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Biomedical subjects

T Endoh

Publications and source records attributed to T Endoh.

99 records · Page 6Linked to original sources
PubMedDate not supplied

Inhibitory effect of beraprost sodium on formation of lipid peroxides in ischemia and recirculation-induced cerebral injury.

A cerebral injury was induced by the bilateral common carotid artery occlusion and recirculation in spontaneously hypertensive rats (SHRs). Employing this ischemia-recirculation rat model, the effects of beraprost sodium (beraprost) on (1) lipid peroxide formation, (2) the increase in the brain water content and (3) neurological signs were examined. In a dosage of 25 micrograms kg-1 or higher, beraprost, administered orally, significantly inhibited the formation of lipid peroxides in the brain and serum induced by cerebral ischemia and subsequent recirculation in a dose-dependent manner. Beraprost also alleviated ptosis and markedly inhibited abnormal running behaviour caused by the ischemia and subsequent recirculation. In addition, although administration of beraprost did not cause marked inhibition of the increase in the brain water content (used as an index of cerebral oedema) during the first 3 h after recirculation, it restored the normal brain water content within 24 h after recirculation. Therefore, this effect was observed evidently later than the effect of inhibition of lipid peroxide formation. Moreover, administration of beraprost resulted in improvement in the symptoms accompanying the ischemic treatment. These results suggest that beraprost is potentially useful for or treatment of the pathological state accompanying cerebral infarction.

Animals↗
PubMedDate not supplied

G protein activation by endomorphins in the mouse periaqueductal gray matter.

The midbrain periaqueductal gray matter (PAG) is an important brain region for the coordination of mu-opioid-induced pharmacological actions. The present study was designed to determine whether newly isolated mu-opioid peptide endomorphins can activate G proteins through mu-opioid receptors in the PAG by monitoring the binding to membranes of the non-hydrolyzable analog of GTP, guanosine-5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS). An autoradiographic [(35)S]GTPgammaS binding study showed that both endomorphin-1 and -2 produced similar anatomical distributions of activated G proteins in the mouse midbrain region. In the mouse PAG, endomorphin-1 and -2 at concentrations from 0.001 to 10 microM increased [(35)S]GTPgammaS binding in a concentration-dependent manner and reached a maximal stimulation of 74.6+/-3.8 and 72.3+/-4.0%, respectively, at 10 microM. In contrast, the synthetic selective mu-opioid receptor agonist [D-Ala(2),NHPhe(4), Gly-ol]enkephalin (DAMGO) had a much greater efficacy and produced a 112.6+/-5.1% increase of the maximal stimulation. The receptor specificity of endomorphin-stimulated [(35)S]GTPgammaS binding was verified by coincubating membranes with endomorphins in the presence of specific mu-, delta- or kappa-opioid receptor antagonists. Coincubation with selective mu-opioid receptor antagonists beta-funaltrexamine or D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH(2) (CTOP) blocked both endomorphin-1 and-2-stimulated [(35)S]GTPgammaS binding. In contrast, neither delta- nor kappa-opioid receptor antagonist had any effect on the [(35)S]GTPgammaS binding stimulated by either endomorphin-1 or -2. These findings indicate that both endomorphin-1 and -2 increase [(35)S]GTPgammaS binding by selectively stimulating mu-opioid receptors with intrinsic activity less than that of DAMGO and suggest that these new endogenous ligands might be partial agonists for mu-opioid receptors in the mouse PAG.

Analgesics, Opioid↗
PubMedDate not supplied

Effect of beraprost sodium (BPS) on the postischemic neuropathological changes and stroke index after left carotid artery occlusion in gerbils.

We investigated the effect of beraprost sodium (BPS), a new prostacyclin analog, on behavioral and neuropathological changes induced by a 10-min occlusion of the left carotid artery in gerbils. Gerbils were treated orally with BPS (1-100 micrograms/kg) 30 min before occlusion. Pathological evaluation of neural damage in the CA1 region of the hippocampus was performed 7 d after the ischemic insults. In the symptomatic group, in which the stroke index score was > 10, symptomatic behaviors, such as head cocked, splayed out hind limb, circling, and various similar behaviors, were observed. Pathologically, almost all CA1 neurons were destroyed 7 d after ischemia in the symptomatic group. BPS improved the stroke index during ischemia and neuropathological changes 7 d later, with statistical significant improvement occurring at a dose of 100 micrograms/kg.

Animals↗
PubMedDate not supplied

Effect of beraprost sodium (BPS), a prostacyclin analog, and dizocilpine (MK-801) on repeated ischemia-induced chronic cortical atrophy in gerbils.

