Biomedical subjects

Y Kasuya

Publications and source records attributed to Y Kasuya.

At least 127 records · Page 7Linked to original sources

PubMed1994

[Objective and subjective response in stage D2 prostate cancer patients with cancer pain].

Fourty-eight patients with stage D2 prostate cancer, initially treated with endocrine therapy at the University of Tokyo between 1981 and 1990, were followed up and analysed. For the assessment of a subjective response, pain score, narcotic score, and performance stages (PS) were used. Of the fourty-eight patients, twenty-one suffered from cancer pain due to bone metastases. These patients showed significantly (p < 0.01) more lesions of bone metastases and higher PS, compared with patients without cancer pain. The progression free survival of these patients was significantly (p < 0.01) lower than that of patients without cancer pain, although the actuarial survival was not significant. In twenty-one patients with cancer pain, the objective and subjective response rates to endocrine therapy were 75% and 86%, respectively. The duration of pain relief was 1.25-54 (median 19) months. Those rates to anti-cancer chemotherapy in refractory patients (8 patients) previously treated with endocrine therapy were both 25% and those to additional administration of flutamide (FUL) or diethylstilbestrol (DES) in refractory patients (6 patients) were 33% and 100%, respectively. Although the duration of pain relief was 0.78-8 (median 2) months, the additional administration of DES or FLU led to pain relief and improved quality of life (QOL) in all 6 patients. Endocrine therapy such as LH-RH agonist and non-steroidal pure anti-androgen, which has no severe side effects, would be of great usefulness in stage D2 prostatic cancer patients with pain on the basis of efficacy and safety.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Vasodilator effects of clonidine on the mesenteric arterial beds in normotensive and spontaneously hypertensive rats.

Clonidine, an alpha 2-agonist, caused a concentration-dependent vasodilation of the mesenteric arterial beds in both normotensive and hypertensive rats. The clonidine-induced vasodilation was inhibited by NG-nitro-L-arginine, and the inhibition was reversed by L-arginine. The concentration-dependent vasodilation was not significantly different between normotensive and hypertensive rats. These results suggest that clonidine has an endothelium-dependent vasorelaxant action in the resistance artery such as rat mesenteric arterial bed, and the endothelium-dependent vasodilator effects of clonidine in the mesentery may be involved in the depressor effect of the drug.

Animals↗

PubMed1994

Antitussive effect of (+/-) pentazocine in diabetic mice is mediated by delta-sites, but not by mu- or kappa-opioid receptors.

The effects of streptozotocin-induced diabetes on the antitussive effect of (+/-) pentazocine were examined in mice. Intracerebroventricular (i.c.v.) administration of (+/-) pentazocine produced a dose-dependent antitussive effect in both diabetic and non-diabetic mice. There were no significant differences in the antitussive effect of (+/-) pentazocine in diabetic and non-diabetic mice. The antitussive effect of i.c.v. (+/-) pentazocine was partially, but significantly, reduced in non-diabetic mice following pretreatment with either beta-funaltrexamine, a selective mu-opioid antagonist, or rimcazole, a specific sigma-site antagonist. The antitussive effect of (+/-) pentazocine in diabetic mice was significantly antagonized by pretreatment with rimcazole. However, beta-funaltrexamine had no effect on the antitussive effect of (+/-) pentazocine in diabetic mice. Furthermore, nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antitussive effect of (+/-) pentazocine in either non-diabetic or diabetic mice. These results suggest that although the antitussive effect of i.c.v. (+/-) pentazocine in non-diabetic mice is mediated by both mu-opioid receptors and sigma-sites, in diabetic mice this effect is mainly mediated by sigma-sites.

Animals↗

PubMed1994

Effects of diabetes on the antinociceptive effect of (+/-)pentazocine in mice.

The antinociceptive effect of (+/-)pentazocine was examined in streptozotocin-induced diabetic mice. Although intracerebroventricular (i.c.v.) administration of (+/-)pentazocine (10 nmol) produced a significant antinociceptive effect in both non-diabetic and diabetic mice, the antinociceptive effect of (+/-)pentazocine was greater in diabetic mice than in non-diabetic mice. The antinociceptive effects of (+/-)pentazocine in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of nor-binaltorphimine, a selective kappa-opioid receptor antagonist. On the other hand, the antinociceptive effects of (+/-)pentazocine were potentiated when non-diabetic mice were pretreated with beta-funaltrexamine, a selective mu-opioid receptor antagonist. Furthermore, there was no significant difference in the antinociceptive effect of (+/-)pentazocine between diabetic mice and beta-funaltrexamine-treated non-diabetic mice. These results suggest that the hypo-responsiveness of mu-opioid receptors may account for the enhanced kappa-opioid receptor-mediated antinociceptive effect of (+/-)pentazocine in diabetic mice.

