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Biomedical subjects

H Mashiba

Publications and source records attributed to H Mashiba.

At least 55 records · Page 3Linked to original sources

Inhibitory effect of fatty acids on glucose and insulin uptake in the perfused rat hindquarter.

To elucidate the effects of fatty acids on the uptake of glucose and insulin in the muscle, the effects of oleic and palmitic acids on the uptake of glucose and insulin were investigated in perfused hind-quarters of rats. In the absence of insulin, glucose uptake in the hindquarter was slightly, but not significantly, decreased by the addition of oleic and palmitic acids. In the presence of 100 or 500 microU/ml insulin, glucose uptake in the hindquarter (243 +/- 58 or 282 +/- 65 mumol/30 min) was significantly decreased by the addition of 1000 microM oleic acid and 500 microM palmitic acid (175 +/- 50 or 207 +/- 47 mumol/30 min). The decrease in insulin uptake rate, although not significant at 500 microU/ml insulin, is of similar magnitude to the decrease in glucose uptake. In the presence of 1000 microU/ml insulin, glucose and insulin uptake was not significantly altered by the addition of fatty acids. These results indicate that fatty acids directly inhibit the muscular glucose uptake via the decrease in muscular insulin uptake at a physiological concentration of insulin.

Adenosine Triphosphate↗

Comparative effects of monatepil, a novel calcium antagonist with alpha 1-adrenergic-blocking activity, and nitrendipine on lipoprotein and carbohydrate metabolism in patients with hypertension.

The effects of monatepil, a new calcium antagonist with alpha 1-blocking activity, and nitrendipine on lipoprotein and carbohydrate metabolism in 86 patients with mild-to-moderate hypertension were examined in a randomized, open-label, multicenter (32 hospitals) study. Thirty-nine patients treated with monatepil and 33 patients treated with nitrendipine completed the 12-week study. Monatepil and nitrendipine each significantly decreased both systolic and diastolic blood pressure. Changes in heart rate were not seen in either group. Monatepil administration significantly decreased total cholesterol, low density lipoprotein (LDL) cholesterol, the LDL cholesterol to high density lipoprotein (HDL) cholesterol ratio, apolipoprotein (Apo) B levels, and HbA1c levels, whereas no changes in these measurements were observed in nitrendipine-treated patients. Monatepil also significantly decreased lipoprotein(a) levels, but there were no significant changes in HDL cholesterol, Apo-AI, or Apo-E levels. After nitrendipine treatment, the C peptide concentration decreased significantly, although no significant changes were observed in fasting blood glucose or immunoreactive insulin levels. On the basis of these results, it can be concluded that monatepil belongs to a new class of antihypertensive calcium antagonist with favorable carbohydrate metabolism and lipid-lowering activity, although the clinical importance of these findings has not been established.

Adrenergic alpha-Antagonists↗

Changes of QRS axis in transient myocardial ischaemia induced by percutaneous transluminal coronary angioplasty.

The QRS axis of 130 consecutive patients with coronary artery disease undergoing percutaneous transluminal coronary angioplasty (PTCA) were measured before balloon inflation and just before balloon deflation. Patients were divided into two groups. Group A (103) had angina pectoris and/or non-transmural old myocardial infarction with no abnormal Q waves; group B (27) had an old transmural myocardial infarction with abnormal Q waves. In group A, the QRS axis had significantly shifted to the left in patients with left anterior descending artery (LAD) occlusion (from 68.0 +/- 42.7 degrees to 40.2 +/- 44.6 degrees, P < 0.001); however in those patients without involvement of the major septal branch, significant axis changes were not observed (from 53.6 +/- 34.1 degrees to 49.8 +/- 33.1 degrees). When the right coronary artery (RCA) was occluded in group A, the QRS axis shifted to the right significantly (from 63.2 +/- 40.0 degrees to 89.8 +/- 30.1 degrees. P < 0.01); during left circumflex artery (LCX) occlusion, no significant axis shift was observed. In group B, no significant axis shift was observed either in patients with occlusion of the LAD or the RCA. It is concluded that transient left axis deviation reflects an obstructive lesion of the proximal portion of the LAD with involvement of the major septal branch, and transient right axis deviation reflects an obstructive lesion of the RCA.

Angioplasty, Balloon, Coronary↗

Perfusion reserve of coronary collateral circulation and its significance in the development of exercise-induced ischemia in patients with multivessel disease.

