Biomedical subjects

T Inukai

Publications and source records attributed to T Inukai.

At least 37 records · Page 2Linked to original sources

PubMed1991

Effects of felodipine on vascular smooth muscle in comparison with nifedipine.

Felodipine (ethylmethyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl- 3,5-pyridine dicarboxylate, CAS 72509-76-3), a vasoselective calcium antagonist, has a slow onset inhibitory effect on high K(+)-induced contractions in vascular smooth muscle and a longer duration than that of nifedipine. In addition it non-competitively inhibits Ca(++)-induced contraction in the depolarized aorta or femoral artery in the rat. Felodipine's inhibitory effect on caffeine or norepinephrine-induced contraction was observed at a micromolar range. This result suggests that felodipine may inhibity Ca++ release from intracellular Ca++ stores through a mechanism of Ca++ or inositol 1,4,5-triphosphate induced Ca++ release in addition to a blockade of Ca++ influx through the sarcolemma.

Animals↗

PubMed1991

General pharmacology of the novel angiotensin converting enzyme inhibitor benazepril hydrochloride. Effects on cardiovascular, visceral and renal functions and on hemodynamics.

The effects of benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4), a novel angiotensin I converting enzyme inhibitor, on cardiovascular, visceral and renal functions and on hemodynamics, were studied in various experimental animals. Even at a high dose of 100 mg/kg p.o. benazepirl hydrochloride had no influence on the respiration, heart rate and ECG of normotensive anesthetized cats and, except at higher doses, had little effect on the contractile tension of mammalian isolated atrium, ileum, trachea, stomach fundus strips, vas deferens or uterus. Benazepril hydrochloride even at a high dose of 100 mg/kg p.o. had little effect on spontaneous uterine motility, charcoal transportation and gastrointestinal tract motility. In addition, it did not cause gastric irritation, alter the secretion of gastric and biliary juices, and did not affect the tension of the nictitating membrane or the twitch tension of the gastrocnemius muscle in various experimental animals. Benazepril hydrochloride had no effect on the blood glucose and cholesterol levels in alloxan-induced diabetic rats but decreased the triglyceride and total cholesterol levels in normotensive rats at a dose of 30 mg/kg p.o. Benazepril hydrochloride at 3 mg/kg.day s.c. for 10 weeks caused a significant decrease in aortic atherosclerosis without reducing hypercholesterolemia in cholesterol-fed rabbits. Benazepril hydrochloride at a high dose of 100 mg/kg p.o. showed no effect on the urine volume and urinary excretion of electrolytes but decreased PSP excretion in normotensive rats. At a dose of 3 or 10 mg/kg.day p.o. for 4 weeks benazepril hydrochloride inhibited the increase in the excretion of urinary protein in DOCA/salt spontaneously hypertensive rats. It caused hemolysis at concentrations as high as 0.1-1% in rabbits, however, even at a high dose of 100 mg/kg p.o. it did not affect red blood cell fragility in rats, and, except at a high dose of 10(-4) g/ml, showed little effect on the platelet aggregation response induced by collagen or arachidonic acid in rabbits. From these results, benazepril hydrochloride is considered to be a safe and well-tolerated addition to the therapeutic armamentarium of cardiovascular drugs.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1991

Effect of benazepril hydrochloride on cardiac hypertrophy in spontaneously hypertensive rats.

To study the effects of a novel angiotensin I converting enzyme inhibitor (ACEI) on hypertension-induced cardiac hypertrophy, benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4) at the dose of 3 and 10 mg/kg/d p.o. was administered to spontaneously hypertensive rats from 4 to 16 weeks of age. In addition to suppression of developing blood pressure, benazepril hydrochloride reduced both the wet weights of whole heart and left ventricle dose-dependently and significantly. Benazepril hydrochloride had no effect on hydroxyproline concentration and content or protein concentration in the left ventricle, whereas is reduced the total protein content dose-dependently. Serum ACE activity was significantly reduced at 10 mg/kg/d of benazepril hydrochloride, but renin activity, aldosterone and noradrenaline concentration in serum were not changed. From the microscopic findings of the left ventricle, benazepril hydrochloride reduced the myocardial hypertrophy significantly. From these results, benazepril hydrochloride seems to suppress the increase in volume load by acting through the renin-angiotensin-aldosterone system, and dose not seem to cause a significant reflex of catecholamine which often occurs with peripheral vessels dilation. Thus, benazepril hydrochloride may be expected to suppress cardiac hypertrophy in patients with hypertension.

