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Biomedical subjects

K Ogino

Publications and source records attributed to K Ogino.

At least 163 records · Page 9Linked to original sources

Thromboxane as a possible hepatotoxic factor increased by endotoxemia in obstructive jaundice.

In a study using rats, we investigated whether liver damage induced by endotoxemia in obstructive jaundice is associated with thromboxane (TX) in order to acertain whether its vasoconstrictive and platelet aggregating properties play a role in reducing liver blood flow. The rats were divided into the following 5 groups; a control group, an endotoxin (Et) group, a bile duct ligation (BDL) group, a bile duct ligation and endotoxin (BDL + Et) group and an OKY046 (Thromboxane synthetase inhibitor) treated bile duct ligation + endotoxin (OKY-BDL + Et) group. The blood TXB2 levels in the Et, BDL and BDL + Et groups were higher than those in the control group. The liver TXB2 levels in the Et and BDL + Et groups were also higher than those in the control group. Liver phospholipids and liver blood flow decreased in the BDL + Et group, whereas in the OKY-BDL + Et group they returned close to the control group levels by decreasing the TXB2 levels in both the liver and blood to normal. These results suggest that the high level of TX in the blood and liver tissue may further aggrevate the liver during endotoxemia in obstructive jaundice by inhibiting liver blood flow.

Animals↗

Hypouricaemia with acute viral hepatitis.

We report five female cases of hypouricaemia accompanied by acute viral hepatitis (serum urate 101 +/- 12 mumol/l, mean +/- SD). Their urate clearance was increased to 14.2 +/- 3.4 ml/min during hyperbilirubinaemia but 24-h urate excretion was not elevated (2.09 +/- 0.64 mmol/24 h). No other renal tubular abnormalities were detected. Comparing urate metabolism with that of four cases of inborn renal hypouricaemia, the degree of uricosuria was lower. One patient showed elevation of serum and urinary oxypurine, which normalized with return of a normal blood uric acid level. In all cases, the serum urate returned to normal after improvement of liver function. We suggest that renal uricosuria due to an isolated renal defect of urate transport might contribute to hypouricaemia in these cases but that inhibition of xanthine oxidase activity might also contribute to this phenomenon.

Acute Disease↗

Transient QRS axis shift to the right during right coronary artery and/or left circumflex artery spasms.

The QRS axis was measured in 24 patients during ergonovine malate provocation test (EM test). Of 12 patients with significant spasm of the right coronary artery (RCA) and/or left circumflex artery (LCX), the QRS axis shifted to the right in 7 patients after the EM test (mean 8.2 degrees), and the axis shifted back to the left in 9 patients after nitroglycerin administration (mean -9.1 degrees). The sensitivity of right axis shift for RCA and LCX spasm was 58% and the specificity was 80%. Thus, right axis shift seems to be associated with myocardial ischemia due to RCA and LCX spasm and to be useful for the detection of RCA and/or LCX spasms.

Coronary Vasospasm↗

Cause of persistent hypouricemia in outpatients.

We measured serum urate in 3,258 Japanese outpatients. Five of them had persistent hypouricemia. Three also had microhematuria. Four of the five patients were proven to have renal uricosuria with hypouricemia, but otherwise normal tubular function. When tested with both pyrazinamide and benzbromarone, 1 patient had a presecretory reabsorption defect, 2 had postabsorption defects, and 1 an enhanced renal tubular secretion of urate. These results suggest that persistent hypouricemia in outpatients is of very low incidence, is usually caused by an isolated metabolic error of urate transport, and is not related to drug ingestion or systemic disease.

Benzbromarone↗

A case of paroxysmal ventricular tachycardia during pregnancy.

We report a case of a 37-year-old woman who had paroxysmal ventricular tachycardia (VT) during early pregnancy. She had severe hyperemesis, palpitation at 6 weeks of gestation and many episodes of paroxysmal VT, but no apparent organic heart disease. At that time she had a transient increase of thyroid hormone levels. With bed rest and without medication, her symptoms and episodes of VT disappeared in accordance with the improvement of hyperemesis and thyrotoxicosis. She demonstrated a rare course of arrhythmias in which the deterioration of VT was observed at transient thyrotoxicosis and hyperemesis.

Adult↗

Effect of oxitropium bromide (Ba253) on isolated respiratory smooth muscle and release of chemical mediators from passively sensitized lung fragments.

