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Biomedical subjects

T Kagaya

Publications and source records attributed to T Kagaya.

At least 19 recordsLinked to original sources
PubMed1995

Involvement of P-type calcium channels in high potassium-elicited release of neurotransmitters from rat brain slices.

Several types of voltage-dependent calcium channels appear to occur in neurons, although coupling of the particular subtype of calcium channels to the release of neurotransmitter has not been clearly understood. We have examined the effects of subtype-specific inhibitors of the calcium channels on depolarization-induced release of endogenous neurotransmitters from brain slices. High potassium-induced release of glutamate and aspartate from hippocampal and striatal slices was almost completely inhibited by a P-type channel blocker, omega-agatoxin IVA. omega-Agatoxin IVA also completely inhibited the release of serotonin from the hippocampal slices with almost the same potency as in the case of glutamate, whereas the potency in blocking the release of serotonin and dopamine from striatal slices was lower than that from the hippocampal slices. Another calcium channel blocker, omega-agatoxin TK, that was recently found to block P-type channels with very similar selectivity and potency to omega-agatoxin IVA, also inhibited the release of amino acid transmitters and monoamines, though its potency was lower than that of omega-agatoxin IVA. An N-type channel blocker, omega-conotoxin GVIA, partially inhibited the neurotransmitter release, but an L-type channel blocker, nifedipine was ineffective. We propose that the activation of P-type calcium channels makes a major contribution to depolarization-elicited neurotransmitter release in the CNS and that multiple P-type channels sensitive to omega-agatoxin IVA and omega-agatoxin TK modulate the neurotransmitter release.

Analysis of Variance↗
PubMed1994

Application of pharmacokinetic studies to a novel antidepressant, E2011.

1. The original drug tested here, (5R)-3-[2-(3-cyanopropyl)benzothiazol-6-yl]-5-methoxymethyl-2-oxaz olidinone (ER-4539), exhibited strong MAO-A inhibitory activity in vitro, but its bioavailability in rat was very low. After ER-4539 was administered orally to dog, a metabolite was found in plasma. 2. The metabolite was isolated by hplc after incubation with dog liver microsomal preparations. Its structure, determined by ms and nmr analysis, was alpha-hydroxy-ER-4539. The configuration of the alpha-hydroxy metabolite was (S), determined in comparison with the authentic sample of (R) and (S) by hplc. The isolated metabolite had potent MAO-A inhibitory action in vitro, indicating that it would have antidepressant action. 3. (5R)-3-[2-((1S)-3-Cyano-1-hydroxypropyl)benzothiazol-6-yl]-5- methoxymethyl-2-oxazolidinone (E2011), the synthesized metabolite, has been improved in regard to biopharmaceutical characteristics in rat and dog.

Animals↗
PubMed1989

[Ulcerative colitis complicated by early carcinoma of the rectum and cholecystolithiasis].

Reported is a case of a 73-year-old male with a history of ulcerative colitis that had started at the age of 57. In 1985, on receiving a barium enema, a polypoid lesion was found in his rectum. In 1986, the results of a colonoscopy showed that the polypoid lesion had reached an IIa-aggregated elevation, and biopsies of this lesion were diagnosed as an adenoma or a hyperplastic polyp. A year later, in 1987, another biopsy specimen was taken and was histologically diagnosed as being an adenomatous cancer. Thus, a pull-through operation and a cholecystectomy were performed. The lesion was 4.5 x 3.0 cm in diameter, and the histological findings showed it to be a well-differentiated adenocarcinoma with a submucosal invasion. Accordingly, physicians should be advised that patients with a longstanding ulcerative colitis ought to undergo periodic examination that includes a colonoscopy and a biopsy of any suspicious growth.

Adenocarcinoma↗
PubMed1987

Effects of caffeine on gluconeogenesis and urea synthesis induced by alpha-adrenergic stimulation in suspensions of rat hepatocytes.

