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Biomedical subjects

A Hirose

Publications and source records attributed to A Hirose.

At least 37 records · Page 2Linked to original sources

Reproductive and developmental toxicity studies of toluene. II. Effects of inhalation exposure on fertility in rats.

Male and female Sprague-Dawley rats were exposed to toluene vapor at 600 and 2000 ppm for 6 h/day, and effects on their fertility were investigated. Females were exposed from 14 days before mating until day 7 of gestation. Males were exposed for a total of 90 days, including the mating period; treatment was begun 60 days before pairing, and toxicity with respect to testicular and reproductive functions was examined. In females of the 2000 ppm-treated group, salivation and lacrimation that may have been caused by CNS depression were observed starting 20 days after exposure. Although no abnormalities were seen in mating behavior or fertility, fetal mortality and the number of dams with dead fetuses increased in the 2000 ppm group. In the males exposed to 2000 ppm toluene for 90 days, an increase in kidney weights and a decrease in thymus weights were observed. Basophilic changes and necrosis of kidney tubules were greater at the higher exposure level. Additionally, decreases in the weights of the epididymides and spermatic count were observed, indicating toxicity of toluene to the male reproductive system in vivo for the first time. In conclusion, embryo-fetal toxic effects were apparent in female rats exposed to toluene before and during the early stage of pregnancy. Subacute exposure to a high level (2000 ppm) of toluene vapor elicited mild toxic changes in the kidneys, thymus, and reproductive organs of males. Toxic effects on fertility and reproduction were thus demonstrated not only in females but also in males exposed to toluene vapor in the present study.

Administration, Inhalation↗

Epidemiologic characteristics of rhegmatogenous retinal detachment in Kumamoto, Japan.

BACKGROUND: The epidemiology of rhegmatogenous retinal detachment in Asians is not well known. We studied the epidemiologic characteristics of rhegmatogenous retinal detachment in Kumamoto, Japan. METHODS: The study was based on a retrospective chart review of hospital patients who were treated for primary rhegmatogenous retinal detachment in 1990. The data were collected from seven hospitals in the Kumamoto area. RESULTS: From a population of 1 840 000, 192 residents developed retinal detachment. The annual incidence was therefore 10.4 per 100 000 population (9.6 for males, 11.2 for females). The incidences of three types of detachment-nontraumatic phakic, aphakic, and blunt trauma--were 9.8, 0.5 and 0.2 per 100 000 population, respectively. In 109 of 180 patients (60.6%) with nontraumatic phakic detachment, retinal breaks were associated with lattice degeneration. In females, 14 of 106 nontraumatic phakic cases (13.2%) were secondary to macular holes. CONCLUSION: Compared with previously published studies from other countries, the incidence of detachments associated with lattice degeneration and macular hole was higher, while the incidences of aphakic detachment and detachment due to blunt trauma were lower in Japan. Racial factors and living habits may affect the development of retinal detachment.

Adolescent↗

Effects of tandospirone on second messenger systems and neurotransmitter release in the rat brain.

1. We studied the effects of tandospirone, a novel serotonin (5-HT)1A receptor-related anxiolytic, on the intracellular second messenger systems and neurotransmitter release. 2. Tandospirone inhibited forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes by activation of 5-HT1A receptors and had high efficacy comparable to 5-HT1A receptor agonists such as 5-HT and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 3. Tandospirone suppressed carbachol-stimulated phosphatidyl-inositol metabolism (PI response), which was shown to be a 5-HT1A receptor-mediated event. 4. Tandospirone did not affect the release of 5-HT, norepinephrine (NE), dopamine (DA) and acetylcholine (ACh) from rat brain slice preparations. 5. These findings suggested that tandospirone shows high agonistic efficacy on the postsynaptic 5-HT1A receptors but does not affect the presynaptic autoreceptors located on nerve endings. The modulation of the second messenger system via postsynaptic 5-HT1A receptors might be involved in the anxiolytic efficacy of tandospirone.

Acetylcholine↗

Reproductive and developmental toxicity studies of toluene. I. Teratogenicity study of inhalation exposure in pregnant rats.

