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Biomedical subjects

Y Okano

Publications and source records attributed to Y Okano.

At least 307 records · Page 17Linked to original sources

Potentiation of phenobarbital-induced anticonvulsant activity by pipecolic acid.

Pipecolic acid (PA) is an intermediate of lysine metabolism in the mammalian brain. Recent findings suggest a functional connection of PA as neuromodulator in GABAergic transmission. Since many drugs are postulated to produce their effects by interaction with the central GABA system, the influence of PA on the anticonvulsant activity of phenobarbital was examined. Pretreatment of mice with 50 mg . kg-1 of PA potentiated the suppressing effects of the barbiturate on electrically and chemically induced convulsions. However, there was no potentiation of the behavioral effects and hypothermia induced by phenobarbital. PA itself had no or only little effect on the convulsions, motor function and rectal temperature when given in i.p. doses up to 500 mg . kg-1. Intraventricular administration of 500 microgram of PA also did not suppress either type of convulsion, although it produced ptosis, hypotonia, sedation and hypothermia. The results are discussed in relation to GABA system.

Animals↗

Pipecolic acid: a new type of alpha-amino acid possessing bicuculline-sensitive action in the mammalian brain.

Using unit recording and electrophoretic techniques, pharmacological properties of pipecolic acid (PA) were studied in the brain neurons of rats. PA response was blocked by bicuculline more effectively than GABA response but not blocked by strychnine. Stereochemical findings obtained using the HGS-model demonstrated that PA structure is almost the same as a part of bicuculline structure. The present results suggest that PA might be a new type of substance possessing bicuculline-sensitive action. The site of the action of PA was also discussed.

Animals↗

Changes in brain piperidine levels under anesthesia: mass fragmentographic analysis.

Piperidine is a biogenic alicyclic amine possessing potent pharmacological activity. Interest has recently been focussed on its possible role as an endogenous hypnogenic substance. Using a mass fragmentographic technique with deuterium-labelled piperidine as an internal standard, the time relations of the change in brain levels of piperidine and the anesthetic activity of urethane were determined in mice. The brain piperidine level increased prior to the loss of the righting reflex and the elevated level declined prior to the reappearance of the reflex. The change in brain piperidine level correlated with neither that in spontaneous motility nor that in body temperature. The findings favor the idea that piperidine might at least partly regulate the level of consciousness.

Anesthesia↗

A simplified method for studying fibrous proteins in psoriatic scales obtained by tape stripping.

Polyacrylamide gel electrophoretic investigations were carried out on solubilized proteins from psoriatic and normal stratum corneum obtained by adhesive tape stripping. The proteins in the scales adhering to the tape were solubilized by incubating the tape in 1% sodium dodecyl sulphate (SDS) solution. The electrophoretic behaviour of these solubilized proteins on SDS-polyacrylamide gel was compared with the alpha-fibrous proteins (keratin) of callus. The proteins isolated from callus of normal human heel showed six main bands which were similar to those of the keratin isolated by the 8 M urea-mercaptoethanol method. The lesional skin of forty-five psoriatic patients consistently showed nine main bands on polyacrylamide gels, but only two main bands were observed in the non-lesional, non-heel skin. Six of these nine bands had mobilities and relative intensities almost identical with those of alpha-keratin extracted by the mercaptoethanol method, but the other three bands had greater mobilities on the gels. These results suggest that this technique may have considerable potential for studying changes in alpha-keratin in patients with psoriasis and other disorders of keratinization.

Callosities↗

A new method for evaluating mucolytic expectorant activity and its application. II. Application to two proteolytic enzymes, serratiopeptidase and seaprose.

Using our new method described in a preceding paper, in vivo effects of two proteolytic enzymes such as serratiopeptidase (SER) and seaprose (SAP) on sputa collected from bronchitis rabbits were examined. SER (20 mg/kg) and SAP (30 mg/kg) significantly reduced the viscosity of sputum (P less than 0.05) at the 1-3-h periods and the 4-6-h periods, respectively, after intraduodenal administration. 50 mg/kg of SER also significantly decreased not only viscosity (P less than 0.001) but also amount of freeze-dried substance (P less than 0.05) of sputum at the 1-3-h periods, but SAP did not affect the amount of dried substance. Both enzymes significantly increased the volume of sputum, probably as the result of liquefaction. Thus, mucolytic expectorant activity of both enzymes can be demonstrated first by the reduction in viscosity and next of the increase in volume of sputa. However, the decrease in amount of freeze-dried substance is not always in accord with the reduction viscosity.

Animals↗

A new method for evaluating mucolytic expectorant activity and its application. I. Methodology.

A new method for evaluating in vivo effect of mucolytic expectorants was devised. In this report, however, the focus is placed on methodology but not on pharmacology. Rabbits with subacute bronchitis were prepared by long-term exposure to minute amounts of SO2 gas. The sputum was quantitatively collected from the animal through a tracheal cannula at suitable time intervals according to the Perry and Boyd's method. As a preliminary study, changes in volume, viscosity and amounts of freeze-dried substance of sputa were examined after intraduodenal administration of water instead of mucolytic expectorants, the effects of which will be described in the subsequent paper, but no significant changes occurred with this test.

Animals↗

Effects of anesthetics on piperidine levels in mouse brain.

Piperidine is one of the biogenic amines possessing potent pharmacological activity. Recent interest has focused on its possible role as an endogenous hypnogenic substance. Using a mass fragmentographic technique with deuterium-labelled piperidine as an internal standard, piperidine concentrations in brains of waking and deeply anesthetized mice were analyzed to compare piperidine levels in the brain under distinctly different states of consciousness. A rapid and significant increase in piperidine concentrations was found in the brain but not in blood of mice anesthetized with any one of pentobarbital, urethane, ether and halothane. The results, showing that CNS depression is accompanied by accumulation of piperidine in the brain, are consistent with the idea that piperidine may have a close connection with the mechanisms controlling the level of consciousness.

Anesthetics↗

Effects of cyclodextrins on chlorpromazine-induced haemolysis and central nervous system responses.

Cyclodextrins (CyDs) protected the human erythrocytes from haemolysis induced with chlorpromazine (CPZ) in isotonic solution, depending upon the magnitude of the stability constant of CPZ-CyD complexes (beta-greater than-gamma-greater than alpha-CyD). From the observations of CPZ uptake into erythrocytes and changes in surface activity of CPZ, the protective effects of CyDs in vitro appeared to be due to the decrease in effective haemolytic concentration of CPZ through inclusion complex formation rather than the direct interaction of CyDs with the erythrocyte membrane. The effect of beta-CyD on some central nervous system (c.n.s.) actions of CPZ in rats was also investigated to see if there were any advantages in the use of beta-CyD complexes given by injection. The results suggest that beta-CyD does not after the time-course or magnitude of the effects of CPZ on the c.n.s.

Animals↗

Mass fragmentographic analysis of piperidine levels in tissues of rats during development.

Piperidine levels in the brain and adrenal gland of rats during development were determined by mass fragmentography with deuterium-labeled piperidine as an internal standard. The levels in both organs showed distinct developmental changes, and two peaks were observed in association with the development of each organ. The initial peaks appeared in the early stage of development, that is, at the 19th day of gestation for the brain and 1 week after birth for the adrenal gland. The second peaks appeared at the age of sexual maturation (10 weeks after birth). The significance of the finding is discussed with respect to a presumed role of piperidine as a neuroendocrine modulator.

Adrenal Glands↗