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Biomedical subjects

H Mashiba

Publications and source records attributed to H Mashiba.

At least 73 records · Page 4Linked to original sources

Correlation between blood pressure and plasma insulin in acromegaly.

OBJECTIVES: The aims of this study were to determine the possible role of hyperinsulinaemia in the increase in blood pressure in acromegalic patients. DESIGN: After an overnight fast, blood samples were obtained at 0. 30, 60, 120 and 180 min after 75 g glucose ingestion, and plasma growth hormone (GH) and plasma insulin (IRI) were measured by radioimmunoassay. The blood pressure was measured at 10.00 hours for 3 days in a supine position. SUBJECTS: Nineteen (nine women and 10 men) untreated acromegalic patients, aged 25-69 years. RESULTS: There were no significant correlations between mean blood pressure (MBP; diastolic+one-third pulse pressure) and basal GH, sum of plasma GH at 0, 30, 60, 120 and 180 min or basal IRI. However, significant correlation was observed between MBP and IRI at 120 min (r = 0.57, P < 0.02) or sum of plasma IRI at 0, 30, 60, 120 and 180 min) (r = 0.58, P < 0.02). CONCLUSIONS: We conclude that hyperinsulinaemia may be involved in an increase in blood pressure in active acromegalics.

Acromegaly↗

Renal hypouricemia due to enhanced tubular secretion of urate associated with urolithiasis: successful treatment of urolithiasis by alkalization of urine K+, Na(+)-citrate.

We encountered a case of hypouricemia with increases both in urate clearance (Cur) and in the ratio of Cur to creatinine clearance (Cur/Ccr), the normal daily urinary excretion of urate, and urolithiasis. Pyrazinamide markedly decreased Cur and Cur/Ccr, and both probenecid and benzbromarone markedly increased Cur and Cur/Ccr, however, benzbromarone did not increase either Cur or Cur/Ccr under pretreatment with pyrazinamide in the patient. Thus, the diagnosis was made of renal hypouricemia due to enhanced tubular secretion of urate. The urinary pH of the patient tended to be acidic. Three months after the start of alkalization of the patient's urine by K+, Na(+)-citrate, both urolithiasis and the symptoms related to urolithiasis disappeared. These results suggest that renal hypouricemia due to enhanced tubular secretion of urate can result in urolithiasis and the alkalization of urine may be an effective treatment for uric acid stones.

Benzbromarone↗

Effects of volume and pressure overloads and myocardial hypertrophy on exercise-induced changes in electrocardiographic QRS amplitude.

To investigate the effects of volume and pressure overloads and myocardial hypertrophy on exercise-induced changes in QRS amplitude, we reviewed treadmill exercise electrocardiograms. In 10 normal young men, Rv5 amplitude decreased and Sv1 amplitude increased at peak exercise, and returned to the resting value in the recovery period. In 10 patients with aortic regurgitation, Rv5 and Sv1 amplitudes increased after 5 min of recovery. In 12 patients with essential hypertension and 10 with idiopathic hypertrophic non-obstructive cardiomyopathy, Rv5 amplitude remained unchanged or higher at peak exercise compared with the resting value, but patterns of serial changes were similar to that of normal subjects. In 9 patients with atrial septal defect, R'v1 amplitude increased with exercise, whereas it remained unchanged in 12 with isolated complete right bundle branch block. In 5 patients with mitral stenosis, Sv1 amplitude decreased at peak exercise. In conclusion, changes in QRS amplitude with exercise are influenced by hemodynamic abnormality and myocardial hypertrophy, and a major determinant of these serial changes seems to be the change in ventricular volume.

Adult↗

Effects of an angiotensin-converting enzyme inhibitor, alacepril, on cardiovascular and sympathetic nervous responses to mental stress in patients with essential hypertension.

The effects of an angiotensin-converting enzyme inhibitor, alacepril, on cardiovascular and plasma catecholamine responses to mental stress were studied. A mental arithmetic test (MAT) was carried out in 9 patients with essential hypertension before and after treatment with alacepril, 25 mg once daily for 2 weeks, and in 9 age- and sex-matched normal subjects. Systolic blood pressure at rest and during MAT and the change in plasma norepinephrine concentrations during MAT were significantly greater in the hypertensive subjects than in the normal subjects. Alacepril significantly reduced systolic blood pressure, both at rest and during MAT, as compared to before treatment in the hypertensive subjects. Furthermore, alacepril significantly attenuated the change in plasma norepinephrine concentrations during MAT (from 127 +/- 76 pg/ml to 66 +/- 42 pg/ml, p < 0.05). These results suggest that alacepril significantly suppresses the augmented cardiovascular and sympathetic nervous responses to mental stress in patients with essential hypertension.

