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Biomedical subjects

S Takeo

Publications and source records attributed to S Takeo.

At least 145 records · Page 8Linked to original sources
PubMed1991

Naftidrofuryl oxalate improves impaired brain glucose metabolism after microsphere-induced cerebral embolism in rats.

The present study was designed to elucidate possible therapeutic effects of naftidrofuryl on the brain glucose metabolism after cerebral ischemia. Cerebral ischemia was induced by injecting 680 microspheres with a diameter of 48 microns into the right internal carotid artery of the rat. After ensuring the onset of symptoms of stroke on the first day after the operation, the rats were treated with intraperitoneal injections of 15 mg/kg naftidrofuryl oxalate twice a day. The behavioral and metabolic changes of operated rats were monitored up to the 5th day after surgery. The symptoms gradually faded away, from the 3rd day on, after microsphere-induced cerebral embolism. Tissue glucose and glycogen greatly increased after cerebral embolism, suggesting embolism-induced inhibition of glycolysis. To elucidate which steps in the glycolytic catabolism are inhibited after cerebral ischemia, biochemical activities of the glycolytic enzymes in the Embden-Meyerhof pathway and tricarboxylic acid cycle were determined on the 3rd day after surgery. Enzyme activities of hexokinase, phosphofructokinase and pyruvate kinase were not inhibited, but rather increased slightly after cerebral embolism. Malate dehydrogenase activity in the brain mitochondria was markedly increased after microsphere-embolism, whereas other enzyme activities in the tricarboxylic acid cycle were never inhibited by the cerebral embolism. Treatment of naftidrofuryl resulted in an appreciable reverse of the brain glucose and glycogen levels and a substantial recovery of altered enzyme activities to normal levels in the Embden-Meyerhof pathway and tricarboxylic acid cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Carbonyl reductases from rat testis and vas deferens. Purification, properties and localization.

Three enzyme forms (T1, T2, T3) from rat testis and two from rat vas deferens (V1, V2) of carbonyl reductase have been highly purified to apparent homogeneity. These carbonyl reductases from rat reproductive organs have several similarities in terms of molecular mass (32-33 kDa), isoelectric point (pI 5.9-6.4), immunochemical properties, cofactor requirement (NADPH dependency) and sensitivity to sulfhydryl reagents. The isoenzymes from the vas deferens (V1, V2) have similar catalytic activities, whereas those from the testis (T1, T2, T3) showed different catalytic activities from each other. All enzymes, however, reduced quinones, aromatic aldehydes and ketones, while T3, V1 and V2 were characterized as possessing high affinity towards prostaglandins. An immunoinhibition study using a specific antibody indicated that these enzymes were solely responsible for the overall catalytic activities of 13, 14-dihydro-15-oxo-prostaglandin F2 alpha, 4-benzoylpyridine, and 4-nitroacetophenone reduction and prostaglandin F2 alpha oxidation in both testis and vas deferens cytosol. The immunohistochemical staining revealed a positive immunoreactivity to antibody only in the Leydig cells of the testis, but neither the germ cells nor Sertoli cells in the seminiferous tubule. The staining also showed that the enzymes in the vas deferens were primarily localized in mucosal epithelium cells.

Alcohol Oxidoreductases↗
PubMed1990

Beneficial effect of tan-shen, an extract from the root of Salvia, on post-hypoxic recovery of cardiac contractile force.

The present study was undertaken to elucidate the possible effects of tanshinone VI, one of the extracts from the root of Salvia, on post-hypoxic recovery of cardiac contractile force. For this purpose, rat hearts were perfused for 45 min under reoxygenated conditions following 20-min hypoxic perfusion, and changes in tissue high-energy phosphates and calcium contents, and release of ATP metabolites and creatine kinase were examined. Post-hypoxic recovery of cardiac contractile force was augmented when hearts were treated with 42 nM tanshinone VI during hypoxia. This beneficial recovery was accompanied by enhanced restoration of myocardial high-energy phosphates, depression of hypoxia- and reoxygenation-induced increase in tissue calcium content, and suppression of release of ATP metabolites such as adenosine, inosine and hypoxanthine from the perfused heart. The results suggest that tanshinone VI is beneficial for the recovery of cardiac contractility after a certain period of oxygen-deficiency, possibly through mechanisms involving improvement of myocardial energy production upon oxygen-replenishment and/or inhibition of calcium accumulation in the cardiac cell.

