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Biomedical subjects

N Yamazaki

Publications and source records attributed to N Yamazaki.

At least 217 records · Page 12Linked to original sources
PubMed1987

Effects of L-carnitine on phospholipids in the ischemic myocardium.

To evaluate the protective effects of L-carnitine on the ischemic myocardium, the effects of its administration on tissue levels of high energy phosphate and phospholipids were studied in ischemic dog hearts. Myocardial ischemia was induced by the ligation of the left anterior descending coronary artery for 40 min. In the experiment, L-carnitine (300 mg/kg) was administered intravenously prior to coronary artery ligation. Mitochondrial phospholipids were extracted from nonischemic and ischemic regions of the myocardium and subsequently analyzed. In ischemic myocardial tissues, levels of adenosine 5'-triphosphate (ATP) were reduced. The decrease was significantly elevated by L-carnitine pretreatment. The mitochondrial fractions obtained from ischemic myocardia had significantly lower levels of phospholipids than those obtained from nonischemic tissues. Moreover, the amounts of phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine were significantly decreased in ischemic myocardial tissues. L-carnitine-pretreatment prevented the reduction of these phospholipids. Lysophosphatidylethanolamine and sphingomyelin did not show statistically significant decreases. This may explain why the administration of carnitine has beneficial effects on ischemic myocardium.

Adenosine Triphosphate↗
PubMed1987

Effect of 3-[p-(trans-4-aminomethylcyclohexylcarbonyl)phenyl]propionic acid hydrochloride on gastric mucosal barrier.

Effects of 3-[p-(trans-4-aminomethylcyclohexylcarbonyl)phenyl]propionic acid hydrochloride (TEI-5103, TG-51) on mucosal protection, ion permeability, potential difference, glycoprotein content, and bicarbonate secretion as parameters of the mucosal barrier in rats were studied. TEI-5103 (50-400 mg/kg p.o.) prevented the formation of gastric lesions induced by 75% ethanol, 0.6N HCl, and 0.1N HCl + 60% ethanol. Indometacin (10 mg/kg s.c.) given 30 min prior to TEI-5103 dosing slightly attenuated this protective effect. TEI-5103 (20 mg/ml intragastrically) prevented the increase in acid back-diffusion and ion permeability induced by acetylsalicylic acid (ASA, 5 mg/kg intragastrically). It also inhibited the decrease in mucosal potential difference induced by ASA and resultant lesion formation at 1 h after ASA dosing. TEI-5103 (400 mg/kg p.o.) improved the decrease in mucosal high molecular glycoprotein content induced by ASA (100 mg/kg p.o.), whereas it did not change the normal mucosal glycoprotein content. By intra-luminal perfusion of TEI-5103 (10 and 20 mg/ml/min), an increase in CO2 concentration in the perfusate was observed, suggesting heightened bicarbonate secretion. Its effect at 20 mg/ml/min was same as that of prostaglandin E2 (20 micrograms/ml/min). These findings suggest that TEI-5103 has a cytoprotective effect like prostaglandin and promotes the integrity of the mucosal barrier. These effects of TEI-5103 may contribute to its overall anti-ulcer effect.

Animals↗
PubMed1987

Effect of 3-[p-(trans-4-aminomethylcyclohexylcarbonyl)phenyl] propionic acid hydrochloride on gastric mucosa directly from the lumen.

The present experiments were designed to determine if the novel anti-ulcer drug 3-[p-(trans-4-aminomethylcyclohexylcarbonyl)phenyl]propionic acid hydrochloride (TEI-5103, TG-51), acts on the gastric mucosa directly from the lumen when given orally. TEI-5103 given orally (50-400 mg/kg) prevented the lesion formation induced by 0.1N HCl + 60% ethanol, but when given intraperitoneally (50-200 mg/kg) or intravenously (40 mg/kg), it did not prevent the formation of lesions. Indomethacin-induced gastric lesions were inhibited by oral administration of TEI-5103, but not by intraduodenal administration. In pylorus-ligated rats, TEI-5103 given intragastrically also inhibited the development of gastric lesions induced by HCl + ethanol. These results suggest that the presence of TEI-5103 in the stomach is necessary to elicit its anti-ulcer effect. In microautoradiographic examination, silver grains corresponding to [14C]-TEI-5103 distributed in the upper part of the mucosa (luminal side) at 0.5 to 4 h after the oral administration. However, when given intraduodenally or intravenously, this high concentration of [14C]-TEI-5103 was not observed in the stomach tissue. When given orally, the content of [14C]-TEI-5103 in rat stomach tissue was about 100 times higher than that in plasma and the time course of distribution was different from that seen in the gastric content. From these results, it seems that TEI-5103 distributes in the gastric mucosa directly from the lumen. In conclusion, TEI-5103, when given orally, distributes in the gastric mucosa as a target issue directly from the lumen; and only the oral and gastric route of administration lead to the anti-ulcer effect.