Adult↗

Hepatic extraction and hepatic action of insulin, glucagon, and epinephrine in bivascularly perfused rat liver.

Using a bivascularly perfused rat liver, we investigated the hepatic extraction and hepatic action on glucose output of insulin, glucagon, and epinephrine. The liver was perfused for 70 min without recirculation via the portal vein and hepatic artery (3.0 ml/(min.g liver) from portal vein and 1.0 ml/(min.g liver) from celiac artery). Low and high concentration of insulin, glucagon, or epinephrine (450 and 4,500 pM, 21.5 and 215 pM, or 410 and 4,100 pM, respectively) was added to the perfusing medium via portal vein (P-liver), via celiac artery (H-liver), or via portal vein and celiac artery (H-P-liver). Hepatic extraction of insulin, glucagon, or epinephrine was not significantly different among H- (56 +/- 9 and 21 +/- 5%, 31 +/- 7 and 24 +/- 6%, or 22 +/- 8 and 17 +/- 5%), P- (50 +/- 10 and 23 +/- 6%, 32 +/- 9 and 23 +/- 7%, or 22 +/- 9 and 18 +/- 6%), and H-P-liver (55 +/- 11 and 24 +/- 6%, 30 +/- 9 and 26 +/- 8%, or 20 +/- 9 and 17 +/- 6%). Glucagon- or epinephrine-induced increase in glucose output was also similar in H- (245 +/- 47 and 498 +/- 82 mumol/30 min, or 112 +/- 21 and 215 +/- 38 mumol/30 min), P- (258 +/- 51 and 512 +/- 95 mumol/30 min, or 128 +/- 20 and 220 +/- 36 mumol/30 min), and H-P-liver (263 +/- 58 and 515 +/- 94 mumol/30 min, or 129 +/- 22 and 225 +/- 39 mumol/30 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Uptake of ketone bodies in perfused hindquarter and kidney of starved, thyrotoxic, and diabetic rats.

To elucidate the peripheral disposal of ketone bodies in hyperketonemia accompanied with starvation, hyperthyroidism, or diabetes mellitus, the uptake of acetoacetic acid (AcAc) and beta-hydroxybutyrate (BOHB) was investigated in the perfused hindquarter and kidney of starved, thyrotoxic, and diabetic rats. Thyrotoxicity was induced by daily subcutaneous injection of thyroxine (100 micrograms/kg/day) for 7 days, and diabetes mellitus was induced by intraperitoneal streptozotocin (50 mg/kg) injection. Plasma concentration of AcAc and BOHB was significantly higher in starved, thyrotoxic, and diabetic rats than in controls. The hindquarter or kidney of rats was perfused with synthetic medium containing 0.2 or 1.5 mM AcAc or BOHB for 30 min at a flow rate of 0.5 ml/g muscle wt/min or 3.2-3.5 ml/kidney/min, respectively. In perfused hindquarter, the uptake of AcAc and BOHB was significantly reduced in starved and diabetic rats, but not in thyrotoxic rats. In perfused kidney, the uptake of AcAc and BOHB was not significantly different between the experimental and control rats. These results suggest that in starvation or diabetes mellitus, disposal of AcAc and BOHB was impaired in the hindquarter but not in the kidney, and that disposal of AcAc and BOHB by hindquarter and kidney was not impaired in thyrotoxic rats.

3-Hydroxybutyric Acid↗

Comparison of coronary responses to intracoronary and intraaortic ergonovine and isosorbide dinitrate in patients with atypical chest pain.

