Biomedical subjects

T Inukai

Publications and source records attributed to T Inukai.

At least 19 recordsLinked to original sources

PubMed1992

Cell swelling induced by medium hyposmolarity or isosmolar urea stimulates gonadotropin-releasing hormone secretion from perifused rat median eminence.

Medium hyposmolarity between 10 and 50% and isotonic urea between 22.5 and 90 mM induced a dose-dependent burst of gonadotropin-releasing hormone (GnRH) secretion from perifused median eminence tissue which was maximal at 2-3 min and returned to near baseline by 5 min in spite of continued exposure to the stimulus. If Ca(2+)-free medium was used, osmotic stimulation of secretion was increased or unchanged, but secretion induced by 30 mM K+ was markedly reduced. Our data indicate that cell swelling induced by medium hyposmolarity or permeant molecules stimulates GnRH secretion from median eminence cells or cell processes as it does secretion from normal endocrine cells containing hormone stored in intracellular vesicles. In both, Ca2+ influx is not required or has a negative modulating influence on cell swelling-induced secretion.

Animals↗

PubMed1992

Both cyclooxygenase and lipoxygenase inhibitor partially restore the anorexia by interleukin-1 beta.

Since the peripheral prostaglandin synthetizing system may at least partly involved in the anorexia that follows central interleukin-1 beta (IL-1) administration, this study was undertaken to investigate the effect of ibuprofen (ip), selective cyclooxygenase blocker and AA 861, selective lipoxygenase inhibitor, on changes of food and water intake by a single injection of IL-1 (2 micrograms/rat, ip). We demonstrated that food and water intake were suppressed by peripheral administration of IL-1. Throughout the entire observation periods, suppressed food intake was partially restored to control levels by ibuprofen, while water intake completely restored. In addition, no significant differences about water/food intake were observed in the IL-1 + ibuprofen-treated groups, respectively. In the next experiment, IL-1 induced anorexia was also partially restored to the control level following pretreatment with AA 861. These results may suggest that other mechanism including lipoxygenase blocker besides prostaglandin production may be involved in IL-1 induced anorexia.

Analysis of Variance↗

PubMed1992

The suppression of olfactory bulbectomy-induced muricide by antidepressants and antihistamines via histamine H1 receptor blocking.

The effects of antidepressants [(+)-oxaprotiline, (-)-oxaprotiline, imipramine, maprotiline, and trazodone] and antihistamines (mepyramine, dimethindene, ketotifen, methapyrilene, and antazoline) on muricidal behaviour in olfactory bulbectomized rats were investigated. All drugs except for dimethindene, which only minimally passes across the blood-brain barrier, suppressed muricide. The drugs which have high affinity for histamine H1 receptor showed potent suppressive effect on muricide. It is suggested that the central histaminergic system is involved via H1 receptors in the expression of muricide in olfactory bulbectomized rats.

Aggression↗

PubMed1992

Alpha-adrenergic inhibition of thyrotropin-releasing hormone-induced prolactin secretion in GH4C1 cells is associated with a depressed rise in intracellular Ca2+.

alpha-Adrenergic receptors are present on the plasma membrane of normal anterior pituitary cells and alpha-adrenergic agonists may play a role in the secretion of corticotropin (ACTH) and thyrotropin (TSH). However, alpha-adrenergic involvement in prolactin (PRL) secretion is uncertain. We have therefore examined this question in the PRL-secreting clonal rat pituitary tumor-derived GH4C1 cells. Norepinephrine (NE), an alpha-adrenergic agonist, had no effect on basal PRL secretion but abolished thyrotropin-releasing hormone (TRH)-induced PRL secretion in a dose-dependent manner (EC50 100 nM). NE also significantly suppressed the TRH-stimulated rise in [Ca2+]i. Phentolamine (PA), a non-selective alpha-adrenergic antagonist, reversed the inhibitory effect of NE on both the TRH-stimulated PRL secretion and [Ca2+]i rise. NE did not inhibit the rise in PRL secretion or [Ca2+]i induced by depolarizing 30 mM K+, 30% hyposmolarity or BAY K-8644, a specific L-type Ca2+ channel agonist. The inhibitory effect of NE on TRH-induced PRL and [Ca2+]i changes was also present when Ca2+ influx was prevented by removing medium Ca2+ or by blocking L-type Ca2+ channels with 2 microM nifedipine. The TRH-stimulated first-phase rise in [Ca2+]i in GH4C1 cells is believed to result primarily from release of sequestered Ca2+ from an intracellular pool through the activation of inositol 1,4,5-trisphosphate (IP3) and this [Ca2+]i spike stimulates PRL secretion. Our data thus suggest that GH4C1 cells have alpha-adrenergic receptors and that alpha-adrenergic agonists either suppress IP3 generation or block IP3 release of sequestered intracellular Ca2+.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1992

[Antihypertensive effect of felodipine, a new calcium antagonist].

