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Biomedical subjects

T Miyata

Publications and source records attributed to T Miyata.

At least 793 records · Page 44Linked to original sources

Metabolites of piperidine in rat urine.

Piperidine is one of pharmacologically active biogenic amines. While two pathways for piperidine production have been reported, little is known about metabolism of the compound. In the present study, piperidine and its hydroxylated, conjugated and unknown metabolites were detected in rat urine by radiochromatographic analysis. Using GC-MS technique, it was confirmed that 3-hydroxypiperidine and 4-hydroxypiperidine are major metabolites of piperidine of either exogenous or endogenous origin. The findings substantiate the existence of a mechanism which inactivates piperidine in the living body, since both metabolites lack the potent pharmacological activities as those induced by piperidine.

Acetylation↗

[Action of 4-amino-alpha-](tertbutylamino) methyl]-3, 5-dichlorobenzylalchol hydrochloride (N-AB 365, clenbuterol) on the respiratory system (author's transl)].

The bronchodilating effect and other related pharmacological properties of N-AB 365 were studied in comparison with those of isoproterenol, salbutamol and clorprenaline. N-AB 365 was found to produce a bronchodilating effect 1/20 approximately 1/100, 1/10 approximately 1/40 and was 2 to 5 times as strong as effects of isoproterenol, salbutamol and clorprenaline, respectively. The bronchodilating effect of N-AB 365 was sustained more than 10 times as long as those of isoproterenol and salbutamol, and in particular with oral administration, was much more potent. The bronchodilating effect of N-AB 365 seems to be due mainly to excitation of the adrenergic beta2-receptor and partially to papaverine-like action. N-AB 365 showed an inhibitory effect on experimentally induced bronchial asthma by spraying of bronchoconstrictors and the effect by oral administration was much stronger than those of isoproterenol and salbutamol. N-AB 365 affected neither the volume output of respiratory tract fluid nor the tracheal ciliary movement with the doses around ED50 in bronchodilating action, however, it increased ciliary activity and decreased the volume output of respiratory tract fluid with large doses. Antitussive effect was also demonstrated only with the large doses. N-AB 365 induced a moderate decrease in blood pressure through vasodilatation but did not influence respiration. The effect of N-AB 365 on heart rate varied. There were cases of no change, slight increase or slight decrease in heart rate.

Acetylcholine↗

Soluble artifical tear inserts.

This article reports a new concept in the treatment of tear film abnormalities. Solubilization of an artifical tear insert provides a continuous flow of polymer into the tear film in place of intermittent drop therapy. The physiochemical properties of succinylated collagen were studied in vitro and compared favorably with presently available tear substitutes. The use of this polymer as a solid solubilizable insert was evaluated in normal patients. It was found to be comfortable, resulted in no blurring of vision, and prolonged the tear film breakup time.

Cellulose↗

Neural mechanism for production of spasmodic expiratory response like cough induced by amygdala stimulation in the cat. I. Pathways from the amygdala to the lower brain stem.

The pathways descending from the amygdala to neural structures in the lower brain stem responsible for production of spasmodic expiratory response like cough (SER), which occurred upon electrical stimulation of the cortical nucleus of amygdala (Aco), were investigated using microinjection and ablation techniques in the cat. 1) Following transection of the bilateral stria terminalis (STT), the threshold for SER production was remarkably elevated. 2) SER was suppressed by administration of procaine (20 microgram) or diazepam (5 microgram) into either side of the hypothalamic ventromedial nucleus (Hvm); furthermore, SER completely disappeared after lesion of bilateral Hvm. After lesion of the ipsilateral Hvm to the side of stimulation, the threshold for SER was obviously elevated, but SER was not affected by lesion of the contralateral Hvm. 3) After section of the substantia grisea centralis at the midcollicular level, SER disappeared. 4) Both SER and peripherally-induced coughs were depressed by codeine (10 microgram), dextromethorphan (10 microgram) or procaine (20 microgram) administered into the solitary tract nucleus (STN) or the nucleus reticularis parvocellularis. 5) SER and coughs disappeared after lesion of the bilateral STN or nucleus ambiguus (AM). These results demonstrate that most of the efferent fibers from Aco get to Hvm via STT, and further to STN and AM in the medulla.

Amygdala↗

Neurobiology of piperidine: its relevance to CNS function.

Piperidine is a normal constituent in mammalian brain, affects synaptic mechanism in the CNS, and influences neural mechanisms governing regulation of emotional behavior, sleeping, and extrapyramidal function. In addition, there are enzyme systems within the brain that synthesize and metabolize piperidine, and uptake and storage mechanisms for piperidine are found in the nerve endings. In conclusions, piperidine seems to be intimately connected with the neuronal function of the brain.