Fifty patients with atypical chest pain were studied to compare coronary responses to intracoronary and intraaortic ergonovine. The diameters of the proximal, middle (1) and (2) (proximal segments of segments 2 and 3 [AHA classification], respectively), and distal segments of the right coronary artery were measured before and after intracoronary ergonovine (4 micrograms/minute over 4 minutes) and isosorbide dinitrate (ISDN) (2 mg) in 24 patients, and before and after intraaortic ergonovine (0.2 mg) and ISDN (5 mg) in 26. Mean vasoconstriction by intracoronary and intraaortic ergonovine were 13 +/- 1.5% and 9 +/- 0.8%, respectively (p < 0.02). Irrespective of the methods of administration, the responses to ergonovine were similar in the 4 segments. Mean vasodilation by intracoronary and intraaortic ISDN, which were used to quantify the degree of basal coronary tone, were 25 +/- 2.2% and 27 +/- 1.5%, respectively (p = not significant [NS]). There were significant negative linear correlations between the responses to ergonovine and ISDN in the middle (2) (r = -0.51; p < 0.05) and distal (r = -0.53; p < 0.01) segments in patients with intracoronary injection, and the proximal (r = -0.41; p < 0.05), middle (1) (r = -0.66; p < 0.01) and middle (2) (r = -0.69; p < 0.01) segments in patients with intraaortic injection. These observations indicate that low-dose administration of intracoronary ergonovine produces sufficient coronary vasoconstriction, similar to or slightly greater than that of intraaortic ergonovine in patients with atypical chest pain, but basal coronary tone may influence the vasoreactivity to ergonovine.

Aorta↗

Effect of a novel class I antiarrhythmic agent, TYB-3823, on the calcium current in single guinea pig ventricular myocytes.

The effect of TYB-3823 on Ca2+ current (ICa) of guinea pig ventricular myocytes was investigated by means of whole-cell patch-clamp technique. TYB-3823 (100-1,000 microM) caused a concentration-dependent decrease in ICa. Furthermore, a reduction of ICa induced by TYB-3823 (1,000 microM) was progressively accentuated by repetitive membrane depolarization, indicating a rate-dependent block of ICa. However, the inhibitory potency on ICa was approximately 1/1000 of a Ca2+ antagonistic agent, verapamil hydrochloride. Considering evidence that 3-30 microM TYB-3823 decreased the maximum upstroke velocity of the action potential of guinea pig ventricular muscles, it is indicated that the drug does not show its Ca2+ antagonistic property in the usual concentration range as a class I antiarrhythmic agent.

Animals↗

Intraduodenal osmolality directly enhances insulin secretion in the rat.

To elucidate the direct effect of an intestinal osmolality on insulin release, we investigated the insulin response to intra-duodenal infusion of mannitol in rats. After the anesthesia with intraperitoneal pentobarbital sodium, one milliliter of mannitol solution (10% or 20%) was infused into the duodenum. Portal and femoral blood insulin concentrations significantly increased at 30, 60, and 120 min after intra-duodenal infusion of mannitol, although the blood glucose level did not change. Subcutaneous pre-administration of propranolol (0.4mg/kg) or metoprolol (25mg/kg) completely abolished this phenomenon. These results suggest that intestinal osmolality can directly enhance insulin secretion and that beta 1-adrenergic mechanism is involved in this phenomenon.

Adrenergic beta-Antagonists↗

Suppression of sympathetic nervous system activity by nicorandil during exercise.

1. Treadmill testing was done and plasma epinephrine and norepinephrine were measured during exercise and recovery in 21 patients with coronary artery disease given nicorandil. 2. Epinephrine levels during exercise did not change significantly with nicorandil, but the percent change in epinephrine with nicorandil tended to be lower during exercise. 3. Norepinephrine levels after exercise were suppressed with nicorandil (with, 424 +/- 15 pg/ml; without, 760 +/- 16, P less than 0.05). 4. Also, the percent change in norepinephrine with nicorandil was significantly decreased during exercise and recovery (with, 259 +/- 11%; without, 555 +/- 19, P less than 0.01). 5. Therefore, nicorandil suppressed the sympathetic nervous system hyper-response to exercise.

Adult↗

Inhibition of Meth-A tumor cell proliferation in combined use of disulfiram with catalase.

The effect of combined use of disulfiram with catalase on Meth-A tumor cell proliferation was studied. The simultaneous addition of 5 x 10(-7) or 1 x 10(-6) M disulfiram with catalase (4-40 micrograms/ml) induced marked inhibition of cell proliferation. A moderate degree of the antiproliferative effect was also obtained by pretreatment of the target cells with 5 x 10(-6) or 1 x 10(-5) M disulfiram in the presence of catalase (40 micrograms/ml). These results suggest that compounds or metabolites with cytostatic activity are newly formed following the reaction of disulfiram with catalase.

Animals↗

In vitro effects of glycosylated insulin in perfused liver and hindquarter in rats.

