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T Noto

Publications and source records attributed to T Noto.

At least 19 recordsLinked to original sources
PubMed2001

Role of adenosine and P2 receptors in the penile tumescence in anesthetized dogs.

We studied the role of adenosine and P2 receptors in the pelvic nerve stimulation-induced penile tumescence in anesthetized dogs. A local intracavernous injection of adenosine induced the tumescence, which was abolished by intracavernous 8-(p-sulfophenyl)theophylline (8-SPT), an unspecific adenosine receptor antagonist, and by 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl amino]ethyl)phenol (ZM241385), an adenosine A(2A) receptor antagonist. ATP also induced the tumescence, which was diminished by 8-SPT, but not by reactive blue-2, a P2 receptor antagonist. Neither intracavernous beta, gamma-meATP nor ADP(beta)S, P2X and P2Y receptor agonists, induced tumescence. N(G)-nitro-L-arginine (L-NAME), a nitric oxide synthase inhibitor, and T-1032, a phosphodiesterase type V inhibitor, had no effects on the tumescence induced by adenosine. 8-SPT and reactive blue-2 had no effects on the tumescence induced by pelvic nerve stimulation. These results show that although exogenous adenosine and ATP induce tumescence, neither the adenosine nor the P2 receptor is involved in the tumescence induced by pelvic nerve stimulation in anesthetized dogs.

Adenosine↗
PubMed2001

T-1032, a novel specific phosphodiesterase type 5 inhibitor, increases venous compliance in anesthetized rats.

Nitric oxide (NO) donors including organic nitrates dilate capacitance vessels. As inhibition of phosphodiesterase type 5 results in the accumulation of guanosine 3'5'-cyclic monophosphate (cGMP), specific phosphodiesterase type 5 inhibitors are expected to have a vasodilator property similar to that of NO donors. To test this hypothesis, we examined the effect of methyl2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate (T-1032), a novel specific phosphodiesterase type 5 inhibitor, on mean arterial pressure and mean circulatory filling pressure (an index of venodilation) compared with that of nitroglycerin and diltiazem in mecamylamine- and noradrenaline-treated anesthetized rats. Intravenous infusion of T-1032 (0.1, 1, 10 microg/kg/min) dose-dependently decreased mean arterial pressure (-3.8+/-0.3%, -9.1+/-0.8%, -16.8+/-1.5% at doses of 0.1, 1 and 10 microg/kg/min, respectively) and mean circulatory filling pressure (-6.1+/-0.9%, -12.5+/-0.7%, -18.6+/-3.0% at doses of 0.1, 1 and 10 microg/kg/min, respectively). The mean circulatory filling pressure-mean arterial pressure relationship revealed that T-1032 had a selective action on the mean circulatory filling pressure compared with diltiazem (10, 100 microg/kg/min) and a similar or more selective effect than nitroglycerin (0.3, 3 and 30 microg/kg/min). In the next study, we calculated venous compliance and unstressed volume from the mean circulatory filling pressure-volume relationship. Intravenous infusion of T-1032 (3 microg/kg/min) increased venous compliance (3.35+/-0.40 in T-1032 vs. 2.31+/-0.15 ml/kg/mm Hg in vehicle, P<0.05) without changing the unstressed volume (37.2+/-2.80 in T-1032 vs. 42.6+/-2.37 ml/kg in vehicle, P>0.05). It was concluded that T-1032 increased venous capacitance by increasing venous compliance, and that this selective phosphodiesterase type 5 inhibitor appeared to have a different vasodilator action from that of an NO donor and a Ca(2+) channel antagonist in that it had a selective action on the mean circulatory filling pressure.

Anesthesia↗
PubMed2001

Pharmacological profile of T-1032, a novel specific phosphodiesterase type 5 inhibitor, in isolated rat aorta and rabbit corpus cavernosum.

