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Biomedical subjects

M Egawa

Publications and source records attributed to M Egawa.

At least 73 records · Page 4Linked to original sources

Adrenal sympathetic nerve activity in response to hypothalamic injections of 2-deoxy-D-glucose.

Adrenal sympathetic nerve activity after microinfusion of 2-deoxy-D-glucose (2-DG) into various hypothalamic nuclei was investigated in anesthetized rats. Infusion of 2-DG into the ventrolateral portion of the lateral hypothalamic area (LHA) induced a large and long-lasting increase (greater than 60 min) in adrenal nerve activity. In contrast, infusion into the dorsal or medial portion of the LHA tended to produce a small decrease with a return to baseline within approximately 60 min after the end of the infusion. The direct administration of 2-DG into either the paraventricular nucleus or the dorsomedial hypothalamic nucleus produced a strong inhibition of adrenal nerve activity. Infusions into the ventromedial hypothalamic nucleus induced either a decrease of adrenal nerve activity or were without effect. These findings provide evidence that induction of glucoprivation in the hypothalamus with 2-DG can excite or inhibit adrenal nerve activity, depending on the hypothalamic region. These data also indicate that the ventrolateral portion of the LHA plays an important role in the regulation of adrenal catecholamine secretion in response to glucoprivic conditions in the central nervous system.

Adrenal Glands↗

Restoration of circadian corticosterone rhythm in ventromedial hypothalamic lesioned rats.

The effects of ventromedial hypothalamic (VMH) lesions on the circadian periodicity of blood corticosterone were studied in female rats. The rats were kept on a 12-hour light/12-hour dark illumination regimen and fed ad libitum. Three, 10 and 12 weeks after the VMH lesions, the concentrations of blood corticosterone were measured every 4 h for 48 h in the same unanesthetized rats. Three weeks after the operation, the circadian rhythm in VMH-lesioned rats was disturbed and disappeared. The corticosterone levels at 03:00, 07:00, and 11:00 were significantly higher than those in sham-operated rats. 10 and 12 weeks after the operation, the circadian rhythm, however, was notable (p less than 0.05, p less than 0.05). The elevated mean corticosterone levels over 48 h at 3 weeks after the operation decreased at 10 and 12 weeks. The sham-operated rats showed a significant circadian rhythm at 3, 10 and 12 weeks after the operation (p less than 0.001 in each period) with a peak concentration at 19:00 and through at 07:00. These findings show that the corticosterone circadian rhythms which were disturbed in the dynamic phase after VMH lesions recovered in the static phase of obesity, suggesting that the ventromedial hypothalamus is not an essential biological clock of circadian corticosterone rhythm.

Animals↗

Effect of corticotropin releasing hormone and neuropeptide Y on electrophysiological activity of sympathetic nerves to interscapular brown adipose tissue.

It has been proposed that there is a reciprocal relationship between food intake and sympathetic activity. To test this hypothesis corticotropin releasing hormone, which suppresses feeding behavior, and neuropeptide Y, which stimulates it, were injected intracerebroventricularly and sympathetic nerve activity to interscapular brown adipose tissue measured in anesthetized rats. Multi-unit discharges of sympathetic nerves to interscapular brown adipose tissue were recorded electrophysiologically. The intracerebroventricular injection of corticotropin releasing hormone (250 and 500 pmol) increased sympathetic nerve activity and the intracerebroventricular injection of neuropeptide Y (250-500 pmol) suppressed sympathetic nerve activity in a dose-dependent manner. The intracerebroventricular injection of vehicle did not affect sympathetic nerve activity. The result is consistent with the hypothesis that these brain peptides are neuromodulators of the sympathetic nervous system which may control energy expenditure in interscapular brown adipose tissue. The effects of these two brain peptides on sympathetic nerve activity are opposite to their effects on feeding behavior suggesting that sympathetic activity and food intake may be reciprocally related.