The antihypertensive effect of felodipine was examined in various hypertensive animal models. In spontaneously hypertensive rats, felodipine administered singly at 0.1-1.0 mg/kg (p.o.) had a dose-dependent antihypertensive effect. Nifedipine was effective at 1 mg/kg. In the repeated oral administration experiment, both the maximum decrease in blood pressure and duration of the effect increased gradually and reached steady levels at 3 weeks of administration, which were maintained thereafter. Similar results were noted with nifedipine, but felodipine was longer-acting (4-6 hr) in the steady state than nifedipine (1-2 hr). No development of tolerance was observed during the administration period. In DOCA-salt and renal hypertensive (2K1C) rats, felodipine at 0.1-0.5 mg/kg (p.o.) was superior to nifedipine in the maximum decrease in blood pressure and duration of the effect. Felodipine up to 1 mg/kg (p.o.) caused no significant heart rate increase in any rat model. In renal hypertensive (2K2C) dogs given felodipine at 0.2-0.5 mg/kg (p.o.), the effect lasted for 2 hr after injection. This felodipine effect was stronger and longer lasting than the nifedipine one. At 0.5 mg/kg of felodipine, the heart rate was transiently increased. The present results show that felodipine has a stronger and long-lasting antihypertensive effect than nifedipine in the hypertension models.

Administration, Oral↗

PubMed1992

Repeated treatment with levoprotiline, a novel antidepressant, up-regulates histamine H1 receptors and phosphoinositide hydrolysis response in vivo.

The effects of repeated administration of levoprotiline, a novel type of tetracyclic antidepressant on histamine H1, muscarinic acetylcholine and alpha 1-adrenergic receptors and the response of phosphoinositide hydrolysis (PI) stimulated by histamine in the cortex of the rat brain were investigated. Histamine H1 receptors were up-regulated to 120% and PI response stimulated by histamine was enhanced to 160%-200% after repeated treatment with levoprotiline (20 mg/kg, i.p., once a day for 28 days) when compared to that of the saline-treated group. No significant alterations of muscarinic acetylcholine and alpha 1-adrenergic receptors were observed. This demonstrates that the repeated treatment with levoprotiline has prominent action on the regulation of histamine H1 receptors and PI response coupling to histamine H1 receptors in vivo.

Animals↗

PubMed1992

Effect of pamidronate in a rat hypercalcemia model induced by cholecalciferol.

Pamidronate (disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate, CGP 23339A, CAS 57248-88-1) has been show to provide a potent antihypercalcemic effect through the inhibition of calcium release from the bone. The time course study on the antihypercalcemic effect of pamidronate was performed using a rat hypercalcemia model induced by orally administered cholecalciferol. The onset of the antihypercalcemic effect was observed within 48 h after a single i.v. injection of pamidronate at 1 mg/kg and this effect was sustained for 19 days. The time course of the antihypercalcemic effect of pamidronate in combination with calcitonin was also examined in the same model. The onset of the antihypercalcemic effect was observed within 4 h after combination therapy with a single i.v. injection of pamidronate at 1 mg/kg and successive i.m. injections of calcitonin at 3.2 IU/kg and the effect was of sufficient duration. These results suggest that pamidronate has a pronounced effect in controlling hypercalcemia and provides a long-lasting effect by a single i.v. administration. Moreover, the use of pamidronate in combination with calcitonin may be useful when a quicker onset of action is required clinically.

Animals↗

PubMed1992

[Clinical and cytological features of CD7 positive biphenotypic leukemias].

Clinical and cytological features of CD7 positive acute leukemias with biphenotypic characteristics in childhood were documented. From 87 patients with CD7+ acute leukemias, nine patients were selected on the basis of the biphenotypic expression of T-lymphoid and myelomonocytic antigens. The blasts of these patients expressed cell surface CD7, cytoplasmic CD3 and cytoplasmic CD13. In addition to these antigens, surface CD13 was also expressed after short term culture without any mitogens or stimulators. The double PAP method for detecting cytoplasmic antigens (CD3, CD13, beta F1, delta TCS1) was employed in this study. The average age of these patients was higher (10.2 y/o) than patients with common ALL. Mediastinal masses were observed in 4 of 9 patients. They were treated according to the diagnoses based on conventional hematological methods and surface antigen expression. In all 9 patients, complete remission was achieved, however, early relapse was noticed in 7. This study suggests that the leukemia cells of these patients may be derived at an early stage during the differentiation of multipotential hematopoietic stem cells. New therapeutic approaches are necessary to improve the outcome of such T/M biphenotypic leukemias.