Aldosterone↗

PubMed1991

General pharmacology of the novel angiotensin converting enzyme inhibitor benazepril hydrochloride. Effects on central nervous and sensory systems and other functions.

The effects of benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4), a novel angiotension I converting enzyme inhibitor, on the central nervous systems, were studied in experimental animals. Benazepril hydrochloride (3 or 10 mg/kg/d, p.o. for 14 days) dose-dependently inhibited the increase in the blood pressure caused by continuous norepinephrine (NE) infusion in spontaneously hypertensive rats (SHR) and suppressed in seizures induced by a monoamine oxidase inhibitor, tranylcypromine in NE infused SHR. Benazepril hydrochloride transiently increased spontaneous motor activity in mice, tended to inhibit acetic acid-induced writhing in mice and decreased fast wave sleep and slow wave deep sleep on EEG in cats at a high dose of 100 mg/kg p.o. However, benazepril hydrochloride at the same dose showed no effect on other central nervous and sensory systems in experimental animals.

Acetates↗

PubMed1991

Antihypertensive action of the novel angiotensin converting enzyme inhibitor benazepril hydrochloride in hypertensive rat models.

Single or repeated administration of benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4), a novel angiotensin I converting enzyme inhibitor, (0.3-10 mg/kg p.o.) caused significant antihypertensive effects in renal and spontaneously hypertensive rats (SHR). The antihypertensive effects of benazepril hydrochloride was about 3 times as potent as that of captopril in these models. Single administration (0.3-3 mg/kg p.o.) of benazepril hydrochloride and enalapril maleate showed an equipotent antihypertensive effect in SHR. Benazepril hydrochloride (3-30 mg/kg p.o.), however, showed no clear effect on the blood pressure and heart rate in normotensive or DOCA/salt hypertensive rats.

Administration, Oral↗

PubMed1991

[Multiple sclerosis with higher cerebral dysfunction: a case report].

Higher cerebral dysfunctions such as aphasia, apraxia and agnosia have seldom been reported in multiple sclerosis (MS). 12 year-old right-handed boy felt unsteadiness of the body and headache for several days. Two months later, he had the same episode and complained of visual disturbance, and weakness and sensory disturbance on the face and the extremities. Additionally, he showed amnestic aphasia, acalculia, ideomotor apraxia, finger agnosia and right-left disorientation. Cerebrospinal fluid examinations revealed increases IgG, myelin basic protein and neuron specific enolase (11%, 25 ng/ml and 28.8 ng/ml, respectively). X-ray CT scan and MRI-CT examinations revealed sclerotic lesions on the left parietal white matter and the right mid-brain. The diagnosis was made as MS. He was treated with m-PSL (methyl-prednisolone) pulse therapy for three weeks and consecutively treated with PSL for four weeks. He recovered gradually, but visual disturbance and facial palsy remained. After seven months MRI-CT showed a high signal intensity on the left parietal white matter in spite of the disappearance of the lesion on X-ray CT scan. We suggest that these higher cerebral dysfunctions may result from the lesion of the left parietal white matter which produces a disconnection between each cortical area.

Agnosia↗

PubMed1990

Inhibitory effects of cadralazine and its metabolite, ISF-2405, on contractions and the level of cytosolic Ca2+ in vascular smooth muscle.

The inhibitory effects of a hypotensive agent, cadralazine and its metabolite, ISF-2405, on the level of cytosolic Ca2+ ([Ca2+]cyt) and on contractions were examined in isolated vascular smooth muscle. Cadralazine slightly inhibited the transient norepinephrine-induced contraction in rabbit aorta and canine femoral, renal and mesenteric arteries and saphenous vein, and prostaglandin F2 alpha-induced contractions in canine basilar and coronary arteries. In contrast, ISF-2405 inhibited the contractions induced by prostaglandin F2 alpha in canine basilar and coronary arteries and those induced by norepinephrine in canine renal and femoral arteries and rabbit aorta. In aorta, ISF-2405 inhibited the increase in [Ca2+]cyt and muscle tension caused by norepinephrine. A Ca2+ channel blocker, verapamil, inhibited the norepinephrine-stimulated increase in [Ca2+]cyt more potently than it inhibited the increase in muscle tension, and ISF-2405 inhibited the verapamil-resistant part of the contraction. In Ca2(+)-free solution, norepinephrine induced transient increases in [Ca2+]cyt and muscle tension. ISF-2405 inhibited these changes. However, ISF-2405 did not inhibit the transient contraction induced by caffeine in the aorta. These results suggest that cadralazine is metabolized to ISF-2405 and inhibits vascular smooth muscle contraction by inhibiting receptor-mediated Ca2+ influx, Ca2+ release and Ca2+ sensitization of contractile elements.