We investigated the effect of beraprost sodium (BPS), a new prostacyclin analog, and dizocilpine (MK-801) on repeated ischemia-induced cerebral atrophy and chronic cortical neuronal loss in gerbils. The left common carotid artery of gerbils was repeatedly occluded (for 10, 7, 7, and 7 min) at intervals of 24 h. The thickness of the cerebral cortex of the ischemic hemisphere diminished with increasing time of reperfusion after an ischemic insult. The animals were given BPS (1-100 micrograms/kg, po) or MK-801 (3-300 micrograms/kg, sc) after the first ischemic insult, and then twice daily for 4 wk. Increases in the amount of neuronal loss and acidophilic neurons, and progressive atrophy were observed with increasing time of reperfusion in the cerebral cortex of the ischemic hemisphere. Cortical sections revealed no astrocytes positive for glial fibrillary acidic protein (GFAP), whereas the hippocampal CA1 area showed neuronal loss accompanied by GFAP-positive astrocytes. In control animals at 4 wk survival, the area ratio (area of ischemic cortex/area of opposite cortex) and the cortical neurons ratio (number of neurons in ischemic cortex/number of neurons in opposite cortex) were 89.8 +/- 3.0% and 74.6 +/- 3.4%, respectively. BPS was found to inhibit atrophy and chronic cortical neuronal loss in the ischemic hemisphere in a dose-dependent manner, whereas MK-801 showed no inhibitory effects at any dose tested. These results may suggest that the nature of neuronal degeneration differs between the cortical and hippocampal areas, that cortical neuronal degeneration might not involve glutamate pathways with NMDA receptors in this model, and that prostacyclin could play an essential role in prevention of ischemia-induced progressive neuronal loss.

Animals↗
PubMedDate not supplied

Comparative changes in the liver of female Fischer-344 rats after short-term feeding of a semipurified or a semisynthetic L-amino acid-defined choline-deficient diet.

Groups of female Fischer-344 rats were fed a semipurified choline-deficient (CD) diet, or a semisynthetic L-amino acid-defined choline-deficient (CDAA) diet, for up to 12 wk and effects of the 2 diets on the liver were compared. Steatosis was diffuse and more severe throughout in rats fed the CDAA diet than in rats fed the CD diet. Greater elevations in serum aspartate and alanine aminotransferase activities were also present in the former rats, along with higher 2-bromodeoxyuridine labeling indices in the liver. Discrete amounts of 8-hydroxyguanine were detected in liver DNA, but were not significantly different in rats fed the 2 diets, or from those present in a group of control rats killed at 0 time. Glutathione S- transferase placental form-positive focal lesions were not observed in any of the rats. The results show that the CDAA diet causes more severe degrees of steatosis and liver cell death and proliferation than the CD diet, raising the possibility that it may, in contrast to the CD diet, result in the eventual induction of hepatocellular carcinomas in female Fischer-344 rats.

Alanine Transaminase↗
PubMedDate not supplied

Diagnostic significance of serum angiotensin-converting enzyme activity in biochemical tests with special reference of chronic liver diseases.

To assess the degree of the differential ability of serum angiotensin-converting enzyme (ACE) activity as compared with 13 conventional biochemical tests, we studied 76 healthy subjects and 107 patients with chronic liver diseases. It was found that the mean values of serum ACE activity were significantly different between the healthy group and groups with liver disease. According to discriminant function analysis, the diagnostic accuracy reached 82.2% in 14 tests. In order to analyze the extent of contribution of each test to the entire diagnostic accuracy, we made an indicator of the relative decrease rate expressed as a percentage, which is 100-100 x (13-test diagnostic accuracy less one test/14-test diagnostic accuracy). The relative decrease rate of serum ACE activity was 11.4%, the largest in value. In conclusion, serum ACE activity may be one of the best discriminators to characterize chronic liver disease.

Adult↗
PubMedDate not supplied

Neoadjuvant intraarterial high-dose chemotherapy and autologous peripheral blood stem cell transplantation for advanced breast cancer.

Eight locally advanced breast cancer patients were treated with neoadjuvant intraarterial high-dose chemotherapy (epirubicin) plus MPA combined with autologous PBSCT. All patients completed the scheduled treatment, and there were no toxic deaths. Patients were treated with an escalating dose of epirubicin (370-480 mg) and cyclophosphamide (0-6000 mg). The rate of clinical response was 100%. The rate of good histologic response was 87.5% in the main tumor and 75% in diseased lymph nodes. The 2-year survival rate was 100%. Six patients were disease-free at the time of writing. This treatment resulted in higher rates of clinical and histologic response when compared with standard-dose intraarterial chemotherapy.

Adult↗
PubMedDate not supplied

Nor-binaltorphimine: a potent and selective kappa-opioid receptor antagonist with long-lasting activity in vivo.

The kappa-receptor selectivity of nor-binaltorphimine (nor-BNI), a highly selective kappa-opioid receptor antagonist in vitro, was examined in vivo by measuring the time course of the antagonistic action of nor-BNI (5 and 20 mg/kg, s.c.) against the responses to U-50488H (10 mg/kg, s.c.), morphine (10 mg/kg, s.c.) and fentanyl (50 micrograms/kg, s.c.) in mice. In the tail pinch test, nor-BNI partially antagonized morphine and fentanyl analgesia, but not U-50488H analgesia in the first 30 min after s.c. administration. However, the kappa-antagonistic action gradually increased, reaching a plateau at 2 hr. This antagonistic action was maintained for at least 4 days. In contrast, the mu-antagonistic action declined to the control level at 2 or 4 hr after nor-BNI administration. In the acetic acid-induced writhing test, nor-BNI also exerted a more potent and selective kappa-antagonistic action at 24 hr than at 1 hr after its s.c. administration. Nor-BNI also showed a long-lasting kappa-antagonism against the hyperthermic response induced by U-50488H (5 mg/kg, s.c.). Thus, we found that nor-BNI is a slow-onset, long-lasting, selective kappa-antagonist in vivo.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