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Biomedical subjects

M Egawa

Publications and source records attributed to M Egawa.

At least 55 records · Page 3Linked to original sources
PubMed1994

Effects of an antistroke agent MCl-186 on cerebral arachidonate cascade.

Activation of the cerebral arachidonate (AA) cascade is one of the major causes of edema and tissue injury in cerebral ischemia, particularly after reperfusion. The cascade produces toxic oxygen radicals responsible for peroxidative neurodegeneration and synthesizes, the potent edematous inducer, leukotrienes. The present study was undertaken to evaluate the effect of MCl-186 (3-methyl-1-phenyl-pyrazolin-5-one), a radical scavenger and antioxidant which has beneficial anti-ischemic actions, on the cerebral AA cascade. Postischemic treatment with MCl-186 (1.0 and 3.0 mg/kg i.v.) significantly inhibited the aggravation of cortical edema seen 60 min after recirculation following 30 min of ischemia in gerbils. An antilipoxygenase agent, FPL-55712 (7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2- hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylic acid, monosodium salt; 10 mg/kg i.v.) or AA-861 ((2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinon e; 60 mg/kg i.p.) was also effective in this model; however, indomethacin (4 mg/kg i.p.), a cyclooxygenase inhibitor, was ineffective. Concomitant treatment with MCl-186 (0.1-3.0 mg/kg i.v.) remarkably inhibited the swelling observed 24 hr after cortical infusion of AA (80 micrograms) in rats. Similarly, antilipoxygenase agents clearly inhibited the AA-induced edema. Furthermore, postischemic treatment with MCl-186 (0.3-3.0 mg/kg i.v.) inhibited the facilitation of cerebral leukotriene synthesis seen 15 min after recirculation following 30 min of ischemia in gerbils. These findings suggest that the site of action of MCl-186 as an anti-ischemic agent may be closely associated with the cerebral AA cascade, especially the lipoxygenase system, activated by ischemia-reperfusion.

Animals↗
PubMed1994

Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions.

The anti-ischemic effects and a possible mechanism of a new antistroke agent, 3-methyl-1-phenyl-pyrazolin-5-one (MCI-186), were studied. Preischemic treatment with MCI-186 (3 mg/kg i.v.) facilitated the recovery of electrocorticographic activity and prolonged survival time in global complete ischemia of rats; MCI-186 (1 and 3 mg/kg i.v.) also mitigated dysfunction of the blood-brain barrier and energy failure in hemispheric embolization of rats. Postischemic treatment with MCI-186 (3 mg/kg i.v.) decreased cortical infarction in focal embolization of rats. MCI-186 (0.6-2.4 mM) inhibited the OH.-induced hydroxylation of salicylate (maximal inhibition, 40.2%), but at 100 microM it did not influence O2- generation. MCI-186 inhibited the formation of linoleic acid-conjugated dienes caused by OH. (IC50 = 32.0 microM). Also, concurrent administration of MCI-186 (3-100 mg/kg i.v.) ameliorated hyperglycemia, hyperlipopeoxidemia and degranulation of beta-cells in alloxan (40 mg/kg i.v.)-treated rats. In addition, MCI-186 inhibited iron-dependent peroxidation in rat brain homogenates and mitochondrial homogenates (IC50 = 15.0 and 2.3 microM, respectively) and prevented iron-dependent peroxidative disintegration of mitochondrial membranes (IC50 = 39.0 microM). These findings suggest that MCI-186 has potent anti-ischemic actions and that its mechanism may be closely associated with beneficial antioxidant activities.

Alloxan↗
PubMed1993

Glucagon injected in the lateral hypothalamus stimulates sympathetic activity and suppresses monoamine metabolism.