Administration, Oral↗
PubMed1986

Chronic treatment with nifedipine does not change the number of [3H]nitrendipine and [3H]dihydroalprenolol binding sites.

Possible receptor changes occurring after withdrawal of chronic nifedipine treatment or chronic propranolol treatment were examined by administering nifedipine (100 mg/kg per day) or propranolol (45 mg/kg per day) to rats for 2 weeks and then withdrawing treatment [3H]Nitrendipine and [3H]DHA binding were measured in membrane fragments of the ventricle. In propranolol-treated rats, 8 h after the last administration, the maximum binding for [3H]DHA was significantly increased from 79.9 +/- 8.0 to 139.8 +/- 12.8 fmol/mg protein (mean +/- S.E.); the dissociation constant was significantly increased from 4.9 +/- 0.7 to 10.7 +/- 1.2 nM. On the other hand, in nifedipine-treated rats, 12 and 48 h after the last administration, [3H]nitrendipine binding and [3H]DHA binding had not changed significantly. These results indicate that the mechanism of the calcium antagonist withdrawal syndrome may be different from that of beta-blocker withdrawal syndrome.

Animals↗
PubMed1986

Age-related changes in learning and memory in the senescence-accelerated mouse (SAM).

Age-related changes in learning ability were studied in senescence-accelerated mice (SAM) reared under specific pathogen-free (SPF) conditions. SAM-P/8/Ta (SAM-P/8, senescence-prone substrain) showed an age-associated increase in spontaneous motor activity (SMA) compared with SAM-R/1/Ta (SAM-R/1, senescence-resistant substrain) in a novel environment when the activity was measured in the light period, although there was no significant difference in the dark period. In observations of the circadian rhythm of SMA, SAM-P/8 showed a significant increase in diurnal SMA. In SAM-P/8 mice, the acquisition of passive avoidance response was slightly but significantly impaired even at 2 months of age, compared with SAM-R/1 control; the impairment became obvious with aging. In a one-way active avoidance task, SAM-P/8 did not show any impairment in the acquisition of avoidance response at 2 and 4 months of age. However, significant impairment was observed in SAM-P/8 at 12 months of age. The impairments of avoidance tasks were not due to a decrease in shock sensitivity, as indicated by no significant change in the flinch-jump threshold. In a water-filled multiple T-maze task, there was no difference in the number of errors between the two groups. With regard to the performance time to reach the goal, however, SAM-P/8 showed a mild prolongation at 2 months of age, and the prolongation became marked with advancing age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1986

Effects of L-carnitine and verapamil on myocardial carnitine concentration and histopathology of Syrian hamster BIO 14.6.

In order to investigate the effects of L-carnitine and verapamil on myocardial carnitine metabolism carnitine derivatives were measured and histopathology studied in the BIO 14.6 Syrian hamster. Cardiomyopathic hamsters at 20 days of life were divided into three groups, each given saline solution, L-carnitine, or verapamil. At 90 days of life the myocardial tissue concentrations of free carnitine, short chain acylcarnitine, and total carnitine in Syrian hamsters were significantly lower than those in normal hamsters of the same age. The myocardial tissue concentrations of free carnitine, short chain acylcarnitine, and total carnitine were significantly higher in the L-carnitine group than in the saline group, and the concentrations of free carnitine and total carnitine were significantly higher in the verapamil group than in the saline group. The percentage area of necrosis, fibrosis, and calcification in the L-carnitine and verapamil groups was significantly smaller than that in the saline group. These results suggest that lowered carnitine concentrations in the myocardium might play an important pathophysiological role in the genesis of the BIO 14.6 cardiomyopathic Syrian hamster and that L-carnitine and verapamil might be beneficial in the treatment of cardiomyopathic hamsters.

Animals↗
PubMed1986

Clinical evaluation of bisoprolol in the treatment of extrasystoles and sinus tachycardia: an interim report.