Acute Disease↗

PubMed1992

Pharmacological profile of the new antidepressant levoprotiline.

The pharmacological properties of a new antidepressant, levoprotiline ((-)-R-a-[(methylamino)methyl]-9,10-ethanoanthracene-9(10H)- ethanol hydrochloride, CGP 12103 A, CAS 76496-69-0) were investigated. 1. Central nervous system: Levoprotiline did not have any marked effects on the general behaviour of mice and rats at low doses, however it slightly suppressed the righting reflex and spontaneous motor activity of mice at higher doses. In rats, chewing behaviour and salivation were observed at higher doses. Levoprotiline had no effects on the traction test (mice) and inclined screen test (rats). Levoprotiline induced a slight drowsy EEG pattern, the effect being similar to that of typical antidepressants such as maprotiline or imipramine but the degree of potency of levoprotiline was less than that of the latter two drugs. Levoprotiline and maprotiline did not inhibit the arousal response induced by physostigmine, while imipramine clearly suppressed the response. 2. Respiratory and cardiovascular system: Heart rate decrease and QT prolongation were observed in anesthetized dogs. In an in vitro study, levoprotiline caused only slight stimulation of noradrenaline transmission in the isolated guinea pig atrium. 3. Smooth muscle: The effects of levoprotiline on the contractile response to histamine, acetylcholine and serotonin in the isolated guinea pig ileum were compared with those of maprotiline or imipramine. While levoprotiline potently inhibited the contractile response to histamine, its inhibition of acetylcholine-induced contraction was the weakest of the three compounds studied. No remarkable effect was observed in serotonin induced contractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Possible contributory role of the central histaminergic system in the forced swimming model.

Forced swimming is considered to bring about a depressive or despair state in experimental animals, usually manifested as immobility. Levoprotiline (CAS 76496-68-9), a new antidepressant, clearly reduced the duration of immobility in the forced swimming model in mice. As levoprotiline does not inhibit noradrenaline or serotonin reuptake, this effect did not seem to have been brought about through central monoaminergic systems. Histamine and tele-methylhistamine levels, the main metabolite of histamine in the cerebral cortex, were found to be significantly increased in the forced swimming model. Since the only significant known effect of levoprotiline on the neurotransmitter system is its histamine H1 receptor antagonism, a possible contribution of the central histaminergic system to the forced swimming model is proposed. The action of mepyramine, a histamine H1 receptor antagonist in reducing the duration of immobility seemed to support this proposition. It should be noted that antihistaminergic properties are shared by many antidepressant drugs.

Animals↗

PubMed1991

Purification and characterization of a novel glucooligosaccharide oxidase from Acremonium strictum T1.

A novel glucooligosaccharide oxidase was purified 495-fold from wheat bran culture of a soil-isolated Acremonium strictum strain T1 with an overall yield of 21%. This enzyme was composed of a single polypeptide chain with a molecular mass of 61 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and size-exclusion high-performance liquid chromatography. Its isoelectric point was pH 4.3-4.5. This enzyme contained 1 mol of FAD per mol of enzyme and showed absorption maxima at 274, 379 and 444 nm. This enzyme was stable in the pH range of 5.0 to 11.0 with an optimal reaction pH of 10.0. The optimal reaction temperature was 50 degrees C. It was stable up to 50 degrees C for 1 h at pH 7.8. This enzyme oxidized those oligosaccharides with glucose residue on the reducing end and each sugar residue jointed by alpha or beta-1,4 glucosidic bond. The relative activity of this enzyme toward maltose, maltotriose, maltotetraose, maltopentaose, maltohexaose, maltoheptaose, lactose, cellobiose and glucose was 100:94:74:46:66:56:64:47:59. To our knowledge, this is the first report on the discovery of an glucooligosaccharide oxidase as judged from enzyme substrate specificity.

Acremonium↗

PubMed1991

Enhanced sensitivity to anorexia and consumption of drinking water induced by interleukin-1 beta in obese yellow mice.

Exogenously administered interleukin-1 beta (IL-1) was reported to suppress food intake and endogenous CRF in the brain was reported to be involved in mediating the IL-1-induced anorexia. The present study was undertaken to investigate the effect of IL-1 (i.p.) on food and water intake in obese yellow mice and in lean mice. Enhanced sensitivity to IL-1-induced suppression of food and water intake were observed in obese yellow mice compared to lean mice (food intake suppression: lean 29.92%, obese 88.48%; water intake suppression: lean 25.18%, obese 71.56% of respective controls). After treatment of the mice with ibuprofen (10 mg/kg i.p.), the suppression of food and water intake was prevented in lean mice but unaffected in obese mice. The results suggest that there may be differential sensitivity to activation of CRF neurons induced by the peripheral injection of IL-1 in obese yellow and in lean mice.

