undetectable level. Thus, DPG-3-2 was shown to stimulate insulin biosynthesis in different preparations of pancreas from animals with hyperglycemia.

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Competitive inhibitory behavior among zwitterionic β-lactam antibiotics in the rat intestinal absorption process was examined. Intestinal absorption of cephradine and cephalexin was significantly inhibited by cyclacillin. The mutual inhibition between these amino-cephalosporins was also observed. On the other hand, in the pretreatment experiments with cyclacillin, it was found that absorption of cephradine was significantly inhibited, but the inhibitory effect of cyclacillin was not observed for cephalexin. These results showed that cephradine had a common carrier-mediated transport mechanism with cyclacillin which is not present in the absorption process of cephalexin. It was postulated that the mutual inhibition between cephradine and cephalexin is based on the competitive inhibition in the accumulation or uptake by the intestinal mucosa.

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The motility of ejaculated human sperm which was washed thoroughly by Ficoll gradient centrifugation to remove seminal plasma was investigated in the presence of various concentrations of sugars. Washed human sperm showed high motility in an artificial medium containing glucose and fructose, which were major sugar components of semen. However, marmitol and 3-O-methyl-D-glucose had no effect on sperm motility. Doseresponse curves of sperm motility in the additions of glucose or fructose were bell-shaped. The maximum sperm motility was found in the medium with 1 mM glucose or 15 mM fructose. When, however, both 1 mM glucose and 15 mM fructose were added to the medium, sperm motility was higher than that with an individual sugar. Although phlorizin decreased glucose activated sperm motility, it has no effect in case fructose was the activator. The results suggest that the effect of glucose on human sperm motility is due to a different mechanism from that of fructose.

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Rat erythrocytes incubated in photoactivated riboflavin system in the presence of serum caused a rapid hemolysis. During the course of illumination, a marked efflux of intracellular K⁺, increase in osmotic fragility and promotion of lipid peroxidation of the cell occurred prior to hemolysis indicating that riboflavin-induced photohemolysis is colloidosmotic process. In the absence of serum, however, no hemolysis was observed at any time of incubation, suggesting that membrane damages are enhanced by the illumination in the presence of serum. Furthermore, the illumination of cells in the photoactivated riboflavin system in the presence of serum under continued anaerobic conitions did not exhibit any significant hemolysis. These results indicate that the photohemolysis of cells is due to oxidative damages of cell membrane that initiated te hemolysis. Singlet oxygen (¹O₂) scavengers employed in this study strongly inhibited the photohemolysis, suggesting that cells are damaged oxidatively by ¹O₂ generated in photoactivated riboflavin system in the presence of serum. Furthermore, triplet quenchers and α-tocopherol suppressed this photohemolysis. A reference was made concerning a possible adverse effect of riboflavin on infant erythrocytes in phototherapy.

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An antitumor polysaccharide, EA₃ isolated from a Japanese edible mushroom, Flammulina velutipes (CURT. ex FR.) SING.^1-3) is composed of D-glucose. Studies to determine its structure were performed by mean of partial acid hydrolysis, acetolysis and the chemical analysis of the complete hydrolysates of the fully methylated polysaccharide. Thus the chemical structure of EA₃ was found to be that of a β-(1→3)-glucan. Another antitumor polysaccharide (EA₅) also isolated from F.velutipes^{2, 3)} was fractionated on a concanavalin A-Sepharose 4B column. The active antitumor component was further purified by column chromatography on Sephadex G-200. Among the polysaccharides isolated the highest molecular weight polysaccharide (EA₅₀₁) showed the highest rate of antitumor activity. The component sugar of EA₅₀₁ were found to be D-glucose 42.3%, D-galactose 17.3%, D-mannose 12.2%, D-xylose 6.7% and L-arabinose 14.7%.

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Exposure of rats to restraint plus water-immersion (25°C) stress produces a marked increase in gastric motility with hypothermia. Although this phenomenon was generally considered to be due to centrally mediated cholinergic mechanisms, the present study was designed to elucidate some local peripheral mechanism in enhancing gastric motility with hypothermia. After the onset of water-immersion (37-17°C), body temperature rapidly varied depending on water temperature and gastric motility changed in its pattern with stress duration ; increase in gastric motility reached a maximum at 25°C but declined at 17°C. These alterations of gastric motility pattern were not primarily associated with activation or decline of the sympatho-aderenal system. In these stressed rats, either vagally intact or vagotomized, contractile responses of the stomach to i.v. or i.a. administration of bethanechol and acetylcholine, but not to that of histamine, were markedly augmented by lowering body temperature. Similar observations were noted in rats exposed to restraint plus cold (6°C) stress. These results emphasize the possibility that augmentation of gastric motility during waterimmersion (25°C) occurs at least in part through local peripheral mechanisms of increasing the contractile sensitivity of the stomach to acetylcholine with hypothermia.

