Biomedical subjects

T Egashira

Publications and source records attributed to T Egashira.

At least 55 records · Page 3Linked to original sources

PubMed1995

Effect of vagal autotransplantation and bifemelane hydrochloride on cholinergic markers and event-related potentials in rats with lesions of the nucleus basalis magnocellularis.

In rats lesioned by injecting the ibotenic acid (8 micrograms/site) into the unilateral nucleus basalis magnocellularis (NBM), the effect of treatment with bifemelane hydrochloride (BIF) or autotransplantation of the vagal nodosal ganglion was studied electrophysiologically by serial measurement of the event-related potential (ERP, P300) for 4 weeks. In addition, the effects on cholinergic markers were assessed by determining the specific binding of [3H]QNB (quinuclidinyl benzilate) to the muscarinic acetylcholine receptor (mAChR) as well as the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). The P300 latency was delayed and its amplitude remained low for 4 weeks in NBM-lesioned rats. In contrast, a return to normal occurred after 2-3 weeks in rats given daily intraperitoneal injections of BIF (15 mg/kg) and in autotransplanted rats. In lesioned rats, the cortical ChAT and AChE activities on the affected side did not recover, but the postsynaptic receptor response was transiently activated soon after lesioning. BIF increased specific mAChR binding (an early increase of affinity and a subsequent increase of receptor density) as well as presynaptic ChAT activity. Transplantation achieved the early activation of mAChR binding (increased receptor density) and continuously increased ChAT activity. Thus, the postsynaptic compensatory receptor mechanism of denervation supersensitivity acted as an early response to the depression of presynaptic cholinergic activity, but it could not improve the P300 response until the subsequent increase of cortical ChAT activity. Improvement of P300 combined with cortical cholinergic recovery after nodosal ganglion grafting or administration of BIF suggests that the neocortical ACh level may play an important role in regulating ERP.

Acetylcholine↗

PubMed1995

Importance of hepatovenous back-perfusion for maintenance of liver viability during the Pringle manoeuvre.

The role of hepatovenous back-perfusion in maintaining hepatic viability was investigated during inflow occlusion (Pringle manoeuvre) of the pig liver. The study compared two ischaemia procedures of 60 min duration: hepatic inflow occlusion and inflow plus outflow occlusion (vascular exclusion). Each procedure was carried out in six pigs and liver tissue perfusion, energy metabolism, lipid peroxidation and 7-day survival were assessed. Although all pigs survived after inflow occlusion, five of six died after vascular exclusion (P < 0.01). Exclusion induced a significant decrease in perfusion to 15.3 per cent of the value before ischaemia compared with 32.4 per cent after hepatic inflow occlusion alone (P < 0.01). Although cellular adenosine 5'-triphosphate levels were significantly decreased by ischaemia in both groups, the fall was less in pigs with inflow occlusion alone (to 55 per cent of the preclamp value) than in those with exclusion (to 24 per cent of the preclamp value) (P < 0.01). The plasma phosphatidylcholine hydroperoxide level rose immediately after reperfusion in pigs with exclusion, while the level remained constant after inflow occlusion alone. There is a fundamental difference between the two ischaemia procedures: back-perfusion from the vena cava contributes to the maintenance of liver function during inflow occlusion.

Adenosine Triphosphate↗

PubMed1995

[Protective effects of LipoPGE1, prostaglandin E1 incorporated in lipid microspheres, against liver injury caused by ischemia-reperfusion].

