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Biomedical subjects

R Takeda

Publications and source records attributed to R Takeda.

At least 199 records · Page 11Linked to original sources

Effects of aldose reductase inhibitor (ONO-2235) on human erythrocyte sorbitol concentrations in 75 g oral glucose tolerance tests.

In order to evaluate the effects of the aldose reductase inhibitor, ONO-2235, on the short-term response of human erythrocyte sorbitol to hyperglycemia in vivo, eleven diet-treated Type 2 (non-insulin-dependent) diabetic patients were studied twice in 75 g oral glucose tolerance tests - with and without ONO-2235 (200 mg p.o.) premedication. The erythrocyte sorbitol concentrations increased with the increments of blood glucose and erythrocyte glucose concentrations in the test performed without ONO-2235. The erythrocyte sorbitol response in the test performed with administration of ONO-2235 30 min prior to glucose load was lower than that in the test performed without ONO-2235 (F = 5.782, P less than 0.05). No significant differences were found between the two tests in blood glucose and erythrocyte glucose concentrations (F = 0.092, P = 0.761; F = 0.029, P = 0.860, respectively). It is concluded that human erythrocyte sorbitol concentrations change promptly in response to rapid changes in erythrocyte glucose concentrations and that administered ONO-2235 is effective in inhibiting the human erythrocyte sorbitol pathway in man.

Adult↗

Endothelin-1 release from mesenteric arteries of spontaneously hypertensive rats.

Release of endothelin-1 (ET-1) from the mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were measured by radioimmunoassay after purification using immunoaffinity column. The identity of ET-1 in perfusate was established using reversed-phase high-performance liquid chromatography. The mesenteric arteries from 5- to 6- and 9- to 10-week-old SHR released a significantly higher level (mean +/- SEM) of ET-1 (32.8 +/- 2.8 and 47.5 +/- 4.1 pg/h, respectively) than WKY age-matched rats (23.4 +/- 2.1 and 34.8 +/- 3.7, respectively). There was an age-related increase in ET-1 release in both groups of rats. Though the SHR studied were in the hypertensive stage, the present results suggest that locally produced ET-1 may contribute to the development of hypertension independent of the plasma levels.

Aging↗

Renal pelvic carcinoma which shows metastatic potential to distant organs, induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in NON/Shi mice.

Renal pelvic carcinoma was induced in mice by giving N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Initially, differences in renal pelvic carcinogenesis by BBN were examined in three male mouse strains: NON/Shi, which demonstrate spontaneous hydronephrosis with incidences of 10-30%, and DS/Shi and B6C3F1, which do not exhibit hydronephrosis. When mice of these strains were given 0.05% BBN in the drinking water for 12 weeks followed by water without BBN for 8 weeks, renal pelvic carcinoma morphologically similar to human carcinomas developed in 8 of 23 NON/Shi mice (35%). Metastasis to the lung was found in one of them (13%). B6C3F1 and DS/Shi mice had no pelvic tumors, but the response to urinary bladder carcinogenesis in NON/Shi mice was nearly equal to that in DS/Shi and B6C3F1 mice. These results suggest that renal pelvic carcinogenesis is related to the presence of stagnant urine containing carcinogen in the renal pelvis. In a second experiment, we examined renal pelvic carcinogenesis in NON/Shi mice given BBN for 4 weeks followed by water without BBN for 32 weeks. The incidence of renal pelvic carcinoma (28%) was similar to that in the first experiment, but the incidence of metastasis was markedly elevated to 60%. These results indicate that BBN treatment can induce renal pelvic carcinoma which often metastasizes to the lung in NON/Shi mice.

Abdominal Neoplasms↗

Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pravastatin, on corticosteroid metabolism in patients with heterozygous familial hypercholesterolemia.