Abietanes↗
PubMed1990

Possible involvement of membrane-stabilizing action in beneficial effect of beta adrenoceptor blocking agents on hypoxic and posthypoxic myocardium.

The present study was designed to elucidate a possible involvement of membrane-stabilizing action of beta blocking agents in posthypoxic recovery of cardiac contractile function and myocardial metabolism. Propranolol and acebutolol, which possess a membrane-stabilizing action, and atenolol and metoprolol, which lack this action, were used in the isolated, perfused rabbit heart. The membrane-stabilizing effects of these agents were assessed on the basis of the effects on the maximal driving frequency of the left atria. Reoxygenation of hearts for 45 min following 20-min hypoxia resulted in little recovery of cardiac contractile force, sustained rise in resting tension, insufficient recovery of myocardial high-energy phosphates, accumulation of the tissue calcium and sodium and marked release of creatine kinase and ATP metabolites from the hearts. Treatment of hypoxic hearts with either 100 microM propranolol, 200 microM acebutolol, 200 microM atenolol or 100 microM metoprolol was commenced when the contractile force declined to 30% of the initial level and terminated at 20-min hypoxia. Treatment with either propranolol or acebutolol produced a significant posthypoxic recovery of cardiac contractile force, resting tension and myocardial high-energy phosphates, and a profound suppression of the tissue calcium and sodium accumulation and the loss of ATP metabolites from perfused hearts. In contrast, neither atenolol nor metoprolol affected these changes induced by the hypoxic insult and the following reoxygenation. The results suggest that membrane-stabilizing action of beta blocking agents plays an important role in the protection against posthypoxic cardiac contractile dysfunction and metabolic disturbances.

Adenosine Triphosphate↗
PubMed1990

Cardiac sarcolemma as a possible site of action of caffeine in rat heart.

Caffeine (0.1-10 mM) produced a biphasic effect on Na(+)-K+ ATPase activity in the rat heart sarcolemmal preparations. The Na(+)-K+ ATPase activity was stimulated by about 25% at low concentrations (0.1-1 mM), whereas the enzyme was inhibited by about 25% at higher concentrations (10 mM) of caffeine. The stimulatory effect of 1 mM caffeine was associated with about 30% increase in the Vmax value for Na(+)-K+ ATPase, whereas the depressant action of 10 mM caffeine was associated with an increase of the Km value from 1.4 to 2.1 mM ATP. The Na(+)-induced Ca++ release from the sarcolemmal vesicles was stimulated with caffeine in a concentration-dependent manner; about 80% increase in the activity was observed at 0.1 mM caffeine. The apparent Ka (millimolar Na+) values for the Na(+)-induced Ca++ release were about 17 and 6 in the absence and presence of 1 mM caffeine, respectively. However, the sarcolemmal Na(+)-dependent Ca++ uptake and ATP-independent Ca++ binding were not affected, whereas the ATP-dependent Ca++ accumulation and Ca+(+)-stimulated ATPase activities were depressed by 1 to 10 mM caffeine. This agent at concentrations of 0.1 to 10 mM produced a biphasic effect on the contractile activity of the isolated perfused rat heart. The initial transient positive inotropic (30-60%) effect was followed by a sustained negative inotropic (50-80%) response of the drug; the delayed decrease in contractile force was associated with a significant increase (35-50%) in the resting tension. The initial positive inotropic effect of caffeine was dependent on the concentration of Ca++ (0.2-3 mM) in the perfusion medium; however, this response was attenuated either by lowering the concentration of Na+ from 140 to 35 mM or by different concentrations (0.5-1 mM) of amiloride in the medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1989

Protective action of YM-12617, an alpha 1-adrenoceptor antagonist, on the hypoxic and reoxygenated myocardium.