Effect of LipoPGE1 on liver injury caused by ischemia-reperfusion were compared with that of PGE1-CD, cyclodextrin clathrated PGE1, in rats. LipoPGE1 (10 micrograms/kg) and PGE1-CD (10 micrograms/kg) were gradually injected into the portal vein 5 min both prior to ischemia and prior to reperfusion. In only the group receiving injections of vehicle alone, rats died within 2 days after the episode of 90-min liver ischemia. The survival rate of all rats treated with LipoPGE1 was higher than that of rats who received vehicle alone, which indicates that LipoPGE1 pretherapy improved the survival of rats after liver ischemia-reperfusion. LipoPGE1 markedly suppressed elevations of GOT, GPT, and LDH, lipid peroxide and aromatic amino acid levels in the plasma caused by ischemia-reperfusion of the liver. When animals were given a single dose of LipoPGE1 prior to reperfusion, LipoPGE1 also suppressed elevations of GOT, GPT, LDH and lipid peroxide levels caused by 30-min of liver ischemia followed by 12-hr reperfusion. These suppressive effects with LipoPGE1 were stronger than those of PGE1-CD. These findings suggest that LipoPGE1 may have therapeutic applications in the treatment of hepatic injury.

Alprostadil↗

PubMed1995

Effect of long-term fluvoxamine treatment on endogenous serotonin uptake inhibitor-like substance in monkey cerebrospinal fluid.

We found that substances present in monkey cerebrospinal fluid (CSF) could inhibit [3H]-paroxetine binding in monkey brain preparations. The molecular weight of one of these inhibitory substances was approximately 2000, which is in agreement with earlier studies using human CSF. We also found that the inhibitory effect of the substances present in monkey CSF on [3H]-paroxetine binding decreased after 8 weeks of chronic fluvoxamine (5 mg/kg day, p.o.) treatment. These results suggest that the ability of a drug to decrease the activity of endogenous 5-HT uptake modulators may related to its antidepressive effects.

Animals↗

PubMed1995

[Study on the anti-dementia therapies for rats with a unilateral basal forebrain lesion--serial changes of the cholinergic markers' activities and event-related potentials after the administration of bifemelane hydrochloride or autotransplantation of the vagal nodosal ganglion].

Using rats with a unilateral lesion in the nucleus basalis magnocellularis (NBM), we examined electrophysiologically the therapeutic effects of bifemelane (BIF) and autotransplantation of the vagal nodosal ganglion (X) on the event-related potential (P300) serially for 4 weeks, and also neurochemically their effects on cholinergic markers--the specific binding of 3H-QNB (quinuclidinyl benzilate) on muscarinic acetyl-choline receptor (mAChR) and the activities of acetylcholinesterase (AChE) and choline acetyltransferase (CAT). The latency of P300 was continuously delayed and its amplitude remained low voltage until 4 weeks in the NBM-lesioned rats (No-Tx group). Whereas the latency and amplitude returned to normal after 2-3 weeks in the rats given daily intraperitoneal injection of 15 mg/kg BIF (BIF group) and autotransplanted ones (X group). The cortical CAT and AChE levels on the lesion side did not recover until 4 weeks in No-Tx group, but the CAT levels recovered after 3 weeks in both BIF and X group; the AChE levels, after 1 week in BIF group and after 3 weeks in X group. The cortical mAChR on the lesion side was within or more than normal range in all rats. These results might indicate as follows: 1) Compensatory postsynaptic process such as cortical mAChR increase and AChE decrease occurred after acute cholinergic depletion. 2) Administration of BIF and X autotransplantation recovered cortical CAT and AChE levels and normalized cholinergic neuronal activity of P300.

Acetylcholinesterase↗

PubMed1994

Effect of methylprednisolone on plasma lipid peroxidation induced by lipopolysaccharide.

The effects of methylprednisolone succinate (MP) on plasma lipid peroxidation, plasma SOD activity and superoxide production in polymorphonuclear leukocytes (PMNs) induced by lipopolysaccharide (LPS) were examined in rats in vivo and in vitro. In rats subjected to LPS treatment, plasma phosphatidylcholine hydroperoxide (PCOOH) levels significantly increased, and the plasma Cu,Zn-SOD activity decreased by about 75%. When rats were given 30 mg/kg of MP intravenously, MP suppressed the elevation of plasma PCOOH levels and partially inhibited the decrease in plasma Cu,Zn-SOD activity. MP also suppressed PMA-induced superoxide production in PMNs primed by LPS. In in vitro experiments, low concentrations of MP had no effect on NADPH-dependent lipid peroxidation, but 4 mM MP produced 50% inhibition. MP had little effect on PMA-induced superoxide production in PMNs primed by LPS. Moreover, MP had no radical-trapping effect on superoxide, hydroxyl radical and stable DPPH radical. These results suggest that the suppressive effect of plasma lipid peroxidation by MP is not due to radical-trapping effects or preventive anti-oxidation, but may involve the suppression of the lipid chain reaction in liver membrane resulting from PMA-induced superoxide anions generated by PMNs.