This study was designed to examine the pharmacological properties of T-1032 (methyl-2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate), a novel phosphodiesterase type 5 inhibitor, in isolated rat aorta and rabbit corpus cavernosum. T-1032 (3x10(-11) to 3x10(-7) M) caused an endothelium-dependent relaxation in the isolated rat aorta precontracted with phenylephrine, and the relaxation was accompanied by an increase in cGMP but not cAMP levels. The T-1032-induced relaxation was attenuated by N(G)-nitro-L-arginine methyl ester (L-NAME) (10(-3) M), a nitric oxide (NO) synthase inhibitor, or 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ) (10(-5) M), a guanylyl cyclase inhibitor. T-1032 (10(-9), 10(-8) M) produced a potentiation of the relaxation induced by sodium nitroprusside, but not of the relaxation induced by isoproterenol. In the isolated rabbit corpus cavernosum precontracted with phenylephrine, the electrical field stimulation-induced relaxation was attenuated by treatment with tetrodotoxin (10(-6) M) as well as L-NAME (10(-4) M). The L-NAME-inhibited relaxation was restored by treatment with L-arginine (5x10(-4) M). T-1032 (10(-9) to 10(-6) M) and sildenafil (10(-9) to 10(-6) M) produced a potentiation of the electrical field stimulation-induced relaxation as well as a decrease in basal tension in a concentration-dependent manner. It was concluded that T-1032 had potentiating effects on the NO/cGMP signaling pathway in isolated tissues, probably through specific blockade of phosphodiesterase type 5. T-1032 would be a useful compound to examine the physiologic functions of phosphodiesterase type 5 in mammalian tissues.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 7). Effects of reserpine in 2- and 4-weeks studies.

To assess the efficacy of different period of treatment for evaluating male reproductive toxicity in rats, reserpine was subcutaneously administered on a daily basis to male Sprague-Dawley rats at dosages of 0.05, 0.1 or 0.2 mg/kg for 2 weeks or at dosages of 0.05 or 0.1 mg/kg for 4 weeks. At the end of the administration period the animals were sacrificed and sperm counts, organ weights and histopathological changes in the reproductive organs were examined. The sperm number in the caudal epididymis and genital organ weights were not affected by reserpine with either 2- or 4-weeks treatment. In the 4-weeks study, histopathological examination of the testes revealed retention of step 19 spermatids in the seminiferous tubules of stages IX to XII and decreased secretory content of the prostate in the 0.05 and 0.1 mg/kg groups. In the 2-weeks study, although no distinct histopathological changes were observed in the 0.05 mg/kg group, decreased secretory content of the prostate, apoptosis of spermatocytes in the seminiferous tubules of stage VII and cell debris of the epididymis were observed in the 0.1 and 0.2 mg/kg groups. These results suggested that 2-weeks treatment with reserpine is sufficient for detection of testicular toxicity, although higher dosage levels are appropriate than for 4-weeks treatment.

Animals↗
PubMed2000

Potentiation of penile tumescence by T-1032, a new potent and specific phosphodiesterase type V inhibitor, in dogs.

We examined the mechanism underlying the potentiation of penile tumescence by methyl 2-(4-aminophenyl)-1, 2dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4, 5-trimethoxyphenyl)3-isoquinoline carboxylate sulfate (T-1032), a new potent and selective phosphodiesterase type V inhibitor. In vivo, pelvic nerve stimulation induced a penile tumescence together with increase of total nitric oxide metabolite levels within the corpus cavernosa of anesthetized dogs. Intravenous (1-100 microg/kg) and intraduodenal (3, 30, 300 microg/kg) treatment with T-1032 dose dependently potentiated the tumescence. The potency of T-1032 was equivalent to that of sildenafil. T-1032 did not influence the intracavernous pressure when the pelvic nerve stimulation was absent. The potentiation of tumescence was more pronounced by intracavernous than i.v. injection. Intracavernous N(G)-nitro-L-arginine, a nitric-oxide synthase inhibitor, but not N(G)-nitro-D-arginine diminished the effects of T-1032 on the tumescence. Furthermore, i.v. T-1032 augmented the tumescence induced by sodium nitroprusside (SNP) but not by vasoactive intestinal polypeptide (VIP). In vitro, in isolated preparations of canine corpus cavernosum precontracted with phenylephrine, SNP (0. 01-100 microM) and VIP (0.01-1 microM) produced a dose-dependent relaxation accompanied by an increase in cGMP and cAMP levels, respectively. T-1032 augmented the relaxation induced by SNP but not by VIP. These data suggest that oral treatment with T-1032 has potential to improve erectile dysfunction through the inhibition of phosphodiesterase type V in the smooth muscles of corpus cavernosa.