The present study was designed to determine whether the 1-form of YM-12617, which was developed recently as an alpha 1-adrenoceptor blocker, is capable of protecting the myocardium from hypoxia-induced disturbances of cardiac function and metabolism. Isolated rabbit hearts were perfused for 25 min under hypoxic conditions in the absence or the presence of 28 microM YM-12617, followed by 45 min with oxygenated perfusion medium, and functional and metabolic changes of the heart were examined. Hypoxia induced several pathophysiological changes. Upon subsequent reoxygenation, there was less than 10% recovery of the contractile force and an approximately 40% recovery of the myocardial high-energy phosphates. Treatment with YM-12617 during the hypoxic periods resulted in approximately 90% recovery of the cardiac contractile function upon subsequent reoxygenation. Treatment with YM-12617 restored the myocardial high-energy phosphates, such as ATP and creatine phosphate, to approximately 90 and 80% of the initial value, respectively, during the subsequent reoxygenation. These results suggest that YM-12617 is capable of protecting the myocardium from hypoxia-induced disturbances of cardiac function and metabolism.

Adenosine Triphosphate↗
PubMed1989

Functional changes of aorta with massive accumulation of calcium.

The present study was undertaken to elucidate pathophysiological changes and functional alterations of the calcified artery. For this purpose, rats were treated with 500,000 units/kg vitamin D3, and tension development of isolated rat aortae was examined. Treatment of rats with vitamin D3 resulted in an increase (approx. 64-fold) in the tissue calcium. Light microscopic examination of the aorta after staining with hematoxylin-eosin and von Kossa indicated numerous plaques in the aortic media. The results indicate a massive accumulation of calcium in the aortic media. Responsiveness of the calcified tissue to norepinephrine, epinephrine, serotonin, prostaglandin F2 alpha was found to be 11-66% when compared to that of the control. Furthermore, the calcified tissue responded minimally to isoproterenol and acetylcholine, which elicited a relaxation in control aortae. Isoproterenol-induced relaxation of the calcified aorta after 100 mM KCl contracture was also diminished. In the present study we have demonstrated poor responsiveness of the calcified aorta to physiological and pharmacological substances relative to normal tissue, which implies a functional damage of the artery upon massive calcium accumulation.

Acetylcholine↗
PubMed1989

Possible active components of tan-shen (Salvia miltiorrhiza) for protection of the myocardium against ischemia-induced derangements.

Extract of Tan-Shen (Salvia miltiorrhiza, Labiatae), a Chinese traditional crude drug, was reported to show beneficial activity for heart disease. Chemical examination on the extract was performed on the basis of screening for protective action on the ischemic myocardium. Isolated hearts were subjected to hypoxic perfusion for 20 min, followed by 45 min reoxygenation, and the recovery of cardiac contractile force and changes in UV absorbance of the perfusate were examined. Among the components isolated, tanshinone I, cryptotanshinone, and tanshinone VI elicited a significant enhanced recovery of the contractile force upon reoxygenation. This was associated with a decrease in the increase in UV absorbance of the perfusate, suggesting the preservation of ATP metabolites in the myocardium. This, in turn, may enhance the restoration of ATP upon oxygen-replenishment. The results suggest that tanshinone I, cryptotanshinone, and tanshinone VI can protect the myocardium against ischemia-induced derangements.

Animals↗
PubMed1989

Beneficial effect of amosulalol and phentolamine on post-hypoxic recovery of contractile force and energy metabolism in rabbit hearts.