The effectiveness and safety of bisoprolol, a newly developed beta-adrenergic blocking drug, in the treatment of arrhythmias were evaluated in 17 patients with premature ventricular contraction (PVC), 8 with premature atrial contraction (PAC) and 7 with sinus tachycardia. More than 50% reduction of the PVC frequency was observed in 7 out of 16 patients. PVC was reduced in 2 out of 5 patients at a daily dose of 2.5 mg. The PAC frequency was decreased in 50% of the patients, and sinus tachycardia was improved in all 7 patients. Adverse reactions were observed in 8 of 32 patients. This preliminary study suggests that the antiarrhythmic effects of bisoprolol could be assessed starting at a daily dose of 2.5 mg to determine its optimal effective dose in Japanese patients.

Adrenergic beta-Antagonists↗
PubMed1986

[A study on the renal action of beta 1- and beta 2-adrenoceptors in rats].

The present experiments were designed to study urine volume and urinary sodium excretion effects of beta-antagonists and beta-agonists with reference to beta 1- and beta 2-adrenoceptors in rats. The beta-antagonists used were atenolol as a selective beta 1-antagonist, butoxamine as a beta 2-antagonist and propranolol as a non-selective beta-antagonist. The beta-agonist used were salbutamol as a beta 2-agonist and isoproterenol as a non-selective beta-agonist. Beta-antagonists increased the urine volume and urinary sodium excretion, but beta-agonists decreased the urine volume and urinary sodium excretion. With regards to these effects, atenolol increased the urine volume more than urinary sodium excretion, isoproterenol decreased the urine volume more than urinary sodium excretion, and salbutamol decreased the urinary sodium excretion more than urine volume. When beta-antagonists were infused with a beta-agonist, the original diuretic effects of these beta-antagonists were inhibited by the beta-agonist. In these effects, beta-antagonists infused with isoproterenol inhibited urine volume more than urinary sodium excretion, but beta-antagonists infused with salbutamol inhibited urinary sodium excretion more than urine volume. These results indicate that the urine volume is related to beta 1-adrenoceptors, while the urinary sodium excretion is related to beta 2-adrenoceptors, although there is no selectivity towards either beta 1-adrenoceptors or beta 2-adrenoceptors as far as diuresis or antidiuresis is concerned.

Adrenergic beta-Agonists↗
PubMed1986

Decreased monoamine oxidase activity in stroke-prone spontaneously hypertensive rat kidneys.

The present study was undertaken to measure kidney monoamine oxidase activity (MAO) isolated from three different rat groups: Wistar Kyoto rats (WKY), stroke-free cases of stroke-prone spontaneously hypertensive rats (SHRSP-control) and SHRSP-stroke cases (SHRSP-stroke). The SHRSP group was found to have less kidney MAO than the WKY group. Conversely, plasma norepinephrine concentration of SHRSP group was significantly higher than that of the WKY group (Jpn. Heart J., 25, 833-835, 1985). These findings suggest that the increased blood pressure in SHRSP may be related to increased plasma norepinephrine concentration caused by a decrease in degradation enzyme, MAO. An attempt was also made to determine the effects of clorgyline and deprenyl. No significant difference in MAO was observed between the kidneys isolated from the WKY, SHRSP-control and SHRSP-stroke groups. However, the inhibition curve of clorgyline reached a plateau after producing 33% inhibition of MAO. It was assumed that rat kidney mitochondrial MAO consists of 33% MAO-A type and 67% MAO-B type.

Animals↗
PubMed1986

[Effect of thyrotropin-releasing hormone (TRH) and its analog DN-1417 on scopolamine-induced impairment of short-term memory in rats].

The effects of a few drugs, which are known to activate central nervous system, on scopolamine-induced impairment of short-term memory (STM) were studied in a delayed alternation task in rats. Rats were initially trained using a delayed alternation task in which a forced run to one arm of a T-maze was followed by a free-choice run. A correct free-choice response was defined as a turn toward the arm opposite to that in the forced run, and was rewarded with food pellets. After repeated training of the 60 sec-delayed alternation task, the treatment with scopolamine (0.2 mg/kg, ip) at 20 min before the test resulted in a significant decrement in the correct response. The scopolamine-induced impairment of STM was significantly antagonized by DN-1417 (10 mg/kg, ip) given 1 hr before the test. However, TRH (3-30 mg/kg, ip) and methamphetamine (0.2-1.0 mg/kg, ip) did not improve the scopolamine-induced impairment in the task. In rats without treatment with scopolamine, these drugs did not affect the percent correct response. These results suggest that DN-1417 may have an improving effect on the impairment of STM induced by a decreased cholinergic activity.

