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Biomedical subjects

T Inami

Publications and source records attributed to T Inami.

13 recordsLinked to original sources

Synergistic actions of pentobarbital and dihydropyridine Ca2+ antagonists on guinea pig isolated thoracic aorta.

In order to elucidate the mechanism(s) behind the interactions between barbiturates and Ca2+ antagonists, the effects of pentobarbital combined with three structurally diverse types of Ca2+ antagonist on CaCl2-induced contractile responses of the guinea pig thoracic aorta in Ca(2+)-free and 40 mM K+ medium and the effects of pentobarbital on Ca2+ antagonist binding to guinea pig aortic membranes were investigated. The dihydropyridine derivatives isradipine (10(-10)-10(-8) M) and nifedipine (10(-10)-10(-8) M) inhibited CaCl2-induced contractions concentration-dependently. Treatment with both pentobarbital (10(-4) M) and dihydropyridine Ca2+ antagonists (10(-9) M) shifted the CaCl2 concentration-response curves to the right significantly compared with those after treatment with the Ca2+ antagonists and pentobarbital alone. However, no synergistic effects of pentobarbital (10(-4) M) with other types of Ca2+ antagonist (verapamil (10(-7) M) and diltiazem (10(-6) M)) were observed. The binding of [3H]isradipine (2 x 10(-9) M) to guinea pig aortic membranes was increased significantly by simultaneous pentobarbital treatment, but no such effect was observed with [3H]verapamil (10(-8) M) or [3H]diltiazem (2 x 10(-8) M). These findings suggest that the synergistic contractile effects of pentobarbital and dihydropyridines were, in part, due to enhancement of dihydropyridine binding to guinea pig aortic membranes (L-type Ca2+ channels) by pentobarbital and that the interactions between pentobarbital and Ca2+ antagonists may be structurally specific.

Animals

Effect of glimepiride (HOE 490) on insulin receptors of skeletal muscles from genetically diabetic KK-Ay mouse.

A new sulfonylurea, glimepiride (HOE 490), has been developed for the glycemic control in non-insulin-dependent diabetes mellitus. We examined the effect of glimepiride on glucose and insulin levels in KK-Ay mice, an animal model of non-insulin-dependent diabetes mellitus, which is characterized by hyperglycemia and hyperinsulinemia. Administration of glimepiride (0.5 mg/kg/day) for 8 weeks to KK-Ay mice resulted in decrease in glucose (297 +/- 36 to 250 +/- 51 mg/dl) and insulin (76 +/- 14 to 41 +/- 14 microU/ml) levels. To clarify the mechanism of the agent, we examined the effect of this new drug on insulin receptors in the skeletal muscles. There was no difference in insulin binding to the receptors from both glimepiride-treated and -untreated KK-Ay mice muscles. The insulin-stimulated autophosphorylation of insulin receptors from KK-Ay mice was decreased compared to that from normal mice (5 +/- 1 vs. 39 +/- 13% over basal). Glimepiride did not ameliorate impaired insulin-stimulated insulin receptor autophosphorylation. To determine the effect of glimepiride on post-insulin receptor signaling pathway, we measured 2-[3H]glycerol incorporation into diacylglycerol in the cultured rat fibroblast cell line overexpressing human insulin receptors. Glimepiride (100 microM) as well as insulin (10 nM) significantly stimulated diacylglycerol production. These results suggest that glimepiride has a potent extrapancreatic effect on glucose metabolism and may directly stimulate glucose transport activity through phospholipid signaling pathway, but not through insulin receptor kinase signaling pathway.

Animals

[A case of acquired immunodeficiency syndrome associated with cryptococcemia and cryptococcal meningitis].

A case of acquired immunodeficiency syndrome (AIDS) developed cryptococcosis which was successfully treated with amphotericin B (AMPH) and fluconazole (FLCZ) is reported. A 52-year-old man was admitted because of pyrexia and oral candidiasis. He had a history of multiple sexual exposures to persons at risk for AIDS in Thailand. On admission, serologic tests for human immunodeficiency virus (HIV)-1 were positive on both EIA and Western blot analysis for anti-HIV-1 antibody. Furthermore, test for cryptococcal antigen and fungal cultures from blood and cerebrospinal fluid revealed that he was suffering from cryptococcemia and cryptococcal meningitis. In spite of identification of Cryptococcus neoformans in his blood and cerebrospinal fluid, the finding of cerebrospinal fluid had a minimal inflammatory response with mild elevation of protein. He was initially treated with intravenous AMPH, 10 to 30 mg a day, for 7 weeks, and then was given oral FLCZ, 400 mg a day, for the suppressive therapy. His fever subsided three weeks after the start of AMPH therapy. He was eventually discharged 9 weeks after the start of therapy without any symptoms, and continued to receive oral FLCZ as an out-patient. Thus, attention should be paid to diagnosis and treatment for cryptococcal meningitis in AIDS patients.