To assess the perfusion reserve of coronary collateral circulation, we analyzed exercise-stress tomographic thallium-201 myocardial images in 12 patients who had total occlusion in the right coronary artery (RCA) or left circumflex coronary artery (LCX) with well-developed collateral circulation and 90% stenosis in the left anterior descending coronary artery (LAD). In 6 of the 12 patients, the collateral circulation was non-jeopardized (group A). In the remaining 6 patients, the collateral circulation was jeopardized (group B). All 6 of the patients in group A had an exercise-induced decrease in thallium uptake in the segments supplied by the occluded RCA or LCX with collateral circulation, and 3 (50%) of these 6 also showed a decrease in thallium uptake in the segments supplied by the LAD. All 6 of the patients in group B also had an exercise-induced decrease in thallium uptake in the segments supplied by the occluded RCA or LCX with collateral circulation, but none showed a decrease in thallium uptake in the segments supplied by the LAD. In conclusion, the perfusion reserve of collateral circulation is equal to or less than 90% stenosis and myocardial ischemia occurs first in the collateralized segments during exercise in patients with jeopardized collateral circulation.

Adult↗

Characteristics of ventricular premature contractions and their clinical course.

One hundred patients with frequent (> 1,000 beats/day) ventricular premature contractions (VPCs) were followed for 4 years. All of the patients, except those with non-cardiac death (n = 8), were classified into 3 groups based on their outcome. Group A consisted of 29 patients with idiopathic VPCs who survived the study period. Group B consisted of 49 patients with underlying diseases who survived the study period. Group C consisted of 14 patients who suffered cardiac death. There was no significant difference in the daily number of VPCs. However, groups B and C had more patients with Lown grade 4a or 4b VPCs than group A. The mean coupling interval was significantly longer in group C than in group A, and the standard deviation of the coupling interval was significantly larger in group C than in group A. Forty patients underwent serial Holter monitorings to assess changes in the number of VPCs. VPCs spontaneously decreased in 13 patients, while the other 27 patients continued to have frequent VPCs. Most of these 13 patients were classified as Lown grade 2. The results suggest that in patients with frequent VPCs, longer and more varied coupling intervals may predict a poor prognosis, and Lown grade 2 may predict a spontaneous regression.

Adult↗

Coronary artery ectasia with annuloaortic ectasia.

A 50-year-old Japanese woman with annuloaortic ectasia was found to have total coronary artery ectasia without evident atherosclerosis. The coronary ectasia may have been secondary to or of similar etiology to the annuloaortic ectasia. There was neither stigmata of Marfan's syndrome nor any sign of dissection of the ascending aorta or coronary arteries. Furthermore, the patient was not elderly, and had no hyperlipidemia, diabetes mellitus, or history of smoking. There was a marked blood pressure difference between the arms, and linear calcification was present in the aortic wall. A stenotic lesion was present in the right mid-subclavian artery. Although it is impossible to rule out atherosclerosis as the etiology of these findings, the possibility that they may be a manifestation of Takayasu's arteritis is discussed.

Angiography↗

Evaluation of negative inotropic and antiarrhythmic effects of class 1 antiarrhythmic drugs.

The effects of 6 class 1 antiarrhythmic drugs (aprindine, cibenzoline, disopyramide, lidocaine, pirmenol, and quinidine) on myocardial action potential, its maximal upstroke velocity (Vmax) and isometric contractile force were evaluated by electrophysiological techniques. All the class 1 antiarrhythmic drugs examined had dose-dependent negative inotropic effects. The inhibitory effects on contractile force (Fc) was compared with the inhibitory effects on sodium channels under fast response. This ratio was indicated by IC50 Vmax/IC50Fc, and when evaluated and arranged in order of descending magnitude, these were the results: pirmenol, disopyramide, lidocaine, quinidine, cibenzoline and aprindine. The negative inotropic effects and the effects on action potential duration induced by these antiarrhythmic drugs were independent of each other; it had been found that classification of the drugs according to their effects on action potential duration did not provide sufficient information about negative inotropic effects. Class 1 antiarrhythmic drugs can be divided into 3 groups depending on the regression pattern of myocardial contractile force and the Vmax of action potentials under fast response and slow response. Drugs, whose inhibitory effects on sodium channels, are the main cause of negative inotropic effects. Drugs, whose inhibitory effects on calcium channels, are the main cause of negative inotropic effects. Drugs for which it is difficult to determine whether sodium channel or calcium channel blockade contributes more to their negative inotropic effects.

Action Potentials↗

The TSH-dependent potassium channel in a cloned rat thyroid cell line.

We found a TSH-dependent K+ channel in the membrane of a rat thyroid cell line (FRTL-5 cell). This K+ channel is activated by extracellular application of the thyroid stimulating hormone (TSH). Treatment of dibutyryladenosine cyclic monophosphate (Bt2 cAMP) also activated the TSH-dependent K+ channel. Intracellular application of protein kinase A activates this K+ channel without the presence of free Ca2+. These findings indicate that the thyroid K+ channel is activated through the TSH-cAMP-protein kinase A system. This is the first report of a polypeptide hormone activated K+ channel and it should be useful for examining the effects of this K+ channel on thyroid cell functions.