Glucagon injected in the lateral hypothalamus stimulates sympathetic activity and suppresses monamine metabolism. The central hypothesis underlying this study is that there is a reciprocal relationship between food intake and sympathetic activity to IBAT. This hypothesis was tested by using intrahypothalamic microinjections of glucagon, a peptide that has been reported to decrease food intake. Sympathetic nerve activity to interscapular brown adipose tissue (IBAT) was measured as electrophysiological discharges of sympathetic nerves to IBAT. The microinjection of glucagon into the lateral hypothalamus (LH) increased sympathetic nerve activity by +103.8 +/- 35.0% (mean +/- S.E.M.) from pre-injection basal level by 30 min after injection. There was a gradual return to baseline. Micro-injection of glucagon into the LH depressed food intake. Monoamine metabolism was measured by using a microdialysis probe attached to a guide cannula for microinjection of glucagon into the LH. After microinjection of glucagon, the dialysates were collected over 30 min intervals and assayed for norepinephrine (NE), serotonin (5-HT), dopamine (DA) and their metabolites (3-methoxy-4-hydroxyphenylglycol (MHPG); 5-hydroxyindole-3-acetic acid (5-HIAA); and 3,4-dihydroxyphenylacetic acid (DOPAC). Glucagon suppressed both NE and MHPG concentrations in the lateral hypothalamus (LH), and the concentration of DOPAC was also decreased. There was no change of 5-HT concentration but 5-HIAA levels were reduced by glucagon treatment. These data show that glucagon injected in the LH stimulates sympathetic activity and suggest that this may have occurred by suppression of norepinephrine, dopamine and serotonin turnover in the LH of freely moving rats. These data support the hypothesis of a reciprocal relationship between food intake and sympathetic activity.

Adipose Tissue, Brown↗
PubMed1993

Sympathetic nerve activity after discrete hypothalamic injections of L-glutamate.

In these experiments L-glutamate, an amino acid which stimulates neuronal discharge, was microinjected into several hypothalamic nuclei and the resultant changes in electrical firing rate of sympathetic nerves innervating interscapular brown adipose tissue (IBAT) were measured. Three patterns of response were seen. A single large stimulatory response was seen when L-glutamate was microinjected into the ventromedial hypothalamus (VMH). Microinjection of L-glutamate into the paraventricular nucleus (PVN) produced a predominantly stimulatory response which was of smaller magnitude than the VMN. However in three animals L-glutamate in the PVN decreased firing rate and in one animal a biphasic response was observed. The second pattern was a decrease in sympathetic activity to IBAT which was the predominant pattern following injection of L-glutamate into the dorsomedial hypothalamus (DMH). However, a biphasic pattern was also observed. Injection of L-glutamate into the lateral hypothalamic area (LHA) produced 3 patterns of response; an increase, a decrease; or a biphasic response in nearly equal numbers of animals. The predominant response to L-glutamate in the preoptic area (POA) was biphasic. These data are consistent with the hypothesis that the VMH is the predominant stimulatory site for activation of the sympathetic nervous system to IBAT in the rat. The DMH and LHA appear to be the predominant inhibitory areas.

Adipose Tissue, Brown↗
PubMed1993

Comparative study of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and tritiated thymidine in a chemosensitivity test using collagen gel matrix.

An organ culture system using collagen gel matrix (CGM) was modified and established successfully as a rapid and convenient method for determination of anti-cancer drug sensitivities. The cell viability of a tumor fragment was measured by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to a colored formazan product, which allowed for quantitative and simple analysis. The sensitivities of KK-47 bladder tumor from nude mice to various anti-cancer drugs tested corresponded closely to those determined in the original CGM assay system using tritiated thymidine, which has a high clinical correlation. Our modified method can be used as a practical and highly reproducible chemosensitivity test in vitro.

Animals↗
PubMed1993

Acute and chronic effects of VMH lesions on circadian rhythms in food intake and metabolites.

In the dynamic phase, 3 weeks after surgery, food intake increased especially during the latter part of the light cycle in VMH-lesioned rats, and the difference between light and dark cycles disappeared. The rhythms of serum insulin, glucose, and triglyceride disappeared. Concentrations of glucose during the light cycle were lower than those of sham-operated rats, although concentrations of triglyceride and insulin were higher than those of sham-operated rats at all times. In the static phase, 12 weeks after surgery, the difference of food intake between light and dark cycle appeared in VMH-lesioned rats, but the loss of rhythmicity for serum glucose, insulin, and triglyceride remained. Concentrations of glucose except early light phase and concentrations of triglyceride and insulin at all times were higher than those of sham-operated rats. VMH lesions thus abolished circadian rhythmicity in serum insulin, glucose, and triglyceride for a long period; however, the disturbed rhythmicity of food intake was reversible.

