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Biomedical subjects

M Miyamoto

Publications and source records attributed to M Miyamoto.

At least 217 records · Page 12Linked to original sources

Dynamic aspects of glutathione and nitric oxide metabolism in endotoxemic rats.

Glutathione is one of the most abundant thiols in mammalian tissues and plays important roles in the defense mechanism and detoxification of various metabolites, such as reactive xenobiotics and free radicals. Nitric oxide (NO) readily reacts with thiol compounds, thereby generating chemically stable S-nitrosothiols. Although endotoxin has been known to induce NO synthase in various organs, particularly liver and spleen, and enhances the production of NO, correlation between NO and glutathione metabolism in endotoxemic subjects remains to be elucidated. The present work examines the changes in NO and glutathione metabolism in endotoxemic rats. Administration of lipopolysaccharide (LPS) markedly decreased the glutathione levels in plasma and bile, whereas it decreased the hepatic level only slightly. NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, inhibited the LPS-induced decrease of glutathione in plasma and bile. Administration of LPS increased the biliary levels of gamma-glutamyl transpeptidase (gamma-GTP) without affecting its thiol levels. Acivicin, a gamma-GTP inhibitor, inhibited the LPS-induced decrease of glutathione in plasma and bile without affecting its hepatic levels. Analysis with the use of L-buthionine sulfoximine revealed that the turnover of hepatic glutathione significantly increased in LPS-treated rats by some L-NNA-inhibitable mechanism. These results suggest that endotoxin might enhance the NO production in the liver and other tissues and significantly modulate the interorgan metabolism of reduced glutathione.

Animals↗

Initial transient phase of salivary secretion by the submandibular glands of rats under anoxic conditions.

Salivary secretion of the rat submandibular gland exhibits two phases upon administration of acetylcholine (ACh, 10(-6) M): an immediate initial transient phase of rapid secretion lasting 5 min followed by a longer steady phase of slower secretion. Application of an anoxic perfusate bubbled with 100% N2 for 10-20 min had no effect on the initial phase of secretion, but caused a marked decrease in secretion in the steady phase following stimulation with 10(-6) M ACh. After secretion under the anoxic condition, a recovery period without stimulation was performed for 30 min by perfusion with HEPES Ringer's solution bubbled with 100% O2 and containing various potassium concentrations. The initial secretion rate measured with application of an anoxic perfusate was markedly increased by the high-K+ recovery perfusate (25 mM) and decreased by the K(+)-free recovery perfusate. Administration of 10(-3) M ouabain in the normal perfusate resulted in inhibition of secretion during the steady phase similar to that seen under the anoxic condition, while the secretory rate during the initial phase remained unchanged. We concluded that the initial phase of secretion is relatively resistant to anoxia, and that oxygen supply and Na(+)-K+ pump activity were essential for maintaining the steady phase of secretion.

Acetylcholine↗

Effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1 -H-1-benzazepin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase inhibitor, on impaired learning and memory in animal models.

We examined the effects of p.o. administered 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-b enzazepin-8- yl)-1-propanone fumarate (TAK-147), a novel AChE inhibitor, on impaired learning and memory in animal models. At 1 to 3 mg/kg, TAK-147 ameliorated the passive avoidance deficit induced by diazepam. TAK-147 did not affect delayed-matching-to-position (DMTP) performance of normal rats at doses of 1 to 30 mg/kg assessed by using a three-lever operant chamber, but 9-amino-tetrahydroacridine disrupted the DMTP response at 5 to 20 mg/kg. Scopolamine (0.02-0.1 mg/kg s.c.) impaired DMTP performance, whereas methylscopolamine did not affect the DMTP task. TAK-147 ameliorated the impairment of DMTP performance induced by scopolamine without affecting the general behavior of the rats; however, 9-amino-tetrahydroacridine produced no significant amelioration of the impairment. The intraventricular injection of AF64A disrupted differential-reinforcement-of-low-rate 10-sec performance in rats, as demonstrated by marked decreases in reinforcement rate and response efficiency. TAK-147 slightly increased the reinforcement rate in AF64A-treated rats at a low dose of 1 mg/kg, but the effect was not significant statistically. TAK-147 had no significant effect on the duration of immobility in rats in a forced swimming test at doses of 2 to 10 mg/kg. 9-Amino-tetrahydroacridine prolonged the duration of immobility at 5 to 20 mg/kg. Furthermore, TAK-147 reversed reserpine-induced hypothermia and ptosis in mice at doses of 3 to 10 mg/kg, a result that implies an antidepressant-like action. These results indicate that TAK-147 ameliorates learning and memory impairment in animal models without affecting the general behavior or causing behavioral depression and suggest that TAK-147 may be useful for the treatment of Alzheimer's disease.

Acetylcholinesterase↗

[Anesthetic and postoperative care of a patient with Crigler-Najjar syndrome type II].

Crigler-Najjar syndrome is a rare inherited deficiency of bilirubin uridine diphosphate glucuronyl transferase, characterised by lifelong unconjugated hyperbilirubinemia. We report anesthetic and postoperative management of a patient with this syndrome. A 64-yr-old man with Crigler-Najjar syndrome type II underwent cholecystectomy. Preoperative laboratory values included total bilirubin 8.4 mg.dl-1 and direct-bilirubin 1.8 mg.dl-1. He received epidural anesthesia combined with general anesthesia with nitorous oxide and isoflurane. He had no remarkable perioperative complications.

Anesthesia, Epidural↗

One-month oral toxicity study of the new quinolone antibacterial agent (S)-10-[(S)-(8-amino-6-azaspiro[3,4]octan-6-yl)-9-fluoro-2,3-dihydro-3- methyl-7-oxo-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6-carboxylic acid hemihydrate in rats and cynomolgus monkeys.