Amino Acid Sequence↗

Effects of hypoxia on the use-dependent inhibition of conduction velocity induced by cibenzoline in guinea pig ventricular myocardium.

The use-dependent effects of cibenzoline, a new anti-arrhythmic drug, on the maximal rate of rise (Vmax) of the action potential and on conduction velocity, and their corresponding recovery kinetics were studied in isolated papillary muscles of guinea pigs under normal and hypoxic conditions. Standard microelectrode techniques were applied to monitor the action potential of the muscles and their conduction. Under control conditions, the amount of use-dependent block of Vmax, conduction velocity, and square of conduction velocity, induced by 10 mumol/L cibenzoline were 26.5 +/- 3.9, 13.8 +/- 1.4, and 25.6 +/- 2.4%, respectively; under hypoxic conditions, these values increased to 32.3 +/- 4.8, 19.7 +/- 1.2, and 35.5 +/- 2.0%, respectively. In the presence of 10 mumol/L cibenzoline, the mean values of time constants for the onset of the use-dependent inhibition of Vmax, conduction velocity, and the square of conduction velocity, during a 2-Hz stimulation, were 3.65 +/- 0.27, 2.77 +/- 0.33, and 2.56 +/- 0.26 seconds, respectively. Under hypoxic conditions, these values changed to 5.10 +/- 0.96, 3.05 +/- 0.44, and 2.84 +/- 0.39 seconds, respectively. The recovery time constants averaged 14.72 +/- 4.08 seconds (for Vmax), 22.23 +/- 3.78 seconds (for conduction velocity), and 23.17 +/- 13.38 seconds (for the square of conduction velocity) in the presence of 10 mumol/L cibenzoline, and 17.19 +/- 8.59 seconds (for Vmax), 15.77 +/- 2.37 seconds (for conduction velocity), and 16.82 +/- 2.61 seconds (for the square of conduction velocity) under hypoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Facilitation of beta-adrenoceptor-mediated slow channel responses by hypoxia in guinea pig ventricular myocardium.

The effects of hypoxia on the beta-adrenoceptor-mediated slow channel responses of guinea pig ventricular muscle in a potassium-rich (27 mM) solution containing Ba2+ were examined using microelectrode techniques. Isoproterenol produced a small depolarization of the resting membrane and also induced repetitive discharges of action potentials at higher concentrations, mainly due to a beta-adrenoceptor-mediated increase in the slow channel conductance. Two different threshold concentrations of isoproterenol, one for inducing depolarization and one for inducing automatic activity, were measured to assess myocardial responsiveness to catecholamines. During hypoxia, the electrically triggered slow upstroke action potentials of muscle were gradually depressed and catecholamine-induced membrane responses mediated by the beta-adrenoceptor/slow channel system were enhanced. The enhancement of the catecholamine effects was accelerated by acidosis and reversed by reoxygenation. Methyl xanthine-induced responses, similar to those induced by catecholamines, were also enhanced during hypoxia. It is suggested that not only changes of catecholamine-beta-adrenoceptor interaction, but also changes of intracellular metabolic processes, may be responsible, at least in part, for the enhancement of abnormal automatic activity mediated by the myocardial beta-adrenoceptor/slow channel system under hypoxic conditions.

Action Potentials↗

Possible role of the adrenergic mechanism in gastric inhibitory polypeptide- and glucagon-like peptide-1 (7-36) amide-induced insulin release in the rat.

Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1(7-36) amide (GLP-1) are thought to be the most probable candidates for incretin. However, the precise mechanism of incretin effect is unclear. In the present study, to elucidate the possible role of the autonomic nervous system in incretin effect, the effects of atropine, propranolol, metoprolol, and phentolamine on GIP- or GLP-1-induced insulin release were investigated in the rat. The GIP-induced (2 or 20 micrograms) insulin release was partly inhibited by propranolol pretreatment (0.5 mg/kg subcutaneously [SC]), and GLP-1-induced (2 or 20 micrograms) insulin release was partly inhibited by propranolol or metoprolol (35 mg/kg SC). These results suggest that a beta-adrenergic mechanism may be involved in the incretin effect, probably through a modulating effect on GIP- or GLP-1-induced insulin secretion.

Animals↗

Acute hemodynamic effects of bunazosin in congestive heart failure--differing responses according to degree of cardiac dysfunction.