Animals↗

PubMed1994

Effect of diclofenac, a non-steroidal anti-inflammatory drug, on lipid peroxidation caused by ischemia-reperfusion in rat liver.

The present study investigated the effects of diclofenac sodium (Dic Na) on lipid peroxidation (LPO) and liver injury in ischemia-reperfused rat. LPO was estimated from the levels of phosphatidylcholine hydroperoxide (PCOOH), a primary peroxidative product of phosphatidylcholine. Hepatic ischemia-reperfusion induced significant elevation of plasma PCOOH and caused liver injury in rats. Rats were treated daily with Dic Na or alpha-tocopherol (alpha-toc.), p.o., for 5 days and once at 1 hr prior to induction of ischemia. Both substances prevented LPO from decreasing the plasma PCOOH level, and they significantly suppressed the elevation of serum GOT and LDH, in a dose-dependent manner. Dic Na was able to scavenge the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), but did not show radical-trapping ability for superoxide anion (O2-) or hydroxyl radicals (.OH), nor a suppressive ability for the NADPH-dependent LPO of microsomes. In contrast, alpha-toc. trapped both DPPH and O2-, but not .OH, and it inhibited the NADPH dependent LPO in vitro. These results suggest that Dic Na may suppress liver injury caused by ischemia-reperfusion through stable radical scavenging and the inhibition of superoxide production in activated phagocytes, both of which may restrain the induction and progression of oxidative stress.

Animals↗

PubMed1994

Age-related changes of cholinergic markers in the rat brain.

To evaluate whether any degenerative changes affect the brain cholinergic systems during natural aging, we compared various cholinergic biochemical markers (number of muscarinic receptors, mAChR; choline acetyltransferase activity, ChAT; acetylcholinesterase activity, AChE; and sodium-dependent high affinity choline uptake) in the cortical (CR) and subcortical (SS) regions of the brains of aged (24 month) and young (2 month) rats. Using [3H]-quinuclidinyl benzilate ([3H]-QNB) as the ligand of muscarinic receptor binding, the numbers of mAChR decreased about 30% in both the CR and the SS of aged rats compared with those in young rats, while a significant age-related increase in the affinity of mAChR was observed. [3H]-QNB binding in both the young and aged rat brain was displaced markedly by pirenzepine, while [3H]-QNB binding in the SS of the aged rat brain was displaced at low concentrations of atropine. The Vmax values of ChAT and AChE also decreased about 20-30% compared with those of young rats. The sodium-dependent high affinity choline uptake was lower in the crude synaptosomal fraction prepared from aged rat brain than in young brain. Hemicholinium-3 inhibited the choline uptake in young rat brain at a concentration range of 1 microM-10 nM, but choline uptake in aged brain was insensitive to hemicholinium-3. These results indicate that natural aging brings about a diffuse and multiple depletion of various biochemical markers in cholinergic neurons.

Acetylcholinesterase↗

PubMed1994

The multiple hydroperoxides of choline phospholipids occurring in plasma after ischemia-reperfusion in rat liver.