Animals↗
PubMed1999

Lessons learned from the review of cardiac catheterization laboratories: a report from the Laboratory Survey Committee of the Society for Cardiac Angiography and Interventions.

The Laboratory Survey Committee of the Society for Cardiac Angiography and Interventions was created as a resource for physicians and administrators to provide comprehensive independent outside review services for cardiac catheterization laboratories. Since 1989, when the committee began its work, surveys of 23 catheterization laboratories have been completed. Our review of this experience identified several recurring problems among the laboratories. The purpose of this paper is to summarize our experience and highlight the lessons we learned in the hope that this information will benefit many other laboratories.

Cardiac Catheterization↗
PubMed1998

Gastric mucosal function following withdrawal of omeprazole in rats.

In the following study the function of gastric mucosa after withdrawal of 4-week suppression of acid secretion was examined. Rats were treated orally for 4 weeks with omeprazole (CAS 73590-58-6, 150 mg/kg/day). While elevated plasma gastrin levels during the treatment returned to normal 4 days after the last dosing, exogenously applied pentagastrin induced higher acid secretion compared with the vehicle-treated controls. Acetylsalicylic acid induced mucosal lesion 3.6-fold over the control as well. In contrast, the HCl-induced lesion was inhibited by 24.4%. These results indicate that not only the acid secretion but also the mucosal protection is enhanced after 4-week treatment with omeprazole in rats.

Analgesics, Non-Narcotic↗
PubMed1997

Role of vagus nerves and gastrin in the gastric phase of acid secretion in male anesthetized rats.

We used the pylorus ligation model to determine the role of vagus nerves and gastrin in acid secretion induced by mechanical and chemical stimulation of the gastric lumen in anesthetized male rats. Gastric distension induced by intragastric instillation of saline resulted in a 17-fold increase in acid secretion over the basal level without an alteration in serum gastrin levels. Distension-stimulated acid secretion was inhibited by bilateral subdiaphragmatic vagotomy but not by CI-988, a gastrin receptor antagonist. Intragastric peptone produced a 71-fold increase in acid secretion over the basal level that was accompanied by a significant increase in serum gastrin levels. Whereas vagotomy almost abolished peptone-stimulated acid secretion, CI-988 inhibited peptone-stimulated acid secretion by only 50%. We conclude that the vagus nerves mediate acid secretion by mechanical and chemical stimulation and that gastrin mediates acid secretion partly by chemical stimulation but not by mechanical stimulation in anesthetized male rats.

Animals↗
PubMed1997

Efficient synthesis and gastric (H+/K+)-ATPase-inhibitory activity of 2-aryl-4,5-dihydro-1H-thieno[3,2-e]benzimidazoles.

A series of 2-aryl-4,5-dihydro-1H-thieno[3,2-e]benzimidazoles (1, 2) was prepared by condensation of 5-acylamino-4,5,6,7-tetrahydrobenzo[b]thiophen-4-ones (9, 10) with ammonium acetate under azeotropic reaction conditions. Various congeners, N-methyl and N-phenyl analogues (3-5), 4,5-dihydro-1H-thieno[2,3-e]benzimidazoles (6), 4,5-dihydro-1H-thieno[2,3-g]benzoxazoles (7), and 4,5-dihydro-1H-thieno[2,3-g]benzothiazoles (8), were also prepared. Several compounds in this series were shown to be K(+)-competitive inhibitors of the gastric (H+/K+)-ATPase and more potent inhibitors than SK&F-96067, 3-butyryl-8-methoxy-4-(2-tolylamino)quinoline, on pentagastrin-stimulated acid secretion in chronic gastric fistula rats after intraduodenal administration.