One-month oral toxicity of (S)-10-[(S)-(8-amino-6-azaspiro[3,4] octan-6-yl)]-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid hemihydrate (CAS 151390-79-3, DV-7751a) a new quinolone antibacterial agent was investigated in Sprague-Dawley rats at doses of 12.5, 50, 200 and 800 mg/kg/d and in cynomolgus monkeys at 10, 30 and 100 mg/kg/d. Rats receiving 200 mg/ kg showed abnormal urine crystals, enhanced deposition of lipid in hepatocytes and exacerbation of osteochondrotic lesions in the femoral condyle. In addition, dosing at 800 mg/kg induced decrease in body weight gain and increased levels of serum alkaline phosphatase (ALP), cholinesterase, leucine aminopeptidase and total cholesterol. Monkeys receiving 100 mg/kg showed abnormal urine crystals and increases in serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and ALP levels. The non-toxic doses of DV-7751a in rats and monkeys were 50 and 30 mg/kg, respectively, under the present experimental conditions.

Animals↗

[Anesthetic management of a patient with erythroderma].

We gave anesthesia to a patient with erythroderma for distal partial gastrectomy. Erythroderma is an inflammatory disorder in which generalized erythema and scaling occur, either as a specific phase of processes such as T cell lymphoma, as a manifestation of underlying malignancy or in the absence of preexisting diseases. Severe cases of erythroderma may involve disturbances in the cardiovascular, thermoregulatory and metabolic systems which make the management of general anesthesia difficult. Systemic scale also causes a difficulty in placing ECG monitor electrodes and endotracheal tube. In the present case, dyspnea and asthmatic bronchitis occurred postoperatively. Therefore, in a patient with erythroderma, we recommend careful systemic management throughout the perioperative period.

Adenocarcinoma↗

[Usefulness of scheduled IABP for CABG].

We examined the usefulness of intra-aortic balloon pumping (IABP) before the coronary arterial bypass grafting (IABP) before the coronary arterial bypass grafting (CABG) in patients with severe ischemic heart disease. Left main trunk (LMT) disease, unstable angina and low ejection fraction (less than 40%) were indications for scheduled IABP. Eleven patients underwent IABP before CABG surgery (the scheduled IABP group), and five patients didn't before CABG surgery (the unscheduled IAPB group). Analysis comprised the duration of IABP and mortality. There were no significant differences between the two groups in age, pre-operational cardiac index, ejection fraction, aorta clamp time or total perfusion time. IABP application times were significantly longer in the unscheduled IABP group than in the scheduled IABP group (p < 0.05). No death occurred in the scheduled group, but three patients in the unscheduled group died (p < 0.05). No complications were observed due to IABP in any patient of either group. We conclude that scheduled IABP is useful for patients with severe ischemic heart disease.

Aged↗

Clinical evaluation of a dental rinse containing aluminum lactate for treatment of dentinal hypersensitivity.

The effectiveness of a dental rinse containing aluminum lactate, which was used as a daily home treatment for dentinal hypersensitivity, was evaluated in a 6-week, double-blind study. Fifty-six subjects who complained of cold and/or tactile hypersensitivity were randomly divided into two groups: one given a dental rinse containing 2.18% aluminum lactate (test group) and the other a vehicle control dental rinse (control group). Subjects in both groups were instructed to rinse with the assigned dental rinse and to brush their teeth twice daily. The hypersensitivity levels of the affected teeth were assessed at baseline and at 4 and 6 weeks by application of tactile, cold air and cold water stimuli, and scored against baseline. All hypersensitivity scores in both groups were decreased significantly at weeks 4 and 6 compared to the baseline (p < 0.001). The hypersensitivity scores for tactile, cold air and cold water stimuli in the test group were significantly lower at weeks 4 and/or 6 compared to those in the control group (p < 0.05). Furthermore, on the analysis for the teeth with apparent pain (score 2 or 3) at the baseline, the reduction rates of hypersensitivity scores for cold air and cold water stimuli in the test group were significantly greater than those in the control group (p < 0.05). These findings suggest that daily home use of a dental rinse containing aluminum lactate is effective for treatment of dentinal hypersensitivity.

Adult↗

Induction of Fas-mediated apoptosis in p53-transfected human colon carcinoma cells.

To investigate the biological function of p53 in colon carcinoma cells, a wild-type p53 expression plasmid under the control of the human cytomegalovirus promoter was stably transfected into the human colon adenocarcinoma cell line WiDr, which carries a mutation of the p53 gene at codon 273. Exogenous wild-type p53 transcripts were detected at various expression levels in 8 of 117 G418-resistant clones. The growth rates of the wild-type p53+ clones in culture did not change significantly. The efficiency of colony formation in soft agar, however, was completely suppressed in two wild-type p53+ clones. This is the first to demonstrate the feasibility of stable transfection of the wild-type p53 gene under the control of non-inducible promoter in human colon cancer cells. The major alteration found was that wild-type p53+ cells which were incubated with anti-Fas IgM showed marked cytolysis with preferential over-expression of wild-type p53 accompanied by overexpression of a cyclin-dependent kinase inhibitor, WAF1, whereas the endogenous mutant p53 retained its expression level. The findings suggest that a Fas-initiated pathway is incidentally linked to a p53-dependent apoptotic pathway through the reconstituted wild-type p53 gene in WiDr cells. This model should help elucidating the additional role of the p53 tumor suppressor gene and the mechanism of apoptosis in colon carcinoma cells.

Adenocarcinoma↗