Effects of caffeine on gluconeogenesis and urea synthesis of rat isolated hepatocytes were investigated in the presence of hormonal agonists. Phenylephrine at 10 microM stimulated 1.7-fold gluconeogenesis and 1.9-fold (compared to control) urea synthesis from 4 mM glutamine. Stimulative effects of caffeine in the range from 0.1 to 10 mM were biphasic depending on its concentration, and it showed maxima at about 1 mM. Caffeine at 1 mM stimulated 2.1-fold gluconeogenesis and 2.4-fold urea synthesis. Caffeine without phenylephrine did not stimulate both syntheses. These effects of caffeine and phenylephrine diminished in the absence of extracellular Ca2+. Results on uptake of 45Ca2+ into hepatocytes and change in quin-2 fluorescence indicated that phenylephrine induced Ca2+ influx into the cell and consequently increased the intracellular Ca2+ concentration, [Ca2+], and that the addition of caffeine did not further stimulate the effect of phenylephrine on [Ca2+]. Therefore, we suggest that stimulation of gluconeogenesis and urea synthesis by phenylephrine is due to increase in [Ca2+]. Since caffeine is known to inhibit phosphodiesterase, the additional stimulation of both syntheses by caffeine plus phenylephrine may be due to the synergistic effect of increases in cAMP and [Ca2+]. The increase in the rates of gluconeogenesis and urea synthesis similarly depended on the caffeine concentration. Furthermore, the ratio of [acetoacetate]/[3-OH-butyrate] which shows intramitochondrial redox state, also depended on the caffeine concentration, indicating a possible coupling of the redox function of mitochondria with [Ca2+].

Adrenergic alpha-Agonists↗
PubMed1985

Studies on complications of diverticular disease of the colon.

Out of 1,124 cases of diverticular disease of the colon seen during the past 15 years, 27 cases (2.4%) of diverticulitis and 44 cases (3.9%) of diverticular hemorrhage were found. The incidence of diverticulitis was more frequent in the both-sides colon type, and also in the multiple form having 10 or more diverticula. The average age was higher in diverticulitis of the sigmoid colon (57.8 years) than in diverticulitis of the right-side colon (47.9 years). Twenty-two cases (81%) of these patients were recovered by medical treatment, and in 5 cases (19%) of these, elective colectomy was carried out. On the other hand, the incidence of diverticular hemorrhage was more frequent in patients over 70 years old, and also in the multiple form having 10 or more diverticula. Though anemia was seen in 11 (25%) of 44 cases, all patients were recovered by medical management. Namely, diverticulitis of the right-side colon is more frequent in middle age, and both diverticulitis of the sigmoid colon and diverticular hemorrhage are more frequent in old age.

Adult↗
PubMed1984

[The effect of oral synthetic protease inhibitor (FOY 305) on endocrine pancreas and carbohydrate and lipid metabolism in normal and streptozotocin-induced diabetic rats].

The effect of long-term oral synthetic protease inhibitor (FOY 305) administration on fasting blood sugar (FBS), body weight, glucose tolerance, plasma insulin and glucagon levels, pancreatic insulin and glucagon contents, hepatic enzyme activities, and plasma lipids in normal and streptozotocin (STZ)-induced diabetic rats was studied. Normal rats treated with oral FOY 305 for 9 weeks were found to have pancreatic hypertrophy and decreased body weight gain as compared with the untreated normal controls. FBS, glucose tolerance, plasma insulin and glucagon levels, pancreatic insulin and glucagon contents, and plasma lipids were uninfluenced in FOY 305 treated normal rats. STZ-induced diabetic rats treated with oral FOY 305 were found to have decreased FBS for 5 weeks after the beginning of FOY 305 administration as compared with the untreated diabetic controls, whereas at the 7th and 9th week after treatment there was no difference in FBS between FOY 305 treated and untreated diabetic rats. In the metabolic balance observed at the 4th week after treatment, a slight improvement of the diabetic state was found in FOY 305 treated diabetic rats. There was no apparent difference in the blood sugar curve and insulin response following oral glucose load between diabetic rats treated for 7 weeks and untreated diabetic rats. All the rats were sacrificed after 9 weeks of treatment. Diabetic rats treated with oral FOY 305 for 9 weeks showed pancreatic hypertrophy and decreased plasma glucagon level and decreased pancreatic glucagon content as compared with the untreated diabetic controls, whereas there was no difference in body weight, plasma insulin level and pancreatic insulin content between FOY 305 treated and untreated diabetic rats. Furthermore, oral FOY 305 treatment improved hyperlipidemia in STZ-induced diabetic rats and also significantly improved the hepatic pyruvate kinase and phosphoenlpyruvate carboxykinase activities of diabetic rats. These improvements might partly be due to a decreased pancreatic content and secretion of glucagon and/or a direct action of the synthetic PI, FOY 305 to tissues.

Animals↗
PubMed1982

[Antineoplastic effect of UFT therapy (uracil-FT-207 combination therapy) on experimental pancreatic cancer transplanted in the pancreas and subcutaneous region].

