Biomedical subjects

A Iguchi

Publications and source records attributed to A Iguchi.

At least 199 records · Page 11Linked to original sources

PubMed1993

Intrahypothalamic, but not hippocampal, administration of muscimol suppresses hyperglycemia induced by hippocampal neostigmine in anesthetized rats.

We investigated the effects of intrahypothalamic or hippocampal injection of GABA receptor agonists on hyperglycemia induced by hippocampal neostigmine. Prior to the injection of neostigmine (50 nmol) into the hippocampus (HPC), muscimol (0.01-1 nmol) or baclofen (1 nmol) was injected into the bilateral ventromedial hypothalamus (VMH). Muscimol suppressed the hyperglycemia in a dose-dependent manner, but baclofen affected it only minimally. In contrast, neither hippocampal muscimol (1 or 2.5 nmol) nor baclofen (1 nmol) suppressed the hippocampal neostigmine-dependent hyperglycemia. Intrahypothalamic muscimol (1 nmol) also decreased the changes in hepatic venous plasma glucagon and epinephrine significantly. These results indicate that intrahypothalamic muscimol suppresses hyperglycemia caused by cholinergic neurons originating from the HPC, indicating existence of the location specificity.

Analysis of Variance↗

PubMed1993

Histamine-induced, central nervous system-mediated hyperglycemia is suppressed by atropine in the brain.

We investigated the relationship between histamine and muscarinic cholinergic neurons in central nervous system (CNS)-mediated glucose regulation in anesthetized fed rats. The injection of pyrilamine (5 x 10(-7) mol) into the third cerebral ventricle suppressed the hyperglycemia induced by intraventricular injection of histamine (5 x 10(-7) mol). Ranitidine (5 x 10(-7) mol), however, did not suppress this hyperglycemia. The injection of atropine (5 x 10(-9)-5 x 10(-7) mol) into the third cerebral ventricle suppressed the histamine-induced hyperglycemia in a dose-dependent manner. These findings suggest that histamine induction of CNS-mediated hyperglycemia involves neuronal transmission not only via H1 receptors but also, at least in part, by muscarinic cholinergic neurons.

Animals↗

PubMed1993

Activation of GABAA receptor in the brain suppresses neostigmine or histamine-induced central nervous system-mediated hyperglycemia.

We investigated the effect of GABA receptor agonists on the central nervous system (CNS)-mediated hyperglycemia induced by neostigmine or histamine in anesthetized fed rats. The injection of muscimol, GABAA receptor agonist (1, 2.5 nmol) into the third cerebral ventricle suppressed the hyperglycemia induced by intraventricular injection of neostigmine (1 x 10(-8) mol) or histamine (5 x 10(-7) mol). Baclofen, GABAB receptor agonist (1, 2.5 nmol), however, did not suppress these hyperglycemia. Neither muscimol nor baclofen (2.5 nmol) affected plasma glucose levels. These findings suggest that activation of GABAA receptor in the CNS suppresses the hyperglycemia induced by the stimulation of cholinoceptive neuron or histaminergic neuron, but activation of GABAB receptor does not affect them.

Animals↗

PubMed1993

Activation of GABAA receptors in hypothalamus modulates PGF2 alpha- or PGE2-induced catecholamine secretion in rats.

We previously reported that injection of PGF2 alpha into the third cerebral ventricle produces hyperglycemia and hyperthermia associated with catecholamine secretion in anesthetized rats. We have also studied the potency of catecholamine secretion induced by injecting PGE2 or PGF2 alpha into the third cerebral ventricle and the effect of the GABA-selective agonist, muscimol, on the catecholamine secretion induced by PGE2 or PGF2 alpha. Administration of 50 micrograms of PGE2 into the third cerebral ventricle increased norepinephrine secretion to a greater extent than the same dose of PGF2 alpha, whereas the latter increased epinephrine secretion to a greater degree. These effects paralleled the potencies of the hyperglycemic and hyperthermic effects of PGF2 alpha and PGE2, respectively. Simultaneous injection of 2.5 nmol of muscimol into the third cerebral ventricle with 50 micrograms of PGF2 alpha or PGE2 completely suppressed epinephrine and norepinephrine secretion induced by PGF2 alpha or PGE2. These findings suggest that central PGF2 alpha and PGE2 stimulate epinephrine and norepinephrine secretion with different potencies, and that brain GABAA receptors suppress catecholamine secretion induced by PGF2 alpha or PGE2.