Animals↗
PubMed1996

Five year trends in cardiac catheterization: a report from the Registry of the Society for Cardiac Angiography and Interventions.

The Society for Cardiac Angiography and Interventions has maintained a registry of cardiac catheterizations since 1979 and of percutaneous cardiac interventions since 1990. Data from 392,923 procedures (317,592 diagnostic catheterizations, 74,963 coronary interventions, and 368 valvuloplasties) for the years 1990-1994 inclusive are presented. Over the 5 year period there was a trend toward same day and 23 hr discharges (19% in 1990 to 29% in 1994), and a decrease in combined right and left heart procedures from 38% to 26%. For cardiac catheterizations ionic contrast use declined from 26% of procedures to 13% in 1994. The use of ionic contrast was even lower in interventional procedures, with laboratories reporting use in 21% of procedures in 1990 dropping to 9% in 1994. Balloons were the first choice device in 92.5% of native arteries and 82.7% of grafts in 1994. For the first time in 1994 more mitral than aortic valvuloplasties were reported.

Angioplasty, Balloon, Coronary↗
PubMed1996

Advantages of using the midline incision right retroperitoneal approach for abdominal aortic aneurysm repair.

This study was conducted to compare the midline incision right retroperitoneal approach for repairing abdominal aortic aneurysms (AAA) with the transperitoneal approach. The intra- and postoperative course of 15 patients who underwent AAA repair using the transperitoneal approach between 1987 and 1991 and another 15 patients who underwent AAA repair using the retroperitoneal approach between 1991 and 1994 were evaluated. The incidence of postoperative wound complications was also assessed. There was no operative or hospital death in either group. Although a significantly longer interval was required from the incision to the aortic clamp using the extraperitoneal method, there were no statistical differences in the aortic clamping time, total operation time, or blood loss between the two groups. On the other hand, there was a statistically significant improvement in bowel function and a significant reduction in the length of postoperative hospitalization following the extraperitoneal procedure. Furthermore, no wound complications such as those associated with the left flank incision developed after the extraperitoneal procedure. Thus, we recommend the midline incision right retroperitoneal approach for AAA as it does not involve muscle division and is associated with fewer complications.

Aged↗
PubMed1996

Reversible inhibition of rat gastric H+/K+-ATPase by T-330, 2-[2-dimethylaminobenzyl)sulfinyl]-1-(3-methylpyridine-2-yl)imidazole.

The effect of 2-[(2-dimethylaminobenzyl)sulfinyl]-1-(3-methylpyridine-2-yl)imidazole (T-330), on rat gastric H+/K+-ATPase was studied in vitro and in vivo in comparison with the irreversible proton pump inhibitor omeprazole. T-330 and omeprazole inhibited rat gastric H+/K+-ATPase at pH 6.1, and their IC50 values were 75 microM and 4.6 microM, respectively. Recovery from the T-330-inhibited H+K/+-AtPase activity was effected by beta-mercaptoethanol at concentrations above 10 microM, whereas significant recovery from the inhibition by omeprazole required 100 mM. When intraduodenally administered, T-330 (0.6-10 mg/kg) induced a more potent yet shorter-lasting inhibition of both gastric H+/K+ -ATPase activity and gastric acid secretion than did omeprazole (2.5-40 mg/kg). Recovery of the gastric H+/K+-ATPase activity depressed by omeprazole was completely blocked by an inhibitor of protein synthesis, cycloheximide, whereas that by T-330 was not prevented. This indicates that restoration of the enzyme activity after inhibition in vivo by T-330 does not require de novo synthesis of the enzyme in contrast to inhibition by omeprazole. beta-Mercaptoethanol (1 mM) fully restored the H+/K+-ATPase activity inhibited in vivo by T-330 but not by omeprazole. These observations indicate that T-330 reversibly inhibits gastric H+/K+-ATPase, resulting in a short-lasting antisecretory effect, and that the sulfhydryl groups of the enzyme are involved in the action of T-330.

