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Biomedical subjects

N Awata

Publications and source records attributed to N Awata.

At least 37 records · Page 2Linked to original sources
PubMed1988

Protective effect of taurine on the irregular beating pattern of cultured myocardial cells induced by high and low extracellular calcium ion.

Abnormal beating patterns were induced in spontaneously contracting cultured embryonic mouse myocardial cells either by elevating or by lowering extracellular calcium. At low calcium (0.4 mM), the number of beating cells and beating rate decreased while the number of arrhythmic cells increased. By contrast, at high calcium (20 mM), the number of beating cells decreased while beating rate and the number of arrhythmic cells increased. Addition of taurine (20 mM) to the medium attenuated the response to varying calcium; the taurine effect appeared to be specific since neither taurine analog tested (beta-alanine nor glycine) provided much protection against these abnormalities. The protective effect of taurine also appeared to differ from that of verapamil, which was effective only in decreasing beating rate in the high calcium condition. Uptake of 14C-taurine by the cells was higher at both low and high extracellular calcium when compared to the normal calcium (2 mM) concentration. The results raise the possibility that the protective effect of taurine on beating abnormalities caused by low or high calcium is related to taurine uptake.

Animals↗
PubMed1988

Mechanism of the protective action of taurine against isoprenaline induced myocardial damage.

The effect of the sulphur amino acid, taurine, on the biochemical changes induced by a toxic dose of isoprenaline was examined in chick hearts. Isoprenaline treatment (80 and 240 mg.kg-1 subcutaneously twice a day for four days) caused a dose dependent increase in heart to body weight ratio. Isoprenaline administration induced a substantial accumulation of calcium and caused a profound decrease of adenosine triphosphate content and creatine phosphokinase activity in the myocardium. A pronounced increase in lipoperoxide and decrease in phospholipid and reduced glutathione concentrations were also seen. Oral administration of taurine (200 mg.kg-1 for seven days) partially protected against these changes induced by isoprenaline. It is suggested that the beneficial effect of taurine may be due in part to inhibition of lipoperoxide formation and calcium accumulation and to protection against the deterioration of membrane phospholipids.

Adenosine Triphosphate↗
PubMed1988

Binding of 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1, 4-diazepin-1-yl) benzimidazole difumarate (KG-2413) to serum or plasma proteins in man, guinea pig and rat.

Human, guinea pig and rat sera or plasma protein binding of 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1, 4-diazepin-1-yl)benzimidazole difumarate (KG-2413) were investigated by equilibrium dialysis. There were pronounced interspecies differences in binding affinity and binding capacity which were the highest in guinea pig and human species, respectively. In humans, the binding index (n1P1/Kd1) of isolated alpha 1-acid glycoprotein (alpha 1-AG) was seven times higher than that of isolated albumin, and the dissociation constant for human serum at the high affinity binding site was comparable to that for alpha 1-AG. These facts suggested that the free base of KG-2413 was mainly bound to alpha 1-AG in human serum. The contribution of albumin to the binding of KG-2413 in guinea pig and rat plasma may be relatively small. The interspecies differences in KG-2413 binding observed in this study may be due to species differences in the binding affinity and/or capacity of alpha 1-AG.

Adolescent↗
PubMed1988

The effect of additives on the oral mucosal absorption of human calcitonin in rats.

The oral mucosal absorption of human calcitonin (HCT) was investigated in rats. Enhanced absorption of HCT was observed by coadministration of additives such as sodium deoxycholate, sodium tauroglycocholate, quillajasaponin (Quillayannin P-20), sodium lauryl sulfate, sodium myristate and sugar esters. The contribution of sugar esters to oral mucosal absorption of HCT was studied in some detail. The addition of a sugar ester having a hydrophilic-lipophilic balance value between 11 to 16 was found to be effective in increasing the absorption of HCT. Furthermore, it suggested that the type of constituent fatty acid of sugar ester was one of several important factors for the promotion of the oral mucosal absorption of HCT.

Absorption↗
PubMed1988

[Synthesis of carbon-14 labeled 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride (14C-KB-2796)].

Benzyl-14C-1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl) piperazine dihydrochloride (14C-KB-2796), a new cerebral vasodilator, was synthesized in order to investigate the metabolic fate. The synthesis of carboxy-14C-2,3,4-trimethoxybenzoic acid (IV) was accomplished by the reaction of 2,3,4-trimethoxybromobenzene (II) with ter-butyllithium followed by carboxylation with 14C-carbon dioxide generated from 14C-barium carbonate. Formyl-14C-2,3,4-trimethoxybenzaldehyde (VI) was prepared by the reduction of the methyl ester of IV. The free base of 14C-KB-2796 was obtained by the condensation of VI with bis(4-fluorophenyl)methyl-piperazine, and converted to I. An overall radiochemical yield from 14C-barium carbonate was 39%, the specific activity was 1,816.7 MBq/mmol (49.1 mCi/mmol) and its radiochemical purity was 99% in reverse isotope dilution analysis and thin layer chromatographic method.