Animals↗

PubMed1993

Involvement of central cholinergic muscarinic receptors and histamine H1 receptors in hyperglycemia induced by prostaglandin F2 alpha in rats.

We studied the effects of the histamine H1 receptor antagonists diphenhydramine and pyrilamine, the H2 receptor antagonist ranitidine and the muscarinic receptor antagonist atropine injected into the third cerebral ventricle on prostaglandin F2 alpha (PGF2 alpha)-induced hyperglycemia in anesthetized fed rats. The concomitant injection of diphenhydramine (1 x 10(-8), 5 x 10(-8) mol) with 50 micrograms PGF2 alpha significantly suppressed the increase in hepatic plasma glucose concentrations induced by PGF2 alpha. The concomitant injection of 1 x 10(-8) mol pyrilamine with 50 micrograms PGF2 alpha did not suppress the above-mentioned parameter, while 5 x 10(-8) mol pyrilamine significantly suppressed it. Diphenhydramine suppressed the PGF2 alpha-induced hyperglycemia to a greater extent than did pyrilamine. In contrast, concomitant injection of the H2 receptor antagonist ranitidine (1 x 10(-8), 5 x 10(-8) mol) did not suppress the hyperglycemia induced by PGF2 alpha. The concomitant injection of 5 x 10(-8) mol diphenhydramine or pyrilamine with 50 micrograms PGF2 alpha significantly suppressed the increase in plasma epinephrine induced by PGF2 alpha, but the same dose of ranitidine had no effect. The concomitant injection of atropine (5 x 10(-8), 5 x 10(-7) mol) with 50 micrograms PGF2 alpha significantly suppressed the increase in hepatic plasma glucose and epinephrine induced by PGF2 alpha. These findings demonstrate that PGF2 alpha-induced hyperglycemia is mediated by the muscarinic receptors of cholinoceptive neurons and in part by H1 receptors in the central nervous system.

Animals↗

PubMed1993

Protective effects of idebenone on vascular endothelial cells against toxicity induced by oxidatively modified low density lipoprotein.

We examined the protective effects of idebenone, 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone, on the cytotoxicity of oxidatively-modified low density lipoprotein (oxLDL), using cultured vascular endothelial cells from fetal bovine aorta. When the cells were incubated with idebenone, the toxicity of oxLDL was inhibited dose-dependently (10(-7)-10(-5) M). When cells were preincubated with idebenone, the toxicity of oxLDL was inhibited only at a high concentration (10(-5) M). However, idebenone had no significant effects on copper-induced modification of LDL. The protective effects of idebenone on oxLDL-induced endothelial toxicity may be beneficial for the inhibition of the development of atherosclerosis in the brain and other arterial systems.

Animals↗

PubMed1993

Effects of dexamethasone on migration of human monocytes in response to oxidized beta-very low density lipoprotein.

OBJECTIVE: We previously showed that dexamethasone inhibited the development of atherosclerosis in cholesterol-fed rabbits. In the present study, we investigated the mechanisms of this inhibition. METHODS: Monocytes were isolated from the peripheral blood of healthy donors. Cell suspensions were incubated with dexamethasone, 10(-11)-10(-4)M, for 90 minutes at 37 degrees C. Rabbit beta-very low density lipoprotein(beta-VLDL) was obtained from New Zealand White rabbits that had been fed chow containing 1% cholesterol. Oxidative modification of beta-VLDL was performed by auto-oxidation. We measured the migration of monocytes in response to native and oxidized beta-VLDL using a 48-well microchemotaxis chamber. RESULTS: Oxidized beta-VLDL stimulated the migration of monocytes dose-dependently in the range between 0.5 and 2 nmol/mg protein. Dexamethasone inhibited the chemotaxis of monocytes exposed to oxidized beta-VLDL in a dose-dependent manner more than 10(-9)M. CONCLUSIONS: Inhibition of the chemotactic response of monocytes exposed to oxidized beta-VLDL may be a mechanism for the anti-atherogenic effect of dexamethasone in cholesterol-fed rabbits.