Animals↗
PubMed1996

[Cross sectional study of the relationship between bone density to diet and life style using ultrasound bone densitometry].

The relationship between bone density to diet and life style was investigated in pre- and postmenopausal women in Kyoto Prefecture in 1994 by a cross-sectional study. Bone densities of 453 women aged 30-86 years were measured by ultrasound bone densitometry. History of pregnancy and delivery, menstruation, medical history, bone and arthral symptoms, life style, food intake frequency, current and past intake of dairy products, and physical activity were examined by self-administered questionnaire. Analysis of covariance and multiple-regression analysis were performed to determine the relation between bone density and life style adjusted for age and obesity index among 151 premenopausal women (PRE), 244 postmenopausal but not sedentary (under 65 years of age) women (POST), and 58 sedentary (older than 65 years of age) women (SED). The results were as follows; 1) A marked age-related decline in bone density was observed at 45-55 years of age. The correlation coefficient between age and bone density was significant at -0.65 (p < 0.01). 2) Obesity index and bone density were positively correlated in each group. 3) Among the PRE group women, there was no relation between life style and bone density. Those who experienced bone fractures tended toward low bone density. Among the POST group, time since menopause, exercise, and current milk intake were significantly correlated with bone density. In the SED group, women with arthralgia showed significantly lower densities. 4) From multiple-regression analysis, age, obesity index, and milk intake during childhood were shown to be related to bone density in each group.

Adult↗
PubMed1995

Immunohistochemical localization of carcinoembryonic antigen as a predictor of lymph node status in submucosa-invasive colorectal carcinoma.

PURPOSE: Submucosa-invasive colorectal carcinoma is a colorectal carcinoma extending only into the submucosal layer. To clarify the metastatic potential of submucosa-invasive colorectal carcinoma, we studied the relationship between the immunohistochemical staining pattern of carcinoembryonic antigen (CEA) and that of lymphatic invasion/lymph node metastasis. METHODS: We investigated 49 submucosa-invasive colorectal carcinomas resected surgically or endoscopically. CEA distribution patterns of the neoplastic tissues were divided into three patterns: Pattern 1 = luminal type; Pattern 2 = apical cytoplasmic type; and Pattern 3 = diffuse cytoplasmic type. We also observed the submucosal stromal staining of CEA. RESULTS: Lymphatic invasion and lymph node metastasis were found in 48.8 percent (21/43) and 11.6 percent (5/43) of the Pattern 2/Pattern 3 cases, whereas these were seen in none (0/6) of Pattern 1 cases. Lymphatic invasion and lymph node metastasis were found in 63.3 percent (19/30) (chi-squared = 21.94; P < 0.001) and 16.7 percent (5/30) of the positive stromal CEA cases, whereas these were seen in 10.5 percent (2/19) and none (0/14) of the negative stromal CEA cases, respectively. CONCLUSION: Pattern 2/Pattern 3 and stromal CEA can be predictors of the lymph node metastasis with 11.6 percent and 16.7 percent risks.

Adult↗
PubMed1995

Fluctuation of blood pressure and pulse rate during colostomy irrigation.