Since phosphatidylcholine is a primary membrane component, and its peroxidation may result in disruption and dysfunction of the biomembrane, we used phosphatidylcholine hydroperoxide (PCOOH) as an index of oxidative-stress-related injury. We detected the occurrence of PCOOH in both liver and plasma from rats subjected to hepatic ischemia-reperfusion, and demonstrated that liver and plasma PCOOH levels reflect the extent of liver injury. However, the accuracy in measuring PCOOH levels, particularly in blood samples, is still in question since PCOOH may be rapidly eliminated by phospholipase A2 enzymes, which are widespread, easily activated, and have a preference for oxidized glycerophospholipids. When PCOOH levels were determined, using high-performance liquid chromatography to detect chemiluminescence (CL), the plasma samples showed a broad CL peak that began to elute at the same time as in the liver samples, but lasted longer. The peak appeared to contain hydroperoxides from multiple lipid classes. In addition to PCOOH, the hydroperoxides of sphingomyelin and lysophosphatidylcholine (SPHOOH and LPCOOH) were identified in the plasma of rats subjected to ischemia-reperfusion using thin layer chromatography separation and subsequent visualization, infrared spectroscopy, and hydrolysis under mild alkaline conditions. These results indicate that the occurrence of SPHOOH and LPCOOH, as well as PCOOH, may reflect liver damage related to ischemia-reperfusion.

Animals↗

PubMed1994

[Experimental techniques for developing new drugs acting on dementia (4)--Aged rats].

We have devised a method for the procurement and breeding of aged rats used for aiding in the development of drugs for disease, involving Alzheimer's disease and cerebrovascular dementia. The changes in choline acetyltransferase (ChAT), acetylcholinesterase (AChE), muscarinic receptor binding (mAChR) and Na(+)-dependent high affinity choline uptake (HACU) are generally consistent with age-dependent declines in cholinergic neurotransmission, although these decreases may include differences in strain/species, sex, tissue sampling and assay procedures. So, the choice of time points during the life cycle selected for comparison between young and aged rats is particularly important when using laboratory animals. These observations support the utility of the senescent rat model in studying aging and development of nootropic drugs.

Acetylcholinesterase↗

PubMed1993

Effects of anti-free radical interventions on phosphatidylcholine hydroperoxide in plasma after ischemia-reperfusion in the liver of rats.

The present study set out to investigate whether plasma phosphatidylcholine hydroperoxide (PCOOH) levels could accurately reflect lipid peroxidation linking to liver damage due to ischemia--reperfusion. PCOOH is a primary peroxidative product of phosphatidylcholine (PC), which is the most important functional lipid in the hepatocellular membrane, and may mediate oxidative stress. We quantified PCOOH and PC in the plasma and liver of rats subjected to hepatic ischemia-reperfusion by chemiluminescence detecting HPLC (CL-HPLC) method. Plasma PCOOH levels showed no significant rise in either the ischemia only group or in the sham-operation group, compared to controls (0.7 nmol/mL plasma). At 60 min subsequent to reperfusion, the PCOOH levels in plasma and liver, as well as the levels of several serum markers of liver injury [lactic dehydrogenase (LDH), glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)] increased in proportion to the duration of ischemia (up to 60 min). During periods of reperfusion following 30 min of ischemia, plasma PCOOH increased biphasically (2 nmol/mL; 12-24 hr duration of reperfusion), and generally ran parallel to that in the liver after more than 60 min of reperfusion. Dose-dependent protective effects against warm ischemia (30 min)-reperfusion (12 hr) injury were clearly demonstrated in the groups treated with allopurinol, diclofenac Na, ascorbic acid (V.C), alpha-tocopherol and coenzyme Q10, but not in those treated with r-h-superoxide dismutase or betamethasone. The rises in plasma PCOOH and serum GOT, GPT and LDH of the ischemia-reperfused rats were ameliorated most in the group pretreated with diclofenac Na, and next most in the group pretreated with V.C. These results indicate that the plasma PCOOH levels are a useful index both for liver cell damage induced by oxygen free radicals generated during ischemia-reperfusion, and to investigate the efficacy of drugs against oxidative stress.

Animals↗

PubMed1993

Changes in monoamine oxidase activity in mouse brain associated with d-methamphetamine dependence and withdrawal.