Animals↗

PubMed1993

[Carbohydrate metabolism].

This review summarizes progress in glycosylation research of relevance to atherosclerosis. Glucose reacts in vivo with cellular proteins nonenzymatically and forms Amadori products. The Amadori products proceed very slowly to undergo a number of further dehydration and rearrangement to form advanced glycosylation end products (AGE). The AGE moiety are characterized by being brown, fluorescent chromophores that can cross-rink proteins. In contrast Amadori products, AGE are irreversible and accumulate on long-lived proteins (eg, collagen, enzyme, lens crystallins) for many years. AGE proteins can modify lipoproteins fibrinogen, collagen and DNA. AGE protein receptor is identified on macrophages. AGE may accelerate development of atherosclerosis by various manner.

Aging↗

PubMed1993

[The study of neuropsychological alterations following coronary artery bypass operation as predicted by computed tomography scan of the brain].

The objective of this clinical study is to provide information regarding the association between coexistent cerebrovascular disease and neuropsychological abnormalities after coronary artery bypass operations. Computed tomography scan of the brain was performed in 104 patients pre-operatively, and their post-operative neuropsychological functions were evaluated. The patients were categorized as follows according to the CT findings: Seventy-three patients showed normal or slight cerebral cortical atrophy which usually seen in patients over fifty of age (group A). Sixteen showed moderate or severe cortical atrophy (group B). Fifteen patients demonstrated the characteristic findings of Binswanger type; severe white matter hypodensity especially in frontal horns and dilated ventricles (group C). Overt neuropsychological dysfunction was not observed in patient in groups A and B. Six patients in group C showed a combination of dementia, bizarre behavior, disorientation and gait dyspraxia following bypass operations. The pseudobulbar signs were also found in 3 patients. These clinical abnormalities persisted for six days to three weeks, and were most often reversible. Although the underlying mechanism of these deleterious alterations is not elucidated, the ischemic nature of the characteristic white matter lesions was highly suspected. The arteriosclerotic changes of the arteriole of the cerebral cortex and hypoperfusion during cardio-pulmonary bypass were supposed to be responsible. Therefore it was concluded that special attention should be focused on neurological evaluation for bypass surgery in group C patients.

Adult↗

PubMed1992

Genetic alteration of catecholamine specificity in transgenic mice.

Epinephrine-producing cells are characterized by the presence of phenylethanolamine N-methyltransferase (PNMT), which catalyzes the formation of epinephrine from norepinephrine. We generated a line of transgenic mice carrying a chimeric gene containing human PNMT cDNA fused to the 4-kilobase fragment of the human dopamine beta-hydroxylase (DBH) gene promoter, to switch catecholamine phenotype in the nervous and endocrine systems. Human PNMT transcripts and immunoreactivity were mainly detected in norepinephrine neurons in brain and sympathetic ganglion as well as in norepinephrine-producing cells in adrenal medulla of transgenic mice, indicating that the human DBH gene promoter of 4 kilobases is sufficient to direct expression of the gene in norepinephrine-producing cells. Analysis of catecholamines in the various tissues showed that the expression of human PNMT in transgenic mice induced the appearance of epinephrine in sympathetic ganglion and dramatic changes in norepinephrine and epinephrine levels in brain, adrenal gland, and blood. These results indicate that the additional PNMT expression in norepinephrine-producing cells can convert these cells to the epinephrine phenotype, and suggest that norepinephrine-producing cells normally possess the basic machinery required for the synthesis of epinephrine except for PNMT. Thus it appears that the only major difference between norepinephrine- and epinephrine-producing cells is the expression of PNMT. Our transgenic animals provide an experimental model to investigate the functional differences between norepinephrine and epinephrine.