Action Potentials↗

Preoptic area injection of corticotropin-releasing hormone stimulates sympathetic activity.

To investigate the sites of action of corticotropin-releasing hormone (CRH) on sympathetic nerve activity to interscapular brown adipose tissue (IBAT), we injected CRH into the third cerebroventricle, medial preoptic area (MPOA), and other hypothalamic areas in anesthetized rats. The multiunit discharges of sympathetic nerves to IBAT were recorded electrophysiologically. The intracerebroventricular injection of CRH increased sympathetic nerve activity in a dose-dependent manner over the range 250-1,000 pmol. The microinjection of CRH (200 pmol) into the unilateral MPOA increased the sympathetic nerve activity to IBAT by +150.6 +/- 25.9% at 30 min after injection. However, the injection of saline (0.15 M NaCl) and glucagon (200 pmol) into the MPOA did not increase sympathetic nerve activity. The microinjection of CRH (200 pmol) into the anterior hypothalamic area, paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, and lateral hypothalamic area had no significant effect on nerve activity. We conclude that central administration of CRH increases the sympathetic nerve activity to IBAT and that the MPOA is one of the sites for this action. The result is consistent with the hypothesis that CRH is a neurochemical stimulator of the sympathetic nervous system, which may be involved in control of energy expenditure in rodents.

Adipose Tissue, Brown↗

Transethnic adoption and personality traits: a lesson from Japanese orphans returned from China to Japan.

The authors interviewed 25 Japanese who had been left as orphans in China at the end of World War II and who had recently returned to Japan with their Chinese spouses after almost four decades. It was found that even though they had been raised as Chinese culturally for almost their entire lives, most of these subjects had retained certain Japanese personality traits and social behavior from early childhood, and these characteristics distinguished them from their Chinese counterparts.

Adoption↗

Catecholamine-induced desensitization of brain beta adrenoceptors in vivo and reversal by corticosterone.

The function of beta adrenoceptors in the brain was studied with a new technique involving the microdialysis collection of extracellular cyclic AMP (cAMP). Prolonged infusion of isoproterenol (2 hr) was found to induce a marked desensitization of the beta receptor-cAMP response. Administration of corticosterone (10 mg/kg) 3 hrs prior to the infusion markedly attenuated the desensitization. The results indicate that the catecholamine-induced densensitization of brain beta adrenoceptors can be studied in vivo and that corticosterone is capable of reversing this effect in the brain as has been reported previously for peripheral tissues.

Animals↗

Effects of 2-deoxy-D-glucose on sympathetic nerve activity to interscapular brown adipose tissue.

The effects on firing rate of sympathetic nerves to interscapular brown adipose tissue were measured after induction of intracellular glycopenia by peripheral or central administration of 2-deoxy-D-glucose (2-DG). Injection of 2-DG (250 mg/kg body wt) into the jugular vein rapidly suppressed the sympathetic activity, which declined 84% within 10 min after the injection. This suppression persisted for at least 40 min. Hyperglycemia did not affect the sympathetic activity but partially inhibited the suppressive effect of 2-DG injection. Acute vagotomy failed to block the suppressive effect of 2-DG. Injection of 2-DG (2.5 mg/rat) into the third cerebral ventricle suppressed the sympathetic activity. This suppression was followed by gradual recovery. Saline injection did not affect the sympathetic activity. We conclude that cellular glycopenia induced by injecting 2-DG peripherally or into the third cerebral ventricle suppresses the sympathetic activity to brown adipose tissue. The results are consistent with the hypothesis that an acute energy shortage decreases the thermogenesis in interscapular brown adipose tissue by suppressing sympathetic neural activation of this tissue.

Adipose Tissue, Brown↗

Lateral hypothalamic injection of 2-deoxy-D-glucose suppresses sympathetic activity.