1. The effects of phentolamine, an alpha-adrenoceptor blocking agent and amousulalol, an alpha 1 and beta-adrenoceptor antagonist on hypoxia-induced impairment in cardiac function and metabolism were examined using the isolated heart Langendorff preparation of the rabbit. 2. Hypoxia induced cessation of cardiac contractile force, a rise in resting tension, a decrease in myocardial high-energy phosphates, an increase in tissue calcium content and the release of ATP metabolites from the heart. Subsequent reoxygenation resulted in little recovery of cardiac contractile force, and there were further increases in tissue calcium content and in the release of creatine kinase from the heart. 3. Treatment of hypoxic hearts with either 83 microM phentolamine or 45 microM amosulalol resulted in a suppression of the rise in resting tension, the tissue calcium accumulation and the release of creatine kinase and ATP metabolites during hypoxia. This treatment also elicited significant recovery of cardiac contractile force, restoration of myocardial high-energy phosphates, suppression of the release of creatine kinase and the accumulation of tissue calcium during reoxygenation. Both 83 microM phentolamine and 45 microM amosulalol a significant prolongation of the effective refractory period of rabbit isolated atria. 4. Lower concentrations of phentolamine (16 microM) and amosulalol) (9 microM), which are sufficient to exert an alpha-adrenoceptor blocking action, did not elicit an appreciable effect on the post-hypoxic recovery of cardiac contractile force. 5. These results suggest that phentolamine and amosulalol are capable of protecting the myocardium from hypoxia-induced derangements in cardiac function and metabolism. This effect is probably attributable to their membrane stabilizing effect, rather than to their alpha-adrenoceptor blocking action.

Adenosine Triphosphate↗
PubMed1989

Possible therapeutic effect of naftidrofuryl oxalate on brain energy metabolism after microsphere-induced cerebral embolism.

1. The present study was designed to determine whether naftidrofuryl oxalate exerts a possible therapeutic effect on brain energy metabolism impaired by microsphere-induced cerebral embolism in vitro. 2. Injection of microspheres into the right carotid canal resulted in a decrease in tissue high-energy phosphates both in the right and left hemispheres, and an increase in tissue lactate in the right hemisphere, on the 3rd and the 5th day after the embolism. The embolism also induced a marked reduction in mitochondrial oxidative phosphorylation ability and succinate dehydrogenase activity. The results suggest that severe ischaemia was induced in the brain by the microsphere administration. 3. Treatment of microsphere-injected rats with naftidrofuryl oxalate (15 mg kg-1) for 3 or 5 days elicited a significant recovery of tissue high-energy phosphate and lactate levels. The recovery was associated with a significant restoration of mitochondrial succinate dehydrogenase activity on the both days and of mitochondrial oxidative phosphorylation rate on the 5th day. 4. The results suggest that naftidrofuryl oxalate is beneficial in the recovery of cerebral energy metabolism impaired by microsphere-induced cerebral ischaemia, presumably through a mechanism involving its direct effect on the cerebral mitochondrial enzyme activities.

Adenosine Triphosphate↗
PubMed1989

In vitro effect of naftidrofuryl oxalate on cerebral mitochondria impaired by microsphere-induced embolism in rats.

The present study was designed to determine whether naftidrofuryl oxalate (Naftidrofuryl) may exert a beneficial effect on the cerebral mitochondria after microsphere-induced embolism assessed under in vitro conditions. For this purpose, 600 microspheres (48 microns in diameter) were injected into the right carotid canal of rats, which induced an irreversible embolism in the right cerebrum. Three days after the operation, the cerebral mitochondria were isolated and their oxidative phosphorylation ability and succinate dehydrogenase activity were determined. Two types of mitochondria were obtained after cerebral embolism: one was mitochondria which revealed a marked decline in the oxidative phosphorylation activity when measured in the presence of glutamate or succinate as a substrate (severely injured mitochondria), and the other, those which revealed a decrease in the activity in the presence of succinate and an appreciable increase in the activity in the presence of glutamate (mildly injured mitochondria). Naftidrofuryl at the concentration of 3 microM elicited slight but significant restoration of the oxidative phosphorylation ability of the mildly injured mitochondria isolated from rats after the cerebral embolism, but not of the severely injured mitochondria. The succinate dehydrogenase activity of the brain mitochondria isolated from rats 3 days after the cerebral embolism was significantly decreased. Exposure of these mitochondria to 0.1 to 1 microM Naftidrofuryl significantly restored the succinate dehydrogenase activity. The results suggest that Naftidrofuryl is capable of exerting a beneficial effect in vitro on the brain mitochondria activity impaired by the cerebral embolism, particularly on the activity of mildly injured mitochondria.