Animals↗

PubMed1992

Adjuvant chemotherapy with early intravesical instillation of adriamycin and long-term oral administration of 5-fluorouracil in superficial bladder cancer. The Kyushu University Urological Oncology Group.

A randomized controlled trial was performed to study the efficiency of adjuvant chemotherapy with early intravesical instillation of Adriamycin and long-term oral administration of 5-fluorouracil in 275 patients with superficial bladder cancer. All of the patients were randomized into four groups. Group A received early (immediately and 2 days after transurethral resection) instillation of Adriamycin alone; Group B received early instillation of Adriamycin with oral administration of 5-fluorouracil; Group C received delayed (7 days after transurethral resection) instillation of Adriamycin alone; and group D received delayed instillation of Adriamycin with oral administration of 5-fluorouracil. All patients subsequently received instillations weekly for 2 weeks and then every 2 weeks for a further 14 weeks. After 4 months, they received monthly instillations for 8 months. 5-Fluorouracil (groups B and D) was given daily p.o. for 1 year. Evaluation was possible in 187 patients. The postoperative follow-up period for determination of non-recurrence rates was 36 months, during which no significant difference was detected among the four groups. Moreover, no statistically significant difference was found between the early- and delayed-instillation groups. However, the non-recurrence rates obtained in the groups undergoing early instillation were higher than those determined in the delayed-instillation groups during the 36-month follow-up period, and this difference was especially significant at 4 and 5 months. In addition, the early-instillation groups showed significantly higher non-recurrence rates than did the delayed-instillation groups in terms of primary cases (P less than 0.01), tumor size of less than 1 cm (P less than 0.05), multiple tumors (P less than 0.01), pathological stage pTa (P less than 0.01), and histological grades G1 and G2 (P less than 0.05). Groups B and D, which were treated by intravesical instillation of Adriamycin with oral administration of 5-fluorouracil, showed no significant prophylaxis of recurrence during the 36-month follow-up as compared with groups A and C, which received intravesical instillations alone. The main side effect, which required discontinuation of the treatment, was bladder irritation. However, no significant difference in its incidence was found between the early- and delayed-instillation groups. No severe systemic side effect was encountered in this study. These results suggest that early as well as repeated intravesical instillation of Adriamycin is clinically tolerable and may be effective in preventing the recurrence of superficial bladder cancer.

Administration, Intravesical↗

PubMed1992

Stimulation of muscarinic cholinoceptive neurons in the hippocampus evokes a pressor response with bradycardia.

The injection of neostigmine into the hippocampus of anesthetized rats increased the mean arterial blood pressure (17% of baseline after 60 min injection) and decreased the heart rate (24% of baseline after 60 min injection). These changes were blocked by the co-administration of methylatropine into the hippocampus. Intrahippocampal injection of neostigmine stimulated the secretion of epinephrine and norepinephrine. Adrenodemedullation did not suppress the increase in blood pressure and the decrease in heart rate. It is concluded that the stimulation of muscarinic cholinoceptive neurons in the hippocampus evokes a hypertensive response via an increase in sympathetic drive to the heart and peripheral vasculature, with bradycardia possibly mediated via the parasympathetic system.

Animals↗

PubMed1992

Role of brain histamine H1- and H2-receptors in neostigmine-induced hyperglycemia in rats.