The pancreatic duct cell adenocarcinoma induced by di-isopropanol nitrosamine could be easily and repeatedly transplanted into the subcutaneous or pancreatic tissues of the homologous animals. We established a tumor bearing animal design in which tumor tissues were transplanted simultaneously into subcutaneous and pancreatic tissues. At the first week after the transplantation, the animals were divided into three groups: In FT group FT-207 was given at a dose of 15 mg/kg/day, in UFT group FT-207 and uracil were given at a dose of 3 mg/kg/day and; 6.7 mg/kg/day (molar ratio; 1:4), respectively and in control group a solvent of FT-207 was given. In all groups the drugs were administrated orally for ten days. The size of tumors transplanted in subcutaneous and pancreatic tissues increased more slowly in FT and UFT groups, as compared with that of control group. The inhibitory effect on tumor growth observed in UFT group was more striking than that in FT group. No major side effects were observed in all groups. At the fourth weeks after subcutaneous and intrapancreatic transplantation, the animals were divided into two groups: In FT group FT-207 was given at a dose of 30 mg/kg and in UFT group FT-207 and uracil were given at a dose of 30 mg/kg and 67.2 mg/kg, respectively. In both groups the drugs were given orally, and at one hour after the administration all the animals were killed to determine 5-FU concentration in various tissues. The 5-FU concentrations of subcutaneous and intrapancreatic transplanted tumor tissues were significantly higher in UFT group than those in FT group. UFT therapy, therefore, seems to be hopeful for the treatment of human pancreatic cancer.

Animals↗
PubMed1979

Effect of long term alcohol feeding on the pancreas in rat.

To elucidate the pathophysiological process of alcoholic pancreatitis, chronic alcohol intoxication was made in Wistar rats on balanced diet giving 20% ethanol freely for 60 weeks. The control rats received water. Histological picture of the pancreas, hormonal activity in the mucosa of upper digestive tract and the nature of pancreatic juice were examined in every 15th week. The results were as follows. 1) No histological changes were noted in the pancreas of control group. In the ethanol group, morphological abnormalities of the pancreas appeared after 30 weeks. Of the histological findings, the changes on the ductal system such as dilatation of pancreatic duct, plug formation in the ductal lumen and periductal fibrosis were significant. 2) The long term ethanol administration tended to decrease the amounts of gastrin, secretin and cholecystokinin contained in the gastrointestinal mucosa. 3) Regardless of the histological changes of the pancreas, almost no changes were noted in the bicarbonate and protein concentration during the experimental period of 60 weeks. From the above results, a mechanism obstructing pancreatic ductal system is considered to be important in the pancreatic lesions by alcohol rather than a mechanism of stimulating pancreatic exocrine secretion.

Alcoholism↗
PubMed1978

Reserve capacity of bicarbonate secretion in chronic pancreatitis.

When secretin was given by continuous intravenous infusion in the control subjects, the dose of secretin inducing maximal bicarbonate output was found to be around 6.0 CHR U/kg/hr. Then the pancreatic exocrine secretory response to sequential standard (1.2 CHR U/kg/hr) and augmented (6.0 CHR U/kg/hr) dose of secretin was studied in the controls, in patients with chronic pancreatitis and in its suspected cases. This new method for exocrine pancreatic function did not offer advantage for the diagnosis of well established chronic pancreatitis. But from the results obtained in suspected chronic pancreatitis it was supposed that the decline of increasing rate of bicarbonate output with augmentation of dose and the decrease of response to augmented dose of secretin might be one of functional disorders occurred in the early stage of chronic pancreatitis.

Adolescent↗
PubMed1978

Secretin-like bioactivity in the duodenal mucosa in patients with peptic ulcer and chronic pancreatitis.

Biopsy specimens of the duodenal mucosa were assayed to determine their secretin-like activity in 9 controls, 9 patients with gastric ulcer, 19 patients with duodenal ulcer, 4 patients with gastric and duodenal ulcer, and 13 patients with chronic pancreatitis. The bioassay of secretin was done on the pancreatic secretion in anesthetized rats. The sensitivity was in the orcer of 0.0625 CHR unit/rat (4 ng/rat). In the range between 0.0625 and 0.5 CHR units a satisfactory dose dependency was recognized. The following results were obtained. 1) The level of duodenal mucosal secretin-like activity in patients with gastric ulcer was the same as that in the controls, but was elevated in 32% of the patients with duodenal ulcer, 50% of those with gastric and duodenal ulcer, and 8% of those with chronic pancreatitis. 2) The high level of secretin-like activity noted in patients with duodenal ulcer was suspected to be related to the hypersecretion of gastric acid which is characteristic of this disease, but there was no correlation between gastric acid secretion and secretin-like activity in the duodenal mucosa.

Adolescent↗