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Biomedical subjects

N Inoue

Publications and source records attributed to N Inoue.

At least 451 records · Page 25Linked to original sources
PubMed1990

Activation of a brain type Na pump after glutamate excitation of cerebral neurons.

Rat cerebral neurons matured in culture were stimulated with glutamate, and the effects of glutamate on the activities of the Na pump isoforms were investigated. Glutamate increased the total Na pump activity via a remarkable increase in the activity of the brain type (highly digitalis-sensitive) isoform and a slight decrease in the common type (weakly digitalis-sensitive) isoform activity. The effects of glutamate were produced in response to an enhancement of [Na+]i in the neurons, which resulted from passive Na+ influx through glutamate receptor-mediated cation channels. These results suggest that the Na pump isoforms in neurons differ in their physiological significance and that the brain type isoform plays an important role in restoring concentration gradients of Na+ and K+ after neuronal excitation.

Animals↗
PubMed1990

[Effects of sex difference on the toxicity of ethylene oxide. IV. Anemia].

Wistar male and female rats were exposed to ethylene oxide (EO) at a concentration of 250 ppm, 6 hours a day, 5 days a week for 17 weeks simultaneously, and the sex difference of anemia induced by EO was investigated. Hemoglobin concentrations of both the male and female exposed groups were decreased when compared with each control group, and the anemia in the female exposed group was more severe than that in the male exposed group. Absolute spleen weight increased only in the female exposed group. We have already reported that a decrease of the glutathione reductase activity in the erythrocyte plays an important role in the EO-induced anemia. In the present study, the activity in both male and female exposed groups decreased when compared with each control group, and there was no sex difference in the degree of the decrease. From these observations, we concluded that there was a sex difference in the EO-induced anemia.

Anemia↗
PubMed1990

[Effects of sexual difference on the toxicity of ethylene oxide. II. Glutathione metabolism and lipid peroxidation in the liver].

Wistar male and female rats were exposed to ethylene oxide (EO) at a concentration of 250 ppm, 6 hours a day, 5 days a week for 17 weeks simultaneously, and the effects of EO on the glutathione metabolism and lipid peroxidation in the liver in regards to sexual difference were studied. Although the liver weight of the male exposed group did not alter, that of the female exposed group increased when compared with the control group. This increase was not accompanied with the alteration of protein content per gram of liver in the cytosol fraction and total homogenate. Among the glutathione related enzymes in the liver, the glutathione reductase activity of both male and female exposed groups decreased compared with each control group, and there was no difference in the degree of the decrease. The glutathione peroxidase activity increased only in the male exposed group. The glutathione-S-transferase activity of both male and female exposed groups increased significantly. In the male exposed group, the activity increased greater than that in the female exposed group. In the male exposed group, the lipid peroxide level in the liver increased slightly but not significantly.

Animals↗
PubMed1990

[Effects of sexual difference on the toxicity of ethylene oxide. III. The rat hepatic monooxygenase system].

Wistar male and female rats were exposed to ethylene oxide (EO) at a concentration of 250 ppm, 6 hours a day, 5 days a week for 17 weeks and the effect of EO on the hepatic monooxygenase system in regards to the sex difference was investigated. Serum GOT of the exposed male rat slightly increased, but that of the female did not change. Contents of microsomal protein and cytochrome P-450 of the male exposed group decreased significantly compared to the male control group, but that of the female exposed group did not change. The change of cytochrome b5, protoheme and NADH-ferricyanide reductase activity of the female exposed group was the same as that of the male. Although NADPH-cytochrome c reductase activity of the male exposed group did not change, that of the female group exposed increased significantly when compared to the female control group. From these observations, we concluded that the effect of EO on the hepatic monooxygenase system was different between male and female.

Animals↗
PubMed1990

Somatostatin co-localizes with tyrosine hydroxylase in the nerve cells of discrete hypothalamic regions in rats.