Animals↗
PubMed1993

Effect of beta-endorphin on sympathetic nerve activity to interscapular brown adipose tissue.

beta-Endorphin was injected into the third cerebroventricle to investigate its effects on sympathetic nerve activity to interscapular brown adipose tissue (IBAT) in rats. Multiunit discharges of sympathetic nerves to IBAT were recorded electrophysiologically in anesthetized rats. The intracerebroventricular injection of beta-endorphin (125, 250, and 500 pmol/rat in 10 microliters) suppressed sympathetic nerve activity in a dose-related fashion (-23.9 +/- 20.4, -38.7 +/- 7.1, and -66.7 +/- 7.6% 30 min after injection) compared with preinjection baseline. N-acetyl-beta-endorphin (250 pmol) had no effect on sympathetic nerve activity to IBAT. The intraperitoneal injection of naloxone (5.0 mg/rat) did not affect sympathetic nerve activity, but preinjection of naloxone inhibited the suppressive effect of intracerebroventricular injection of beta-endorphin (250 pmol). We conclude that the intracerebroventricular administration of beta-endorphin suppressed the sympathetic nerve activity to IBAT through opioid receptors. The results of this experiment are consistent with the hypothesis that beta-endorphin has a reciprocal effect on food intake and the sympathetic nervous system.

Adipose Tissue, Brown↗
PubMed1993

In vitro chemosensitivity test for human genitourinary tumors using collagen gel matrix.

An in vitro chemosensitivity test using collagen gel matrix assay with quantitative evaluation of cell viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide was applied to 40 human genitourinary tumor specimens. Chemosensitivity was determined in 34 (85%) of the 40 specimens. The anticancer drugs tested against 14 renal cell carcinomas showed lower activities than against 15 transitional cell carcinomas with different sensitivity patterns among the individual specimens demonstrated. Our assay system could be successfully applied to human genitourinary tumors and can be used as a practical and highly reproducible chemosensitivity test in vitro.

Antineoplastic Agents↗
PubMed1993

Impaired growth hormone secretion in VMH lesioned rats.

To investigate impaired growth hormone (GH) secretion in ventromedial nuclei (VMH) lesioned rats, we examined spontaneous plasma GH secretion, and plasma GH responses to arginine, clonidine and growth hormone releasing factor (GRF) under unanaesthetized and unrestrained conditions. Spontaneous GH secretion was blunted with 75% decrease of peak value in VMH lesioned rats, while it clearly existed in control rats. When rats were pre-treated with chlorpromazine (1-2 mg/kg, i.v.) which eliminates pulsatile GH secretion, no difference was observed in the plasma GH response to arginine (1 g/kg, i.v.) or to clonidine (100 micrograms/kg, i.v.) between VMH lesioned and control rats, but response to GRF (10 micrograms/kg, i.v.) was enhanced in the former animals. Administration of antiserum against somatostatin (1 ml) plus chlorpromazine significantly elevated the basal plasma GH level and GH response to arginine in control rats, but did not elevate them in VMH lesioned rats. These results suggest that reduction of both hypothalamic GRF and somatostatin release contribute to the impaired GH secretion in VMH lesioned rats. Reduction of somatostatin caused enhanced GH response to GRF and no increase in basal GH level with pre-treatment of antiserum against somatostatin. Reduction of GRF resulted in a failure to restore GH response to arginine with pre-treatment of antiserum against somatostatin. Reduction of both GRF and somatostatin caused blunted spontaneous GH secretion and normal GH response to arginine and clonidine.

Animals↗
PubMed1993

Osteosarcoma of the talus. A case report.

A 20-year-old man complained of increasing pain and swelling in the right ankle joint. Radiographs of the ankle demonstrated an ill-defined osteolytic lesion in the talus associated with a small, round bone formation just proximal to the neck of that bone. Histologic examination of the lesion showed osteoblastic osteosarcoma originating in the talus. Below-knee amputation was performed because of the peripheral location of the tumor and the close anatomic confines of the foot. A literature review demonstrated that the calcaneus and metatarsals are favorite sites of this tumor in the foot, with only one case in the talus. A second case of osteosarcoma in the talus seems to have not been previously reported.

Adult↗
PubMed1992

Effects of cholecystokinin on sympathetic activity to interscapular brown adipose tissue.