PURPOSE: The aim of this study was to determine the effects of colostomy irrigation on the vital signs of patients with left colostomy. METHODS: Twenty-two consecutive patients who underwent abdominoperineal resection for cancer of the lower rectum and had left lower quadrant end colostomy were included in this study. Subjective symptoms, blood pressure, and pulse rate during the first irrigation were investigated. RESULTS: Fluctuation of blood pressure during instillation was 8.0/8.5 mmHg (average) and 25.0/17.9 mmHg during evacuation. Fluctuation of pulse rate was 5.5 per minute (average) during instillation and 11.5 per minute during evacuation. The number of subjects who showed more than 20% fluctuation of systolic pressure was 12 (54.5 percent) and that of diastolic pressure was 14 (63.6 percent). One of 22 patients complained of illness during irrigation. CONCLUSION: Although colostomy irrigation showed no significant effects on vital signs in the majority of patients, it caused a significant reduction in both blood pressure and pulse rate in a small number of patients. Careful attention should be paid to vital signs considering the possibility of such effects, especially on the initial irrigation.

Aged↗
PubMed1995

Effect of a combination of ecabet sodium and cimetidine on experimentally induced gastric lesions and gastric mucosal resistance to ulcerogenic agents in rats.

We studied the effect of single oral administration of ecabet sodium (ecabet), a gastroprotective agent, in combination with the histamine H2-receptor antagonist cimetidine on gastric acid secretion, mucosal prostaglandin E2 (PGE2) production and experimentally induced acute hemorrhagic gastric lesions in rats. The effect repeated administration of ecabet in combination with cimetidine on the vulnerability of gastric mucosa to the ulcerogenic agents 0.6N HCl and aspirin was also studied. In pylorus-ligated rats, oral administration of cimetidine reduced gastric acid secretion, whereas ecabet did not affect the cimetidine-induced reduction in acid secretion. On the other hand, ecabet increased the capacity of gastric mucosa to synthesize PGE2, while cimetidine showed no effect on this parameter either in the presence of absence of ecabet. Both ecabet and cimetidine inhibited the formation of aspirin-induced gastric mucosal lesions, and the combination of ecabet and cimetidine showed a more potent inhibition than either drug alone. After cessation of repeated administration of cimetidine, but not ecabet, the 0.6N HCl- and aspirin-induced gastric lesions were significantly aggravated. The co-administration of ecabet improved the cimetidine-induced aggravation of these gastric lesions. These results suggest that ecabet in combination with cimetidine augments the antiulcer effect of cimetidine and improves the cimetidine-induced increase in gastric mucosal vulnerability to the ulcerogenic agents.

Abietanes↗
PubMed1994

A study on the metabolism of spermidine in mammals: purification and identification of a newly identified metabolite, 2-oxo-1-pyrrolidinepropionic acid, in rat urine.

In order to study the metabolism of spermidine in mammals, radioactive spermidine was injected intraperitoneally into a rat and urine was collected for analysis. Incorporation of radioactivity into putreanine, isoputreanine, spermidic acid, and N-aminopropylpyrrolidin-2-one was confirmed by ion-exchange chromatography, thin layer chromatography, and paper electrophoresis, the highest radioactivity being observed in the non-polar and acidic fraction of the collected urine. A radioactive compound was purified from the non-polar and acidic fraction, and identified as 2-oxo-1-pyrrolidinepropionic acid by comparison of its behavior on ion-exchange chromatography and thin layer chromatography with that of authentic 2-oxo-1-pyrrolidinepropionic acid, and recrystallization with the authentic compound. Acid hydrolysis of the radioactive compound produced radioactive spermidic acid, confirming the identification. To examine the interconversion between isoputreanine and N-aminopropylpyrrolidin-2-one, these compounds were deuterated and then intraperitoneally injected into a rat. Analysis of 24-h urine by gas-chromatography-mass-spectrometry indicated no interconversion between the two metabolites of spermidine under these conditions. An intracerebroventricular injection of radioactive spermidine into a rat showed that radioactivity was also incorporated into the metabolites of spermidine in the brain, and oxidative deamination of the aminopropyl moiety of spermidine was thought to be dominant in the central nervous system and vice versa in peripheral organs.

Amino Acids, Diamino↗