Animals↗

PubMed1990

Effects of peripheral administration of recombinant human interleukin-1 beta on feeding behavior of the rat.

This study was undertaken to investigate the changes in feeding behavior, including ambulatory activity, induced by a single injection of Interleukin-1 beta (IL-1) (2 micrograms/rat) at 18:00, just before the dark phase. For this purpose, we used the Gunma University-type automatic apparatus for continuous and direct measurement of ambulation and drinking. A significant decrease in food intake was observed for 12 hours after treatment with IL-1. Peripheral administration of IL-1 also produced a marked decrease in ambulatory activity within 3 hours which continued for 6 hours. In addition, IL-1 produced a marked decrease in drinking behavior during the first 6 hours. We reported here the changes in consummatory and ambulatory behavior of rats after acute administration of IL-1. The sickness which IL-1 produced may, at least in part, contribute to these phenomena, although precise mechanisms are still unknown.

Animals↗

PubMed1990

Abnormal feeding behavior and insulin replacement in STZ-induced diabetic rats.

The present studies were undertaken to investigate whether or not decreased ambulatory activity, including abnormal feeding behavior in diabetic rats, will be simultaneously normalized by insulin administration. To do this, we used the Gunma University-type automatic apparatus for continuous and direct measurement of ambulation and drinking. In this study, 3 U NPH insulin were administered at 1800, just before the dark phase, and 2 U were administered at 0600, just before the light phase. With these insulin doses, we found that 5 weeks were needed to normalize ambulatory activity, 4 weeks were necessary for food intake, 6 weeks for drinking and 2 weeks for body weight. Since ambulatory activity is reported to be related to changes in dopamine turnover, further studies are in progress to determine whether or not dopamine turnover is normalized when there is no difference in ambulatory activity due to insulin replacement.

Animals↗

PubMed1990

Influence of thyrotropin-releasing hormone on autonomic nervous system determined by the variations in R-R interval on electrocardiogram.

The change of variation in R-R interval on electrocardiograms (CVq) was examined in healthy subjects and patients with Graves' disease before and after an intravenous administration of 500 micrograms of Thyrotropin-releasing hormone (TRH). CVq was significantly elevated after TRH stimulation and returned to the control level within 120 min. This phenomenon was found not only in healthy subjects but also in patients with untreated Graves' disease whose levels of CVq were lower than in normal subjects. Pretreatment with atropine inhibited the response of CVq to TRH. These data suggest that TRH has a stimulatory effect on the parasympathetic nervous system, determined by the variations in R-R interval.

Adult↗

PubMed1990

Parasympathetic nervous system in patients with Graves' disease determined by R-R interval variations on electrocardiogram.

Little is known about an interrelationship between thyroid dysfunction and parasympathetic nervous system. R-R interval variations on electrocardiogram (ECG) have been considered to be reliable indicator reflecting abnormalities of parasympathetic nervous system. We have attempted to apply this technique in patients with hyperthyroidism. Studies were conducted in 60 healthy subjects and 57 patients with Graves' disease. R-R interval variations were expressed as coefficient of variation on 100 heart rates at the time of resting (CVq) and deep respiration (CVd). A negative correlation between R-R interval variations (CVq, CVd) and ages was observed in healthy subjects. CVq was significantly lower in untreated Graves' disease than in antithyroid drug-treated Graves' disease and control subjects. A similar result also was obtained in CVd. Decreased CVq in untreated patients with Graves' disease was restored by administration of beta blockades, propranolol and metoprolol, but not by administration of alpha blockade, bunazosine. The present investigation suggests that there are hypofunctions in parasympathetic nervous system associated with beta (especially beta one) effects in patients with hyperthyroidism due to Graves' disease.

Adrenergic alpha-Antagonists↗

PubMed1990

Parasympathetic nervous system activity in hypothyroidism determined by R-R interval variations on electrocardiogram.