The present study examined whether hypolipidemic therapy with a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pravastatin, influences corticosteroid metabolism in patients with heterozygous familial hypercholesterolemia (FH). Urinary excretion of tetrahydrocortisone, tetrahydrocortisol, 6 beta-hydroxycortisol and free cortisol were determined in 22 patients with heterozygous FH before and after pravastatin administration (10 mg/day for 2 months). Pravastatin induced a statistically significant decrease in serum total cholesterol in patients with heterozygous FH from 6.9 +/- 0.1 to 5.9 +/- 0.1 mmol/l (p less than 0.05). No significant changes were seen in the urinary tetrahydrocortisone, tetrahydrocortisol and free cortisol levels before and after pravastatin therapy. Urinary excretion of 6 beta-hydroxycortisol was significantly (p less than 0.05) increased after pravastatin administration. These results suggest that the hypolipidemic effect of pravastatin in patients with heterozygous FH does not influence the corticosteroid metabolism. The increase in urinary 6 beta-hydroxycortisol may be caused by pravastatin-induced hepatic microsomal 6 beta-hydroxylase induction.

Adrenal Cortex Hormones↗

Characteristics of systolic time intervals in patients with pheochromocytoma.

The effect of chronic catecholamine excess on cardiac function was assessed in 8 patients with surgically proven pheochromocytoma and the results compared with data obtained from normal controls and essential hypertensives. Major findings in systolic time intervals (STI) in patients with pheochromocytoma were a marked shortening of electromechanical systole and left ventricular ejection time (ET), but pre-ejection period (PEP) remained within normal limits. These findings were not altered by correction for heart rate. The ET/PEP ratio was very low (1.87 +/- 0.31) due to the remarkable shortening of ET. The ET/PEP ratio in essential hypertensives was also low (1.77 +/- 0.38), but this was mainly due to a remarkable prolongation of PEP. Low cardiac index, low stroke index and high total peripheral resistance index were preoperative characteristics in patients with pheochromocytoma, but returned to normal after operation. These results suggest that chronic excessive production of catecholamines from pheochromocytoma has deleterious effects on the heart, and that wide differences in STI exist between patients with pheochromocytoma and those with essential hypertension.

Adrenal Gland Neoplasms↗

Increase in left ventricular chamber stiffness in patients with non-insulin dependent diabetes mellitus.

Indices of left ventricular ejection and diastolic filling were measured by cineventriculography in 11 patients with non-insulin dependent diabetes mellitus without significant coronary stenosis and 11 control subjects without diabetes mellitus. Indices of left ventricular ejection, such as ejection fraction and peak ejection rate, were the same in the two groups. The left ventricular end-diastolic volume index and the rapid filling volume index were significantly smaller, the peak filling rate was lower, the left ventricular end-diastolic pressure was higher and the modulus of left ventricular chamber stiffness was larger in the diabetic patients than in the control subjects. These results indicate that left ventricular chamber stiffness is increased in patients with non-insulin dependent diabetes mellitus.

Adult↗

[A case of cerebral arteriovenous malformation revealed at repeated subcortical hematoma with initially normal angiogram].

An 18-year-old male admitted to our hospital suffered left temporal subcortical hemorrhage. No abnormality was demonstrated on carotid or vertebral angiography at that time. On the day following the onset, left frontotemporal craniotomy was performed and the subcortical hematoma was evacuated. No vascular malformation was found despite careful investigation. On 30th day after the onset, the repeat cerebral angiography was performed but failed to show any vascular abnormalities. After discharge he was in good health, and had had some follow up, CT were normal except for the hematoma cavity. Just two years after the first operation he suffered a second left temporal hemorrhage. Cerebral angiography was repeated and a temporal arteriovenous malformation (AVM) was found with feeding vessels from the M-1 and M-2 portion of the left middle cerebral artery and from the left anterior choroidal artery, and draining veins to vein of Rosenthal and the straight sinus. One month after the second hemorrhage, left frontotemporal craniotomy was performed and complete excision of the AVM was carried out. Only five cases of AVMs in patients with normal angiograms several years before have been reported previously in the literature. But there are no cases in which surgery has been performed. Differently to those cases, in this case it was investigated operatively whether there was a vascular abnormality at the first hemorrhage. We didn't think, however, that the AVM demonstrated at the second hemorrhage had developed spontaneously because there had been a hemorrhage of unknown origin previous to it. It was assumed that a small angiographically occult AVM connected to the hematoma cavity existed at the time of the first hemorrhage but it was too small to be found even during surgical procedure. Such an angiography occult AVM had been growing for two years, and its growth had probably been facilitated by the presence of the hematoma cavity left after the first operation.

Adult↗

Urine anion gap in patients with chronic renal insufficiency.