The co-expression of somatostatin (SOM)- and tyrosine hydroxylase (TH)-like immunoreactivities in nerve cells of the rat hypothalamus was investigated by the simultaneous application to the same sections of immuno-beta-galactosidase staining and the peroxidase-antiperoxidase (PAP) method. SOM-like immunoreactive cells stained blue with immuno-beta-galactosidase staining and TH-like immunoreactive cells stained brown with the PAP method. Double-labeled cells with overlapping blue and brown immunoreaction products were frequently identified in the preoptic periventricular nucleus (pope). These double-labeled cells were seen in clusters within the ventral half of the rostral pope. The periventricular hypothalamic nucleus at the level of the anterior hypothalamic nucleus contained only scattered nerve cells with both SOM- and TH-like immunoreactivities, despite the presence of many nerve cells immunoreactive for either SOM or TH in this nucleus. Double-labeled cells were also observed in some regions of the medial-basal hypothalamus, including the boundary between the ventromedial hypothalamic nucleus and the arcuate hypothalamic nucleus, and areas dorsal and lateral to the ventromedial hypothalamic nucleus. These findings may provide insight into the mechanisms underlying previously described catecholamine-mediated modulation of SOM release from the hypothalamus.

Animals↗
PubMed1990

Neurotoxicity and pharmacokinetics of intrathecal perfusion of ACNU in dogs.

To test the feasibility of intrathecal perfusion of ACNU (3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitro sou rea hydrochloride) in the treatment of subarachnoid dissemination of malignant glioma, the neurotoxicity and pharmacokinetics of ACNU were studied in dogs. ACNU [1-2 mg dissolved in 10-20 ml of lactated Ringer's solution or artificial cerebrospinal fluid (CSF)] was administered via the right lateral ventricle by constant drip infusion and CSF was drained by lumbar puncture. The infusion time was from 15 to 71 min. For the control, a bolus injection was given. No neurological and systemic symptoms were noted after perfusion. Histological examination of the brain and spinal cord revealed only mild denudation of ependyma in the wall of the ventricles in a dog treated three times with 2 mg ACNU (perfusion twice, bolus injection once) and in 2 dogs perfused with 1 mg ACNU once a week for 10 weeks. ACNU was not detected in lumbar CSF after bolus injection into the lateral ventricle. When 1 mg of ACNU, dissolved in 10 ml of artificial CSF, was perfused for a duration of 22 to 31 min, it started to appear in the lumbar CSF 10 to 15 min after the start of perfusion, reaching a maximum concentration of 13.88 to 22.31 micrograms/ml. The area under the drug concentration-time curve was 344 to 706 micrograms x min/ml; the half-time was 15.5 to 19.5 min. The distribution volume was 30.6 to 54.1 ml. These findings suggest the feasibility of intrathecal perfusion of ACNU in the treatment of patients with subarachnoid dissemination of glioma.

Animals↗
PubMed1990

Chronic inhalation effects of ethylene oxide on porphyrin-heme metabolism.

The effects of chronic ethylene oxide (EtO) inhalation on porphyrin-heme metabolism were investigated. When Wistar male rats were exposed to 500 ppm EtO for 6 h a day, 3 times a week for 13 weeks, hemoglobin content significantly decreased, and a normocytic and normochromic anemia was found. In the liver, cytochrome P-450 and protoheme significantly decreased but wet weight, microsomal protein and cytochrome b5 were not affected. The activity of delta-aminolevulinic acid (ALA) synthase increased while ALA dehydratase did not change. The activity of hepatic ferrochelatase decreased time-dependently. Uroporphyrin increased 37% and coproporphyrin tended to increase in the liver. The concentration of protoporphyrin in the liver and erythrocytes tended to increase. Coproporphyrin excretion in the urine showed a 5-6-fold increase while there was no significant increase in urinary ALA excretion. These results indicate that chronic inhalation of EtO causes alterations of hepatic porphyrin-heme metabolism as well as anemia and may affect mechanisms of adaptation to xenobiotics.

5-Aminolevulinate Synthetase↗
PubMed1990

[Effects of sexual difference on the toxicity of ethylene oxide. I. Polyneuropathy].

Male and female Wistar rats were exposed to ethylene oxide (EO) at a concentration of 250 ppm, 6 hours a day, 5 days a week for 17 weeks simultaneously, and the sexual difference in susceptibility of the peripheral nerve to EO was investigated. Both male and female rats of the exposed group showed paresis of the hindlegs, but sexual difference did not affect the degree of this abnormality. In histopathological examinations, axonal degeneration of the myelinated fibers in the peroneal nerve, the nerve to the soleus muscle and in the gracile fascicles of the spinal cord was revealed. The nerve to the soleus muscle degenerated more severely than the peroneal nerve. Sexual difference played no part in the severity of the degenerations in each nerve or in the gracile fascicles. From these observations, we concluded that there was no significant difference in the susceptibility of the peripheral nerve to EO between male and female rats.