The long-term effects of d-methamphetamine (MP, 5 mg/kg) on brain mitochondrial monoamine oxidase (MAO) activity were studied in mice given MP intraperitoneally daily for 4 weeks. The MAO activities decreased when serotonin (5-HT) and dopamine (DA) were used as substrates. A marked elevation in MAO activity was seen during MP withdrawal when 5-HT, DA, beta-phenylethylamine (beta-PEA) and norepinephrine (NE) were used as substrates. The kinetics of MAO showed a significant decrease in Km values, but no significant change in Vmax values during MP withdrawal, despite the presence of NE. The Km and Vmax values increased when NE was the substrate. Inhibition of MAO by MP or its metabolites (amphetamine, p-hydroxyamphetamine and p-hydroxymethamphetamine) increased with the use of the following substrates in the order: DA, 5-HT, NE and beta-PEA.

Animals↗

PubMed1993

Investigation of the renal injury caused by liver ischemia-reperfusion in rats.

To explain the mechanism of renal injury caused by liver ischemia-reperfusion, we investigated biochemical and morphological changes in the liver and kidney in rats. After reperfusion following 60 min of liver ischemia, numerous changes were found. The level of serum transaminases and lipid peroxide formation in the liver tissue increased significantly. Electron microscopic studies revealed that most of the hepatocytes had swollen mitochondria and clumping of the nuclear chromatin. The sinusoidal endothelium was disrupted and the sinusoidal lumen was filled with numerous erythrocytes. Blood endotoxin concentration, plasma lipid peroxide levels, and serum beta-glucuronidase activities were significantly higher than in the control group. Biochemical and morphological renal injury was also observed. Tissue lipid peroxide levels increased in both the kidney and the liver. Microscopic examination revealed damage to the renal tubules, including interstitial edema, dilatation of the lumen, and granular casts derived from necrotic cells in the proximal convoluted tubule. The levels of urinary N-acetyl-beta-D-glucosaminidase (NAG) in the liver ischemia-reperfusion group were also higher than in the control group. These results suggest that the renal injury was caused by an increase in endotoxin, lipid peroxide, and lysosomal enzymes in the blood following the liver injury induced by the ischemia-reperfusion.

Animals↗

PubMed1993

Augmentation of hepatocyte proliferation by immunosuppressant pretherapy is associated with up-regulation of malondialdehyde production.

We studied the relationship between augmentation of liver regeneration with immunosuppressants and malondialdehyde (MDA, an end-product of lipid peroxides) production. MDA was determined using the thiobarbituric acid reaction. Rats underwent a 4-day treatment of FK506 (FK, 1 mg/kg per day), cyclosporine (Cs, 10 mg/kg) or azathioprine (AZA, 1 mg/kg) by gavage prior to 70% hepatectomy. They were then divided into four groups: (1) controls (vehicle-treated); (2) FK; (3) Cs; (4) AZA. MDA levels, uptake of BrdU (5-bromo-2-deoxyuridine) in the liver and serum biochemistry were investigated 24 h after hepatectomy. Immunosuppressant pretherapy significantly stimulated BrdU uptake by hepatocytes, in association with increased MDA production, while there were no differences in serum liver injury parameters among the groups given or not given immunosuppressants. The implications of the rising MDA values during liver regeneration are discussed with respect to immunosuppression and a measure of lipid peroxidation. Additional study indicated that one immunodepressant pretreatment (24 h prior to hepatectomy) was effective for up-regulation of liver regeneration.

Animals↗

PubMed1993

Neuroleptics induce penile erection in the rabbit.

1. Intramuscular (i.m.) administration of the neuroleptics chlorpromazine, haloperidol and spiperone at doses ranging from 0.1 to 0.4 mg/kg in male rabbits induced a dose-dependent penile erection. 2. The i.m. administration of the alpha 1-adrenoceptor antagonists prazosin and bunazosin (0.1-0.4 mg/kg), induced a dose-dependent penile erection. However, that of the peripheral dopamine receptor antagonist domperidone (0.4-4.0 mg/kg) and the dopamine receptor agonist apomorphine (0.1-1.0 mg/kg) did not. Penile erection was not induced by i.m. injection of chlorpromazine in combination with intrapenile administration of the alpha 1-adrenoceptor agonist methoxamine. 3. Penile erection was induced by the administration of chlorpromazine (0.25-1.00 mg/body) into the lateral cerebral ventricle. At a low dose, however, the administration of chlorpromazine into the lateral ventricle induced a less notable penile erection than that induced intramuscularly. 4. Penile erection was induced by i.m. injection of the ganglionic blocker hexamethonium (5-20 mg/kg). When chlorpromazine was given after pretreatment with hexamethonium, penile erection was more notable than that induced by either drug given alone. 5. These results suggest that neuroleptics could act locally in the penile structure to cause penile erection by alpha 1-adrenoceptor-blocking actions.