Animals↗

Deposition of platelets and fibrin on chemically modifide collagen hollow fibers.

A new technique was devised for interaction studies between human blood and chemically modified amorphous collagen surfaces. Blood is drawn directly from an antecubital vein, through saline-filled collagen hollow fibers, at either constant flow for varying time or constant time at varying flow. Platelets and fibrin were deposited more rapidly and in greater numbers on methylated surfaces and more slowly and to a lesser extent on succinylated surfaces than on native surfaces. Increasing blood flow was associated with increased fibrin formation. Adherent platelets spread over 3-8 mu of methylated surface, but retained a spherical shape (1-2 mu) on succinylated and native surfaces. Thus, charge modification of collagen significantly alters platelet adhesion, subsequent platelet morphology, and fibrin deposition. Methylated surfaces are thrombogenic and succinylated ones are relatively thrombo-resistant.

Biocompatible Materials↗

Antitussive activity and other related pharmacological properties of d-3-methyl-N-methylmorphinan (AT-17).

Antitussive activity and some other related pharmacological properties of d-3-methyl-N-methylmorphinan were studied. Toxic symptoms in mice and dogs were due to the CNS excitation. Acute toxicity of (AT-17) in mice was slightly (s.c.) or far (p.o.) weaker than that of codeine, but it was three times as toxic as codeine in dogs (i.v.). Antitussive efficacy was about 40% of that of codeine in dogs, whereas 77% as potent as codeine in cats. It showed no relaxing effect on the bronchial muscle of guinea pigs in either normal tone or histamine-induced spasms. It had analgesic effect 1/3 as potent as codeine in mice but it was not antagonized by levallorphan. The prolongation of hexobarbital sleeping time by AT-17 was similar extent to that by codeine. Anti-electroshock effect was half as potent as that of phenobarbital. The inhibitory effect on the transportation of intestinal contents in mice was far weaker than that of codeine. Effect on the respiratory and circulatory systems were also investigated.

Analgesia↗

On the sites of antitussive action of d-3-methyl-N-methylmorphinan (AT-17).

The sites of antitussive action of d-3-methyl-N-methylmorphinan (AT-17) were studied. It was assumed from the following results that AT-17 acts on the cough centre per se. a) When AT-17 was given by the routes leading to the brain stem such as the cerebello-medullar cistern, far smaller doses were sufficient to obtain the same effect as that by i.v. administration. b) It showed neither effect on the afferent pathway for cough reflex nor influence on pulmonary stretch receptors. c) Decerebration exerted no influence on the antitussive efficacy. d) It definitely depressed the potentials of both the recurrent and internal intercostal nerves evoked by the superior laryngeal nerve stimulation. e) Micro-injection of AT-17 into the bilateral solitary nuclei or their adjacent regions inhibited coughs induced by peripheral stimulation. f) In deafferentated and decerebrate cats, AT-17 increased the spontaneous discharges of the phrenic nerve, whereas codeine decreased them.

Animals↗

Deposition of blood cells on collagen and cuprophane membranes.

Dogs were dialyzed with collagen and cuprophane membranes, human renal failure patients were dialyzed with cuprophane membranes, and samples of the membranes were observed by scanning electron microscopy at different time periods. Fixation was done in glutaraldehyde and cacodylate buffer, and samples were dried at the critical point. All cellular elements were well preserved and appeared viable. Cuprophane adsorbed platelets almost selectively in dog dialyses, whereas collagen adsorbed a smaller number and more heterogeneous group of cells. In contrast to these findings, when cuprophane was used in clinical dialyses, the cell population was predominantly polymorphonuclear leukocytes.

Adsorption↗

Chemico-pharmacological studies on saponins of Panax ginseng C. A. Meyer. I. Chemical part.

For the purpose of clarification of pharmacological actions of ginseng saponins we tried the isolation of ginseng saponins on a larger scale and succeeded in the isolation of eight saponins in a pure state and in sufficient amounts for the pharmacological assay. These eight saponins agreed all completely with the authentic samples of Shibata-Shoji and co-workers in molecular formula of saponins and sapogenins, sugars and TLC. The physical properties of saponins were shown. As other components of ginseng, there were isolated small amounts of panaxadiol, panaxatriol, daucosterol from the first running of column chromatography and mannitol, sucrose and glucose from the ethanol insoluble aqueous extract.

Chromatography, Thin Layer↗

Application of a live attenuated varicella vaccine to hospitalized children and its protective effect on spread of varicella infection.