Animals↗
PubMed1990

Effects of acrylamide and N,N'-methylene-bis-acrylamide on creatine kinase activity.

In vitro, both acrylamide and N,N'-methylene-bis-acrylamide inhibited creatine kinase (CK) activity from brain or sciatic nerve with almost the same potency. In vivo, only acrylamide (50 mg/kg b. wt./day, 8 days) caused paralysis of hind limbs and suppressed CK activity in cerebrum, cerebellum, spinal cord and muscle in rats. Bis-acrylamide (50 mg or 100 mg/kg b. wt./day, 8 days) caused no paralysis nor inhibition of CK activity in any tissue examined. Definite inhibition of CK was not found in sciatic nerve from rats given either chemical. The inhibition of CK may play a role in the genesis of toxicity of acrylamide especially in the central nervous system.

Acrylamide↗
PubMed1990

Co-localization of arginine vasopressin- and enkephalin-like immunoreactivities in nerve cells of the rat hypothalamus.

The co-localization of arginine vasopressin- and enkephalin-like immunoreactivities in nerve cells of the rat paraventricular hypothalamic nucleus and adjacent areas was investigated by the simultaneous application of immuno-beta-galactosidase staining and the peroxidase-antiperoxidase method to sections. Arginine vasopressin-like immunoreactive cells were stained blue with immuno-beta-galactosidase staining and enkephalin-like immunoreactive cells brown with the peroxidase-antiperoxidase method. Double-labeled cells with overlap of blue and brown immunoreaction products were identified in the anterior, medial, and lateral parvocellular parts of the paraventricular hypothalamic nucleus as well as in the previously indicated posterior magnocellular part. Other regions that contained double-labeled cells were the lateral hypothalamic area, anterior hypothalamic nucleus, area between the lateral hypothalamic area and anterior hypothalamic nucleus, suprachiasmatic nucleus, and bed nucleus of the stria terminalis, medial division, posterolateral part. These findings suggest that nerve cells with both arginine vasopressin- and enkephalin-like immunoreactivities may be more actively involved in neuroendocrine regulation and neural transmission than previously considered. They may provide a morphological basis for an increase in enkephalin-like immunoreactivity within the anterior pituitary in cases of hemorrhagic shock which is presumably accompanied by arginine vasopressin hypersecretion.

Animals↗
PubMed1990

Subcortical auditory agnosia.

A case of generalized auditory agnosia without aphasia secondary to cardiogenic cerebral embolism is reported. The infarcts in this patient were localized within the bitemporal subcortices as confirmed by computerized axial tomography and magnetic resonance imaging. The findings suggested that interruption of both auditory radiations by bilateral subcortical lesions may play an important role in the occurrence of "cerebral auditory disorders."

Aged↗
PubMed1990

Biochemical changes in rat erythrocytes caused by ethylene oxide exposure.

When Wistar male rats were exposed to ethylene oxide (EtO) at a concentration of about 500 ppm, 6 hr a day, 3 days a week for 2, 6, or 13 weeks, hematological examination showed macrocytic, normochromic anemia with a high reticulocyte count. This result raised the possibility that the hemolytic process was responsible for the anemia. Thus, the following possible causes of hemolysis were investigated with erythrocytes obtained from control and EtO-exposed rats. (1) Metabolism in erythrocytes; (a) Hexose monophosphate cycle: The activity of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, or glutathione peroxidase was not affected, but the activity of glutathione reductase (GR) significantly decreased and did not recover by the addition of flavin adenine dinucleotide. Reduced glutathione content also decreased and the glutathione stability test was positive. (b) Embden-Meyerhof pathway: Adenosine triphosphate content did not decrease. (c) Lapoport-Luebering cycle: 2,3-Diphosphoglycerate content was not affected. (2) Membrane alterations: Osmotic fragility was not affected and the activity of acetylcholine esterase in the ghost membranes of the exposed group increased. (3) Hemoglobin stability: The heat test and the isopropanol test were negative. GR has an important function in maintaining the reducing power in erythrocytes, and the decrease in the activity caused by EtO induced an alteration of the glutathione stability. Although the mechanism of EtO-induced anemia could not be clearly explained, the inhibition of GR activity might be related to the anemia.