Adenosine Triphosphate↗
PubMed1989

Beneficial effects of lidocaine and disopyramide on oxygen-deficiency-induced contractile failure and metabolic disturbance in isolated rabbit hearts.

The purpose of the present study was to determine whether antiarrhythmic agents, lidocaine and disopyramide, which reveal a membrane stabilizing action, may exert a beneficial effect on posthypoxic recovery of cardiac function and metabolism. Rabbit hearts were perfused for 20 min under hypoxic conditions, followed by 45-min reoxygenation. Hypoxic insults induced cessation of cardiac contractile force, rise in resting tension, depletion of myocardial high-energy phosphates, accumulation of tissue calcium and release of creatine kinase and ATP metabolites such as adenosine, inosine and hypoxanthine. These alterations were not returned to the initial levels upon reoxygenation. Administration of either 69 microM lidocaine or 55 microM disopyramide after the onset of oxygen deficiency (between 8th and 20th min of the hypoxia) resulted in a significant suppression of hypoxia-induced rise in resting tension, tissue calcium accumulation and release of creatine kinase and ATP metabolites, whereas hypoxia-induced decline in cardiac contractile force and depletion of myocardial high-energy phosphates were not affected by the treatment. The latter two variables were improved markedly during 45-min reoxygenation when the heart had been treated with the agents. The improvement was accompanied by a suppression of the release of creatine kinase and ATP metabolites and the tissue calcium accumulation. The results suggest that lidocaine and disopyramide are beneficial for posthypoxic recovery of cardiac function and metabolism.

Adenosine Triphosphate↗
PubMed1988

Role of tumor-infiltrating lymphocytes in the host defense mechanism against lung cancer.

Tumor-infiltrating lymphocytes (TIL) and tumor-associated macrophages (TAM) were recovered from 22 patients with primary lung cancer. The TIL did not exhibit any cytolytic activity against various target cells. The average percentage of TIL recovered was 6.7 +/- 1.3% in patients without recurrence, as compared to 3.6 +/- 0.6% in those with recurrence within 2 years after complete resection of lung cancer (P less than 0.05). The average cytostatic activity of TAM was 38.5 +/- 6.8% in patients without recurrence, although it was 25.2 +/- 4.6% in those with recurrence within 2 years after complete resection (P less than 0.1). The activity of macrophage activating factor (MAF) induced by TIL was also higher in patients showing no recurrence. A significant positive correlation was observed between MAF activity induced by TIL and the cytostatic activity of individual TAM. These results suggest that antitumor activity of TAM may be controlled by specifically sensitized TIL through lymphokines.

Adenocarcinoma↗
PubMed1988

Adenine nucleotide metabolites are beneficial for recovery of cardiac contractile force after hypoxia.