Little is known about the relationship between hypothyroidism and the parasympathetic nervous system. R-R interval variations revealed by electrocardiogram (ECG) are known to be a useful clinical indicator of abnormalities of parasympathetic nervous system activity. Studies were conducted in hypothyroid patients, and significant reductions in R-R interval variations were observed in patients with primary severe hypothyroidism due to Hashimoto's thyroiditis, and in patients with Graves' disease who became severely hypothyroid during antithyroid drug therapy. R-R interval variations were restored to normal levels in both groups of patients after treatment. The present investigation suggests that in marked hypothyroidism there are hypofunctional abnormalities in the parasympathetic nervous system in association with a reduction in the levels of serum T4 and T3.

Adult↗

PubMed1990

A possible direct precursor of thyrotropin-releasing hormone, pGlu-His-Pro-Gly, stimulates prolactin secretion in anorexia nervosa.

TRH is produced from its possible direct precursor, pGlu-His-Pro-Gly (TRH-Gly), by alpha-amidating enzyme. The quantitative response of TRH-Gly-stimulated PRL, TSH, and GH was evaluated in nine patients with anorexia nervosa, six age-matched normal women, eight patients with uremia, five patients with acromegaly, and two patients with prolactinoma. Intravenous injection (500 micrograms) of TRH-Gly caused a 2.6-fold increase in PRL secretion in patients with anorexia nervosa (basal level, 10.0 +/- 1.4 vs. 25.9 +/- 2.5 micrograms/L 15 min after injection; P less than 0.01). In contrast, no significant change was observed in TRH-Gly-stimulated PRL secretion in normal women (basal level, 13.5 +/- 2.3 vs. 15.3 +/- 2.5 micrograms/L 15 min after injection; P greater than 0.05). TRH-Gly did not alter PRL levels in patients with uremia, acromegaly, or prolactinoma. Secretion of TSH, but not GH, was slightly increased by TRH-Gly injection in patients with anorexia nervosa (basal level, 1.41 +/- 0.13 vs. 2.86 +/- 0.22 min/L 30 min after injection; P less than 0.01), whereas no significant secretory response was observed in normal women. These data provide evidence that PRL secretion in anorectic patients is quantitatively different from that in normal persons.

Adult↗

PubMed1990

Studies on the T3 suppression test with reference to the thyroidal 123I uptake in Graves' disease: comparison of 24-hour and 3-hour uptake.

Eighty-three patients with Graves' disease had been treated with methylmercaptoimidazole (MMI). They were prescribed a maintenance dose of antithyroid drug (MMI, 5 mg/day) at the time of a T3 suppression test. The 3-hour and 24-hour thyroidal 123I uptake after T3 administration (75 micrograms/day, 2 weeks) were measured (post T3 uptake). In 38 patients whose post T3 uptake was below 35% in post T3 24-hour uptake, treatment was stopped. The T3 suppression test was then repeated 1 and 3 months later. During a one-year follow up, 26 remained well, while 12 relapsed within 6 to 12 months. We have observed a good correlation between 3-hour uptake and 24-hour uptake of 123I after T3 administration (r = 0.847, p less than 0.001). In 38 patients who showed positive T3 suppression, most patients with MMI withdrawal produced a marked overshoot of post T3 3-hour and 24-hour uptake at one month. Retrospective analysis indicated that there was no significant difference in circulating thyroid hormone levels between remission and relapse groups. The present study provides evidence that 3-hour uptake values are able to be substituted for 24-hour uptake values during a T3 suppression test. In addition, overshoot of thyroidal uptake after antithyroid drug withdrawal was observed in 3-hour values, similar to 24-hour values.

Female↗

PubMed1990

Changes in thyroid volume during antithyroid drug therapy for Graves' disease and its relationship to TSH receptor antibodies, TSH and thyroglobulin.