1. Hemodynamic responses to Bunazosin (BZN) in congestive heart failure (CHF) were evaluated for 6 hours (hr) in 30 patients (A, normal cardiac function; B, mild cardiac dysfunction; C, severe cardiac dysfunction). 2. For 6 hr after BZN, the increments of cardiac index (delta CI) and stroke volume index (delta SVI) with BZN were higher in groups A and B than in group C. 3. A significant positive correlation was observed between ejection fraction and maximum delta CI and SVI, and between % fractional shortening and maximum delta CI and SVI. 4. These data showed that BZN improved the hemodynamics of CHF patients and that patients in groups A and B responded well to this vasodilator, however, patients in group C did not.

Adrenergic alpha-Antagonists↗

Relationship between negative inotropic and chronotropic effects of tocainide and five class I antiarrhythmic drugs in the coronary perfused guinea-pig heart.

1. The relationship between the negative inotropic and chronotropic effects of tocainide and 5 other class I antiarrhythmic drugs was evaluated in Langendorff-perfused guinea-pig hearts. 2. All 6 drugs reduced the contractile force (Fc) and the heart rate (HR) of spontaneously beating guinea-pig hearts in a dose-dependent manner. The order of crude negative inotropic potency was: quinidine (Qui) = aprinidine (Apr) > mexiletine (Mex) > lidocaine (Lid) > disopyramide (Dis) > tocainide (Toc); and the order of negative chronotropic effect was: Apr > Qui > Mex > Dis > Lid > Toc. 3. The order of the negative inotropic potency relative to chronotropic effect (expressed as a ratio: ID50 for Fc/ID50 for HR) was Lid > Qui > Dis > Toc > Mex > Apr (n = 6). 4. For heart electrically stimulated at a constant rate, the order of crude negative inotropic potency was: Apr > Qui > Mex > Dis > Lid > Toc, and the order of negative inotropic potency (determined by the ratio: ID50 for Fc in driven heart/ID50 for spontaneously beating HR) was: Mex > Apr > Toc > Dis > Qui > Lid (n = 6). 5. There was a significant influence of negative chronotropic effect on the inotropic potency and the order was: Lid > Qui > Dis > Toc > Apr > Mex. The potency of various drugs is clinically useful in the choice of drugs when considering cardiac function and heart rate.

Animals↗

Effect of trapidil on serum lipid and apolipoprotein levels in patients with ischemic heart disease.

1. Serum total cholesterol (TCH), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein (LDL-C), atherosclerotic index (AI) and apolipoprotein (apo A-I, A-II, B, C-II, C-III and E) levels were investigated in patients with ischemic heart disease before and after medication of trapidil. 2. Twenty-one patients were orally given 100 mg of trapidil, three times daily (300 mg/day). After 8 weeks' administration, serum HDL-C level increased (P < 0.01) and AI decreased (P < 0.02) significantly, whereas TCH, TG and LDL-C levels tended to decrease but not significantly. 3. Among the parameters of apolipoproteins, apo A-I, a main protein of HDL-C, was significantly increased (P < 0.05) by trapidil. 4. These results indicate that trapidil has a beneficial effect on the coronary risk profile as reflected by lipid measurements.

Aged↗

Augmented inhibition of MethA tumor cell proliferation in combined use of diethyldithiocarbamate with catalase or by a nondialysable fraction from co-incubation.

The antiproliferative effect of diethyldithiocarbamate (DDC), a metal chelator, in combined use with catalase on MethA tumor cells was studied. Marked augmentation of the antiproliferative effect was observed when 1 x 10(-7) M DDC was used in combination with catalase (0.004-40 micrograms/ml). Further augmentation of the cytostatic effect was obtained by the simultaneous addition of 2 x 10(-7) M DDC with catalase and more than 97% inhibition of [3H]thymidine uptake by target cells was observed. A nondialysable fraction from the co-incubation of DDC with catalase was also remarkably cytostatic to the target cells. Serum factor(s), probably metal ions, was suggested to be necessary for the induction of the nondialysable fraction with cytostatic activity. The activity was not nullified by the pretreatment of a nondialysable fraction with anti-catalase antibody. These results suggest that an active substance or compound exhibiting an antiproliferative effect on tumor cells might be newly formed as the result of the interaction of DDC with catalase.

Animals↗

Case report: a case of multiple coronary artery to left ventricular communications.

A 39-year-old man with anginal pain had multiple coronary artery to left ventricular communications. His electrocardiogram showed evidence of left ventricular hypertrophy, and an echocardiogram revealed a dilated left ventricle. A coronary angiogram revealed multiple coronary artery to left ventricular fistulae involving three major coronary arteries with no evidence of atherosclerotic lesions. Only 17 cases of such fistulous communications involving three major coronary arteries have been reported in the literature. It is suggested that the fistulous communications to the left ventricle was a cause of his angina pectoris, probably because of the coronary steal phenomenon.

Adult↗