We previously reported that when neostigmine, an inhibitor of acetylcholine esterase, was injected into the third cerebral ventricle, the concentration of hepatic venous plasma glucose was increased via central muscarinic receptors in anesthetized rats. To determine whether brain histamine receptors are involved in cholinergic system transmission with regard to central nervous system (CNS)-mediated glucoregulation, we examined the effects of the H1 receptor antagonist pyrilamine and the H2 receptor antagonist ranitidine on neostigmine-induced hyperglycemia in anesthetized rats. The injection of pyrilamine (5 x 10(-9)-5 x 10(-7) mol) into the third cerebral ventricle suppressed hyperglycemia induced by intraventricular injection of neostigmine (1 x 10(-9) mol) in a dose-dependent manner. Injection of ranitidine (5 x 10(-9)-5 x 10(-7) mol) into the third cerebral ventricle did not suppress the hyperglycemia induced by neostigmine, but enhanced it in a dose-dependent manner. These findings suggest that neostigmine-induced CNS-mediated hyperglycemia is transmitted by not only brain cholinergic muscarinic receptors but also in part by histamine H1 receptors.

Animals↗

PubMed1992

Relationship between hypothalamic noradrenergic activity and the sympathetic activity in interscapular brown adipose tissue after cold-swim stress in rats.

Noradrenaline (NA) activities in both hypothalamus and interscapular brown adipose tissue (IBAT) were simultaneously assessed before and after cold-swim stress in rats. The technique of gas chromatography-mass spectrometry was employed for the analysis of NA and its primary neuronal metabolite, 3,4-dehydroxy-phenylethylenglycol (DHPG), and the ratio of DHPG to NA was used as an index of NA activity. The ratios of DHPG/NA in both hypothalamus and IBAT were significantly elevated 5 and 20 min after cold-swim stress. Moreover, we found that there is a highly significant positive relationship between the hypothalamic DHPG/NA ratio and the ratio of DHPG/NA in IBAT (r = 0.872, p less than 0.0001). This observation strongly supports the concept in which hypothalamic NA neurons play an important role in modulating the sympathetic outflow.

Adipose Tissue, Brown↗

PubMed1992

Effects of adrenergic blockers on central nervous system-mediated hyperglycemia in fed rats.

We studied the effect of adrenergic blockade on hepatic venous hyperglycemia and the activation of a hepatic glycogenolytic enzyme, phosphorylase-a, in response to cerebral cholinergic activation. Neostigmine was injected into the third cerebral ventricle of bilaterally adrenodemedullectomized (ADMX) rats, while somatostatin and insulin were administered intravenously. Hepatic venous plasma glucose concentrations and hepatic phosphorylase-a activity were measured. Intracerebroventricular injection of neostigmine (5 x 10(-8) mol) caused increases in hepatic venous glucose concentrations and hepatic phosphorylase-a activity. Both of these changes were prevented by intraperitoneal (IB) pretreatment with phentolamine (5 x 10(-7), 1 x 10(-6) mol) without the intervention of insulin secretion, but not by pretreatment with the alpha-adrenoreceptor antagonist phenoxybenzamine (1 x 10(-6) mol), the beta-adrenoreceptor antagonist propranolol (1 x 10(-6) mol), the alpha 1-antagonists prazosin or bunazosin (1 x 10(-6) mol), the alpha 2-antagonist yohimbine (1 x 10(-6) mol), or prazosin (5 x 10(-7) mol) plus yohimbine (5 x 10(-7) mol). These results suggest that phentolamine prevented brain-mediated hepatic glycogenolysis by a mechanism that may not be classified pharmacologically as involving either alpha 1- or alpha 2-receptors.

Adrenalectomy↗

PubMed1992

Influence of sympatho-adrenal system on insulin sensitivity using the euglycemic clamp technique.