We investigated the urinary acid excretion and urine anion gap (AG) (Na+ + K(+)-Cl-) during NH4Cl-induced metabolic acidosis in 38 normal subjects and 53 patients with chronic renal diseases in order to clarify the significance of the urine AG as a useful marker of the ammonium (NH4+) excretion even in a state of chronic renal insufficiency. The urine pH became higher, and the urinary excretions of titratable acid (TA) and NH4+ decreased significantly, in parallel with a reduction of the creatinine clearance (Ccr). The urinary electrolyte excretion, especially the chloride excretion, also decreased significantly as Ccr fell. As a result, the urine AG increased from negative to positive values, in proportion to the decrease in Ccr with statistical significance. The urine AG showed the most significant correlation with the urine NH4+ excretion (r = -0.707, p less than 0.001). We conclude that the urine AG provides a significant marker of the urine NH4+ excretion even in a state of moderate to severe renal insufficiency.

Acid-Base Equilibrium↗

[The diagnostic value of In-111 transferrin imaging in protein-losing gastroenteropathy].

The diagnostic value of In-111 transferrin abdominal imaging was studied in 17 patients with clinical suspicion of protein-losing gastroenteropathy, compared to that of alpha-1-antitrypsin fecal clearance test. The presence or absence of gastrointestinal protein-loss was finally decided based on the result of alpha-1-antitrypsin fecal clearance test (normal range, less than 13 ml/day) or of protein content measurement on the gastric juice (normal range, less than 71 mg/dl). In-111 transferrin was labeled in vitro. After intravenous administration, serial anterior abdominal images were obtained. All seven patients with a value equal to or more than 20 ml/day on the alpha-1-antitrypsin clearance test and two out of ten patients with a value less than 20 ml/day showed definite intestinal activity demonstrating protein-loss, and the loss-site was estimated by observing the movement of radiotracer within the bowel lumen. The patients with severe protein-loss showed the intestinal activity on the early image. In the patients with milder protein-loss, on the other hand, the activity was noted on the later image. All two patients with positive In-111 transferrin imaging and negative alpha-1-antitrypsin test were associated with protein-losing gastropathy, where a value of alpha-1-antitrypsin clearance was not increased because of denatured alpha-1-antitrypsin by acidic gastric juice and pepsin. These results suggest that In-111 transferrin abdominal imaging can be more useful for the diagnosis of protein-losing gastroenteropathy, because of its capabilities to evaluate the patients with gastropathy as well as to estimate the loss-site.

Adult↗

Effects of acetaldehyde on contractile response to nerve stimulation in guinea-pig vas deferens.

Twitch contractions of the isolated guinea-pig vas deferens induced by sympathetic nerve stimulation were augmented by acetaldehyde (0.1-10 mM). With high concentrations (5-10 mM), acetaldehyde produced a biphasic response consisting of an initial brief depression and a subsequent potentiation of the contraction. The late effect was associated with repetitive contractions that were not prevented by tetrodotoxin. A low concentration of phentolamine (27 microM) increased and a high concentration (1.3 mM) suppressed the potentiating action of acetaldehyde. Acetaldehyde did not induce contractions in surgically sympathectomized vasa or vasa pretreated with reserpine. Acetaldehyde caused a dose-dependent increase in noradrenaline release into the bathing fluid. The study shows that acetaldehyde has a dual effect on sympathetic neuroeffector transmission, and that an increase in noradrenaline secretion appears to contribute to the late facilitatory effect in the isolated vas deferens.

Acetaldehyde↗

Effects of acetaldehyde on electrical activity during neuroeffector transmission in guinea-pig vas deferens.

The effects of acetaldehyde on electrical activity during sympathetic neuroeffector transmission were studied in the guinea-pig vas deferens. Application of 1 mM acetaldehyde produced a slow depolarization of the smooth muscle membrane. The amplitudes of facilitated excitatory junction potentials (EJPs) evoked by nerve stimulation were slightly decreased. A higher concentration of acetaldehyde (5 mM) initially hyperpolarized and later depolarized the membrane. The decrease in EJP amplitudes was more pronounced during hyperpolarization. Acetaldehyde (5 mM) increased the frequency of the spontaneous EJPs and reduced their amplitudes, whereas action potentials in postganglionic nerves were unaffected. Acetaldehyde (1-5 mM) decreased the amplitudes of EJPs in vasa pretreated with reserpine but did not alter the resting membrane potentials. The decrease in the EJP amplitudes together with the hyperpolarization of the membrane could be responsible for the early inhibitory effect of acetaldehyde on neuroeffector transmission. The slow depolarization, which is presumably mediated by endogenous noradrenaline, may cause the late facilitatory effect.

