Biomedical subjects

H Takase

Publications and source records attributed to H Takase.

At least 55 records · Page 3Linked to original sources

PubMed1997

Comparative study of the effects of indomethacin and NS-398, a selective cyclooxygenase 2 inhibitor, on duodenal bicarbonate secretion induced by luminal acidification in rats.

To clarify the mechanisms of duodenal ulcerogenic activity of non-steroidal anti-inflammatory drugs (NSAIDs), the effects of indomethacin (IND) on acid-stimulated duodenal bicarbonate secretion and histamine-induced duodenal ulcerogenic responses were studied in comparison with NS-398, a selective cyclooxygenase (COX)-2 inhibitor, in rats. IND (1 and 5 mg/kg, s.c.) significantly decreased duodenal bicarbonate secretion and potentiated duodenal lesion in a dose-dependent manner. On the other hand, NS-398 had no effect on these parameters. These findings suggest that duodenal ulcerogenicity of IND in the presence of histamine is mainly due to the inhibitory action on acid-stimulated bicarbonate secretion mediated by COX-1, but not by COX-2.

Animals↗

PubMed1996

Localized right ventricular structural abnormalities in patients with idiopathic ventricular fibrillation: magnetic resonance imaging study.

Lethal arrhythmias, including ventricular tachycardia and ventricular fibrillation, may occur in the absence of apparent morphological abnormalities. However, a recent study using magnetic resonance imaging (MRI) has suggested that localized, minor structural abnormalities of the right ventricle are responsible for right ventricular outflow tract ventricular tachycardia in a number of patients. We demonstrated regional wall thinning and systolic dyskinesia of the right ventricle by MRI in two patients with idiopathic ventricular fibrillation in whom other cardiac imaging modalities failed to show abnormalities. This finding implies that minor structural abnormalities do exist in patients with so-called idiopathic ventricular fibrillation.

Adult↗

PubMed1996

Antibody responses and protection in mice immunized orally against influenza virus.

Antibody responses and protection were studied in BALB/c mice immunized orally with formalin-inactivated influenza viruses (A/PR/8/34) combined with cholera toxin B subunit as adjuvant. Influenza virus-specific IgA as well as IgG antibody responses were induced in the mice, depending on the oral dosage frequency. The oral immunization by multiple doses resulted in reduction of viral replication in the nose and prevention of development of infection in the lung after intranasal (i.n.) challenge. The protective effect in the nose was thought to be related to the nasal IgA antibody response. The oral immunization was, however, less efficient for induction of the IgA antibody response and protection in the nose, compared with an i.n. immunization. The oral immunization following subcutaneous priming led to the complete protection in the nose, accompanied-by a prompt local IgA antibody response.

Adjuvants, Immunologic↗

PubMed1996

Effect of endothelin antagonists on the responses to prostanoid endothelium-derived contracting factor.

1. The effect of endothelin antagonists on endothelium-dependent contractions was studied in conditions of stimulated endothelium-derived contracting factor (EDCF) release and with exogenous activation of thromboxane A2-endoperoxide receptors in the rat aorta. 2. The incubation of aortic rings with N omega-nitro-L-arginine methyl ester (L-NAME) led to EDCF-mediated contraction upon stimulation with acetylcholine (24 +/- 3% of KCl contraction). When vessels were preincubated with bosentan, an endothelinA- and endothelinB-receptor antagonist, in addition to L-NAME, acetylcholine-induced contraction was reduced to 8 +/- 2% (P < 0.01) of KCl contractions. PD147953, a selective endothelinA-receptor antagonist, reduced the contraction to 14 +/- 4% (P < 0.05) of KCl contractions. 3. Bosentan preincubation produced a significant parallel rightward shift of the contractions to U46619, a selective thromboxane A2 receptor agonist. In contrast, PD147953 failed to exhibit any inhibitory effect on U46619 contractions. 4. These results suggest that endothelin antagonists inhibit EDCF-mediated contractions by blocking endothelinA receptors and that, in addition, bosentan antagonizes the direct stimulation of thromboxane A2 receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1996

Antihypertensive therapy prevents endothelial dysfunction in chronic nitric oxide deficiency. Effect of verapamil and trandolapril.