Toluene is a widely used solvent in industry which is the subject of abuse among the younger generation. A teratogenicity study of toluene by inhalation exposure was carried out in Sprague-Dawley rats and the effects on dams, fetuses and offspring were assessed. Pregnant females were exposed to 600 or 2000 ppm toluene for 6 h/day from day 7 to day 17 of pregnancy. The control group inhaled conditioned clean air under the same exposure conditions. Maternal exposure to 2000 ppm toluene caused significant toxic effects such as body weight suppression of dams and offspring, high fetal mortality and embryonic growth retardation, but no external, internal or skeletal anomalies were observed in the fetuses of any treated group. In addition, there were no differences in the results of pre- and postweaning behavioral tests of the offspring. However, no toxic or teratogenic changes which could be related to toluene exposure were apparent in the 600 ppm group. Further studies are warranted with toluene at higher concentrations applied during the period of organogenesis.

Abnormalities, Drug-Induced↗

Toxicity study of europium chloride in rats.

EuCl3.6H2O was administered by gavage for 28 consecutive days to groups of 10 male and 10 female rats (Slc:Wistar strain) at doses of 0, 40, 200, or 1000 mg/kg/day. Additional groups of male and female rats receiving the 0 and 1000 mg/kg doses were used to assess recovery after 14 days subsequent to cessation of compound administration. Body weights and food consumption were measured, and hematological, clinical biochemistry, and histopathological examination were performed. The concentrations of europium (Eu) and of essential elements in organs were determined by ICP-MS or ICP-AES. In the rats of each sex dosed at 200 and 1000 mg/kg, the body weight gain significantly decreased because of reduction in food consumption. Hyperkeratosis of the forestomach and eosinocyte infiltration of the stomach submucosa were found in both sexes receiving the 1000 mg/kg dose group, suggesting an irritation effect by EuCl3.6H2O. The Eu levels increased dose dependently in the liver, kidneys, spleen, and femurs, and the accumulated volume of Eu in these organs was estimated to be about 1/100,000 of the total dosed amount. The administration of EuCl3.6H2O increased the serum iron concentration in males and the serum total iron binding capacity in each sex and decreased cholinesterase activity in females in the 1000 mg/kg dosed group. Iron concentrations in the spleen and strontium concentrations in the femurs of rats of both sexes dosed at 1000 mg/kg were significantly decreased. We concluded that the no-observed-effect level is 200 mg/kg/day. Our investigation demonstrated that elemental analyses of organs is a useful approach to toxicological study.

Animals↗

[Acute pulmonary embolism after radical operation for renal cell carcinoma with vena caval extension: a case cured by thrombolytic therapy].

A 54-year-old man was hospitalized for a right renal tumor with intraluminal extension into the vena cava. He underwent radical nephrectomy with thrombectomy and regional lymphadenectomy. On the 8th postoperative day, he suddenly complained of dyspnea with tachypnea and cyanosis. Arterial blood gas analyses under an oxygen flow of 4L/min revealed PaO2 32.1 mmHg. Pulmonary angiography revealed filling defects in the right main pulmonary artery and left descending branch. Under the diagnosis of acute pulmonary embolism, thrombolytic and anti-coagulation therapy was performed and the patient recovered from the disease. We should be aware of pulmonary embolism as a postoperative complication of urological surgery.

Acute Disease↗

Regulation of hepatic level of fatty-acid-binding protein by hormones and clofibric acid in the rat.

Regulation of the hepatic level of fatty-acid-binding protein (FABP) by hormones and p-chlorophenoxyisobutyric acid (clofibric acid) was studied. The hepatic level of FABP, measured as the oleic acid-binding capacity of the cytosolic FABP fraction, was decreased in streptozotocin-diabetic rats. The level of FABP was markedly increased in adrenalectomized rats, and the elevation was prevented by the administration of dexamethasone. Hypothyroidism decreased the level of FABP and hyperthyroidism increased it. A high correlation between the incorporation of [14C]oleic acid in vivo into hepatic triacylglycerol and the level of FABP was found for normal, diabetic and adrenalectomized rats. The level of FABP was increased by administration of clofibric acid to rats in any altered hormonal states, as was microsomal 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase, a peroxisome-proliferator-responsive parameter. These results suggest that the hepatic level of FABP is under regulation by multiple hormones and that clofibric acid induces FABP and 1-acyl-GPC acyltransferase by a mechanism which may be distinct from that by which hormones regulate the level of FABP.