Carbon Radioisotopes↗
PubMed1988

Reduction of doxorubicin-induced cardiotoxicity in mice by taurine.

The effect of taurine on doxorubicin-induced cardiotoxicity was examined in mice. A single intraperitoneal injection of doxorubicin (15 mg/kg) produced a significant elevation of calcium and lipoperoxide content at 72 hr, as well as a significant depletion of creatine phosphokinase, glutamic oxaloacetic transaminase and lactate dehydrogenase activities at 48 hr and glutathione peroxidase activity at 24 hr in the myocardium. These results suggest that a substantial myocardial damage had occurred. All biochemical alterations except depletion of glutathione peroxidase, were markedly attenuated by the combined oral and intraperitoneal administration of taurine. Taurine significantly improved the survival rate of the mice treated with doxorubicin. These results demonstrate that taurine antagonized doxorubicin-induced cardiotoxicity.

Animals↗
PubMed1987

Mechanism of direct cardiostimulating actions of hydralazine.

The vasodilator, hydralazine, was reported to also exert a direct positive inotropic effect on the myocardium at high concentrations. In the present study we investigated the mechanism of this positive inotropic action by using the ventricular myocardium of isolated perfused chick hearts. Hydralazine (10(-3) M) enhanced contractile force and heart rate, and elevated the myocardial cyclic AMP level. To study the Ca2+-dependent slow action potentials, the fast N+ channels were voltage-inactivated with elevated K+ (25 mM), resulting in a loss of electrical excitability. Hydralazine (10(-4) M) rapidly (less than 3 min) allowed the generation of slow action potentials and accompanying contractions by electrical stimulation. These effects of hydralazine were only partially prevented by propranolol. The results suggest that the increase of myocardial contractility produced by hydralazine is the result, at least in part, of a direct effect on the myocardium to increase Ca2+ inflow. The increased Ca2+ influx and inward slow current is due partly to activation of beta-adrenoceptors, with resultant elevation of cyclic AMP, and partly to another mechanism.

Action Potentials↗
PubMed1987

Acute haemodynamic effect of taurine on hearts in vivo with normal and depressed myocardial function.

The acute haemodynamic effects of taurine were studied in normal and in beta blocker (propranolol) or calcium antagonist (diltiazem) treated rabbits and in rabbits with experimentally produced chronic aortic regurgitation. The administration of taurine (25 mg.kg-1) did not affect heart rate and left ventricular end diastolic pressure but produced significant increases in left ventricular dP/dtmax, cardiac output, and left ventricular systolic pressure in control hearts, indicating that intravascularly administered taurine substantially increased cardiac performance. In propranolol (1 mg.kg-1) treated rabbits taurine significantly improved left ventricular dP/dtmax and cardiac output, which were previously depressed by propranolol. Taurine had the same effect on diltiazem (1 mg.kg-1) treated rabbits. In rabbits with aortic regurgitation a bolus injection of taurine improved cardiac performance. Continuous infusion of taurine (100 mg.h-1) also produced a significant increase in left ventricular dP/dtmax. These results suggest that taurine has a unique action as an inotropic agent and that it may be useful in the treatment of patients with congestive heart failure.

Animals↗
PubMed1986

Beneficial effect of taurine in rabbits with chronic congestive heart failure.

To examine the effect of daily treatment with taurine on improving the status of congestive heart failure (CHF), we used rabbits with artificially induced aortic regurgitation. Ten rabbits were treated daily with taurine (100 mg/kg by mouth) and eight with guanidinoethyl sulfonate (GES) (100 mg/kg by mouth) immediately after induction of aortic regurgitation. The cumulative mortality rate at 8 weeks in the taurine-treated CHF group was 10% (1 of 10) compared with 53% (16 of 30) in the nontreated CHF group and 75% (6 of 8) in the GES-treated CHF group (p less than 0.05). Although cardiac function (max dP/dt) in CHF rabbits was significantly decreased (p less than 0.001), taurine-treated CHF rabbits maintained the same values as control rabbits. Taurine content of the left ventricular tissue of the CHF rabbits was significantly increased (p less than 0.01). Administration of taurine and GES to control rabbits for 8 weeks affected neither the hemodynamics nor the taurine content of the heart. It was concluded that taurine slowed the rapid progression of heart failure and consequently prolonged life expectancy.