The objective of this study was to examine the effects of long-term antihypertensive therapy on blood pressure and vascular responses of resistance arteries during prolonged inhibition of nitric oxide synthesis. Four groups of 6-week-old Wistar-Kyoto rats were treated with either placebo as controls or N omega-nitro-L-arginine methyl ester (L-NAME) alone or in combination with verapamil or with trandolapril. Drugs were given orally for 6 weeks or short-term in vitro to vessels obtained from untreated rats. Endothelium-dependent and -independent relaxations as well as contractions were studied in isolated perfused mesenteric and renal arteries with an arteriograph. Kidney nitric oxide synthase activity was also evaluated. Verapamil and trandolapril prevented the increase in systolic blood pressure and the blunted acetylcholine-induced relaxations that occurred with L-NAME treatment without improving the nitric oxide synthase activity. Both antihypertensive regimens also normalized sensitivity to sodium nitroprusside, which was enhanced by L-NAME. In contrast, short-term in vitro preincubation with verapamil or trandolaprilat in the presence of L-NAME did not improve the impaired relaxations to acetylcholine. Long-term but not short-term therapy with a calcium antagonist or angiotensin-converting enzyme inhibitor improved the blunted endothelium-dependent relaxations in nitric oxide-deficient hypertension. These findings strongly suggest that the role of other vasodilator systems, which normally do not regulate vascular tone, is enhanced with long-term but not short-term treatment with these drugs. These observations emphasize the potential importance of these treatments in the management of hypertension in which nitric oxide production is diminished.

Animals↗

PubMed1996

[Studies on solid phase extraction of bile acids from biological matrix].

To quantify bile acids in biological samples, a solid phase extraction method was examined. This method is known as simpler procedures with less contamination compared with solvent extraction methods. Rat bile, feces and urine were used as biological samples. Since Bond Elut C18 and C8 were proved to be more suitable than the other phases (CH and SAX) so far examined using standard bile acids, Bond Elut C18 was used for biological samples. Quantification of biological sample was carried out by gas chromatography after the extracted sample was derivatized to methyl ester by treatment with trimethylsilyldiazomethane then to trifluoroacetyl ester by trifluoroacetic anhydride. On the gas chromatography, two columns (Rtx-50 and Rtx-200) were connected to the injector with Y-tube for elimination of interference. Except for a few bile acids, high recovery with less biological contamination was obtained by this solid phase extraction method.

Animals↗

PubMed1996

Influence of cholesterol feeding on bile acid metabolism in young and aged germ-free rats.

The effects of cholesterol feeding on serum and liver cholesterol levels, fecal and biliary bile acid levels, bile acid pool size and bile acid composition were examined in 2-, 12- and 24-month-old male germ-free rats. The major bile acids in these animals were cholic and beta-muricholic acids. Cholesterol feeding increased synthesis of bile acids by 3- to 4-fold, especially that of chenodeoxycholic acid (mainly beta-muricholic acid in the rat), decreasing the cholic acid/chenodeoxycholic acid (CA/CDCA) ratio in all rats regardless of age, even though the CA/CDCA ratio increased as a linear function of age in both diet groups. Cholesterol feeding increased the serum cholesterol level markedly in aged rats. This hypercholesterolemia may be produced by the increase in CA/CDCA ratio in aged rats.

Aging↗

PubMed1996

Antinociceptive activity of a novel non-steroidal anti-inflammatory drug (M-5011) with low ulcerogenic effects in mice.