Animals↗

The age of onset of posterior vitreous detachment.

The age of onset of posterior vitreous detachment (PVD) was studied in 930 eyes with a clearly defined onset time and no vitreoretinal diseases except refractive error or equatorial degeneration. We found a positive correlation between onset age of PVD and refractive error, with the regression line y = 0.91 x + 60.93 (y onset age, x diopter of refractive error). The higher the degree of myopia, the younger the onset age of PVD. Comparing onset ages for 240 eyes from males and 690 eyes from females, there was a possible tendency toward a lower PVD onset age for females. There was no significant difference in onset age between 112 eyes with and 818 eyes without equatorial degeneration of the retina.

Adult↗

Distribution of carbon-11 labeled methamphetamine and the effect of its chronic administration in mice.

[11C]Methamphetamine, a psychotropic agent, was synthesized by N-methylation of amphetamine with [11C]CH3 I in hopes that it could be applied in the near future to assist positron emission tomography (PET) in the imaging of its distribution in the human brain. The regional distribution of [11C]methamphetamine was investigated in the mice brain at various intervals after an intravenous (i.v.) injection. Radioactivity was higher in the hypothalamus, cortex, striatum and hippocampus. Furthermore, in chronically administered mice, the uptake of [11C]methamphetamine was higher in the striatum than those in other regions. The regional differences in the distribution of methamphetamine in the mice brain may enable the imaging of its distribution by PET using [11C]methamphetamine.

Animals↗

Effects of SM-9018, a potential atypical neuroleptic, on the central monoaminergic system in rats.

The effects of SM-9018, a potential atypical neuroleptic, on monoamine metabolism were studied in rats. SM-9018 dose-dependently increased the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the cerebral cortex and striatum without affecting the levels of 5-HT, norepinephrine and their metabolites. This action persisted for 8 hr with a maximum effect at 1-2 hr. The SM-9018-induced increase of dopamine (DA) turnover, as indexed by HVA/DA and DOPAC/DA ratios, was comparable in the cerebral cortex and striatum, whereas the typical neuroleptic haloperidol preferentially enhanced the striatal DA turnover. These findings suggest that SM-9018, unlike haloperidol, increases DA turnover to a similar extent both in the cerebral cortex and striatum.

Animals↗

[Twenty-eight-day repeated dose toxicity test of Ajicoat SPG and Bionole in Wistar rat].

A twenty-eight-day repeated dose toxicity test of Ajicoat at dose levels of 0, 0.05, 0.2 or 1.0% and Bionole at dose levels of 0.2, 1.0, or 5.0% in the feed was carried out in male and female Wistar rats. Three groups, at the dose levels of 1.0% of Ajicoat, 5.0% of Bionole and control groups, were used for investigation of recovery. No animals died during the administration period. There were no significant differences in body weight gain, food consumption and organ weight between the treated and control groups. No specific changes were observed in any parameters of hematological investigations. At doses higher than 1.0% of Ajicost and Bionole groups, a significant increase of BUN value in serum was observed in both sexes. The serum glucose value increased and NEFA value decreased in male at a dose of 1.0% of Ajicoat group. These changes observed at the end of the administration period were no longer detected after the recovery period, suggesting that these effects were reversible. On histopathological examination, no specific changes were observed in the Ajicoat and Bionole treated rats. Based on these results, the no-observed-effect level was 0.2% (174 mg/kg) for both Ajicoat and Bionole.

Administration, Oral↗

cDNA cloning of mitochondrial delta 3, delta 2-enoyl-CoA isomerase of rat liver.