Analgesics↗

PubMed1994

[Stable isotope methodology in the pharmacokinetic study of steroids].

Stable isotopically labeled steroids can, without radiation hazards, be safely used as biological internal standards to perform pharmacokinetic studies of steroids in man. This technique offers an advantage in that an endogenous steroid and its stable isotopically labeled analogue exogenously administered can be differentiated easily by employing mass spectrometry. For example, we can examine the pharmacokinetics of cortisol and investigate the metabolic conversion of cortisol to cortisone in man by administering deuterium-labeled cortisol to human subjects as a tracer. The number and the stability of the label are fundamental requisites in stable isotope methodology. Successful application of methodology with stable isotopes is then always dependent on the availability of compounds that are labeled at predesignated chemically inert positions.

Adolescent↗

PubMed1993

Antitussive effects of naltrindole, a selective delta-opioid receptor antagonist, in mice and rats.

The effects of naltrindole, a selective delta-opioid receptor antagonist, on the capsaicin-induced cough reflex in mice and rats were studied. Intraperitoneal administration of naltrindole decreased the number of coughs both in mice and rats dose dependently. The cough-depressant effects reached a peak 15 min after the administration of naltrindole and lasted more than 120 min. Pretreatment with [D-Pen2,D-Pen5]enkephalin, a selective delta-opioid receptor agonist, partially but significantly reduced the antitussive effect of naltrindole. Blockade of kappa-opioid receptors by pretreatment with nor-binaltorphimine also partially antagonized the antitussive effect of naltrindole. However, the antitussive effect of naltrindole was not antagonized by beta-funaltrexamine, a selective mu-opioid receptor antagonist. Thus, it is possible that the antitussive effect of naltrindole may be mediated, in part, by kappa-opioid receptors. The present results provide evidence for the development of delta-opioid antagonists, especially naltrindole, for use as antitussive drugs.

Animals↗

PubMed1993

Effects of rimcazole, a specific antagonist of sigma sites, on the antitussive effects of non-narcotic antitussive drugs.

We examined the effects of rimcazole, a specific antagonist of sigma sites, on the antitussive effects of dextromethorphan and noscapine in mice. Intraperitoneal injection of rimcazole, in doses from 1 to 10 mg/kg, significantly and dose dependently antagonized the cough depressant effect of N,N'-di(orthotolyl)guanidine (DTG), a sigma ligand. The cough depressant effects of dextromethorphan (3 mg/kg i.p.) and noscapine (10 mg/kg i.p.) were also significantly and dose dependently reduced by pretreatment with rimcazole. However, rimcazole (10 mg/kg i.p.) did not have a significant effect on the antitussive effect of morphine (3 mg/kg i.p.). Furthermore, rimcazole by itself (10 and 30 mg/kg i.p.) had no significant effect on the number of coughs. These results suggest that sigma sites may be involved in the antitussive mechanism of centrally acting non-narcotic antitussive drugs.

Animals↗

PubMed1993

Simultaneous measurement of vasodilation and changes in cyclic nucleotides in the perfused mesenteric arterial bed of the rat.

We examined the relationship between relaxation responses of the mesenteric arterial bed and the levels of cAMP and cGMP released from the rat mesenteric arterial bed. Perfusions of mesentery preparations with 1 microM acetylcholine, 0.1 microM calcium ionophore A23187, and 1 microM sodium nitroprusside all produced complete and long-lasting relaxation and increased the levels of cAMP as well as cGMP in the effluent. In endothelium-denuded preparations, acetylcholine did not elicit either vasorelaxation or an increase in cAMP and cGMP levels. Perfusion of the endothelium-denuded preparation with 1 microM sodium nitroprusside evoked complete relaxation and a marked increase in cGMP levels but not cAMP levels. Isoproterenol (1 microM) produced complete relaxation and an increase in cAMP levels, but did not affect cGMP levels either in the preparation with or in that without endothelium. Acetylcholine (0.001-1 microM) relaxed the preparation and increased cAMP and cGMP levels in the effluent in a dose-dependent manner. The acetylcholine-induced relaxation was reversed by 45% following perfusion with 10 microM methylene blue, and both the cAMP and cGMP levels were decreased. L-NG-Monomethyl arginine (L-NMMA) (100 microM), a nitric oxide synthase inhibitor, completely reversed the relaxation induced by 0.1 microM acetylcholine and reduced the elevated cGMP levels. Indomethacin (1 microM) reduced the acetylcholine-induced cAMP release, but did not alter the vasorelaxation in response to acetylcholine. We propose a novel method for the simultaneous measurement of vasodilation and changes in cAMP and cGMP levels released from the rat mesenteric arterial bed. We conclude that this method may provide information about the function of the endothelium of resistance vessels.