Both analgesic and ulcerogenic activities of d-2-[4-(3-methyl-2-thienyl)phenyl] propionic acid (M-5011), a novel non-steroidal anti-inflammatory drug (NSAID), were compared with those of indomethacin (IND), ketoprofen (KP), diclofenac sodium (DIF), zaltoprofen (ZLT) and tiaprofenic acid (TIA) in mice. All orally administered NSAIDs including M-5011 inhibited kaolin-induced writhing in a dose-dependent manner. M-5011 had an effective antinociceptive activity (ED50 value) of 0.63 mg/kg, being more potent than ZLT (16.80 mg/kg) and TIA (4.78 mg/kg), equipotent to DIF (0.68 mg/kg), and less potent than IND (0.21 mg/kg) and KP (0.28 mg/kg). All drugs tested significantly reduced peritoneal 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) levels at the peak kaolin-induced writhing time (7.5 min post-kaolin injection) without affecting peritoneal bradykinin (BK) levels. Antinociceptive effects of all drugs were closely correlated with inhibition of peritoneal 6-keto-PGF1 alpha levels. Ulcerogenic activities (UD50 value) of M-5011 in the stomach and small intestines were 88.23 and 46.09 mg/kg, respectively. UD50 values of other drugs in the stomach and small intestines were as follows: 8.96 and 4.78 mg/kg, 20.04 and 10.75 mg/kg, 4.19 and 2.24 mg/kg, 62.86 and 46.55 mg/kg, and 110.92 and 54.78 mg/kg for IND, KP, DIF, TIA, and ZLT, respectively. Thus, the safety indexes (UD50/ED50) of the stomach (or small intestine) for M-5011, IND, KP, DIF, TIA and ZLT were 140.05 (73.16), 42.67 (22.76), 71.57 (38.39), 6.16 (3.29), 13.15 (9.74) and 6.60 (3.26), respectively. These findings suggest that M-5011 is a useful NSAID that shows potent antinociceptive effects with low ulcerogenic activities.

6-Ketoprostaglandin F1 alpha↗

PubMed1996

Effects of toborinone (OPC-18790), a new positive inotropic agent, on action potential in guinea pig sinoatrial node: compared with milrinone and E-4031.

The effects of toborinone ([(+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2 (1H)-quinolinone], OPC-18790), milrinone and E-4031 (1-(2-(6-methyl-2-pyridil)-1-ethyl)-4-(4-methanesulfonyl-amino-1-b enzoyl) piperidine dihydrochloride) on membrane potential were examined in isolated guinea pig sinoatrial node preparations. Toborinone, a new positive inotropic agent, prolonged cycle length (CL), depolarized maximum diastolic potential (MDP) and decreased maximum upstroke velocity (Vmax) and action potential amplitude (APA). On the other hand, milrinone, a peak III phosphodiesterase (PDE III) inhibitor, increased Vmax and APA and shortened CL and action potential duration. E-4031, an IK blocker, prolonged CL, depolarized MDP and decreased Vmax and APA. These results suggest that toborinone modulates the action potential like an IK blocker rather than a PDE III inhibitor in a sinoatrial node.

Action Potentials↗

PubMed1996

Lipase activities in post-heparin plasma and tissues, and susceptibilities of lipoproteins in experimental diabetic rats.

Heparin administration to diabetic rats caused no change in VLDL, an increase in IDL and a decrease in LDL on electrophoretic analysis of plasma lipoproteins, while the administration to control rats markedly decreased VLDL and increased IDL and LDL. Both hepatic triglyceride lipase (HTGL) and lipoprotein lipase (LPL) activities in the postheparin plasma were lower in the diabetic rats than in the controls, and the reduction of HTGL activity was greater than that of LPL activity in the diabetic rats. The LPL activity in the adipose tissue was lower in the diabetic rats than in the controls, but the activities in the cardiac and skeletal muscles were similar in the two rats. The HTGL-catalyzed fatty acid (FA) releases from the diabetic VLDL and IDL were lower than those from the normal rat VLDL and IDL, while the LPL-catalyzed FA release in the diabetic rats was not different from those in the controls. The decreases in LPL and HTGL activities and the markedly impaired susceptibility of IDL to HTGL coincide well with the postheparin changes in plasma lipoproteins in diabetic rats, an increase in IDL and a decrease in LDL.

Adipose Tissue↗

PubMed1996

Altered bile acid metabolism related to atherosclerosis in alloxan diabetic rats.