A 1.08 kbp cDNA encoding rat liver mitochondrial delta 3, delta 2-enoyl-CoA isomerase (ECI) of 298 amino acid residues (Mr 32,895) was isolated from rat liver lambda gt11, lambda gt10 cDNA libraries by the combination of an immunochemical method with a rabbit-antibody against rat liver ECI and a plaque hybridization method. The deduced amino acid sequence from the cDNA indicates that ECI is synthesized with an amino-terminal extrasequence of 35 amino acid residues and processed to the mature enzyme (Mr 29,256).

Amino Acid Sequence↗

Anticonflict action of tandospirone in a modified Geller-Seifter conflict test in rats.

Tandospirone is a novel non-benzodiazepine compound possessing potent anxiolytic properties in a water lick conflict paradigm in rats and a high affinity for central 5-HT1A receptors. In the present study, tandospirone was evaluated for anxiolytic activity in a modified Geller-Seifter conflict paradigm in rats. Tandospirone produced significant increases in the punished responding at doses of 1.25, 2.5 and 5.0 mg/kg, i.p. or 20 mg/kg, p.o., although it decreased unpunished responding at doses of 2.5 and 5.0 mg/kg, i.p. or 20 mg/kg, p.o. Likewise, diazepam was also effective after i.p.-administration in this test, and its minimum effective dose was slightly higher than that of tandospirone. This suggests that tandospirone might be as effective in the treatment of anxiety as diazepam. The anticonflict action of tandospirone was not inhibited by Ro-15-1788, a benzodiazepine antagonist, although that of diazepam was completely inhibited. 8-OH-DPAT, a full agonist of 5-HT1A receptors, was also effective in this test with a high potency. Therefore, the possibility exists that the anticonflict action of tandospirone is related to its agonist action on 5-HT1A receptors, not on benzodiazepine receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Serotonergic mechanisms in anxiolytic effect of tandospirone in the Vogel conflict test.

To clarify which 5-HT1A receptors, autoreceptors located in the raphe nuclei or post-synaptic receptors in the forebrain areas receiving a 5-HT input, mediate the anticonflict action of tandospirone (a 5-HT1A receptor-related anxiolytics), the behavioral effects of tandospirone were studied in 5,7-dihydroxytryptamine (5,7-DHT) treated rats. By measuring both monoamines and their metabolite levels and densities of [3H]8-OH-DPAT binding in 5,7-DHT-treated rat brain, we confirmed that pretreatment with 5,7-DHT destroyed 5-HT neurons selectively without affecting postsynaptic 5-HT1A receptors located on the postsynaptic neurons. This selective destruction produced no significant changes in the drinking behavior of rats in either punished or unpunished sessions of the Vogel conflict test. Furthermore, this destruction altered neither the effect of tandospirone on punished responding in this procedure nor the potency of tandospirone to induce a flat body posture in rats, which is known as the "serotonin behavioral syndrome". These results suggested that the anticonflict action of tandospirone may be produced, at least in part, by binding to postsynaptic 5-HT1A receptors and activating them as agonists, and not to 5-HT1A autoreceptors located on the cell bodies of 5-HT neurons.

5,7-Dihydroxytryptamine↗

Neovascularization of the iris in rhegmatogenous retinal detachment.

To identify conditions associated with neovascularization of the iris in rhegmatogenous retinal detachment, we examined 36 eyes with this disorder seen at our hospital between 1979 and 1990. Clinical courses of disease were divided into the following three groups: (1) neovascularization of the iris without a history of a vitreoretinal operation (four eyes), (2) neovascularization of the iris after an unsuccessful vitreoretinal operation (26 eyes), and (3) neovascularization of the iris after surgical complications (six eyes). In all eyes of Groups 1 and 2, retinal detachment persisted at the onset of iris neovascularization; however, in six eyes, iris neovascularization subsided after retinal reattachment. Characteristic features of Groups 2 and 3 were patient age of 50 years or more, severe myopia, a history of increased intraocular pressure, a history of choroidal detachment, and a large scleral buckle.

Age Factors↗