Acetylcholine↗

PubMed1993

The effects of cyclosporine on morphine-induced antinociception in diabetic mice.

The effects of cyclosporine on the antinociceptive effect of morphine were examined in diabetic mice. Sensitivities to the antinociceptive effect of morphine (5 mg/kg s.c.) in diabetic mice which had been pretreated with cyclosporine (30 mg/kg per day s.c.) for 14 days returned to those in vehicle-treated nondiabetic mice. Naive mice which had been injected with the supernatant of spleen cell homogenate (SSCH) from vehicle-treated diabetic mice were less sensitive to morphine-induced antinociception. However, adoptive transfer of SSCH from cyclosporine-treated diabetic mice to naive mice had no effect on the recipients' antinociceptive sensitivities to morphine. These results suggest that the abnormal antinociceptive effect of morphine and the immune responses of diabetic mice may somehow be related.

Analgesics↗

PubMed1993

Effect of diabetes on the antinociceptive effect of beta-endorphin.

We examined whether streptozotocin-induced diabetes can modulate beta-endorphin-induced antinociception in mice. While beta-endorphin administered i.c.v. produced a dose-dependent inhibition of the tail-flick response in both diabetic and non-diabetic mice, the antinociceptive response was greater in diabetic mice than in non-diabetic mice. The ED50 value of beta-endorphin administered i.c.v. in diabetic mice was significantly lower than that in non-diabetic mice. The antinociceptive effects of beta-endorphin administered i.c.v. in both diabetic and non-diabetic mice were significantly antagonized by s.c. administration of naltrindole, a selective delta-opioid receptor antagonist. beta-Endorphin administered i.t. also produced a dose-dependent antinociception in both diabetic and non-diabetic mice. However, the ED50 value of kappa-opioid receptor antagonist. On the other hand, the antinociceptive potency of DPDPE, a selective delta-opioid agonist, administered i.t. is significantly increased in diabetic mice, as compared with non-diabetic mice, whereas, the antinociceptive potency of U-50,488H, a kappa-opioid receptor agonist, administered i.t. is significantly less than in non-diabetic mice. These results suggest that diabetes may modulate beta-endorphin-induced antinociception differently at the spinal and supraspinal levels.

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

PubMed1993

The role of the mu 2-opioid receptor in the antitussive effect of morphine in mu 1-opioid receptor-deficient CXBK mice.

The effect of morphine on the capsaicin-induced cough reflex was studied in mu 1-opioid receptor-deficient CXBK mice. There was no significant difference between the morphine-induced antitussive effect in CXBK mice and C57BL/6 mice, a progenitor strain. Furthermore, the antitussive effects of morphine in both the CXBK and C57BL/6 mice were antagonized by pretreatment with either naloxone or beta-funaltrexamine, a mu-opioid receptor antagonist, whereas pretreatment with naltrexonazine, a selective mu 1-opioid receptor antagonist, had no effect. Moreover, naltrindole, a selective delta-receptor antagonist, also had no significant effect on the antitussive effects of morphine in either CXBK or C57BL/6 mice. These results support our previous hypothesis that mu 2- rather than mu 1-opioid receptors are involved in morphine-induced antitussive effects.

Animals↗

PubMed1993

Antitussive effects of mu- and kappa-agonists in diabetic rats.

We evaluated the antitussive effect of morphine and U-50,488 in diabetic and non-diabetic rats. The antitussive potency of morphine (0.3 mg/kg, i.p.) in diabetic rats was significantly reduced as compared to the results in non-diabetic rats. The antitussive effect of U-50,488, a kappa-agonist, was also significantly lower in diabetic rats than in non-diabetic rats. When naltrindole (0.03 mg/kg, i.p.), a delta-antagonist, was administered 15 min before morphine or U-50,488, there was no difference between the antitussive potencies of these two opioid agonists in non-diabetic rats and in diabetic rats. Furthermore, naltrindole produces a reduction of the number of coughs in diabetic rats, but not in non-diabetic rats. It is possible that the enhancement of the antitussive potency of morphine and U-50,488 in naltrindole-treated diabetic rats is the result of the antitussive synergy produced by these opioid agonists and naltrindole. It seems likely, therefore, that delta-receptor-mediated endogenous inhibitory systems in mu- and kappa-receptor-mediated antitussive processes may be activated under diabetic conditions.

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

PubMed1993

Antinociceptive effects of intrathecally administered endothelin-1 in mice.

Intrathecal administration of endothelin-1 (ET-1) produced dose-dependent antinociceptive effects in the tail-flick test. The antinociceptive effects of ET-1 were attenuated significantly by pretreatment with naloxone and the delta receptor-selective antagonist naltrindole. The antinociceptive effects of ET-1 were also significantly attenuated by pretreatment with verapamil, an L-type Ca(2+)-channel blocker. These results suggest that the mechanism underlying the antinociceptive effects of ET-1 involves mediation, at least in part, by Ca(2+)-induced release of endogenous opioids, which act on delta-opioid receptors.