To investigate the effects of glucoprivation on sympathetic nerve activity to interscapular brown adipose tissue (IBAT), 2-deoxy-D-glucose (2-DG) was injected into the third cerebral ventricle (icv), lateral hypothalamic area (LHA), and ventromedial hypothalamic nucleus (VMN) of rats. The multiunit discharges of sympathetic nerves to IBAT were recorded electrophysiologically. The icv injection of high and low doses of 2-DG (5.0 and 2.5 mg/rat) suppressed sympathetic nerve activity by 76.9 and 49.8% respectively, 30 min after injection compared with preinjected base line. After the low dose of 2-DG, there was a gradual recovery, but after the high dose recovery did not occur. The unilateral microinjection of 2-DG (0.25 mg/rat) into the LHA induced a similar suppression of sympathetic nerve activity to that observed after icv injection of 10 times as much 2-DG (-25.3%). The injection of vehicle or sucrose into the LHA did not suppress sympathetic nerve activity. The microinjection into the VMN either unilaterally or bilaterally did not suppress sympathetic nerve activity to IBAT. We conclude that the LHA but not the VMH is one site of action of 2-DG. The data are consistent with the hypothesis that the brain senses glucoprivation in the LHA and reduces sympathetic drive to thermogenic tissues such as IBAT.

Adipose Tissue, Brown↗

[Responses of tumor cell lines and surgical specimens transplanted into chorioallantoic membrane of chick embryo to anticancer agents in combination with/without hyperthermia].

The chorioallantoic membrane of chick embryo was used to examine the responses of tumor cell lines and surgically resected specimens to anticancer agents in combination with or without hyperthermia. B16-F10 melanoma, KK-47 cell line derived from a transitional cell carcinoma of the bladder and surgical specimens from urological malignancies were transplanted onto the chorioallantoic membrane of chick embryo 10 days after fertilization. The effects of intravascularly injected cyclophosphamide, cisplatin, adriamycin, mitomycin C, vincristine and vinblastine, in combination with or without hyperthermia, on the growth of the grafts were investigated. A 15-minute 42.5 degrees C hyperthermia exhibited most favorable anticancer effects in B16-F10 grafts (P less than 0.01) of all heating conditions tested. A combined use of hyperthermia and cisplatin, cyclophosphamide or adriamycin demonstrated a significantly high tumor regression rate in B16-F10 grafts (P less than 0.01). In KK-47 grafts, a single use of cyclophosphamide and a combined use of hyperthermia and cyclophosphamide exhibited a highly significant antitumor regression (P less than 0.05). Surgical specimens from 14 urological malignancies were subjected to this assay. Growth which was adequate for sensitivity test was obtained in 11 of the 14 malignancies. The results obtained suggest that this assay system may be a useful chemohyperthermia sensitivity test.

Allantois↗

Use of microdialysis to measure brain noradrenergic receptor function in vivo.

The present studies were undertaken to explore the use of intracerebral microdialysis to measure brain adrenergic receptor activity in vivo using the efflux of cyclic adenosine monophosphate (cAMP) in the extracellular fluid as an index of receptor function. An initial study with brain slices showed that extracellular levels of cAMP were highly correlated with intracellular levels after noradrenergic receptor activation. Detectable levels of extracellular cAMP were obtained from microdialysis probes implanted in the frontal cortex. Stable levels (3.5 +/- 2.7 pmol/ml) were obtained between 1.5 and 7 h after implantation. Perfusion of probes with NE (10(-5) to 10(-3) M) led to dose-dependent increases in cAMP efflux. The response to NE was blocked by infusion of the beta-antagonist, timolol, indicating that it reflected beta-receptor activation. Similar responses were obtained at 2 and 24 h after implantation indicating that the responses were not affected by acute traumatic effects of implantation. The findings show that the microdialysis technique can be successfully applied to the in vivo study of central adrenoceptor function. This suggests that the in vivo measurement of second messengers by microdialysis will provide a valuable new neurochemical and neuropharmacological technique.