Normal and alloxan diabetic rats were kept on a 0.25% cholesterol diet for 12 months and the changes in serum cholesterol levels, and fecal excretion of sterols and bile acids were examined to elucidate the influence of changes in bile acid metabolism on manifestations of hypercholesterolemia and development of atheromatous lesions. Diabetic rats fed the cholesterol diet showed increases in bile acid synthesis and in the cholic acid group/chenodeoxycholic acid group (CA/CDCA) ratio, and developed significant hypercholesterolemia and atheromatous lesions. In contrast, normal rats showed increased bile acids synthesis but a decreased CA/CDCA ratio after feeding with the cholesterol diet, and developed neither hypercholesterolemia nor atheromatous lesions. Fecal sterol excretion and the cholesterol/sitosterol ratio decreased in diabetic rats. Positive correlations were found between the cumulative serum cholesterol level and the atheromatous lesion area, and between the fecal CA/CDCA ratio and the serum cholesterol level, in the latter of which the correlation was higher in rats on the cholesterol diet than in those on the standard diet. These findings suggest that alteration of bile acid metabolism with increases in cholic acid synthesis and CA/CDCA ratio in diabetic rats enhances cholesterol absorption to produce significant hypercholesterolemia, which in turn leads to development of atheromatous lesions.

Alloxan↗

PubMed1996

Positive inotropic and chronotropic effects of toborinone and its electrophysiological properties in the isolated hearts of rabbits and guinea-pigs.

The inotropic and chronotropic actions of toborinone ((+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxy-propoxy]-2(1H)-qu inolinone CAS 128667-95-8, OPC-18790) in the isolated right atrial and papillary muscles of rabbit and guinea-pig were examined and compared with those of milrinone (CAS 78415-72-2), a pure cyclic GMP-inhibited phosphodiesterase inhibitor. OPC-18790 (10(-7)-10(-4) mol/l) and milrinone (10(-3)-10(-4) mol/l) exerted concentration-dependent increases of contraction in both atrial and papillary muscles isolated from rabbits and guinea-pigs. In the isolated right atrium of rabbits and guinea-pigs, OPC-18790 showed limited increase in heart rate, while milrinone increased heart rate concentration-dependently. OPC-18790 (10(-6) and 10(-5) mol/l in guinea-pigs and 10(-7)-10(-4) mol/l in rabbits) prolonged the action potential duration in the isolated papillary muscles, while milrinone exerted no such change. In whole-cell voltage clamp experiments using isolated cardiac myocytes of guinea-pigs, OPC-18790(10(-5) mol/l) increased the L-type calcium current and inhibited outward potassium currents such as inward rectifying currents and delayed rectifier currents. OPC-18790 and milrinone (10(-6), 3 x 10(-5) mol/l) increased intracellular cyclic AMP levels with an increase in developed tension in isolated right ventricular muscles of guinea-pigs. From the above results, OPC-18790 was shown to be a positive inotropic agent with limited chronotropic effect and electrophysiologically properties different from those of milrinone. It was suggested that the prolongation of action potential duration, which is due to the inhibition of potassium currents, may be involved in OPC-18790's mechanism of positive inotropic action with limited chronotropic effect in addition to the inhibition of cyclic GMP-inhibited phosphodiesterase.

Action Potentials↗

PubMed1995

Vascular protective effects of ACE inhibitors and calcium antagonists: theoretical basis for a combination therapy in hypertension and other cardiovascular diseases.

