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Biomedical subjects

K Tasaka

Publications and source records attributed to K Tasaka.

At least 271 records · Page 15Linked to original sources

Effect of sulpiride-induced hyperprolactinaemia on catecholamine turnover and LRH concentration in the medial basal hypothalamus of rats.

In order to clarify the mechanism of hyperprolactinaemic anovulation, the medial basal hypothalamic (MBH) catecholamine (CA) turnover and LRH concentration, and the serum levels and pituitary contents of gonadotrophins and prolactin (Prl) in hyperprolactinaemic female rats were examined. Hyperprolactinaemia (HPrl) was produced by oral administration of sulpiride for 10 consecutive days; each measurement made on the sulpiride-treated rats was compared with that of control dioestrus rats. Prl, LH, FSH and LRH were determined by radioimmunoassay; CA turnover, as assessed by the accumulation of CA following monoamine oxidase inhibition, was assayed by high performance liquid chromatography with electrochemical detection. Sulpiride treatment induced (1) an increase in the serum Prl and a decrease in the serum LH, (2) an increase in the pituitary FSH and LH contents, (3) an increase in the MBH LRH concentration, and (4) an increase in the MBH dopamine (DA) turnover. These results suggest that HPrl may induce anovulation by impaired LH secretion which was caused by the suppression of LRH release due to an increase in DA turnover in the MBH.

Animals↗

Clomiphene citrate induces luteinizing hormone release through hypothalamic luteinizing hormone-releasing hormone in vitro.

The releasing effects of clomiphene citrate (clomiphene) on luteinizing hormone (LH) and LH-releasing hormone (LRH) were examined in a sequential double chamber superfusion system by superfusing the mediobasal hypothalami (MBH) and/or pituitaries excised from normal female rats in dioestrus. When the MBH and the pituitary were superfused in sequence with medium containing 2 X 10(-10) M oestradiol (E2), two significant peaks in LH release (60-130% increase, P less than 0.05) were observed 40 min and 90 min after the administration of 3 X 10(-8) mol clomiphene. Administration of clomiphene in medium without E2 induced a low peak (25-50% increase, P less than 0.05) of LH released from the pituitary perfused in series with the MBH. Administration of clomiphene did not cause a marked increase of LH from the pituitary superfused alone, when superfused with or without E2 containing medium. The concentration of LRH in the efflux was significantly increased (50-100%) 40 min and 90 min after clomiphene administration when MBH was superfused with medium containing E2, whereas clomiphene had no effect when superfused with medium alone. These data indicate: 1) that clomiphene induces LRH release from the MBH, that it may induce LH release, in part, by acting directly at the pituitary level; 2) that changes in LH after clomiphene administration coincide with LRH release, and 3) that a certain concentration of E2 may be necessary for the secretion of LRH by clomiphene.

Animals↗

Arginine vasopressin suppresses oxytocin release from the superfused rat hypothalamo-pituitary complex.

The role of arginine vasopressin (AVP) in the regulation of oxytocin secretion was studied in a superfusion system of the hypothalamo-pituitary complex from cycling female rats in dioestrus of the oestrous cycle. After perfusion with Medium 199 alone at 37 degrees C for an equilibration period of 2.5 h, perfusion with Medium 199 containing 10 mU/ml AVP for 30 min caused a prompt and significant (P less than 0.05) decrease in the oxytocin level of up to 60% of that before AVP perfusion, whereas Medium 199 containing 0.1 mU/ml AVP had no effect on oxytocin efflux. This finding suggests that AVP may be involved in the regulation of oxytocin release from the hypothalamo-pituitary system.

Animals↗

Prostaglandin D2 stimulates secretion of luteinizing hormone from pituitary gland in vitro.

The effect of prostaglandin D2 on the release of luteinizing hormone was studied in a superfusion system by superfusing human pituitary gland. Perfusion with 30 micrograms of prostaglandin D2 induced a significant increase of luteinizing hormone secretion. This is the first evidence of a direct effect of prostaglandin D2 on the secretion of luteinizing hormone from the human pituitary gland. This finding suggests the possible role of prostaglandin D2 in human reproductive function.

Adult↗

Prostaglandin D2 induces release of luteinizing hormone from the rat pituitary gland without the modulation of hypothalamic luteinizing hormone releasing hormone.

The effect of prostaglandin D2 (PGD2) on release of LH and LH releasing hormone (LHRH) was studied in a sequential double-chamber superfusion system using the medial basal hypothalamus (MBH) and the pituitary gland from female rats at dioestrus. Infusion of PGD2 (5.7 or 57 mumol/l) caused a significant (P less than 0.05) increase in LH release to values 40-60% above the preinjection values from the pituitary gland superfused either alone or in series with the MBH. No release of LHRH in response to PGD2 was observed from the superfused MBH. These data demonstrate that PGD2 causes LH release from the pituitary gland not by inducing release of hypothalamic LHRH but by a direct action on the gland.

Animals↗

[Experimental study on abdominal arterial infusion of anti-cancer agents].