Animals↗

PubMed1993

Differential modulation of mu-opioid receptor-mediated antitussive activity by delta-opioid receptor agonists in mice.

We examined the effect of [D-Ala2]deltorphin II, a selective delta 2-opioid receptor agonist, on the antitussive effect of [D-Ala2, MePhe4,Gly-ol5]enkephalin (DAMGO), a selective mu-opioid receptor agonist. [D-Ala2]deltorphin (3 nmol i.c.v.) had no significant effect on the number of coughs. However, upon i.c.v. pretreatment with [D-Ala2]deltorphin II (3 nmol) the antitussive activity of DAMGO (0.03 nmol) was significantly enhanced. The enhancement of the antitussive activity of DAMGO caused by [D-Ala2]deltorphin II was prevented by a benzofuran derivative of naltrindole (0.1 mg/kg s.c.), a selective delta 2-opioid receptor antagonist. These results suggest that delta 2-opioid receptors may play a synergistic role in antitussive processes that are mediated by mu-opioid receptors.

Animals↗

PubMed1993

Antitussive effect of beta-endorphin is mediated by mu-opioid receptors, but not by kappa- or epsilon-opioid receptors.

The present study examined the opioid receptors involved in the antitussive effect of beta-endorphin in mice. beta-Endorphin injected i.c.v. depresses coughs dose dependently in doses from 0.1 to 1 microgram. Blockade of mu-opioid receptors by pretreatment with beta-funaltrexamine significantly reduced the antitussive potency of i.c.v. beta-endorphin. However, the antitussive effect of beta-endorphin was not antagonized by nor-binaltorphimine, a kappa-opioid receptor antagonist. Moreover, i.c.v. injection of beta-endorphin-(1-27), an epsilon-opioid receptor antagonist, did not affect the antitussive effect of beta-endorphin. The results indicate that the antitussive effect of beta-endorphin is mediated by activation of mu-opioid receptors, but not of kappa- or epsilon-opioid receptors.

Animals↗

PubMed1993

Formalin-induced nociceptive responses in diabetic mice.

In non-diabetic mice, s.c. injection of formalin to the hindpaw had a biphasic effect: an immediate nociceptive response (first-phase) followed by a tonic response (second-phase). However, only the immediate nociceptive response was observed in diabetic mice. The duration of the first-phase response was significantly longer in diabetic mice than in non-diabetic mice. In diabetic mice, when spantide, an antagonist of substance P, reduced the duration of the nociceptive response in the first-phase to the levels that were observed in non-diabetic mice, the second-phase response appeared. The second phase also became apparent in diabetic mice after pretreatment with naltrindole (3 mg/kg), an antagonist of delta-opioid receptors. These results suggest that a negative control system, which is mediated by delta-opioid receptors and links substance P with somatostatin-mediated nociceptive transmission, may inhibit the formalin-induced second-phase of the nociceptive response in diabetic mice.

Analgesics↗

PubMed1993

Possible involvement of mu 2-mediated mechanisms in mu-mediated antitussive activity in the mouse.

The effect of pretreatment with naloxonazine on mu-opioid agonist-mediated antitussive effects was studied in mice. The antitussive effects of [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAMGO) and morphine were significantly antagonized by naloxone pretreatment, 1 mg/kg given i.p. 5 min earlier, but not by naloxonazine pretreatment, 35 mg/kg given s.c. 24 h earlier. In contrast, the antinociceptive effects of these mu agonists, as determined by the tail-flick method, were significantly reduced by pretreatment with both naloxone and naloxonazine. These results suggest that mu 2 rather than mu 1 mechanisms are involved in mu-mediated antitussive effects.

Analgesics↗

PubMed1993

Delta-opiod receptor-mediated forced swimming stress-induced antinociception in the formalin test.

Forced swimming stress-induced antinociception (FSSIA) was assessed using the formalin test. Male ICR mice, weighing about 30 g, were forced to swim in water at 20 degrees C for 3 min. In unstressed mice, SC injection of formalin (0.5%) to the hindpaw caused a biphasic response: an immediate nociceptive response (first phase) followed by a tonic response (second phase). Although forced swimming stress (FSS) had no effect on the duration of the first-phase response, FSS significantly reduced the duration of the second-phase response. The effect of FSSIA on the second-phase response was blocked by naltrindole (1 mg/kg, SC), a selective delta-opioid receptor antagonist, but not by beta-funaltrexamine (20 mg/kg, SC), a selective mu-opioid receptor antagonist. These results indicate that FSS may selectively reduce the second phase of the formalin-induced nociceptive response, primarily through delta-opioid receptors.

Animals↗