Hypertension is an important cardiovascular risk factor. High blood pressure per se is not a disease but a hemodynamic alteration associated with vascular disease. Two classes of drugs are especially effective in lowering blood pressure and preventing cardiovascular complications, angiotensin converting enzyme (ACE) inhibitors and calcium antagonists. The hemodynamic effects of ACE inhibitors and calcium antagonists are complementary. While ACE inhibitors inhibit the renin-angiotensin system and reduce sympathetic outflow, calcium antagonists dilate large conduit and resistance arteries. Certain calcium antagonists, such as verapamil, lower heart rate. In the blood vessel wall, the local vascular effects of ACE inhibitors and calcium antagonists are also complementary. While ACE inhibitors inhibit activation of angiotensin I into angiotensin II and prevent the breakdown of bradykinin (which stimulates nitric oxide and prostacyclin formation), calcium antagonists inhibit the effects of vasoconstrictor hormones such as angiotensin II at the level of vascular smooth muscle by reducing calcium inflow and facilitating the vasodilator effects of nitric oxide. Calcium antagonists reduce smooth muscle cell proliferation and atherosclerosis. In hypertensive animals, verapamil and trandolapril normalize endothelial dysfunction. In large angiographic trials, nifedipine and nicardipine reduced the development of new atherosclerotic plaques. After myocardial infarction, verapamil reduces mortality and cardiac events in patients without heart failure. In contrast, ACE inhibitors are effective after myocardial infarction in patients with impaired left ventricular function. Urinary albumin excretion rate decreases during ACE inhibitor therapy or with a calcium antagonist such as verapamil; combination of the two drugs has an additive effect. In resistance arteries, hypertension is associated with an increased media/lumen ratio. ACE inhibitors, but not beta-blockers, markedly improve these structural changes. In summary, ACE inhibitors and calcium antagonists have a complementary profile, both in their hemodynamic and local vascular action. Hence, combination therapy with these two classes of drugs appears particularly useful in patients with hypertension, not only to lower blood pressure, but hopefully to achieve improved cardiovascular protection.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

Endothelin receptor subtypes in small arteries. Studies with FR139317 and bosentan.

We studied the effects of the selective endothelin A receptor antagonist FR139317 and the combined endothelin A/endothelin B receptor antagonist bosentan in rat mesenteric arteries by using a video dimension analyzer. In endothelium-denuded arteries, increasing concentrations of endothelin-1 evoked a biphasic vasoconstriction. The first phase was observed at low concentrations (10(-16) to 10(-11) mol/L) of endothelin-1 and was relatively weak. However, the contractions characterizing the second phase, which occurred at higher concentrations (10(-10) to 3 x 10(-8) mol/L) of endothelin-1, were much stronger. FR139317 concentration-dependently shifted the second phase of the endothelin-1-induced contraction curve to the right without affecting the first phase. In contrast, bosentan inhibited both the first and the second phase. Even after the blockade of endothelin A receptor, increasing concentrations of the endothelin B receptor agonists endothelin-3 and sarafotoxin S6c still induced small contractions. Maximal contractions induced by single-bolus extraluminal application of endothelin-3 (10(-9) mol/L) or sarafotoxin S6c (3 x 10(-8) mol/L) were markedly more pronounced than responses induced by cumulative concentrations, suggesting endothelin B receptor downregulation upon repeated and sustained activation. The response induced by a single bolus of endothelin-3 (10(-9) mol/L) was antagonized by bosentan but not by FR139317, confirming that endothelin B receptors were involved. In endothelium-intact arteries half-maximally precontracted with norepinephrine, bosentan but not FR139317 inhibited the relaxations induced by intraluminally applied endothelin-3. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

L-NAME hypertension alters endothelial and smooth muscle function in rat aorta. Prevention by trandolapril and verapamil.

Nitric oxide is an important regulator of vascular function and blood pressure. Chronic administration of nitric oxide inhibitors provides a new model of hypertension with pronounced target organ damage. We investigated the effects of oral treatment with N omega-nitro-L-arginine methyl ester (L-NAME) for 6 weeks on vascular reactivity of the aorta in Wistar-Kyoto rats. Certain rats received verapamil or trandolapril in addition to L-NAME. Systolic blood pressure increased in the L-NAME group (by approximately or equal to 80 mm Hg systolic) but not in controls or rats treated with verapamil or trandolapril. Isometric tension changes of aortic rings were recorded. Endothelium-dependent relaxations to acetylcholine were reduced in the L-NAME group (58 +/- 6% versus 104 +/- 1% in placebo, P < .05) but were normalized by treatment with verapamil or trandolapril. In contrast, endothelium-independent relaxations to sodium nitroprusside were not significantly reduced in L-NAME hypertension but were slightly enhanced by trandolapril therapy (P < .05) in the L-NAME group only. In quiescent rings, acetylcholine caused endothelium-dependent contractions in particular after in vitro incubation with L-NAME. These contractions tended to be enhanced in L-NAME hypertension (23 +/- 4% versus 14 +/- 3% in the placebo group; P = NS) and were significantly reduced after treatment with verapamil or trandolapril (P < .05). Concentrations to norepinephrine and angiotensin I and II were unaffected by L-NAME hypertension, whereas those to endothelin-1 were reduced (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1995