The effect of oxitropium bromide (Ba253), a quaternary scopolamine derivative, on the resting tonus and agonist-induced contraction of isolated guinea pig airway smooth muscle and on the anaphylactic release of histamine and immunoreactive leukotrienes (i-LTs) from lung fragments were investigated and compared with those of Sch1000, atropine and isoproterenol. Ba253 dose-dependently inhibited the acetylcholine (ACh)-induced contraction of the isolated trachea and lung parenchyma. The degree of inhibitory potency was similar to that of Sch1000 and 10 times higher than that of atropine. Ba253 minimally influenced the resting tonus or contractions induced by other agonists including histamine, serotonin and LTD4. Sch1000 and atropine had similar or slightly stronger inhibitory effects on the tonus and contractions than Ba253. On the other hand, low concentrations of isoproterenol solely relaxed the resting tonus and inhibited the the agonist-induced contractions of both preparations. Neither Ba253 nor Sch1000 inhibited the anaphylactic release of histamine and LTs from both guinea pig and human lung fragments, but both mediator releases from either species were slightly inhibited with dose-dependency by atropine and potently inhibited by isoproterenol. From these results, it is suggested that Ba253 is a relatively specific antagonist to cholinergic receptors and might be possibly effective as an inhalant for asthma.

Animals↗

Effect of oxitropium bromide (Ba253) on increased airway resistance induced by various agonists and antigen in the guinea pig.

Effects of oxitropium bromide (Ba253), which was administered by inhalation, on the resting and stimulus-induced airway resistance were examined in the artificially ventilated guinea pig and compared with those of ipratropium bromide (Sch1000), atropine and isoproterenol. Results obtained were as follows: 1) Ba253 as well as other reference compounds hardly affected the resting resistance. 2) Ba253 strongly and persistently inhibited the acetylcholine (ACh)-induced resistance. Sch1000 caused a similar but relatively weaker inhibition than Ba253. Either atropine or isoproterenol caused only a transient inhibition. 3) The increase in resistance induced by histamine, serotonin, leukotriene D4 or antigen was prevented by Ba253. Atropine, Sch1000 and isoproterenol also inhibited these reactions, but the effects and the duration were generally weaker and shorter than those of Ba253. 4) Repeated inhalations of Ba253 for 7 days did not influence the inhibition of the ACh-induced increase in airway resistance by this drug. However, isoproterenol tended to attenuate the suppression of the resistance by the drug. From these results, it is suggested that Ba253 is a useful inhalant drug for asthma.

Acetylcholine↗

[Inhibitory effect of amlexanox (AA-673) on the immunological and non-immunological release of histamine or leukotrienes].

The effect of amlexanox on the non-immunological or immunological release of histamine or leukotrienes (LTs) from passively sensitized human lung fragments and atopic human leukocytes was investigated and compared with those of AA-861, tranilast, azelastine and disodium cromoglycate. 1) Amlexanox at concentrations of 10(-7)-10(-4) M showed an inhibition of histamine, LTB4, LTC4, LTD4 and LTE4 release from passively sensitized human lung fragments in a concentration-dependent fashion. A selective and competitive inhibitor of the 5-lipoxygenase activity, AA-861 modestly affected the histamine release and potently suppressed the any LT release at 10(-7) and 10(-6) M. Antiallergic drugs, tranilast and disodium cromoglycate also suppressed these chemical mediator release, but the inhibition potency was somewhat weaker than that of amlexanox. 2) Ca ionophore A23187-induced release of LTB4 and LTC4 from atopic human leukocytes was slightly enhanced up to 10(-6) M of amlexanox. However, 10(-4) M of the drug strongly diminished both of LT release. From these results, it is suggested that amlexanox is a clinically effective drug for atopic diseases, especially allergic asthma and rhinitis.

Aminopyridines↗

[Sympathetic nervous system response to exercise in patients with congestive heart failure].

The response of the sympathetic nervous system to exercise in patients with congestive heart failure was studied in 65 patients (NYHA functional class I 28, II 23, and III 14) and 22 normal subjects (N) by submaximal treadmill testing with the modified Bruce's or Sheffield's protocols. Plasma norepinephrine (NE) and epinephrine (E) levels were also measured at rest, at the end of each stage, and immediately after and 5 min after exercise. In accordance with the severity by NYHA functional class, the exercise duration became shorter and the discontinuation of exercise with symptoms occurred more frequently. Systolic blood pressure and double products (DP) at the peak exercise were significantly lower in patients with NYHA class III. NE and increments of NE increased during exercise [peak NE (pg/ml); N: 589, I: 646, II: 1253, and III: 997] and were higher at rest, during exercise and in recovery in patients with NYHA classes II and III than in the normal subjects and NYHA class I patients. E increased gradually during exercise [peak E (pg/ml); N: 60, I: 66, II: 63, and III: 66] and there were no significant differences among the four groups. A negative correlation (r = -0.53) between the peak NE and exercise duration was observed in normal subjects, while a positive correlation (r = 0.55) was observed in patients with NYHA class II. A positive correlation (r = 0.54) between DP at the peak exercise and the peak NE was observed in patients with NYHA class I, whereas a negative correlation (r = -0.46) was observed in patients with NYHA class III. The NE response in patients with NYHA classes II and III increased significantly, suggesting compensatory activation of the sympathetic nervous system for impaired cardiac function. In conclusion, the NE response to submaximal exercise testing differs in each NYHA functional class and it might be a useful indicator to evaluate cardiac function of patients with congestive heart failure.

