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Biomedical subjects

Y Nakane

Publications and source records attributed to Y Nakane.

At least 217 records · Page 12Linked to original sources

Direct renal action of captopril (SQ 14225): dissociation of natriuretic and vascular actions in isolated perfused rat kidney.

Direct effects of captopril on renal function were examined in isolated perfused rat kidneys. Captopril induced a significant increase in urinary volume and urinary sodium excretion (1.8- and 1.7-fold, respectively; both p less than 0.005), whereas urinary potassium excretion and renovascular resistance were not significantly changed. Because the perfusion medium lacks angiotensinogen, kininogen and aldosterone, the natriuretic action in perfused kidneys may not be related to its inhibitory action on angiotensin I converting enzyme or kininase II. Because the natriuresis was not accompanied by changes in renovascular resistance, it is suggested that captopril possesses a direct natriuretic action and that this property may partly explain the mechanism of captopril-induced natriuresis clinically observed.

Animals↗

Activities of various enzymes of pyrimidine nucleotide and DNA syntheses in normal and neoplastic human tissues.

The activities of the key enzymes of pyrimidine nucleotide and DNA syntheses in 43 human tumors and 28 normal human tissues were investigated. The activities of cytidine triphosphate synthetase, deoxycytidine monophosphate deaminase, uridine kinase, thymidine kinase, thymidine monophosphate kinase and DNA polymerase were markedly increased in tumor tissues, compared with those in the corresponding normal tissues, while the activities of deoxycytidine kinase, cytidine deaminase and deoxycytidine deaminase were only slightly increased. The use of thymidine and deoxyuridine as substrates of human pyrimidine nucleoside phosphorylase gave 1 to 2 orders of magnitude higher activity than that of uridine.

Carbon-Nitrogen Ligases↗

Sodium balance and renin regulation in rats: role of intrinsic renal mechanisms.

Renin secretion was compared in vivo and in vitro among five groups of rats, each group subjected to a different sodium balance for 10 to 14 days. The state of the renin-angiotensin system in vivo was evaluated by measuring the renal renin (RR) and the plasma renin concentration (PRC) in both anesthetized and nonanesthetized animals. The in vitro renin secretion rate (RSR) was determined in isolated perfused kidneys. RR was reduced (-48%) by sodium loading and deoxycorticosterone (DOCA) and increased (+27%) by sodium deprivation and furosemide. Sodium loading and DOCA reduced both the PRC and the RSR to less than 20% of control values. By contrast, sodium deprivation and furosemide induced a more than fourfold rise in the PRC but only a small increase in the RSR (+37%). These results indicate that changes in fractional renin release are induced by sodium balance variation, and these changes are preserved in vitro only in sodium-loaded states. The inability of sodium-deprived kidneys to maintain high renin release in vitro suggests that high plasma renin levels in these rats depend on mechanisms that are not preserved in vitro. There was no evidence supporting the participation of inactive renin secretion in the regulation of fractional renin release under varying sodium balance.

Animals↗

A comparison of multiple forms of renin in rat renal perfusate with those in renal extract.

1. Physicochemical properties of renin secreted by isolated perfused rat kidney were examined and the results compared with those obtained for the renin in renal extract. 2. In renal extract, two high-molecular-weight renins (molecular weight 65 000 and 55 000) and one low-molecular-weight renin (molecular weight 39 000) were found. Their relative proportion varied depending on extraction conditions. By acidification, high-molecular-weight renins were converted into low-molecular-weight renin without marked changes in activity. 3. In renal perfusate only low-molecular-weight renin was found after renin stimulation by isoprenaline or anoxia. Inactive renin was not found. 4. Renin in renal extract and perfusate samples were both found to consist of at least four isoenzymes having different isoelectric points (pI). The pI patterns were identical in renal extract and perfusate samples: pI 5.7 (60-70%), 5.5 (15-25%), 5.3 (5-10%) and 5.0-5.2 (2-5%). 5. These results indicate that the native renin secreted by rat kidney consists entirely of the low-molecular-weight and active form comprising multiple isoenzymes with a stable pI pattern.

Animals↗

Multi-institutional study on the teratogenicity and fetal toxicity of antiepileptic drugs: a report of a collaborative study group in Japan.

A multi-institutional collaborative study was conducted concerning the course of pregnancy and delivery and the incidence of abnormal infants delivered of epileptic women. Of 657 women receiving antiepileptic drugs, 73% delivered live infants, 14% had miscarriage or stillbirth, and 13% underwent induced abortion. In contrast to the above findings, 80% of 162 patients not receiving antiepileptic drugs delivered live infants and 4% had miscarriage or stillbirth. The latter outcome was significantly increased in the medicated patients. In this series, 63 (9.9%) of 638 live births were malformed, 55 (11.5%) being from medicated mothers and 3 (2.3%) from nonmedicated mothers. The incidence of fetal malformation in medicated mothers was thus five times as high as that in nonmedicated mothers. Cleft lip and/or palate and malformations involving the cardiovascular system were found frequently in the infants from medicated mothers. General background factors that might exert teratogenic effects on pregnant patients with epilepsy were studied, and the potential toxicity of antiepileptic drugs to the fetus was also analyzed. In this regard, consideration should be given to whether the patient has partial epileptic seizures, whether the patient herself exhibits any malformation, or whether her previous pregnancy resulted in an abnormal outcome. The incidence of fetal malformation was the highest (12.7%) in the medicated patients who had epileptic seizures during the pregnancy. It is presumed on the basis of the results of analysis of the data that a combination of more than three drugs and a daily dose greater than a certain minimal level is likely to produce malformed infants.