Animals↗

PubMed1991

Failure of anti-TSH receptor antibodies (TRAb) to predict the outcome of the course of Graves' disease following withdrawal of antithyroid drug.

Nineteen patients with Graves' disease were regarded as euthyroid at the end of therapy. Follow-up studies were performed for further 3 years. TSH binding inhibitor immunoglobins (TBII) were measured by radioreceptor assay. Thyroid stimulating antibodies (TSAb) were measured by a sensitive cAMP accumulation using FRTL-5 cells. Most of the patients showed negative TBII at the end of therapy, while TSAb-positive patients were approximately 50%. The relapse rates during post therapeutic period were 33.3% in TSAb-positive group and 40% in TSAb-negative group, which were not significantly different between the two groups. It was thought that determination of TSAb activity at the end of therapy, in addition to TBII, appears to play a permissive role in predicting the outcome of the course of Graves' disease following discontinuation of antithyroid drug therapy.

Adolescent↗

PubMed1991

Novel plasmid vectors for gene cloning in Pseudomonas.

Novel host-vector systems have been developed for gene cloning in the metabolically versatile bacterial genus Pseudomonas. We found that a new Pseudomonas strain, Pseudomonas flavida IF-4, isolated from soil, carried two small cryptic plasmids, named pNI10 and pNI20. They were multi-copy, but not self-transmissible, and the genome size was 3.7 kb for pNI10 and 2.9 kb for pNI20. Several types of cloning vectors containing a kanamycin or streptomycin resistance (Kmr or Smr) gene were constructed from pNI10 and pNI20. These plasmid vectors were efficiently transformed into several strains of Pseudomonas at a frequency up to 4 x 10(5) transformants per 1 microgram plasmid DNA by the usual competent cell method. The vectors derived from pNI10 replicated not only in Pseudomonas but also in some other Gram-negative enteric bacteria such as Escherichia coli, Enterobacter aerogenes, and Proteus mirabilis.

Blotting, Southern↗

PubMed1991

Efficacy of the glyceryl trinitrate transdermal therapeutic system in a dog model of heart failure.

The efficacy of a controlled-release topical dosage form of glyceryl trinitrate (Nitroglycerin Transdermal Therapeutic System, Nitroderm TTS, NTG-TTS; CAS 55-63-0) was studied in the experimental model of congestive heart failure in beagles. NTG-TTS suppressed the increase in left ventricular end-diastolic and central venous pressure, and total peripheral resistance resulting from propranolol, dextran and l-phenylephrine infusion. NTG-TTS antagonized the decrease in cardiac output in this model. These effects of NTG-TTS on congestive heart failure were presumably attributable to the reduction of pre-load, together with direct vasodilation of the peripheral arteries.

Administration, Cutaneous↗

PubMed1991

Effect of oxiracetam on cerebrovascular impairment in rats.

The effect of oxiracetam (CGP 21690E, CAS 62613-82-5) on cerebrovascular impairment was investigated in rats. 1. After injection of tranylcypromine (a MAO inhibitor), spontaneously hypertensive rats (SHR) which had been previously infused with norepinephrine (NE) for 14 days displayed stroke-related behaviour including kangaroo-like posture, seizures and death. Administration of oxiracetam at doses of 400 and 800 mg/kg/d p.o. for 14 days before tranylcypromine injection inhibited the stroke-related behaviour. 2. Bilateral common carotid and vertebral artery occlusion induced electroencephalogram (EEG) flattening, the EEG recovering gradually after re-perfusion of cerebral blood flow. Oxiracetam administered after the re-perfusion at a dose of 100 mg/kg, i.v. accelerated the recovery. This facilitatory effect was not seen when either piracetam (50 and 100 mg/kg i.v.) or idebenone (50 and 100 mg/kg i.v.) were administered. 3. Occlusion of middle cerebral artery produced cerebral infarction and disturbed the circadian rhythm of spontaneous motor activity with an relative increase of activity in the light period. Treatment with oxiracetam (400 mg/kg/d p.o.) for 14 days after the occlusion showed a tendency to an improvement in the disturbed circadian rhythm but did not influence the size of brain infarction. From these results, oxiracetam is thought to have a protective effect in cerebrovascular impairment.

Animals↗

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↗