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Biomedical subjects

Y Akimoto

Publications and source records attributed to Y Akimoto.

At least 127 records · Page 7Linked to original sources
PubMed1988

Long-lasting hypotensive and antihypertensive effects of a new 1,5-benzothiazepine calcium antagonist in hypertensive rats and renal hypertensive dogs.

The hypotensive effect of a new 1,5-benzothiazepine derivative, TA-3090 ((+) (2S,3S)-3-acetoxy-8-chloro-5-(2-(dimethylamino)ethyl)-2, 3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4-(5H)-one maleate), was studied in various models of experimental hypertension. In conscious spontaneously hypertensive rats (SHR), TA-3090 at a dose of 3 mg/kg p.o. or more caused significant hypotension. The effect was long-lasting, being observed for more than 8 h and 24 h at doses of 30 and 100 mg/kg p.o., respectively. Heart rate was not increased with doses up to 30 mg/kg p.o. TA-3090 like diltiazem, showed more potent hypotensive effect in SHR than in Wistar Kyoto rats (WKY). The enhancement of the hypotensive effect in SHR was more evident with TA-3090 and diltiazem than with 1,4-dihydropyridine calcium antagonists (1,4-DHPs). The enhanced hypotensive effect of TA-3090 was also observed in deoxycorticosterone acetate (DOCA)-salt hypertensive rats in which the minimum hypotensive dose of TA-3090 was 1 mg/kg p.o. In SHR, reflex tachycardia induced by TA-3090 was smaller than those induced by 1,4-DHPs, while diltiazem decreased the heart rate. In WKY, all calcium antagonists except diltiazem at a low dose (30 mg/kg p.o.) increased the heart rate. Development of hypertension in young SHR was significantly suppressed by chronic treatment with TA-3090 at a daily dose of 10 mg/kg p.o. or more. The antihypertensive effect of TA-3090 was also observed by administration in the diet in matured SHR. In addition, TA-3090 exhibited a dose-related natriuretic but not kaliuretic effect in SHR at doses slightly higher than the hypotensive ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Response of the mouse femoral muscle to an implant of a composite of bone morphogenetic protein and plaster of Paris.

A composite consisting of 1 mg of bone morphogenetic protein (BMP) and 5 mg of plaster of Paris (PLP) was implanted into the mouse femoral muscle. Control PLP without BMP was implanted into the contralateral muscle. The BMP/PLP composite induced cartilage formation within two weeks, trabecular bone within three weeks, and lamellar bone including bone marrow within six weeks. PLP did not disturb BMP-induced bone formation. In addition, the BMP/PLP composite was resorbed early after implantation. These results suggest that PLP composite system is one of the most suitable BMP delivery systems currently available.

Animals↗
PubMed1987

Inhibition by epidermal growth factor of glucocorticoid-induced epidermal alpha-type keratinization of chick embryonic skin cultured in the presence of delipidized fetal calf serum.

When a 13-day-old chick embryonic tarsometatarsal skin was cultured for 4 days in medium containing hydrocortisone (20 nM) and 5% delipidized fetal calf serum (FCS), epidermal growth factor (EGF, 100 ng/ml) decreased epidermal DNA content 42% and inhibited epidermal DNA synthesis 87%. Tonofilament bundles within the basal and intermediate cells of the EGF-treated epidermis were not as conspicuous as those in the glucocorticoid-induced keratinized epidermis, and the upper region of the EGF-treated epidermis did not form either the filament bundles or the electron-dense amorphous masses seen in the cytoplasm of the glucocorticoid-induced keratinized layer. EGF stimulated degradation of glucocorticoid-induced alpha-keratin. Furthermore, EGF caused a twofold increase in glucocorticoid-induced epidermal transglutaminase activity and in the amount of epidermal glucocorticoid receptor. In the absence of FCS, however, EGF did not inhibit steroid-induced alpha-type keratinization and did not affect either steroid-induced epidermal transglutaminase activity or amount of epidermal glucocorticoid receptor. Hence, the effect of EGF on glucocorticoid-induced epidermal transglutaminase activity was observed only in the presence of delipidized FCS and might be supported by an increase in the amount of glucocorticoid receptor.

Animals↗
PubMed1987

Nitroglycerin-sensitive and -resistant contractions mediated by receptor-operated calcium channels in rabbit ear artery.

In isolated rabbit ear arteries incubated in a Ca2+-free medium with EGTA and nifedipine in the presence of norepinephrine, serotonin or histamine, an addition of Ca2+ induced a tonic contraction which is due to Ca2+ entry through receptor-operated Ca2+ channels (ROCs). Nitroglycerin (10(-4) M) significantly inhibited the ROCs-dependent contractions produced by serotonin or histamine, but failed to inhibit the ROCs-dependent contraction by norepinephrine. These results suggest the possible existence of two types of receptor-operated Ca2+ channels in rabbit ear artery.

Animals↗
PubMed1987

Effects of NC-1300 and its degradation products on gastric secretion and HCl.ethanol-induced gastric lesions in rats.