Abnormalities, Drug-Induced↗

Effects of selective and nonselective beta adrenergic agents on renin secretion in isolated perfused rat kidney.

The effects of selective and nonselective beta adrenergic drugs on the renin secretion rate (RSR) in isolated perfused rat kidneys were studied. Both isoproterenol (Ipr) (nonselective agonist) and salbutamol (Salb) (beta-2 selective agonist) stimulated RSR in a dose-dependent manner. The lowest doses able to induce a significant RSR increase were 5 nM for Ipr and 50 nM for Salb. A 5-fold increase in RSR was induced by 500 nM Ipr and a 3.2-fold increase by 5 microM Salb. Renin stimulation by both agonists was suppressed by propranolol (nonselective) and by acebutolol and its derivative M&B 16,942 (beta-1 selective antagonists). Thus, renin release was stimulated or inhibited effectively by all the drugs tested, regardless of the beta selectivity of agonists and antagonists. There were no consistent relationships observed between changes in renal hemodynamics and in RSR, suggesting that the used drugs affected renin release from in vitro-perfused rat kidney through their direct effects on juxtaglomerular cells. These results indicate that renal beta adrenoreceptors involved in renin release do not fall into two distinct beta subtypes.

Acebutolol↗

Congenital malformation among infants of epileptic mothers treated during pregnancy--the report of a collaborative study group in Japan.

A multi-institutional collaborative study was conducted on the risk of congenital abnormalities among infants of pregnant epileptics. The 902 pregnancies collected by July, 1977, were divided into the treated group, the non-treated group and the unknown group. The malformation rates among live births of the first and the second groups were 11.5% and 2.3%, respectively; however, it was estimated that the rate would have been 6.75% among the treated group if trimethadione-treatment had been avoided. The effects of maternal background and antiepileptic treatment were analyzed fully in connection with the possibility of congenital malformation.

Abnormalities, Drug-Induced↗

Lithium treatment in affective disorders from viewpoint of transcultural psychopharmacology: therapeutic plasma level.

The double-blind controlled studies on lithium carbonate therapy conducted in Japan have demonstrated that there are no significant correlations between clinical effectiveness and serum lithium level in manic patients as well as depressed patients and also that Japanese patients seem to require less lithium carbonate than their U.S. counterparts as an effective therapeutic dose, both in terms of mean maximum dose and serum level. Although any international comparison cannot be fully valid without using transculturally standardized assessment, the data of these studies were examined from the viewpoint of transcultural psychopharmacology and compared to the data from studies in U.S.A.

Bipolar Disorder↗

Aldosterone metabolism in isolated perfused rat kidney.

The renal metabolism and handling of [1,2-3H]aldosterone ([3H]A) was studied using isolated perfused rat kidney under different perfusion conditions. The metabolite production rate (MPR) and the urinary excretion of [3H]A together with its radiometabolites (UV/P3H) were studied. Among the formed metabolites, no acid-labile conjugate of aldosterone (ALC) was detected. The MPR was not altered in studies using nonfiltering kidney, a result that suggests that the majority of metabolites were formed without requirement of the process of glomerular filtration and tubular uptake of the hormone. High perfusion pressure (high PP) resulted in a striking increase in whole metabolic clearance rate of aldosterone (MCR[3H]A) due mostly to an enhanced urinary excretion of intact aldosterone and, to a lesser degree, to a significant increase in MPR. Factors determining the excretion rate of [3H]A and its metabolites were than investigated under administration of diuretics. Mannitol (44 mM) induced a marked increase in urine volume (UV) accompanied by a significant UV/P3H increase. Meanwhile, 0.1 mM furosemide resulted in an increase only in UV, but not in UV/P3H. These results revealed the UV dependence of aldosterone excretion in certain diuretic conditions.

Aldosterone↗

Cortisol metabolism and excretion in the isolated perfused rat kidney.

The isolated perfused rat kidney allows a simultaneous kinetic study of both the renal metabolism and the urinary excretion of cortisol and its metabolites in the rat. In this system, cortisol was completely metabolized within 120 minutes. The main renal metabolites of cortisol (cortisone, 20 reduced cortisol and 20 reduced cortisone) were found in the recirculating perfusate and in urine. The formation of these metabolites was quantitatively evaluated and compared to a theoretical model.

Animals↗