Search PubMed⌕ Search

Biomedical subjects

N Iwata

Publications and source records attributed to N Iwata.

At least 181 records · Page 10Linked to original sources

Synthesis and analgesic activity of novel heterocycles, [1]benzothiopyrano[3,4-b]pyrrole derivatives.

In order to develop analgesic compounds possessing a sulfur atom in the alicyclic ring, novel cis-fused heterocycles, [1]benzothiopyrano[3,4-b]pyrrole derivatives (II) were synthesized via a unique cyclization reaction starting from 4-(4-methoxyphenylthio)-2-butanone (1) or 6-methoxy-3,4-dihydro-2H-1-benzothiopyran-4-one (7). The analgesic effects of benzothiopyranopyrroles (16, 18) were measured by means of the writhing test. The phenolic derivative 18 completely inhibited the appearance of writhing at the dose of 50 mg/kg, but the methoxy derivative 16 had no analgesic effect.

Analgesics↗

S-adenosyl-L-methionine improves the changes of calcium content and glucose metabolism after transient ischemia in the rat.

Effects of S-adenosyl-L-methionine on Ca accumulation as well as the changes of electrolytes contents and glucose metabolism after transient ischemia were investigated. In the 4-vessel occlusion model of rats, brain Ca content increased to 200-250% of that in sham operated rats 1 day after 60 min transient ischemia. The change in the striatum was more severe than that in the cortex or hippocampus. Na content increased and K content decreased, and glucose, pyruvate and lactate contents increased significantly in the striatum 1 day after transient ischemia. SAM (100 mg/kg, i.p.) was injected at the end of occlusion and every hour for 5 hr thereafter. Treatment with SAM reduced Ca accumulation, decrease of K, and increase of lactate and pyruvate in the striatum significantly. The present results suggest that the inhibition of Ca accumulation might partly explain the beneficial effects of SAM on the cerebral dysfunction following ischemia.

Adenosine Triphosphate↗

S-adenosyl-L-methionine ameliorates ischemic brain metabolism in spontaneously hypertensive rats.

Effects of S-adenosyl-L-methionine (SAM) on the metabolism in ischemic brain were investigated. The ischemic model employed was an incomplete cerebral ischemia of the spontaneously hypertensive rat (SHR) produced by the occlusion of both common carotid arteries. One hundred mg/kg of SAM was administered (i.p.) 6 times from the beginning of occlusion at 30 min intervals. At 3 hr after the onset of occlusion, animals were killed by microwave irradiation and creatine phosphate (CrP), ATP, glucose, lactate and gamma-aminobutyric acid (GABA) contents in the brain were measured. SAM significantly mitigated both the reductions in CrP, ATP and glucose levels and the increase in GABA level due to the cerebral ischemia. In another set of experiments with the same experimental schedule, water content in the brain was examined. SAM significantly suppressed the increase in water content due to the cerebral ischemia. These results indicate ameliorating effects of SAM on the metabolism in ischemic brain.

Adenosine Triphosphate↗

Prevalence of depressive symptoms in a Japanese occupational setting: a preliminary study.

We measured the prevalence of depressive symptoms in 2,190 Japanese tax office workers using the Japanese version of the Center for Epidemiologic Studies Depression Scale (CES-D). Score distribution by sex was more symmetrical and the mean score of each sex was higher than in the United States population. A high level of depressive symptoms was found in 15.2 percent of males and 10.6 percent of females by controlling for age and marital status. Males aged 50 years and over had more depressive symptoms than other male age groups. Perceived stress, related both to family life and the workplace, was associated with a high level of depressive symptoms. "Long-distance marriage" ("business bachelorhood"), peculiar to Japanese occupations, had little influence on depressive symptomatology.

Adult↗

[Pernicious anemia with indicanuria].