Structure and function of the rat basilar artery during chronic nitric oxide synthase inhibition.

BACKGROUND AND PURPOSE: Nitric oxide is an important regulator of vascular tone and may also be implicated in the modulation of vascular growth and structure. This study presents the effects of chronic nitric oxide inhibition, with or without antihypertensive treatment, on the structure and function of the basilar artery in rats. METHODS: Rats were treated for 6 weeks with N omega-nitro-L-arginine methyl ester (50 mg/kg per day) alone or in combination with verapamil (100 mg/kg per day) or with trandolapril (1 mg/kg per day). Untreated rats served as controls. The structure and reactivity of perfused and pressurized basilar arteries were analyzed in vitro using a video dimension analyzer. RESULTS: Systolic arterial pressure increased only in the nitro-arginine-treated group, as did the media-to-lumen ratio of the basilar artery. This structural alteration, which was prevented by verapamil and trandolapril, was mainly due to remodeling and not to growth. Chronic inhibition of the L-arginine pathway increased the response of the basilar artery to serotonin, while the opposite was found for endothelin. Verapamil and trandolapril prevented these functional alterations that seemed related to the changes in the vascular structure. CONCLUSIONS: The remodeling and functional alterations of the basilar artery seem to depend mainly on the elevation of arterial pressure with little contribution of the L-arginine pathway. Furthermore, nitric oxide does not seem to be implicated in the modulation of normal cerebral vascular growth in vivo. However, hypertension-induced changes in vascular reactivity and structure could alter cerebral blood flow and eventually contribute to the development of stroke in this model of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

[Effects of chronic losartan treatment on myocardial, vascular structure and reactivity with aging in spontaneously hypertensive rats (SHR): its effects compared with those of captopril].

To compare the effects of an angiotensin II (Ang II)-receptor antagonist and an angiotensin-converting enzyme (ACE) inhibitor on myocardial, vascular structure and reactivity, SHR (5-week-old) were treated with losartan of captoril for 16 weeks. Losartan (10 mg/kg/day, p.o.) and captopril (30 mg/kg/day, p.o.) significantly prevented the development of hypertension with aging, and the effects by these drugs were almost similar. Losartan and captopril significantly reduced the ventricular weight and the thickening of the coronary artery. Maximal coronary flow (MCF) induced by adenosine in the isolated heart was significantly higher in both the losartan and captopril groups. However, MCF in the captopril group was significantly lower than that in the losartan group. The pressor response to exogenous norepinephrine in the mesenteric arterial bed was significantly lower in the losartan group, whereas that in the captopril group was not. These findings suggest that the local Ang II produced by enzymes other than ACE also may play a role in vascular hypertrophy and hyperresponsiveness in SHR.

Aging↗

PubMed1995

[Partial resection of the lung under thoracoscopic guidance using endo GIA to treat giant bulla: a case report].

A 47-year-old male was admitted because of an abnormal shadow on chest X-ray. Computed tomography showed a giant bulla in the right lung. The giant bulla was resected under thoracoscopic guidance using endoscopic GIA by three puncture technique. The thoracoscope was inserted through the 5th intercostal space in the mid-axillar line. The forceps was inserted through the 5th intercostal space below the inferior angle of the right scapula. The Endo GIA was inserted through the 3rd intercostal space in the anterior axillar line. The residual lung expansion was good enough. The chest drain was removed 5 days after operation thoracoscopic surgery with Endo GIA can be useful in treatment of patients with emphysematous giant bulla.

Humans↗