Animals↗
PubMed1986

[The function of the sympathetic nervous system determined by humoral factors in the maintenance hemodialysis patients].

Dialysis-induced hypovolemia in renal patients might accompany with decreased sympathetic tone and decreased baroreflex sensitivity. Present study was undertaken to elucidate the sympathetic nervous activity in terms of biogenic amines [plasma norepinephrine (NE), epinephrine (E) concentrations, dopamine-beta-hydroxylase activity (DBH) and plasma serotonin (5-HT) concentration] in 17 patients with chronic renal failure in whom renal hemodialysis were continuously performed. During pre-dialysis period, in these hemodialysis patients, heart rate, systolic blood pressure and plasma 5-HT were significantly elevated as compared with those on sex and age-matched controls; plasma NE and plasma DBH were not changed in these hemodialysis patients as compared with those in controls. After hemodialysis, increased plasma NE and increased DBH were observed in parallel with the significant weight loss. Mean blood pressure did not change after dialysis. Dialysis produced an increasing tendency of heart rate. Dialysis also produced a significant decrease in plasma 5-HT. Hemodialysis-induced weight loss was approximately 2 kg body weight after 5 hours dialysis; these patients were done 3 times dialysis during one week. However, hypotension and dizziness were not demonstrated under this condition. Present study revealed that long term maintenance hemodialysis produced increased sympathetic nervous system activity; the assumed explanation would be relevant to the simultaneous recovery of baroreflex sensitivity and sympathetic tone, because of the long-term continuous hemodialysis.

Adult↗
PubMed1985

Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris.

The effects of coenzyme Q10(CoQ10) on exercise performance were studied in 12 patients, average age 56 years, with stable angina pectoris. The study involved a double-blind, placebo-controlled, randomized, crossover protocol, using multistage treadmill exercise tests. CoQ10(150 mg/day in 3 daily doses) was administered orally for 4 weeks, tended to reduce anginal frequency from 5.3 +/- 4.9 to 2.5 +/- 3.3 attacks for 2 weeks and nitroglycerin consumption from 2.6 +/- 2.8 to 1.3 +/- 1.7 tablets for 2 weeks compared with patients receiving the placebo, but the reduction was not statistically significant. Exercise time increased from 345 +/- 102 seconds with placebo to 406 +/- 114 seconds during CoQ10 treatment (p less than 0.05). The time until 1 mm of ST-segment depression occurred increased from 196 +/- 76 seconds with placebo to 284 +/- 104 seconds during CoQ10 treatment (p less than 0.01). During the exercise test, ST-segment depression, heart rate and pressure-rate product at the same and at the maximal workload showed no significant difference between patients after placebo and CoQ10 administration. The average CoQ10 plasma concentration increased from 0.95 +/- 0.48 microgram/ml to 2.20 +/- 0.98 microgram/ml after CoQ10 treatment. This increase was significantly related to the increase in exercise duration (r = 0.68, p less than 0.001). Only 1 patient had a loss of appetite, but continued therapy. This study suggests that CoQ10 is a safe and promising treatment for angina pectoris.

Aged↗
PubMed1985

Effects of propranolol and diltiazem on carnitine derivatives and acyl CoA in ischemic myocardium.

The accumulation of intermediates subsequent to impaired beta-oxidation of free fatty acid (FFA) has been suggested as a cause of cellular damage in ischemic myocardium. We investigated the effects of propranolol and diltiazem on carnitine metabolism in ischemic myocardium. Propranolol (0.2 mg/kg/min, i.v.) and diltiazem (0.1 mg/kg/min, i.v.) were administered for 5 min, the administration started 10 min before coronary occlusion. ECGs were continuously recorded throughout the experiment. Myocardial samples were prepared from both the non-ischemic and ischemic areas 40 min after coronary ligation. Adenosine triphosphate (ATP), free carnitine, long chain acyl carnitine and long chain acyl CoA were assayed. Propranolol reduced the decrease of ATP and the accumulation of long chain acyl CoA, induced by myocardial ischemia. Diltiazem reduced the decrease of ATP and free carnitine, and the accumulation of long chain acyl carnitine in the ischemic area. Propranolol and diltiazem significantly reduced the grade of ventricular arrhythmia. These results suggest that the protective mechanisms of propranolol and diltiazem on myocardium are based, at least in part, on their beneficial effects upon myocardial carnitine metabolism.

Acyl Coenzyme A↗