Adrenergic alpha-Agonists↗

PubMed1993

Further studies on the endogenous serotonin-uptake-inhibitor-like substances in the human cerebrospinal fluid.

The properties of endogenous substances that inhibit 5HT uptake in human cerebrospinal fluid (CSF) were investigated. Human CSF was loaded onto a Sephadex G-25 column, and each fraction was tested for its ability to inhibit [3H]paroxetine binding in monkey brain preparations. We found four different inhibitory peaks with respective molecular weights (M.W.) of > 12400, 2000 and two of < 1350. The third and fourth peaks (F-3, F-4: < 1350 M.W.) of inhibitory activity were determined to consist of some monoamines (5HT, etc.) or their metabolites (5HIAA, etc.) and other unidentified compounds by using an HPLC-electrochemical detector. The second peak (F-2, M.W. about 2000) displaced [3H]paroxetine binding noncompetitively (decreased Bmax and did not change Kd) and inhibited [3H]5HT uptake noncompetitively (decreased Vmax and did not change Km), but had no effect on either [3H]norepinephrine uptake or [3H]dopamine uptake. These results suggest that the endogenous substances that selectively inhibit 5HT uptake are present in human CSF as low molecular weight compounds.

Animals↗

PubMed1992

Chemiluminescence-HPLC assay of phosphatidylcholine hydroperoxide generated by ischemia-reperfusion in the liver of rats.

To determine cellular damage due to "oxidative stress", we developed a sensitive and specific quantitative assay for phosphatidylcholine hydroperoxide (PCOOH) by coupling HPLC with detection of chemiluminescence (CL). The qualitative and quantitative detection limits of PCOOH by this assay were 0.5 and 2 pmol (based on active oxygen from hydroperoxide). Using this CL-HPLC method, we determined PCOOH levels caused by ischemia-reperfusion in rat livers. The PCOOH levels in livers of control, sham-operated and operated rats with only ischemic treatment were approximately 2 nmol/g wet liver weight. The PCOOH level and several serum parameters of liver injury increased with an increase in the duration of ischemia, and also increased in proportion to the duration of reperfusion. The determination of PCOOH in liver caused by ischemia-reperfusion could be a useful method for investigating liver damage induced by free radicals.

Animals↗

PubMed1992

[Effects of Gomishi and Shosaiko-to on lipid peroxidation of rat brain].

Gomishi and Shosaiko-to were administered to the rats at a dose of 10-100 mg/kg daily for 2 weeks, and their effects on lipid peroxidation of rat brain were compared with that of alpha-tocopherol. Administration of Gomishi and Shosaiko-to showed almost the same suppressive action on the lipid peroxidation. Gomishi and Shosaiko-to exhibited a radical-trapping action on a stable free radical, 1, 1-diphenyl-2-picrylhydrazyl (DPPH), which was estimated photometrically. The effects of Gomishi or Shosaiko-to at concentrations of 10(-3) to 10(-5)g/ml on lipid peroxidation of rat brain homogenates were investigated. The lipid peroxidation was inhibited by the addition of these drugs, and the suppressive effect was also dependent on the concentration. These suppressive effects with Shosaiko-to were stronger than those of Gomishi. These results suggest that the radical trapping action of Gomishi or Shosaiko-to is the likely mechanism suppressing brain lipid peroxidation; Particularly, the suppressive effect on the brain's lipid peroxidation by Shosaiko-to is at least in part due to its radical trapping action and inhibition of O2-. production.

Administration, Oral↗