In a previous study, we demonstrated a significant release of adenosine, inosine and hypoxanthine during hypoxia and subsequent reoxygenation. The present study was designed to determine whether or not exogenous adenosine, inosine and hypoxanthine are beneficial for the recovery of hypoxia-induced loss of cardiac contractile force. Hearts were perfused for 20 min under hypoxic conditions, followed by 45 min-perfusion under reoxygenated conditions, and changes in contractile force, resting tension and metabolic parameters of the perfused heart were examined. When either adenosine, inosine or hypoxanthine were exogenously infused during hypoxia at the rate of 3 mumol/min, remarkable recovery (61 to 68%) of cardiac contractile force was observed upon reoxygenation. The recovery was accompanied by a significant restoration of myocardial ATP (90 to 100%) and CP contents (80 to 86%), suggesting that exogenous metabolites are utilized for the restoration of myocardial ATP during reoxygenation, which may lead to a beneficial recovery of hypoxia-induced loss of cardiac contractile force upon reoxygenation. Infusion of exogenous metabolites also resulted in an almost complete inhibition of hypoxia- and reoxygenation-induced release of creatine phosphokinase from the perfused heart as well as a significant depression of hypoxia-induced calcium accumulation in the cardiac tissue. Since these phenomena are considered to represent increases in cell membrane permeability, protection of the myocardium against hypoxia- and reoxygenation-induced changes in cell membrane permeability may be an alternative mechanism for the beneficial effect of adenosine, inosine and hypoxanthine on the hypoxic myocardium.

Adenosine↗
PubMed1988

Diltiazem and verapamil reduce the loss of adenine nucleotide metabolites from hypoxic hearts.

The present study was undertaken to elucidate possible mechanisms for a protection of myocardial cells from hypoxia-induced derangements in cardiac function and metabolism by calcium antagonists. For this purpose, rabbit hearts were perfused for 20 min under hypoxic conditions in the presence of 312 ng/ml diltiazem or 125 ng/ml verapamil, and then for 45 min under reoxygenated conditions. Metabolic changes in the myocardium and the perfusate were examined throughout. Hypoxia induced a marked decline in myocardial high-energy phosphates and an immediate release of ATP metabolites, such as adenosine, inosine and hypoxanthine, from the perfused heart. These changes were effectively depressed by diltiazem and verapamil. Hypoxia and subsequent reoxygenation resulted in a release of creatine phosphokinase from the heart, which was completely inhibited by the treatment with either diltiazem or verapamil. Myocardial calcium contents were increased by 20 min-hypoxic perfusion. Both diltiazem and verapamil are capable of preventing hypoxia-induced increase in the transmembrane flux of cellular components, which may be beneficial for the preservation of substances necessary for the ATP regeneration after hypoxia and for the inhibition of calcium overload in cardiac cells.

Adenine Nucleotides↗
PubMed1988

[Cerebroprotective action of naftidrofuryl oxalate. I: Prolongation of survival time and protection of cerebral energy metabolism in bilateral carotid artery-ligated mice].

The present study was designed to elucidate whether naftidrofuryl oxalate (LS-121) may exert a beneficial effect on survival time and cerebral energy metabolism of bilateral carotid artery (BCA)-ligated mice. Survival time of BCA-ligated mice ranged from 100 to 308 sec. Administration of 15, 45 and 100 mg/kg, i.p. and 100 mg/kg, p.o. LS-121 significantly prolonged the survival time. Cerebral adenosine triphosphate (ATP), creatine phosphate (CP) and glucose contents were markedly reduced at 2 min after BCA-ligation. Cerebral lactate content was increased by the ligation, whereas the pyruvate content was not altered. Pretreatment of mice with 15, 45 mg/kg, i.p. and 100 mg/kg, p.o. LS-121 suppressed BCA-ligation induced decrease in high-energy phosphates of the mouse brain. Ligation-induced decrease in glucose and increase in lactate content tended to be attenuated by the treatment with 45 mg/kg, i.p. LS-121. Time course of changes in metabolic variables altered by BCA-ligation with and without the pretreatment with 45 mg/kg, i.p. LS-121 showed a significant suppression of ligation-induced decrease in cerebral high-energy phosphates. The results suggest that LS-121 is beneficial for ischemic mouse brain energy metabolism, which may be related to the prolongation of the survival time.

Animals↗