The proton pump inhibitor NC-1300 has antisecretory and cytoprotective activities in rats. The compound is labile at an acidic pH and degrades into various products. We attempted to identify these products after treatment at different pHs in vitro using HPLC. We also examined whether (A) NC-1300 treated at acidic pHs loses its efficacy on gastric secretion and gastric lesions and (B) whether the degradation products of NC-1300 have pharmacological effects in rats. The acidic degradation products proved to be mainly NC-1300-sulfide and partly o-dimethylaminobenzylalcohol (o-DMABA) and benzimidazole (BI). NC-1300, pretreated at pH 1.0, 1.25 or 1.5 for 30 min and given p.o. at 30 mg/kg, significantly inhibited gastric acid secretion in pylorus ligated rats and prevented development of HCl X ethanol-induced gastric mucosal lesions. The degree of antisecretory and cytoprotective activities by NC-1300 treated at pH 1.5 was almost the same as that obtained by NC-1300 treated at pH 7.0. NC-1300-sulfide or mixtures of degradation products, with or without unchanged NC-1300, also significantly inhibited the gastric acid secretion and lesion formation. We conclude that while NC-1300 degrades at low pHs, the compound treated at such a low pH exerts pharmacological effects presumably by the unchanged form of NC-1300 and/or its degradation products.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1986

Effects of antiarrhythmic drugs on the extraneuronal accumulation of isoprenaline in perfused rat hearts.

The effects of class I, II, III and IV antiarrhythmic drugs (as classified by Vaughan Williams 1974), tetrodotoxin and beta 2-adrenoceptor antagonists on the extraneuronal accumulation of isoprenaline were examined in isolated rat hearts perfused with 3H-isoprenaline (1 mumol/l) and tropolone (100 mumol/l) for 30 min at a constant flow rate (6.5 ml/min) at 40 degrees C. Quinidine (class I), verapamil (IV), diltiazem (IV), dilazep (IV), nifedipine (IV), tetrodotoxin and butoxamine, at a concentration of 10 mumol/l, significantly decreased the extraneuronal accumulation of isoprenaline. The present study demonstrated that quinidine (class I) and all of the calcium channel blockers (class IV) had potent inhibitory effects on the extraneuronal accumulation of isoprenaline. The concentrations of these drugs needed for this decrease were nearly comparable to those needed to suppress isoprenaline-tropolone-induced ventricular fibrillation (Sono et al. 1985a). The antiarrhythmic effects of quinidine and calcium channel blockers in this experimental model may be partly due to a decrease in the extraneuronal accumulation of isoprenaline.

Adrenergic beta-Antagonists↗
PubMed1986

Ampicillin concentrations in human serum, gingiva, mandibular bone, dental follicle, and dental pulp following a single oral administration of bacampicillin.

Ninety-six patients who underwent the extraction of impacted mandibular third molars in a nonfasting state were given a single oral dose of bacampicillin preoperatively. Specimens of serum from venous blood (n = 107), gingiva (n = 57), mandibular bone (n = 68), dental follicle (n = 56), and dental pulp (n = 43) were obtained during the operation and assayed for ampicillin content. The mean peak concentrations in serum, gingiva, mandibular bone, dental follicle, and dental pulp all occurred approximately 90 minutes after administration. The concentration ratios of the tissues to the corresponding serum at the peak time were 0.50, 0.20, 0.34, and 0.61, respectively. Bacampicillin showed good absorption by the intestine, and sufficient concentrations of the resulting metabolite, ampicillin, were found in the oral tissues.

Administration, Oral↗
PubMed1986

Ampicillin concentrations in human serum and periodontal membrane following a single oral administration of bacampicillin.

Ampicillin concentrations in human serum and periodontal membrane after a single oral administration of bacampicillin (500 mg) were assayed by the agar diffusion (paper disc) method. The peak times of serum and periodontal membrane were nearly identical, being approx. 90 min after administration. The peak concentrations of serum and periodontal membrane were 12.81 micrograms/ml and 6.97 micrograms/g, respectively. The concentration ratio of periodontal membrane to serum at the peak time was 0.56.

Adult↗
PubMed1986

Experimental neurogenic bladder in rats and effect of Robaveron, a biological prepared from swine prostate, on it.

An experimental neurogenic bladder was induced in rats by an intraspinal injection of 10% phenol-glycerin solution. The functional and biochemical changes in the bladder were studied in vivo and ex vivo, and the effect of Robaveron, a biological prepared from swine prostate, on these changes were examined. The forced voiding pressure in the control rats which had been caused by the neurogenic bladder was reduced to 1/4-1/5 that of the intact animals. Robaveron recovered a decrease in the pressure, and the effect of 150-250 mg/kg, p.o., corresponded nearly to that of 40 mg/kg, i.m. In the ex vivo study with the strips of isolated neurogenic bladder muscle, the time required to cause 50% of the maximum contraction by transmural electric stimulation prolonged to about four times that of the intact one. Such a prolongation was recovered by Robaveron in a dose-dependent fashion, and the effect of Robaveron given p.o. corresponded to about 1/6 that of the drug given i.m. No change in Ca2+-influx, was found, although Ca2+-efflux was inhibited in the strip of neurogenic bladder muscle. Such an inhibition was significantly relieved in that of animals treated with Robaveron. In the neurogenic bladder rat, the ratio of bladder weight to body weight increased, and the activities of total ChE and AChE in the bladder muscle decreased, on which Robaveron did not show any influence. Phasic and tonic contractions in the strips of intact rat bladder and guinea pig ileum were inhibited by La3+, particularly phasic response in both the strips. Robaveron recovered the inhibition in a dose-dependent fashion. The present study suggests that the urinary dysfunction in neurogenic bladder may be caused not only by nervous disorders but also by changes in the bladder muscle itself. Robaveron was found to be effective for most of such changes. These findings may support the clinical efficacy of Robaveron for improving the attenuated bladder function.

Animals↗