The distribution of Adriamycin (ADM), Mitomycin C (MMC) and 7-N-(p-Hydroxyphenyl)-Mitomycin C (KW 2083) in various organs inclusiding plasma level after intraarterial or intravenous infusion was determined in mongrel dogs and experimental dogs. Similar plasma time-course of ADM was obtained with both routes, showing the maximum level at 5 minutes after infusion. The maximum level with intravenous infusion was twice as highs as that with intraarterial administration. High levels of ADM were encountered in the liver, gallbladder and kidney after proper hepatic arterial infusion, in the angular region of the stomach after left gastric arterial infusion and in the gastric antrum after right gastroepiploic arterial infusion (0.8 mg/kg). There was no significant difference in plasma levels of MMC (0.2 mg/kg) and KW 2083 (1.0 mg/kg) between intraarterial and intravenous infusion. It was of interest that MMC was hardly measurable in the liver after proper hepatic arterial infusion of 0.4 mg/kg. On the other hand, rather high level of KW 2083 was observed in the liver, gallbladder and pancreas after proper hepatic arterial infusion of 1.0 mg/kg. Hepatic necrosis around the central hepatic vein noted at the histological examination seems to be due to infusion of above-mentioned anticancer agents. It is worth mentioning that the concentration of KW 2083 in tumor tissue of the stomach of experimental dog after right gastroepiploic arterial infusion was twice as high as that in intact gastric wall. Grade IIA histological alterations of tumor cells by Oboshi and Shimosato's Classification such as vacuolation of cytoplasm and pyknosis of nuclei were noted after KW 2083 infusion.

Abdomen↗

Effects of certain antiepileptics on cephaloridine- and cefazolin-induced seizures in rats.

Effects of phenobarbital, phenytoin and diazepam on cephaloridine-induced spiking activity (focal seizure) and cefazolin-induced violent seizure appearing repeatedly in EEG and general behavior (repeated generalized seizure) were studied in rats with chronically implanted electrodes. Phenobarbital, phenytoin and diazepam showed remarkable inhibition on cephaloridine-induced focal seizure and the ED50 values were 4.52 mg/kg, 9.41 mg/kg and 0.86 mg/kg, respectively. Phenobarbital and diazepam also inhibited cefazolin-induced repeated generalized seizure. The ED50s to inhibit seizure pattern in EEG were 30.5 mg/kg and 3.4 mg/kg, respectively and the ED50 values to suppress seizure behavior were 49.0 mg/kg and 4.7 mg/kg. However, phenytoin did not suppress repeated generalized seizure even at 100 mg/kg. From these results, cephaloridine-induced focal seizure and cefazolin-induced generalized seizure are thought to be useful models for evaluating the inhibitory effect of test compounds on cortical seizure and status epilepticus, respectively.

Animals↗

Progesterone facilitates the LRH releasing action of oestrogen.

The effects of progesterone (P) on the release of LRH and LH were examined in a sequential double chamber superfusion system by superfusing the medial basal hypothalamus (MBH) and/or pituitaries excised randomly from cycling female rats. Addition of 10 microliters of 10(-6) M oestradiol (E2) to the first chamber resulted in a gradual and significant (60-160%) increase in LH release above the pre-injection level from the pituitary in series with MBH. Administration of 10(-8) M P after 10(-6) M E2 caused a prompt and marked increase (300%) of LH (P less than 0.05), whereas 10(-8) M P alone had no effect. Administration of 10(-6) M E2, 10(-8) M P or E2 plus P did not significantly change LH secretion from the pituitary superfused alone. The concentration of LRH in the efflux was significantly increased (150-200%) 150 min after 10(-6) M E2 administration. P administration after E2 injection produced a prompt and significant increase of LRH and the increase of LRH (300-600%) was 2-3-fold that produced by E2. P alone had no effect. These data clearly indicate that P enhances E2-induced LH release by increasing LRH secretion from the MBH.

Animals↗

Synthesis and structure-activity relationship of spiro[isochromanpiperidine] analogues for inhibition of histamine release.

Two types of 1'-alkylspiro[isochroman-3,4-piperidines] and 1'-alkylspiro[isochroman-4,4'-piperidines] were prepared and examined for their biological activity. Several of the compounds inhibited the compound 48/80 induced histamine release from isolated rat peritoneal mast cells. The structural requirements for this activity in the present series are discussed.

Animals↗

Anti-inflammatory mechanism of prozime-10, a proteolytic enzyme.

When Prozime-10 (P-10), a protease extracted from cultured both of Aspergillus melleus, was injected intravenously into anesthetized dogs, plasma ACTH was increased with a latency of 30 min, and this was followed by remarkable elevation of plasma cortisol in many instances. A similar increase in plasma cortisol was elicited after trypsin and alpha-chymotrypsin were injected. Plasma histamine was raised promptly prior to an increase in plasma ACTH after P-10 in every case. However, in certain cases, changes in cortisol occurred simultaneously with ACTH after P-10. Such a rapid elevation of cortisol can be explained, partly, by direct stimulation of the adrenal cortex by histamine.

Adrenal Cortex↗

Anti-inflammatory activity of a proteolytic enzyme, Prozime-10.

Prozime-10 (P-10), a proteolytic enzyme extracted from cultured broth of Aspergillus melleus, was injected intravenously into rats in dosages of 1--10 mg/kg and was found to alleviate carrageenin edema. Thermal denaturation diminished not only the proteolytic activity but also the antiedematous effect. Carrageenin-induced granuloma pouches in rats were reduced by P-10 in a dose-dependent manner (1--5 mg/kg). With P=10 (5 mg/kg i.v.), adjuvant arthritis was inhibited by 62% in the primary phase and by 57% in the secondary phase. Serum concentration of immunoprecipitable P-10 reached 100 mg/l within 30 min after the intraduodenal administration of P-10 (200 mg/kg) and was concomitant with a 3-fold increase in the blood esterolytic activity. When P-10 was injected (5 mg/kg i.v.) into rats, the plasma corticosterone level increased to a maximum of 4 times the preinjection level. These observations indicate that: (a) P-10 can be absorbed from the gut in sufficient quantities to bring about anti-inflammatory activity, and (b) the anti-inflammatory activity of P-10 can be related, in part, to the ability of P-10 to affect the release of glucocorticoids.

Adrenalectomy↗