A 67-year-old female was diagnosed as having classical pernicious anemia. Laboratory data included low serum vitamin B12 concentrations, abnormal deoxyuridine suppression test, methylmalonic aciduria, atrophic gastritis, positive anti-intrinsic factor antibody and Schilling test results typical of pernicious anemia. During hospitalization it was incidentally noted that her urine was green colored. Jaffe' reaction and Obermayer reaction for indicanuria were both positive. Dark purple crystalline material was obtained by centrifugation of her urine. The crystalline substance was soluble in methanol and its absorbance curve was identical to that of authentic indoxylsulphate potassium salt. Daily output of this substance was nearly 50 times normal. There was no increase in urinary excretion of monoamino-monocarboxyl amino acides. The exact reason for her indicanuria was not clear, although abnormal bacterial growth in the intestine remained as a possibility.

Aged↗

[Urinary methylmalonic acid excretion and clinical features in megaloblastic anemia due to vitamin B12 deficiency].

Urinary methylmalonic acid (MMA) excretion in megaloblastic anemia due to vitamin B12 (B12) deficiency was studied using a colorimetric method. Average MMA excretion in 20 patients with untreated B12 deficiency was 164 mg/day, whereas it increased to 518 mg/day following oral administration of 10 g L-valine. Urinary MMA correlated significantly with platelet number, erythroblast percentage and deoxyuridine suppression test, while no correlation was found with hemoglobin, leukocyte number, reticulocyte, serum LDH, serum B12 and folate concentration. Patients with neurological disturbances excreted significantly larger amounts of MMA than those without neurological disorders. The results also indicated that MMA could be a useful adjunct for differentiation of megaloblastic anemia from myelodysplastic syndromes showing marked megaloblastic changes.

Adolescent↗

Psychiatric symptoms and related factors in a sample of Japanese workers.

A survey was conducted to investigate the presence of psychiatric symptoms and associated factors affecting psychiatric impairment among 2190 Japanese tax workers. The Japanese translated version of the General Health Questionnaire (GHQ) was used as a measure of psychiatric symptomatology. Several sociodemographic and psychosocial factors (interpersonal factors and perceived stress) were examined as being related to psychiatric impairment. As with all other language versions, the percentage distribution of the GHQ scores was considerably skewed. Females exhibited more psychiatric symptoms than males. No significant differences were found among four age-groups for both sexes. Perceived stress related to the workplace was correlated more with psychiatric impairment than with other psychosocial factors. It was also observed that the 'long-distance marriage' ('business bachelorhood') peculiar to Japanese occupations had little influence on the impairment levels.

Adult↗

Striatal dopamine release and metabolism in sinoaortic-denervated rats by in vivo microdialysis.

The purpose of this study was to provide new evidence favoring the hypothesis that cardiovascular information from arterial baroreceptors is integrated with the nigrostriatal system that contributes to regulation of motor activity. Samples of extracellular striatal dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were collected by the technique of in vivo microdialysis and analyzed by high-performance liquid chromatography-electron capture detection. Rats were prepared with a guide tube placed in the caudate-putamen for subsequent insertion of microdialysis probes. During the 1st wk after sinoaortic denervation (SAD) or sham operation (SO), a microdialysis probe was inserted and perfused with Ringer solution at the rate of 2 microliter/min in the freely moving rats. Samples were collected every 20 min before and after injection of pargyline, 100 mg/kg ip. The results showed that SAD rats have approximately 50% less extracellular striatal DA, DOPAC, and HVA than SO rats (P less than 0.01). After blockade of monoamine oxidase activity with pargyline, striatal DA accumulated three times faster in SO than SAD rats suggesting DA synthesis is reduced in SAD rats. These data provide further evidence that the arterial baroreceptor system affects dopaminergic metabolism in the nigrostriatal system possibly as a means for integration of cardiovascular and motor activity.

3,4-Dihydroxyphenylacetic Acid↗

Effects of S-adenosyl-L-methionine upon ischemia-induced brain edema in Mongolian gerbils and spontaneously hypertensive rats.