Animals↗

[Effects of o,p'-DDD on pituitary-gonadal function in patients with Cushing's disease].

O,p'-DDD has a cytotoxic action and inhibits the cholesterol side chain cleavage enzyme, 11 beta-hydroxylase, 3 beta-hydroxysteroid dehydrogenase coupled with delta 5 to 4 isomerase and 21-hydroxylase of the adrenal cells. However, the effects of o,p'-DDD on gonadal steroidogenesis are still unknown. In the present study, the effects of o,p'-DDD on Plasma cortisol, pregnenolone, 17 alpha-hydroxypregnenolone (17-OH-pregnenolone), progesterone, 17 alpha-hydroxyprogesterone (17-OH-progesterone), 11-deoxycorticosterone (DOC), corticosterone, dehydroepiandrosterone (DHEA), delta 4-androstenedione (androstenedione), estradiol, and LH and FSH were investigated in 3 patients with Cushing's disease before and after the administration of o,p'-DDD. The results are presented here. In Case 1 (18 yr old female) who had had secondary amenorrhea for 2 years, the plasma levels of cortisol, pregnenolone, 17-OH-pregnenolone, DHEA, androstenedione, testosterone, estradiol and corticosterone were elevated. The basal levels of plasma LH and FSH and the responses of both gonadotropins were lower than those of women with eumenorrhea. The plasma levels of progesterone, DHEA and testosterone decreased to normal 2 months after the beginning of the administration of o,p'-DDD. She restored menstrual cycles ranging from 40 to 50 days 3 months after the administration of o,p'-DDD, but with anovulatory bleeding. She showed a biphasic body temperature pattern with plasma progesterone and estradiol levels indicating corpus luteum formation 11 months after the start of the treatment, when plasma cortisol as well as progesterone and androgen were reduced to normal. The basal levels of FSH and LH and responses of these gonadotropins were slightly improved at that time. The plasma levels of cortisol, DHEA and androstenedione were high in Case 2 (38 yr old male) and Case 3 (45 yr old male), whereas plasma testosterone level was normal in Case 2 and low in Case 3. The plasma levels of these 3 steroids were normalized 28 days after the beginning of the o,p'-DDD administration. These results suggest that o,p'-DDD does not interfere with gonadal steroidogenesis in Cushing's disease.

Adolescent↗

Diminished D2 dopamine receptor function and the emergence of repetitive jaw movements.

Oral movements in rats, repetitive jaw movements (RJM), can be induced in a dose dependent manner by a specific D1 agonist, SKF 38393, and decreased by D2 receptor stimulation with a specific D2 agonist, LY 141865. Irreversible D1 receptor inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline severely reduced oral responses induced by SKF 38393, whereas such blockade of D2 receptors greatly augmented the D1 mediated behavior. Further, we found that chronic prolonged D2 receptor blockade following administration of fluphenazine decanoate facilitated repetitive jaw movements.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Novel effect of chronic corticosterone treatment on escape behavior in rats.

Chronic administration of corticosterone in rats (4-35 mg/kg/day) produces a marked dose-dependent increase in the frequency of escape behavior observed when animals are held by the tail on a flat surface. The effect is fully developed after 3 days treatment. It is not the result of an increase in spontaneous motor activity since the hormone tends to reduce the latter behavior. Adrenalectomy decreases the escape behavior and tends to do so to a greater degree in rats subjected to chronic stress (restraint) than in nonstressed controls. The results suggest that endogenous corticosterone serves to maintain the above escape behavior during chronic stress.

Administration, Oral↗

[Chemosensitivity studies of urological malignancies].