2,3-Diphosphoglycerate↗
PubMed1990

Different responses of cytosolic and mitochondrial glutathione in rat livers after ethylene oxide exposure.

Acute effects of ethylene oxide (EO) at the concentration of 500 and 1500 ppm on glutathione and glutathione reductase of the cytosol and mitochondria in rat liver were examined. The levels of reduced glutathione content and the glutathione reductase activity in the cytosol at 1500 ppm exposure decreased to approximately 10% and 60% of those of control rats, respectively. The decreases in glutathione content and glutathione reductase activity in the mitochondria were less significant than those in the cytosol. Both mitochondrial NADPH-cytochrome c reductase and cytochrome c oxidase activities were only slightly affected by these EO exposures. These results indicate that the change in glutathione content in the cytosol mainly occurred due to the response to EO exposure, and that the mitochondrial glutathione did not serve for such cellular function.

Administration, Inhalation↗
PubMed1990

Inhibition of creatine kinase activity by ethylene oxide.

Exposure of rats to 500 ppm ethylene oxide for six hours a day, three times a week, for 12 weeks, lowered serum creatine kinase activity by more than 40%. The only other change was a slightly decreased triglyceride concentration. After four weeks of exposure, neither aspartate aminotransferase nor lactate dehydrogenase activity in brain, spinal cord, and muscle was affected but creatine kinase activity was clearly inhibited. In vitro, ethylene oxide inhibited creatine kinase activity in brain homogenate and in a purified muscle enzyme preparation. Dithiothreitol did not counteract the effect of ethylene oxide. Though the amount of sulphydryl groups in purified creatine kinase was decreased considerably by exposure to ethylene oxide, the enzyme still showed moderate activity. Thus ethylene oxide inhibits creatine kinase activity in vivo and in vitro and the inhibition appears to be unrelated to the disruption of sulphydryl groups in the enzyme.

Animals↗
PubMed1990

Distribution of peptidergic nerve fibers in rat bronchus-associated lymphoid tissue: light microscopic observations.

The localization of neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) in the nerve fibers of rat bronchus-associated lymphoid tissue (BALT) was investigated by light microscopic immunohistochemistry. Nerve fiber bundles revealing NPY-like immunoreactivity were shown to enter the BALT together with pulmonary artery branches. They frequently reached the central zone of the BALT to give rise to fine, tortuous fibers. On the other hand, nerve fibers immunoreactive for SP and CGRP seemed to distribute in the subepithelial zone of the BALT after dissociating from fiber networks in the walls of bronchi, although small numbers of SP and CGRP fibers were also seen in the BALT central zone. CGRP fibers formed a more intense network than SP fibers in the BALT. Scattered VIP fibers were found only in the subepithelial zone of the BALT. These findings not only suggest that the four kinds of peptidergic fibers act on BALT in multiple ways, but also that these neuropeptides may be involved in the control of mucosal immunity, lymphocyte migration and proliferation within the BALT.

Animals↗
PubMed1990

[Enhanced effect of hepatic arterial infusion of anticancer drugs of rabbit VX-2 hepatic implants].

To obtain a high concentration of adriamycin (ADR) in hepatic malignant tumors, intraarterial injection method was devised depending upon the different application with Lipiodol. The VX-2 carcinoma was implanted in the domestic rabbit after laparotomy. When the tumor grew to 2 cm in size, ADR was infused through the hepatic artery by the following four methods; Group 1, one shot injection of ADR (n = 5); Group 2, ADR infusion between Lipiodol injections (n = 6); Group 3, infusion of Lipiodol suspended with Urographin dissolved in Lipiodol (n = 7); Group 4, ADR dissolved in Lipiodol by Sonicator (n = 5). ADR concentration of the tumor, liver, heart, kidney and bone marrow were measured by HPLC one hour after ADR administration. In Group 3, the concentrations of ADR within tumor were significantly higher than in the other three groups (p less than 0.01 or less than 0.02). In addition, the tumor-to-liver ratio of ADR was significantly higher in the other three groups (p less than 0.05 or less than 0.10). ADR concentration of heart and kidney was lower in Group 3 than in the other groups. These results suggest that Lipiodol may enhance the therapeutic effects of hepatic arterial ADR infusion by hepatic arterial ADR infusion by increasing its tumor uptake.

Animals↗