Twenty-three hospitalized children with no history of varicella or no detectable complement fixing (CF) antibody, were vaccinated with a live attenuated varicella vaccine (Oka strain) immediately after the occurrence of a case of varicella in a children's ward of hospital. These children suffered from the nephrotic syndrome, nephritis, purulent meningitis, hepatitis etc., and 12 of them were receiving steroid therapy. An antibody response was noticed in all the vaccinated children, with mild fever in 6 and a mild rash in 2 of 6. It was uncertain whether these reactions were due to vaccinatin or to naturally acquired infection modified by vaccination. No other clinical reactions or abnormalities of the blood or urine were detected. Thus the spread of varicella infection was prevented, with the exception of one severe case in an unvaccinated patient. In another trial, 16 children with renal diseases were also vaccinated. All the children showed an immune response with no clinical reactions and no abnormalities in blood and urine examinations. Thus live varicella vaccine (Oka strain) can be used safely and effectively for hospitalized children, and its effectiveness in preventing spread of varicella infection was confirmed.

Animals↗

Chemico-pharmacological studies on saponins of Panax ginseng C. A. Meyer. II. Pharmacological part.

The pharmacological properties of seven pure saponins isolated from Panax ginseng C. A. Meyer were studied. 1. The ginseng saponins showed weak toxicities in mice. Especially, Rg1, Rf and Rb 1, which contained glucose as a sugar component, were weaker in their toxicities than the rest, which contained arabinose and/or rhamnose. It was also noted that the saponins containing protopanaxadiol as sapogenin were more toxic than those containing protopanaxatriol. 2. All the saponins diminished ACh-induced contraction of the isolated ileum of the guinea pig. On the other hand high concentrations of Rb 2 caused contraction of the ileum by itself. 3. All of the saponins induced a decrease in heart rate and showed biphasic actions on the blood pressure in rats, while they little affected respiration. They caused blood pressure fall preceded by slight rise. Among them, Rg 1 showed the most prominent action and it produced a blood pressure rise with doses of 30 to 100 mg/kg. The pressor as well as depressor action was not influenced by the pretreatment with any of atropine, diphenhydramine, phentolamine and propranolol. 4. Rg 1 and Re showed vasodilator action in dogs, the potencies of which were 1/20 and 1/50 of that of papaverine, respectively. Rc and Rb 2 showed very weak vasodilator actions but Rb 1 did not. 5. Among the 7 saponins, Rd, Re and Rb 2 showed more potent hemolytic actions than those of the rest and the potencies were proportional to their toxicities. 6. Whereas single administration of Rf, Re and Rd significantly suppressed the conditioned avoidance response, repeated administration of them caused facilitation of the response. On the other hand, Rb 2 always showed very weak suppressant action. 7. Rg 1, Rf, Re and Rd significantly suppressed the fighting of mice induced by foot shock, while Rb 1, Rb 2 and Re little affected the fighting. 8. All the saponins showed antifatigue action. They markedly increased the movement after compulsory gait and the action was consistent and independent of their action on the movement before compulsory gait. 9. The saponins showed moderate depressant actions on the EEG and the behavior in cats. They were qualitatively similar in their actions, although Rg 1, Re and Rb 2 were more potent than the rest. They also suppressed EEG arousal response induced by electrical stimulation of the mid brain in cats.

Acetylcholine↗

Pharmacological studies of 1-(o-chlorophenyl)-2-tert.-butylaminoethanol (C-78), a new bonchodilator.

The bronchodilating effects and other related pharmacological properties of 1-(o-chlorophenyl)-2-tert.-butylaminoethanol-hydrochloride (C-78) were studied in comparison with those of isoproterenol, salbutamol and clorprenaline. C-78 was found to produce a bronchodilating effect 2--10 times stronger and considerably weaker than clorprenaline and isoproterenol, respectively. However, the bronchodilating effect of C-78 was sustained more than 10 times as long as those of isoproterenol and sulbutamol and, especially on oral administration, it was much more potent. The bronchodilating effect of C-78 seems to be due to excitation of the adrenergic beta-receptor, and was antagonized by propranolol. The positive chronotropic and inotropic effects of C-78 on an isolated atrial preparation were less than 1/1000 as potent as those of isoproterenol. C-78 also decreased the tone of smooth muscle, such as the uterus, but its affinity for the bronchial muscle is much higher than for the uterus. C-78 showed strong anti-anaphylactic action and strongly promoted the tracheal ciliary movement. Anitussive effect was also demonstrated, though this was inferior to that of codeine, however, there was no influence on bronchosecretion.

Acetylcholine↗