Effects of S-adenosyl-L-methionine (SAMe).2 sulphate.tosylate upon the ischemia-induced brain edema and survival rate in Mongolian gerbils and spontaneously hypertensive rats were investigated, since SAMe is known to be important as a physiologically active substance in numerous metabolic processes including those that are inhibited in ischemia. SAMe suppressed increases in water and Na+ content in the ischemic brain which was produced by ligation of the common carotid artery for a short term (20-30 min) in Mongolian gerbils. This ameliorating effect of SAMe was observed dose-dependently at higher doses than 100 mg/kg administered repeatedly every 0.5 or 1 hr, starting within 2 hr, at least, after the reperfusion. Similar effects were also obtained in spontaneously hypertensive rats whose common carotid artery on both sides were ligated permanently. SAMe also increased survival rate in Mongolian gerbils with ischemic brain. Although the SAMe solution employed in the present experiments was hypertonic and contained mannitol as a filler, the beneficial effects were due to neither the hypertonicity of the solution nor mannitol, but due to SAMe itself.

Animals↗

S-adenosyl-L-methionine prevents ischemic neuronal death.

The effect of S-adenosyl-L-methionine (SAM) on neuronal degeneration induced by transient forebrain ischemia was studied in rats. Bilateral occlusion of the common carotid arteries for 30 min in a 4-vessel occlusion model caused degeneration of CA1 neurons of the hippocampus. When SAM-HCl or SAM sulphate tosylate (SAM-ST, 100 mg/kg as the free form of SAM, i.p.) was administered just after recirculation and every hour for 5 h after recirculation, the degeneration and loss of pyramidal cells were prevented. However, adenosine, a metabolite of SAM, and glycerol, which has the same osmotic pressure as the solution of SAM-ST, did not show any effects on the neuronal damage. The results showed that SAM has a beneficial effect on neuronal damage induced by ischemia.

Animals↗

Effects of RS-2232, a potential antidepressant, on the levels of monoamines, precursor amino acids and their related metabolites in mouse brain.

The effects of RS-2232, a new antidepressant, on the levels of monoamines, precursor amino acids and their related metabolites in mouse brain were investigated and compared with some clinically effective antidepressants. RS-2232 (3, 10 and 30 mg/kg, p.o.) increased the levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) dose-dependently, 60 min after administration. Tyrosine (TYR) levels were not changed, but tryptophan (TRP) was significantly increased by 20% at 30 mg/kg of the compound. On the other hand, DA metabolites such as 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were significantly reduced at all doses. 5-Hydroxyindoleacetic acid (5-HIAA), a 5-HT metabolite, was decreased by 32% at 10 mg/kg. These changes caused by RS-2232 administration were similar to those of the classical inhibitor of monoamine oxidase (MAO), isocarboxazid (ISO), but rather different from those of imipramine (IMP) and mianserin (MIA). RS-2232 and ISO antagonized against reserpine (2 mg/kg, s.c.)-induced changes in the contents of monoamines and their metabolites. Furthermore, time-course experiments clearly showed that increase in the levels of monoamines by 10 mg/kg of RS-2232 was restored to the control levels within a few hours. These results suggest that RS-2232 has reversible MAO inhibiting properties in vivo in mouse brain.

Amino Acids↗

RS-2232, a compound with a reversible and specific type-A monoamine oxidase inhibiting property in mouse brain.

Effects of RS-2232 on monoamine oxidase (MAO) activities in mouse brain and liver were investigated with 5-hydroxytryptamine (5-HT), beta-phenyl-ethylamine (PEA), and in some cases, kynuramine as substrate. IC50s of RS-2232 for 5-HT (100 microM) and PEA (20 microM) deaminations in brain mitochondrial preparations were 0.14 microM and 52 microM, respectively. RS-2232 was found to be a competitive inhibitor of 5-HT deamination in the preparation, and its Ki was 0.054 microM. The inhibitions of MAO in both brain and liver homogenate by RS-2232 in vitro measured with kynuramine (100 microM) were independent of the prolonged preincubation. 5-HT deaminations in the brain homogenates of mice treated with RS-2232 were decreased significantly by 15% and 59% at 10 and 30 mg/kg (p.o.) of the compound, respectively. On the other hand, PEA deaminations were not changed at the same doses. Pressor responses induced by intravenous tyramine (0.1-1.0 mg/kg) in anesthetized rats was little affected by oral administration of RS-2232 (3-30 mg/kg) once daily for two weeks. These results reveal that RS-2232 has a reversible and specific type-A MAO inhibiting property in mouse brain, and they suggest that RS-2232 is relatively safe in tyramine-potentiation.

Anesthesia↗