Acetaldehyde↗

Cromakalim, a vasodilator, differentially inhibits Ca2+ currents in NG108-15 neuroblastoma x glioma hybrid cells.

Extracellular perfusion with the antihypertensive agent cromakalim produced an inhibition of 22-66% in the low-threshold transient Ca2+ (T-like) current in NG108-15 hybrid cells. Cromakalim suppressed the high-threshold and long-lasting Ba2+ current (L-like Ca2+ current) by 29-73%, but had almost no effect on the high-threshold and inactivating Ba2+ current (N-like Ca2+ current). IC50 for T-like and L-like currents was the same at about 100 microM. The inhibitory effect developed relatively fast and was reversible. These results indicate that cromakalim can selectively inhibit the activity of inward Ca2+ currents.

Animals↗

Selective actions of anesthetic agents on membrane potential trajectory in bulbar respiratory neurons of cats.

The effects of two anesthetic agents, halothane and thiopental, on the membrane potential trajectory of respiratory-related neurons in the ventral respiratory group were investigated in decerebrate cats, of which the carotid sinus and vagal afferents were denervated. Infusion of halothane (2% for 90 s) depolarized the membrane in nearly half of the inspiratory (12/21), post-inspiratory (10/26) and expiratory (4/6) neurons and caused hyperpolarization in the rest of the population. Thiopental (2.5 mg/kg i.v.) produced depolarization in 11 inspiratory and 10 post-inspiratory neurons and hyperpolarization in 1 expiratory, 4 inspiratory and 7 post-inspiratory neurons. In both hyperpolarized and depolarized neurons, reduction of the respiratory membrane potential fluctuations and an increase of input resistance were commonly observed. Both drugs depressed spontaneous firing in most of the neurons studied. An increase of firing was observed in 9 out of 47 depolarized cells. These two contrasting effects on the membrane potential trajectory occurred similarly in the known groups of respiratory neurons, but the response of a given cell was consistent for the two anesthetic agents. The present results demonstrate that the anesthetic drugs exert various influences on the ventral respiratory group neuron population in maintaining the membrane potential trajectory and discharge activity. This may reflect a functional heterogeneity in the bulbar respiratory network of neurons.

Action Potentials↗

Evaluation of clonidine suppression and various provocation tests in the diagnosis of pheochromocytoma.

Recent investigations have shown that the widely used clonidine suppression test is sometimes fallible for the diagnosis of pheochromocytoma. A comparative assessment was made of the following suppression and provocation tests, the clonidine suppression test, and the glucagon, metoclopramide, and naloxone provocation tests. The assessment was performed in 6 patients with pheochromocytoma and in 19 patients without pheochromocytoma who were initially suspected of harboring a tumor. BP response did not predict the presence of pheochromocytoma in any test. Plasma norepinephrine (NE) concentrations determined at 120 and 180 min after oral 150 micrograms of clonidine gave false negative results in 2 of the 5 patients with pheochromocytoma tested. Both plasma NE and epinephrine (E) concentrations were measured before and sequentially after each provocative agent. Neither NE nor E responded to 1 mg of glucagon iv in 2 of the 4 patients with pheochromocytoma tested. Determination of the peak level, peak increment, and % peak increment of NE and E following 10 mg of naloxone iv did not distinguish the two groups. The % peak increments of both NE and E in all 4 patients with pheochromocytoma given 5 mg of metoclopramide iv exceeded the mean + 3 SD values of the patients without pheochromocytoma (25 + 28% for NE, and 25 + 42% for E). These results suggested that, when performed with judicious patient selection (ambiguous plasma or urinary catecholamine levels), the measurement of plasma catecholamines in response to metoclopramide can be a useful adjunctive tool in the diagnosis of pheochromocytoma.

Adrenal Gland Neoplasms↗