AIDS-Related Opportunistic Infections

Effects of ET antagonists (PD143296 and PD145065) on contractions in guinea pig hilar bronchus induced by endothelin-1 and its related peptide.

ETs-induced contractions were resistant to ET(A)-selective antagonists and believed to be mediated by activation of ETB receptors in guinea pig bronchus. In the present study, the effects of the ET antagonists, PD143296 (Ac-D-Phe-L-Leu-L-Phe-L-Ile-L-Ile-L-Trp.2Na) and PD145065 (Ac-[(R)-2-10, 11-dihydro-5H-dibenzo[a, d]cyclohepten-5-yl]Gly)-L-Leu-L-Asp-L-Ile-L-Ile- L-Trp.2Na), on contractions induced by ET-1, ET-3, sarafotoxin S6c (STXc), and IRL1620 in the isolated hilar bronchus of the guinea pig were investigated. An ETA/B nonselective antagonist, PD145065 antagonized contractions induced by ET-1, ET-3, STXc, and IRL1620. Its antagonistic activity against ET-1, with pKB of 5.77 +/- 0.02 (n = 16, 3-10 microM), was significantly lower than that against ET-3, with pKB of 6.18 +/- 0.02 (n = 12, 3-10 microM), STXc, with pKB of 5.97 +/- 0.01 (n = 14, 3-10 microM), and IRL1620, with pKB of 6.80 +/- 0.04 (n = 14, 0.3-1 microM). Conversely, although a putative ETB-selective antagonist, PD143296 (10 microM) slightly but significantly antagonized the concentration-response curve of IRL1620 (pKB = 5.28 +/- 0.14, n = 6), it had no effect on ET-1-,ET-3-, or STXc-induced contractions. These results suggest that ETs possibly activate ETB2 or an atypical ETB receptor subtype in guinea pig hilar bronchus.

Animals

Urinary salt excretion and stomach cancer mortality among four Japanese populations.

A relationship between salt intake and the occurrence of stomach cancer has been suggested by both epidemiologic and experimental data. To test this hypothesis, urinary excretion of salt in 24 hours and dietary intake of salt were measured in four male populations with different levels of stomach cancer mortality. Age-adjusted mortality rate of stomach cancer showed a high correlation (r2 = 0.995) with the average amount of salt excretion in 24-hour urine. This strong correlation, however, was not shown (r2 = 0.265) with dietary salt intake calculated from the standard food-composition table. The results confirmed the important role of salt in the development of stomach cancer in Japan, and raised the problem of evaluating the level of salt intake by using the uniform composition table.

Adult

[The use of the maxillary protractor in the treatment of cleft lip and palate: a report of two cases].

The patients who underwent reconstruction of cleft lip and palate had clinically abnormal characteristics such as cicatricial contracture in the cleft area, narrow arches, missing teeth, and fistula. Most of those patients showed severe class III malocclusion with underdevelopment of the maxillary complex. In such patients, the treatment objectives in orthodontics were mainly anterior and lateral expansions of the maxillary arches, and inhibition of mandibular growth. In recent years, the maxillary protractor has been used positively in the treatment of the underdeveloped maxillary complex. In this study, we report on two patients with cleft lip and palate, and underdevelopment of the maxillary complex. Maxillary protractors were used beneficially at the period of the dento-craniofacial growth spurt. In these two cases, improvement of disharmony was obtained in the antero-posterior relationship between the maxilla and the mandible. The effects of the treatment were forward movement of the maxilla and growth inhibition of the mandible. Accordingly, the use of the maxillary protractor for cleft lip and palate patients with underdeveloped maxilla at the period of the dento-craniofacial growth spurt was shown to be important.

Cleft Lip

Effects of pentobarbital and cyproheptadine on brain ischemia induced by bilateral occlusions of carotid arteries and vertebral arteries of second cervical vertebra in rats.

The bilateral hemispheric ischemia in rats was induced by the occlusion of bilateral common carotid arteries after permanent electrocauterization of bilateral vertebral arteries at the level of the second cervical vertebra. In ischemic rats, (a) electroencephalograms became flat immediately after occlusion of carotid arteries, and (b) mortalities reached maximum levels at day 3 after recirculation. These results suggested that a constant level of cerebral ischemia was produced in this rat model. Pentobarbital markedly inhibited the mortality in these ischemic rats, whereas cyproheptadine did not.

Animals