Animals↗
PubMed1985

Taurine's possible protective role in age-dependent response to calcium paradox.

When hearts were reperfused with Ca++ after a short period of Ca++-free perfusion, irreversible loss of electrical and mechanical activity was observed. This phenomenon, first described by Zimmerman and Hulsmann, was termed the "calcium paradox". Chizzonite and Zak recently reported that rat hearts exhibited an age-dependent response in a calcium paradox model. The taurine (2-aminoethanesulfonic acid) content of hearts in the newborn animal is high, and decreases rapidly during the first few days of life. The present experiments were performed to test whether the myocardial taurine content was closely linked to an age-dependent response in the calcium paradox model, using post-hatched chicks. The mechanical dysfunction of the heart was much more severe in 9-day-old post-hatched chicks than in 2-day-old chicks when the hearts were subjected to the calcium paradox. Myocardial taurine content was lower in the 9-day-old chicks than in the 2-day-old chicks. The age-related response to the calcium paradox was partially protected by oral pretreatment with taurine, and there was a small increase in myocardial taurine level. It is proposed that myocardial taurine is one factor in the protection against the calcium paradox phenomenon.

Administration, Oral↗
PubMed1985

Therapeutic effect of taurine in congestive heart failure: a double-blind crossover trial.

In a double-blind, randomized, crossover, placebo-controlled study, we investigated the effects of adding taurine to the conventional treatment in 14 patients with congestive heart failure for a 4-week period. Compared with placebo, taurine significantly improved the New York Heart Association functional class (p less than 0.02), pulmonary crackles (p less than 0.02), and chest film abnormalities (p less than 0.01). A benefit of taurine over placebo was demonstrated when an overall treatment response for each patient was evaluated on the basis of clinical examination (p less than 0.05). No patient worsened during taurine administration, but four patients did during placebo. Pre-ejection period (corrected for heart rate) decreased from 148 +/- 14 ms before taurine treatment to 137 +/- 12 ms after taurine (p less than 0.001), and the quotient pre-ejection period/left ventricular ejection time decreased from 47 +/- 9 to 42 +/- 8% (p less than 0.001). Side effects did not occur in the patients during taurine. The results indicate that addition of taurine to conventional therapy is safe and effective for the treatment of patients with congestive heart failure.

Administration, Oral↗
PubMed1985

[Metabolism of lenampicillin hydrochloride. I. Metabolism of ampicillin structure].

Metabolism of lenampicillin hydrochloride (LAPC), especially ampicillin (ABPC) structure of LAPC, was investigated after oral administration in human, dogs and rats. The unchanged compound was not detected in blood and urine, furthermore in animal portal vein after oral administration of LAPC in human and 2 animals. Therefore, LAPC seemed to be rapidly hydrolyzed during the process of absorption. The intestinal absorption of LAPC was satisfactory in view of the urinary excretion of metabolites, accounting for 93% of dose in human, 74% in dogs and 55% in rats, respectively. It could be judged by the bioautograms and the correlation between bioassay and HPLC determination of ABPC that the active metabolite in blood or urine was only ABPC. The major urinary metabolites were ABPC, alpha-aminobenzylpenicilloic acid (ABPA) and 5S-penicilloic acid isomer (5S-ABPA) in human and 2 animals, but the differences were observed on the excretion ratio between human, dogs and rats. LAPC was stable in the intestinal contents, but liable to hydrolyze in the intestinal wall, blood and liver of rats. From the facts described above, it was concluded that LAPC was the efficient prodrug of ABPC in terms of the enhancement of absorption and decrease of side effects.

Administration, Oral↗
PubMed1985

[Metabolism of lenampicillin hydrochloride. II. Metabolism of promoiety].

The in vitro and in vivo metabolism of promoiety in lenampicillin hydrochloride (LAPC) were investigated in rats and dogs. After incubation of LAPC with intestinal or liver preparations and blood of rat, diacetyl, acetoin and 2,3-butanediol were identified as metabolites of LAPC. The main metabolite in peripheral plasma was 2,3-butanediol after oral administration of LAPC in rats and dogs. On the other hand, high levels of acetoin were found out in portal plasma for early period after dosing of LAPC. These results suggested that the biotransformation of promoiety in LAPC to acetoin carried out mainly in intestinal tissues, but acetoin was converted to 2,3-butanediol in liver. Acetoin and 2,3-butanediol were also excreted in urine, but their urinary excretion were very low, and the combined excretion were accounting for about 9% of dose up to 48 hours after dosing in rats and less than 1% in dogs, respectively. The major metabolic pathways of promoiety in LAPC were postulated as below. (Formula: see text).

Acetoin↗