Changes in thyroid volume during antithyroid drug therapy for Graves' disease compared with circulating thyroid parameters were evaluated. One hundred and forty-four patients with Graves' disease were treated with methimazole. Thyroid volume was measured by ultrasonography (thyroid volume = pi abc/6, where a is length, b width, and c depth). Serum TSH, TSH-binding inhibitory immunoglobulins, thyroid-stimulating antibodies, thyroglobulin, antimicrosomal antibodies, and antithyroglobulin antibodies were also measured. In the whole group of patients, thyroid volume correlated significantly with thyroglobulin (p less than 0.01) and TSH-binding inhibitory immunoglobulins (p less than 0.01), but not with TSH, antimicrosomal antibodies, and antithyroglobulin antibodies. Furthermore, a positive correlation was found between thyroglobulin and TSH-binding inhibitory immunoglobulins (p less than 0.01). In 11 patients the mean thyroid volume decreased significantly after one year of therapy (p less than 0.01), associated with decreasing levels of serum TSH-binding inhibitory immunoglobulins. Ten patients experienced transient hypothyroidism with an overdose of methimazole, and the mean thyroid volume increased significantly (p less than 0.01) with increasing serum TSH levels. In conclusion, it is suggested that TSH receptor antibodies may have a thyroid growth-stimulating effect. In addition, circulating thyroglobulin levels reflect thyroid volume in Graves' disease.

Adolescent↗

PubMed1990

Antihypertensive mechanism of action of the novel angiotensin converting enzyme inhibitor benazepril. Effect on isolated vascular preparations.

Benazepril (CGS 14824A HCl) is a new prodrug type angiotensin converting enzyme (ACE) inhibitor. The active form is considered to be benazeprilat, a diacid hydrolyzed compound. Benazepril and benazeprilat inhibited the contraction induced by exposure with angiotensin I, not angiotensin II, in the isolated rabbit aorta. The ACE inhibiting activity of benazeprilat was 1000 times more potent than that of benazepril in this experiment. Benazepril as well as benazeprilat and captopril exerted little influence on norepinephrine, serotonin and high K(+)-induced contraction or bradykinin-induced relaxation in isolated blood vessel preparations, thus angiotensin II synthesis inhibition seemed to be the main cause for its vasodilation. Benazepril, unlike benazeprilat or captopril showed considerable influence on prostaglandin (PG)-induced responses at higher concentrations. The vasocontraction induced by PGF2 alpha was competitively antagonized at 10(-5)-10(-4) mol/l, while vascular responses induced by PGE1, PGE2 or PGI2 was inhibited at 3 x 10(-4) mol/l of benazepril. Although these influences on PGs might not contribute much to its vasodilatory mechanism, the action seemed interesting in relation to cough induction, a known side effect of ACE inhibitors in the market. Benazepril has two asymmetric carbon atoms, thus four optical isomers are possible, SS (benazepril), SR (CGP 14'829A), RS (CGP 42'454A), RR (CGP 42'456A). The SS configuration was the most potent for antagonizing angiotensin I-induced vasocontraction, which seemed to be the best fitted for the ACE molecule.

Alprostadil↗

PubMed1990

Improvement of nephrotic syndrome in a massively obese patient after weight loss and treatment with an anti-allergic drug.

An obese patient with nephrotic syndrome was admitted to the hospital because of increasing edema in the legs. With 25 kg weight loss, proteinuria decreased from 15 g to 5 g/day. Renal biopsy revealed mesangial glomerulopathy. The serum IgE level was highly elevated, and the radioallergosorbent test (RAST) was strongly positive for many kinds of allergens. No significant change in proteinuria, compared with the highly right atrial pressure period, was observed after normalization in the right atrial pressure. In spite of a decrease in body weight (27 kg) (113 to 86 kg) in 140 days, no significant change in proteinuria was observed. After additional therapy with an anti-allergic drug, proteinuria was completely abolished. These results suggest that a combination of weight loss and treatment with an anti-allergic drug is very important therapy for massive obesity with nephrotic syndrome. Since RAST was strongly positive for many kinds of allergens, the pathophysiology in this nephrotic syndrome may be, at least partially, related to the immunologic abnormalities.

Adult↗

PubMed1989

Efficacy of the glyceryl trinitrate transdermal therapeutic system in a dog model of myocardial ischaemia.

The efficacy of a controlled-release topical dosage form of glyceryl trinitrate (Nitroglycerin Transdermal Therapeutic System, Nitroderm TTS, NTG-TTS) was studied in the experimental model of myocardial ischaemia in beagles. At blood concentrations similar to those attained in clinical practice, NTG-TTS suppressed the ST elevation in the electrocardiogram (ECG) reflecting ischaemic change due to coronary ligation and antagonized the decrease in coronary blood flow resulting from intracoronary injection of angiotensin II (Ang II). Like those of the well-known, conventionally administered nitrates, these anti-ischaemic effects of NTG-TTS were presumably attributable to the reduction of pre-load, together with direct vasodilatation of the coronary and peripheral arteries.

Administration, Cutaneous↗