The aim of the present study was to further investigate the role of the adrenergic system on insulin action using the euglycemic clamp technique. Whole-body glucose metabolism (GM) was calculated as the glucose infusion rate for maintaining euglycemia under insulin infusion and used as an indicator of insulin sensitivity. Euglycemic clamps were performed in adrenodemedullated, epinephrine-treated, phentolamine-treated (alpha-blockade), propranolol-treated (beta-blockade), and epinephrine plus phentolamine and/or propranolol-treated rats. The following results were obtained at an insulin level of approximately 80 mU/l. GM in adrenodemedullated rats (13.97 +/- 0.98 mg/kg/min) was significantly higher than that of the control rats (10.26 +/- 0.50 mg/kg/min, P less than 0.01). GM in epinephrine-treated rats (1.7 mg/kg body weight/h) was 2.12 +/- 0.49 mg/kg/min (P less than 0.001 vs. control). Dose-response curves for phentolamine and propranolol established maximally effective doses (3.0 mg and 12 mg/kg body weight/h, respectively). Using these doses, GM in epinephrine plus phentolamine-treated rats (4.90 +/- 0.39 mg/kg/min) was significantly higher than that of epinephrine alone and GM in epinephrine and propranolol-treated rats (4.49 +/- 0.47 mg/kg/min) was also significantly higher than that of the epinephrine alone. GM in the epinephrine plus both propranolol and phentolamine (5.94 +/- 0.45 mg/kg/min) was significantly higher than that of the epinephrine alone, but not different from either treatment alone and was not additive. Neither phentolamine alone (9.48 +/- 1.45 mg/kg/min), propranolol alone (10.36 +/- 0.55 mg/kg/min) or the combination of blockades (11.14 +/- 0.65 mg/kg/min) had any effect on GM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

PubMed1992

In vivo detection by microscopic chromocystoscopy of concurrent urothelial atypia in superficial bladder cancer.

Microendoscopic observation of methylene blue-stained urothelial surfaces, so-called microscopic chromocystoscopy (MCC), was undertaken in 65 patients with superficial bladder cancer (Ta and T1) and its effectiveness in detecting concurrent urothelial dysplasia or carcinoma in situ was studied. A total of 166 biopsy samples were taken from 75 stained and 91 non-stained portions. Of 75 methylene blue-stained areas, 21 were judged to be abnormal (MCC-positive) by microscopic observation. Fourteen of these 21 MCC-positive areas (67%) were proven to be abnormal histologically, while 7 of 54 MCC-negative portions (13%) were histologically abnormal. Only 4 of 91 biopsies (4%) from non-stained mucosa were proven to have urothelial atypia. In per patient figures, 1 or more concurrent field changes were detected in 15 of 65 cases (23%). MCC contributed to the diagnosis in 10 of these 15 patients.

Aged↗

PubMed1992

Mechanism of intrahippocampal neostigmine-induced hyperglycemia in fed rats.

We previously reported that the injection of neostigmine, an acetylcholine esterase inhibitor, into the dorsal hippocampus produced hepatic venous plasma hyperglycemia associated with an increase of epinephrine and glucagon in anesthetized fed rats. To evaluate the relative contribution of these glucoregulatory hormones and the nervous system to the net hyperglycemic response, we unilaterally injected neostigmine (5 x 10(-8) mol) into the dorsal hippocampus in the following groups of rats: intact rats with bilateral adrenalectomy to eliminate the action of epinephrine, and rats receiving a constant infusion of somatostatin and insulin to prevent the glucagon response and to maintain the basal insulin level. Hepatic venous plasma levels of glucose, immunoreactive glucagon, immunoreactive insulin, epinephrine, and norepinephrine were determined. The area under the glucose curve during the 120-min period following the injection of neostigmine was compared between groups. The areas under the glucose curve for rats receiving somatostatin and insulin, adrenalectomy rats, and adrenalectomy rats receiving somatostatin and insulin were, respectively, 82, 31, and 61% of that for intact rats. The fashion of hippocampal stimulated hyperglycemia with neostigmine was similar to that after injection of neostigmine into the third cerebral ventricle. Therefore, we investigated hyperglycemia in rats with lesions of ventromedial hypothalamus and found that the response to hippocampal neostigmine was significantly inhibited by the hypothalamic lesion. These findings suggest that the glucoregulatory hippocampal activity evoked by neostigmine may be transmitted to peripheral organs via the ventromedial hypothalamus.

Animals↗