The effects of injecting cholecystokinin (CCK) into the third ventricle or into selected hypothalamic sites on electrical firing rate of sympathetic nerves to interscapular brown fat (IBAT) has been investigated in anesthetized rats. The hypothesis for these experiments was that there was a reciprocal relationship between sympathetic activity and food intake. Since CCK reduces food intake we predicted that CCK would stimulate sympathetic activity to IBAT. Following the injection of CCK into the third ventricle there was an increase in firing rate of sympathetic nerves to IBAT. When the peptide was injected into either the ventromedial hypothalamic nucleus (VMH) or lateral hypothalamic area (LHA), there was likewise an increase in sympathetic firing rate. The injection of CCK into the paraventricular nucleus produced a small decrease in sympathetic firing rate. In contrast, no effect was seen following injection of CCK into the preoptic area or dorsomedial hypothalamic nucleus. Thus, the VMH or LHA appear to be the principal hypothalamic areas mediating the stimulation of sympathetic activity to IBAT which is observed following the third ventricular injection of CCK. These studies support the hypothesis of a reciprocal relationship between the effects of CCK on the thermogenic component of the sympathetic nervous system and food intake and identify the VMH and LHA as the primary sites for this effect.

Adipose Tissue, Brown↗
PubMed1992

The influence of pelvic nerve transection on the neuromuscular system of the canine urinary bladder.

We previously reported that bladder overdistension led to denervation and subsequent supersensitivity of the detrusor muscle to acetylcholine. Therefore, to exclude the influence of bladder overdistension, we produced a low-pressure bladder in female mongrel dogs using an indwelling urethral catheter, and performed pelvic neurectomy (decentralization). We examined the effects of decentralization on the neuromuscular system of the bladder. The contraction response levels of bladder strips in dogs 1 and 2 weeks after neurectomy was low, and significantly different from that of bladder strips in the control group. The dose-response curves of dogs 4 and 8 weeks after neurectomy showed a shift to the left when compared to those of the control group, indicating a significant increase in sensitivity of the bladder strips. Many cholinergic terminal and varicosity profiles had a normal ultrastructure in all of the groups subjected to neurectomy, while some had degenerating profiles representing clear axoplasm without any recognizable organelles. Microphotographs of bladder obtained from dogs with spontaneous catheter loss showed degenerating axons, which were observed more frequently than in bladders kept empty with indwelling urethral catheters. Micturition in the dogs with spontaneous catheter loss was achieved by overflow incontinence without catheterization. These findings suggest that post-synaptic nerve degeneration may be augmented by impairment of micturition, followed by decentralization. Our observations also suggest that post-synaptic nerve degeneration (denervation) plays an important role in the increased sensitivity of the detrusor muscle to acetylcholine in the parasympathetically decentralized urinary bladder, whether denervation is due to trans-synaptic degeneration or impairment of micturition.

Acetylcholine↗
PubMed1992

Responses of tumour cell lines implanted onto the chorioallantoic membrane of chick embryo to anticancer agents in combination with hyperthermia.

The chorioallantoic membrane of chick embryos was used to examine the responses of three tumour cell lines to anticancer agents, alone and in combination with hyperthermia. Fifteen minutes of hyperthermia at 42.5 degrees C produced the most favourable anticancer effect in the B16-F10 grafts. The use of Adriamycin (ADM) alone and the combined use of hyperthermia and either cisplatin (CDDP), cyclophosphamide (CY) or ADM resulted in a significantly higher rate of tumour regression in the B16-F10 grafts from a murine melanoma. In the KK-47 grafts derived from a transitional cell carcinoma of the bladder, the use of CY alone and the combination of CY and hyperthermia produced a significant tumour regression rate. In the T24 grafts neither the use of CY or CDDP alone, nor the combination of these drugs with hyperthermia demonstrated any significant effect. This method of screening anticancer agents was found to be rapid, simple to perform and inexpensive.

Allantois↗
PubMed1992

Clinical and basic aspects of an anorexiant, mazindol, as an antiobesity agent in Japan.

The Japanese Mazindol study group investigated the action of an anorexiant, mazindol, and found that it reduced food intake by directly suppressing neurons in the lateral hypothalamus, inhibited gastric acid secretion, increased motor activity, decreased glucose absorption, and inhibited insulin secretion. It thus appears that the main effect of mazindol is to decrease food intake through suppressing feeding centers in the hypothalamus. A multicenter open study of mazindol in Japan revealed that loss of body weight and relative body weight in 14 wk were 4.6 kg and 9.2%, respectively, with suppression of appetite in the majority of obese patients. A multicenter double-blind study demonstrated that mazindol was superior to the placebo in the treatment of simple obesity. We also suggest that mazindol is effective in the maintenance of reduced body weight after obesity therapy and in the treatment of obesity-related diseases such as diabetes, hypertension, or hyperlipidemia.