Aged↗

[Inhibition of thromboxane production might ameliorate liver blood flow in shock].

UNLABELLED: We investigated whether thromboxane (TX), a vasoconstrictor, contributes to liver disturbance in shock by reducing liver blood flow. SUBJECTS AND METHODS: experimental groups: Sham, Et: endotoxin 4mg/kg, BDL + Et: bile duct ligation with Et, OKY. BDL + BDL + Et with infusion of OKYO46 (TX synthetase inhibitor) 5mg, HT: three days after 70% hepatectomy, OKY. HT: HT receiving OKYO46. We evaluated prostanoid and morbidity in hepatectomized cases. MEASUREMENT: TX, liver phospholipid, liver blood flow, endotoxin. RESULTS: Higher TX levels in blood and liver, and reduced liver phospholipid and liver blood flow in BDL + Et returned close to sham by OKYO46. High blood endotoxin in HT decreased by OKYO46. Intraoperative blood losses in cases with postoperative intraabdominal infection or hepatic failure were greater than those without complication. Hepatectomized cases with intraabdominal infection showed higher blood TX than those without complication. TX might be associated with decreased liver blood flow and with postoperative complication during shock. To reduce TX production would be beneficial in shock by ameliorating liver blood flow.

Animals↗

Differences in urate metabolism between normouricemia and hyperuricemia in coronary heart disease in man.

We examined hyperuricemia in patients with coronary heart disease. In 85 patients with coronary sclerosis confirmed by coronary angiography, the serum urate level (6.08 +/- 1.60 mg/dL) was not different from that in subjects with normal coronary arteries (6.47 +/- 1.69 mg/dL). The incidence of hyperuricemia in patients with coronary sclerosis was 26%, and was significantly correlated with diuretics, obesity and hypertriglyceridemia, but not with hypertension or hypercholesterolemia. To elucidate the mechanism of urate metabolism in coronary sclerosis, we separated coronary sclerosis patients without complicating factors into hyperuricemics and normouricemics, and studied urate metabolism in comparison with subjects with normal coronary arteries. We found that normouricemics with coronary sclerosis had decreases in the filtered urate load and urate clearance with a normal urate-creatinine clearance ratio. Hyperuricemics with coronary sclerosis had decreases in urate clearance and urate-creatinine clearance ratios, but the filtered urate load was similar to that in normouricemics. It is suggested that in coronary sclerosis patients, normouricemics had a low glomerular filtration of urate with normal tubular urate transport, whereas hyperuricemics had enhanced tubular reabsorption of urate without any difference of urate filtration from normouricemics.

Coronary Disease↗

Induction of cytochrome P-450, cytochrome b-5, NADPH-cytochrome c reductase and change of cytochrome P-450 isozymes with long-term trichloroethylene treatment.

Several reports have described the effects of trichloroethylene (TCE) on the microsomal mixed function oxidase system (MFOS). These studies suggest that repeated TCE administration induces MFOS, especially cytochrome P-450 and NADPH-cytochrome c reductase. However, it is uncertain what isozymes are induced by TCE treatment, and it is not clear how microsomal enzymes or cytochrome P-450 isozymes are altered when TCE is administered for a duration longer than 28 days. We investigated the changes of MFOS by long-term TCE treatment. Male Wistar rats were injected with TCE, 1.0 g/kg body weight once a day for 5 continuous days or 2.0 g/kg body weight twice a week for 15 days. The mean body weight of the rats treated with TCE for 15 weeks was slightly, but not significantly, less than that of the control rats. Relative liver weights (liver wt/body wt) of the TCE-treated group were however significantly larger (21%) than those of the control group. The weights of the other organs were not changed by long-term TCE treatment. Trichloroethylene treatments for 5 days and 15 weeks caused significant increases in microsomal protein, cytochrome P-450, cytochrome b-5 and NADPH-cytochrome c reductase. TCE treatments produced an increase in a polypeptide band at 52,000 molecular weight range observed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This increase in similar to, but less pronounced than that induced by phenobarbital (PB) treatment. There were no remarkable changes at 56,000 molecular weight range where a band appeared after the treatment with 3-methylcholanthrene (MC). It is likely that the induction of cytochrome P-450 by TCE is relatively similar to that by PB.

Animals↗

The usefulness of exercise-induced QRS axis shift as a predictor of coronary artery disease.