Chemosensitivity tests to anticancer agents using human tumor clonogenic assay (HTCA), novel dye exclusion method (NDE assay), sub-renal capsule assay (SRCA), and chick embryo method (CE method) were utilized to measure the sensitivity of urological malignancies. Surgical tumor specimens from 67 patients with urological malignancies were subjected to HTCA developed by Hamburger and Salmon. An appreciable growth of colonies was obtained in 20 out of 33 renal cancers, 20 out of 30 urothelial cancers and 1 out of 4 testicular tumors examined and colonial growth adequate for chemosensitivity was obtained in 30 of the 67 patients. More than 70% decrease in the plating efficiency after anticancer drug exposure according to Von Hoff's definition, or more than 1.0 value of the "in vivo -in vitro therapeutic index" in terms of the ratio of IC90 to the peak plasma concentration of the drug tested was defined as susceptible. According to Von Hoff's definition, susceptibility to vinblastine (VBL) and cis-dichlorodiammine platinum (CDDP), was seen in 4 out of 11 patients with renal cancer, in 4 out of 15 patients with urothelial cancer and 1 out of 4 patients with renal cancer, respectively. With adriamycin (ADM) it was seen in 3 out of the 15 patients with urothelial cancer, 2 out of 10 patients with renal cancer and 1 patient with testicular tumor. According to TI, susceptibility to VBL was seen in 3 out of 7 patients with renal cancer, and with CDDP it was seen in 2 out of 12 patients with urothelial cancer, and 1 out of 2 patients with renal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of bifemelane hydrochloride on cortical neuronal activity in cats.

The effects of bifemelane hydrochloride on neuronal activity in the visual cortex of the cat were studied by microiontophoretic application under methoxyflurane anesthesia. Of 195 neurons examined with both acetylcholine (ACh) and bifemelane, 67 cells (34%) were excited and 7 cells (4%) were inhibited by ACh. The effect of bifemelane was excitatory on 122 neurons (63%), inhibitory on 20 (10%) and unchanged on the rest. In 60 cells out of the above 122 neurons, bifemelane showed a similar discharge pattern to ACh with a slow onset and delayed termination. The bifemelane-induced excitation was, in 18 out of 22 cells, antagonized by atropine (30-40 nA). Also, a potentiation in bifemelane-induced discharges by physostigmine (30-50 nA) was observed in 14 of the 32 cells tested. The firing evoked by ACh (80-100 nA) was potentiated during of after the application of bifemelane (30-40 nA) in 9 out of 29 neurons, which were not excited by bifemelane alone. These results suggest that neuronal discharges produced by bifemelane are induced at least in part, through a muscarinic ACh receptor, although other mechanisms may possibly be involved.

Acetylcholine↗

Insulin increases triglyceride secretion rate in rats in vivo.

To investigate whether insulin regulates triglyceride secretion from the liver in vivo, triglyceride secretion rate (TGSR) and serum insulin were measured in the following three experiments: in rats 12 weeks after ventromedial hypothalamic (VMH) lesions (Exp. 1), in rats 12 weeks after a high fat diet-feeding (Exp. 2), and in rats 10 days after streptozotocin treatment (65 mg/kg) (Exp. 3). Under hexobarbital anesthesia, overnight fasted rats were bled for measuring insulin and triglyceride. Rats were again bled 45 and 90 minutes after Triton WR 1339 (120 mg) injection, for measuring triglyceride. TGSR was calculated from serum triglyceride values measured before and after Triton injection. In Exp. 1, VMH obese rats had higher serum insulin concentrations and TGSR than control rats. There was a significantly positive correlation between serum insulin concentrations and TGSR in VMH lesioned rats alone (r = 0.939, P less than 0.001) and in VMH lesioned and control rats combined (r = 0.958, P less than 0.001). In Exp. 2, high fat diet-fed rats gained more weight than control rats, but they had the same levels of serum insulin concentrations and TGSR as those of control rats. In Exp. 3, streptozotocin treated rats had lower serum insulin concentrations and TGSR than control rats. There was a significantly positive correlation between serum insulin concentrations and TGSR in the two groups of rats combined (r = 0.680, P less than 0.05). From the results of these three sets of in vivo studies, we conclude that insulin increases TGSR in vivo.

Animals↗