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The binding characteristics of zwitterionic and monobasic β-lactam antibiotics to the components intestinal mucosa of rat was investigated. From the binding experiments using the brush border membrane preparation and the insoluble cellular fractions, there was no correlation between the binding behavior and the absorption characteristics. However, there was a highly significant correlation between the affinity to the soluble F1 fraction and the absorption characteristics of these antibiotics. It was also found that the binding of these antibiotics to the other soluble protein fractions were significantly smaller than that to F1 fraction. It was postulated that the binding properties of these antibiotics to soluble F1 fraction play an important role in the absorption process.

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The effects of L-cysteine methyl ester on behavior of mucus glycoproteins in canine tracheal secretory cells were investigated histologically and histochemically. Low concentrations (10^-7 and 10^-6M) of L-cysteine methyl ester produced, as histological changes, decreases in the total goblet cell number and the thickness of the acini of submucosal glands, and an increase in the acinar inner diameter. On the other hand, L-cysteine methyl ester at 10^-5 and 10^-4M produced an increase in the thickness of the acini and a slight decrease in the acinar inner diameter. Both the total acid glycoprotein and sulphated glycoprotein contents in glandular cells markedly decreased, whereas the neutral glycoprotein content in the cells increased following L-cysteine methyl ester treatment in a concentration-dependent way. Total saccharide and protein concentrations in the incubation fluid increased with 10^-7 and 10^-6M, but decreased with 10^-5 and 10^-4M L-cysteine methyl ester. N-Acetylhexosamine concentration in the bathing fluid increased at l0^-7 and 10^-6M of the agent. These findings suggest that low concentrations of L-cysteine methyl ester stimulate secretory activities of tracheal secretory cells, while at high concentrations the agent stimulates synthesis of mucus glycoproteins in the submucosal glands. Additionally, it is suggested that L-cysteine methyl ester has a marked viscosity lowering effect on the mucus in the secretory cells.

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Lipid-lowering effects of KF1492, N-[4-methylbenzylthiocarbonyl]-L-phenylalanine, were evaluated in comparison with clofibrate. This compound lowered serum cholesterol (s-CL) and triglyceride(s-TG) in cholesterol-fed, Triton-injected and glycerol-fed rats as well as in normal rats. The dose of KF1492 required to show these effects was almost equal to that of clofibrate. In addition, KF1492 produced significant reductions of s-CL and s-TG in thiouracil-fed rats and decreasing phase of Triton-induced hyperlipemia of rats. In these models, clofibrate produced no significant reductions. Clofibrate produced a marked increase of liver size and shortened the pentobarbital-induced sleeping time in rats. On the contrary, the increase of liver size by KF1492 was less marked than clofibrate, and KF1492 caused no change in the sleeping time. Thus, it is apparent that KF1492 is a new lipid-lowering compound with less hepatic effect than clofibrate and that the lipid-lowering profile of KF1492 differs from that clofibrate in some points.

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The effect of zinc on bone metabolism was investigated in weanling rats orally administered zinc sulfate (0.1, 1.0 and 10 mg Zn/100g body wt) for 30 d. The administration of zinc produced dose-dependent increases in zinc contents of the femoral diaphysis and epiphysis. The dry weight of the femur was significantly increased by the doses of 0.1 and 1.0 mg Zn/100 g for 3d, while significant reduction of that was observed by zinc administration for 30 d. Meanwhile, DNA content, calcium content and alkaline phosphatase activity in the femoral diaphysis and epiphysis were significantly increased by the doses of 0.1 and 1.0 mg Zn/100 g for 3 d. However, by the 30 d administration of zinc (0.1, 1.0 and 10 mg/100 g), calcium contents in the femur and serum were markedly decreased. These results suggest that comparatively low dose of zinc may stimulate the bone growth and calcification of weanling rats.

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To evaluate the distribution of water soluble macromolecular compound in the body, heparin was selected as one of the model compounds. Urinary and fecal excretion, and plasma levels following intravenous administration of commercial ³H-heparin were investigated at three different dose levels. Whole-body autoradiography was also carried out periodically following intravenous administration of ³H- heparin at single dose level. The distribution of radioactivity following the administration of ³H-heparin was compared with that of ¹⁴C-polyethylene glycol 6000. The statistically significant but only very small differences in the pharmacokinetic parameters and in the urinary excretion were observed over the wide range of dose (0.20, 2.0 and 20 mg/kg). The decline of plasma radioactivity following the administration of ³H-heparin appeared to be biexponential with time and pharmacokinetic constants were calculated according to a two-compartment open model. Whole-body autoradiograms showed that the reticulo-endotherial system (R.E.S.) may play an important role in removal of the radioactivity of heparin from the circulating blood.

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Effects on CCl₄-induced liver lesion in mice and on D-galactosamine-induced liver lesion in rats of desoxypodophyllotoxin (1) and its analogs, podophyllotoxin (2), podophyllotoxon (3), β-peltatin (4), α-peltatin (5), 4'-demethylpodophyllotoxin (6) and picropodophyllin (7), were investigated. 1 and 7 in CCl₄-induced liver lesion and 1, 4, 5, and 6 in D-galactosamine-induced liver lesion have shown marked protective actions. These results suggest that these analogs have liver-protective actions in general and the substituents at C-4 in ring C, C-5 in ring B and C-4' in ring E, and the configuration at C-2 in ring C are important for the revelation of the activity.

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