Animals↗
PubMed1992

[Clinical application of the smell identification test].

Clinical application of the standardized "scratch and sniff" olfactory test in Japanese is described. Over 300 subjects participated in three experiments. In experiment 1, 29 odorants used in the smell identification test were rated as to their experiences. The ratios of the experiences in each combination of odorants were compared. In experiment 2, the test was applied to normal subjects. Average test scores decreased as a function of age, with the greatest decline occurring between the sixth and tenth decades of life. In experiment 3, the test was shown to differentiate between subjects with olfactory disorders and normal controls. This self-administered test now makes it possible to rapidly and accurately assess general olfactory function in the laboratory, clinic, or through the mail without complex equipment or space consuming stores of chemicals.

Adult↗
PubMed1991

Effect of hypothalamic administration of growth hormone-releasing factor (GRF) on feeding behavior in rats.

To examine the role and working site of growth hormone-releasing factor (GRF) in feeding behavior, we first tested the effect of the intracerebroventricular (i.c.v.) injection of GRF on food intake after 24 h of food deprivation. Cumulative food intake was measured 1, 3 and 6 h after injection. A lower dose of GRF stimulated food intake in a dose dependent manner (3 h; GRF 100 pmol 8.64 +/- 1.06 g vs saline 5.50 +/- 0.60 g, P less than 0.05), while a higher dose (1 nmol, 500 pmol) suppressed food intake (3 h; GRF 1 nmol 2.65 +/- 0.70 g vs saline 5.50 +/- 0.60 g, P less than 0.01). Second, the effect of i.c.v. injection of 100 pmol of GRF on peripheral metabolites was examined. The subsequent levels of plasma insulin, glucagon, glucose and non-esterified fatty acid showed no significant difference from those of saline administration. Third, the effect of microinjection of GRF (5 pmol) into several hypothalamic areas on food intake was examined. Injection into the ventromedial hypothalamic nucleus (VMN) stimulated food intake (3 h; GRF 5 pmol 10.32 +/- 1.04 g vs saline 6.92 +/- 0.32 g, P less than 0.05), but no significant effect was observed following injection either into the lateral hypothalamic area (LHA), paraventricular nucleus (PVN) or medial preoptic area (MPOA). Finally, we tested the stimulatory effect of GRF on food intake in bilateral VMN lesioned rats. I.c.v. injection in these animals had no more significant effect on food intake than did saline injection in VMN lesioned rats (3 h; GRF 100 pmol 6.27 +/- 0.87 g vs saline 5.34 +/- 0.44 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Neuropeptide Y suppresses sympathetic activity to interscapular brown adipose tissue in rats.

To investigate the effects of neuropeptide Y (NPY) on sympathetic nerve activity to interscapular brown adipose tissue (IBAT), we injected NPY into the third cerebroventricle (icv), medial preoptic area (MPOA), anterior hypothalamic area (AHA), paraventricular hypothalamic nucleus (PVN), ventromedial hypothalamic nucleus (VMN), and lateral hypothalamic area (LHA) of anesthetized rats. Multiunit discharges from sympathetic nerves to IBAT were recorded electrophysiologically. The icv injection of NPY suppressed sympathetic nerve activity in a dose-dependent manner, followed by a gradual recovery. The microinjection of NPY (25 pmol) unilaterally into the PVN also significantly suppressed the sympathetic nerve activity to IBAT. In contrast, microinjection of NPY into the MPOA significantly increased the sympathetic nerve activity. The injection of saline into either the PVN or MPOA had no significant effect on sympathetic nerve activity. The microinjection of NPY (25 pmol) into the AHA, VMN, or LHA did not change sympathetic nerve activity to IBAT. We conclude that central administration of NPY affects the sympathetic nerve activity to IBAT and that the suppressive effect of NPY, which may act in part through the PVN, is dominant to the stimulatory effect. The result is consistent with the hypothesis that NPY is a neurochemical modulator of the sympathetic nervous system which controls energy expenditure in IBAT.

Adipose Tissue, Brown↗