The QRS axis of 101 patients with coronary artery disease (CAD) and 57 normal subjects without CAD who underwent coronary arteriograms were measured before and after exercise testing. There was no improvement in the sensitivity of positive axis shifts (15 degrees or greater) for CAD (18%) when compared to the value of positive ST depression (61%). However, the specificity of positive axis shifts for CAD was significantly increased (98%) when compared to the value of positive ST depression (77%). In addition, 39% of those patients with CAD (39 of 101) showed false negative ST depression, but 18% of these patients (7 of 39) showed a positive axis shift. In normal subjects 21% (12 of 57) showed false positive ST depression, but all of the 21% (12 of 12) showed negative axis shift. There was no significant difference in the increments of heart rate between positive ST depression, positive axis shift, and negative ST depression, negative axis shift. No statistical differences in the sensitivity of ST depression and an axis shift for one-, two- and three-vessel diseases were noted. The specificity of left-axis shift for the left anterior descending artery lesion was 98% and the specificity of right-axis shift for the right coronary artery and/or left circumflex artery lesion was 91%. Therefore, the axis shift response is no more sensitive for the detection of CAD than ST depression. However, when a positive axis shift is observed, one can predict two things: the CAD and the localization of the coronary stenosis.

Arrhythmias, Cardiac↗

Metabolism of chloral hydrate in the anoxic perfused liver.

The metabolism of chloral hydrate (CH) under anoxic conditions was investigated in the non-recirculating, hemoglobin-free liver perfusion system. CH uptake in the anoxic liver decreased to about 80% of that in the oxygen-supplied liver. The reduction of CH to trichloroethanol (TCE) increased and the oxidation of CH to trichloroacetic acid (TCA) decreased. The TCE/TCA ratio increased; however, the total trichloro compounds, that is TCE and TCA, were not significantly altered by anoxia. Though approximate 14% of the CH infused into the oxygen-supplied liver was changed to substances other than TCE or TCA, the unknown part was a very small portion in the anoxic liver. The decrease in CH uptake, by the anoxic liver, is thought to be equivalent to the decrease of the unknown metabolites. The TCE/TCA ratio under anoxia was also altered by pyruvate or lactate infusion.

Animals↗

Gastric mucosal protection and superoxide dismutase.

Diethyldithiocarbamate (DDC), an inhibitor of Cu,Zn-superoxide dismutase (SOD), at a dose of 500 mg/kg or aminotriazole (AT), an inhibitor of catalase, at a dose of 2,000 mg/kg reduced slightly gastric mucosal SOD activity, did not change gastric mucosal blood flow (GMBF), and did not cause gastric ulcers. However, when both DDC and AT were administered together, gastric mucosal SOD activity and GMBF remarkably decreased, and gastric ulcers appeared. Moreover, the administration of SOD attenuated gastric ulcer induced by DDC plus AT. These results suggested that SOD may play an important role in the gastric mucosal defense mechanisms against active oxygen species.

Amitrole↗

Renal hypouricemia due to an isolated renal defect of urate transport.

A 22-year-old man was found to have low serum urate concentration (1.1-1.7 mg/dl). His urate clearance was markedly increased (26.9-35.5 ml/min) and was not decreased after administration of pyrazinamide, but was even more increased after administration of benzbromarone. No other renal tubular abnormalities were detected. The young man has one sister and two brothers. His sister also has hypouricemia and hyperuricosuria. We suggest that the present case had a genetically determined renal abnormality affecting tubular presecretory reabsorption of urate.

Adult↗

[Perfluorochemical emulsion as a perfusate in 24-hour liver preservation prior to transplantation in the rat].

Perfluorochemical (PFC) emulsion as a perfusate of liver preservation prior to transplantation was evaluated in continuous hypothermic perfusion for 24 hours followed by orthotopic transplantation in inbred male Lewis rat. Three different contents of PFC emulsion that is, 20% (original Fluosol DA), 10% and 0% PFC solution were prepared as a perfusate. Isolated liver was stored for up to 24 hours using a continuous non-pulsatile perfusion technique of closed circuit with each perfusate. Gas content, GOT, GPT, LDH, potassium and glucose of the perfusate were measured. Oxygen consumption of perfused liver was higher in PFC emulsion than non PFC perfusate. Biochemical analysis of perfusate suggested that liver was preserved best in 10% PFC emulsion. Histological findings, especially, acid phosphatase staining, showed better result in PFC groups. One week survival rates after liver graft were 4/6 (66.7%) in 10% PFC solution, 1/6 (16.7%) in 20% and 0/6 (0%) in 0% solution. In spite of the highest oxygen consumption of perfused liver in early phase, 20% PFC emulsion did not bring the good preservation of perfused liver because of impaired circulation due to higher viscosity in low temperature. Ten percent PFC solution is considered the best in hypothermic preservation of the liver.

Animals↗