Using the perfused liver and hindquarter of the rat, the uptake of glycosylated insulin and its effect on glucose output were investigated. Insulin was glycosylated in ambient high glucose concentration, and glycosylated insulin GI80 (insulin incubated with 0.08% glucose), GI350 (incubated with 0.35% glucose), and GI1000 (incubated with 1% glucose) were prepared. The liver and hindquarter were perfused with nonglycosylated insulin (N-GI) or glycosylated insulin at a concentration of 100 or 1000 microU/ml. There were no significant differences in the fractional uptake of insulin by perfused liver and hindquarter despite glycosylation. Insulin-induced decrement in glucose output was significantly lower in the liver perfused with GI1000 than that in the liver perfused with N-GI, GI80, and GI350 at an insulin concentration of 100 microU/ml. There were no significant differences in insulin-induced decrement in glucose output between the hindquarter perfused with N-GI, GI80, GI350, and GI1000. These results suggest that when insulin (100 microU/ml) is incubated with a markedly elevated concentration of glucose (1000 mg/dl) its biological activity is reduced in the liver, but not in the hindquarter.

Animals↗

Adrenergic mechanism in hyperketonemia in thyrotoxic and starved rats.

To evaluate the possible role of the adrenergic mechanism in hyperketonemia in hyperthyroidism and starvation, the plasma concentrations of FFA, acetoacetate (AcAc), and beta-hydroxybutyrate (BOHB) were measured in thyrotoxic and starved rats for 96 hours. Thyrotoxemia was induced in rats by a daily subcutaneous thyroxine (100 micrograms/kg/day) injection carried out for 7 days. Some of the thyrotoxic and starved rats were administered subcutaneous phentolamine (2 mg/kg, twice daily) or propranolol (0.1 mg/kg, twice daily). Plasma levels of FFA, AcAc, and BOHB were significantly increased in thyrotoxic and starved rats compared with the control rats. Phentolamine and propranolol administration did not alter plasma levels of FFA, AcAc, and BOHB in thyrotoxic rats. In starved rats, propranolol did not alter plasma levels of FFA, AcAc, and BOHB, however, phentolamine did increase plasma levels of FFA, AcAc, and BOHB. These results indicate that the adrenergic mechanism may not contribute to the hyperketonemia in thyrotoxic rats, but may have a slight inhibitory effect on ketogenesis in starvation probably due to alpha-antilipolytic action.

3-Hydroxybutyric Acid↗

In vitro effects of glycosylated insulin and glucagon in perfused liver of the rat.

Using perfused liver of the rat, the hepatic uptake of glycosylated insulin (GI) and glucagon (GG) and its effects on hepatic glucose output were investigated. Insulin and glucagon were glycosylated in ambient high glucose concentration, and GI80 or GG80 (insulin or glucagon incubated with 0.08% glucose), GI350 or GG350 (incubated with 0.35% glucose), and GI1000 or GG1000 (incubated with 1% glucose) were prepared. The liver was perfused with the medium containing 1000 microU/ml insulin and 200 pg/ml glucagon or 200 microU/ml insulin and 1000 pg/ml glucagon. The fractional uptake of insulin or glucagon by perfused liver was not significantly altered by the glycosylation. In the liver perfused with 1000 microU/ml insulin and 200 pg/ml glucagon, glucose output was not changed by the glycosylation of the hormones, while in the liver perfused with 200 microU/ml insulin and 1000 pg/ml glucagon, GI1000 reduced its biological activity, as reflected by insulin-mediated decrease in glucose output. These results suggest that in the liver insulin incubated with markedly high concentration of glucose reduces its biological activity at a physiological concentration in the presence of high concentration of glucagon.

Animals↗

Development of nitrate tolerance and usefulness of pulse therapy in a patient with vasospastic angina.

In a 58-year-old man with vasospastic angina, we investigated the relationship between the antianginal effects of isosorbide dinitrate (ISDN) and plasma ISDN concentration. Despite adequate plasma ISDN levels, sustained therapy using ISDN tapes and oral ISDN (transcutaneously 160 mg and orally 100 mg ISDN day-1) failed to exhibit antianginal effects. However, pulse therapy using sublingual short-acting ISDN prevented anginal episodes, although the plasma ISDN levels were less than those of sustained therapy. Nitrate tolerance of the antianginal effects was avoided by creating an abrupt plasma ISDN concentration gradient using sublingual ISDN.

Administration, Oral↗