Effects of oxymorphindole on morphine induced-antinociception in mice and rats.
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Biomedical subjects
Publications and source records attributed to Q Jiang.
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To search for more ideal antithrombotic drugs sixteen 6-(4-substituted phenyl)-4,5-dihydro-3(2H)-pyridazinones were designed and synthesized. Some improvement of the synthetic method involved in constructing the piperazinyl group by cyclization of bisbromoethyl amine with 4-pyridazinonyl anilines. Preliminary pharmacological tests showed that all of the target compounds inhibited ADP induced platelet aggregation. Compounds II2, II3 and II4 were more potent than CCI-17810. The 5-methyl derivative of CCI-17810 (II4) was the most potent compound.
G banding chromosome analysis of bone marrow cells from 51 cases of MDS, including 34 cases of RA, 4 cases of RAS, and 13 cases of RAEB, was carried out using a short term culture method. The morphological abnormalities of dyspoiesis of 46 patients were studied and correlated with chromosomal changes. The results were as follows: Forty-nine percent of the cases had abnormal karyotypes. The frequency of clonal abnormalities was 36.8 percent in RA and RAS, and 84.6 percent in BAEB. The most important aberrations were +8 in 7, HSR in 2, and "spontaneous" PCC in 6 cases. The latter 2 abnormalities had rarely been reported in the literature. Other findings included 1p+, dup (1) (q25q44), -2, 4p+, -5, 5q-, +8p, -12, 12p+, 12q-, -14, 14q+, t (1; 14), -15, +/-16, +/-17, -18, +19, +20, 20q-, +/-21, +/-22, -X, -Y, +Mar, etc. The study also showed a close relation between chromosome aberrations and dyspoiesis. +8 patients tended to have a high percentage of micronuclei in their erythroblasts, and their dyspoiesis usually involved three cell lineages. Patients with PCC were found to have more polyploid metaphases (in cytogenetic studies) and more multinuclear cells (in bone marrow aspirate slides). The results of our study revealed that the more severe dyspoiesis is, the higher the frequency of chromosome aberrations. We consider chromosome abnormalities to play an important role in the pathogenesis of MDS, with cell fusion being involved as well.
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Central and peripheral sites of opioid action on net basal fluid transport were studied in loops of jejunum in urethane-anesthetized mice. Intracerebroventricular administration of morphine, [D-Ala2, N-MePhe4, Gly-ol]enkephalin (DAMGO), D-Pen2, D-Pen5] enkephalin (DPDPE) or U50,488H produced dose-related increases in net basal intestinal absorption. Intracerebroventricular DAMGO was approximately 2.6, 1278 and 2674 times more potent than morphine, DPDPE and U50,488H, respectively. The increase in net basal fluid absorption mediated by i.c.v. administration of all these compounds, except DPDPE, was antagonized in a dose-related manner by coadministration of i.c.v. naloxone, an opioid antagonist which did not produce any effects when given alone. Neither the increase in net basal fluid absorption produced by DPDPE nor the fluid transport effects produced by the other agonists tested was antagonized by the delta antagonist, N,N-diallyl-Tyr-alpha-aminoisobutyric acid [( Aib]-Aib-Phe-Leu-OH) and no effects were observed with this delta antagonist alone. Intracerebroventricular administration of beta-funaltrexamine (18.8 nmol, 4 hr before testing) blocked the i.c.v. effects of DAMGO, but not those of U50,488H. In contrast to the effects seen following i.c.v. administration of these agonists, no changes in net basal fluid transport were obtained by the i.p. route for DAMGO, DPDPE, [D-Ala2,D-Leu5]enkephalin, [D-Ala2, Met5]enkephalinamide or U50,488H; of the compounds tested, only morphine produced an increase in net basal fluid absorption after i.p. administration. The effects of i.c.v. or i.p. morphine were blocked by i.c.v. SR 58002C, a quaternary opioid antagonist which had no effects alone.(ABSTRACT TRUNCATED AT 250 WORDS)
The metabolic response of mammary carcinoma in the C3H mouse to photodynamic therapy (PDT) was measured using in vivo 31P nuclear magnetic resonance (31P-NMR) spectroscopy and pH microelectrodes. Twenty-four hours after administration of Photofrin II (12.5 mg/kg), the tumor was subjected to photoactivation using an argon dye laser. Optical treatment doses were 200, 400, and 600 J/cm2 and corresponded to the following tumor control doses: TCD10/30, TCD50/30, and TCD90/30, respectively. In vivo 31P-NMR spectra and pH micro-electrode measurements were obtained prior to treatment and at 4, 24, 48, and 72 h and 1 week post-treatment. The data revealed a significant (P less than 0.0002) alkalosis as indicated by the pH measured by NMR compared to pH measured by microelectrodes at all treatment levels and time points. Spectral differences between treatment groups were apparent as early as 4 h after treatment. The ratio of beta-nucleoside triphosphate to inorganic phosphate at 4 h after treatment was significantly (P less than 0.01) smaller for 600 J/cm2 treatment than for 200 J/cm2 treatment. At curative (600 J/cm2) levels, from 48 h on, no phosphate resonances were detected in the spectra. The pH measured by NMR transiently decreased from pretreatment levels after 200 and 400 J/cm2 treatment (P less than 0.002, P less than 0.009, respectively), while no change in pH from pretreatment values was found after 600 J/cm2 treatment. The data suggest that the early metabolic response of mammary carcinoma to PDT, as indicated by 31P-NMR spectroscopy, is dose dependent, and may be a sensitive indicator of biological outcome to treatment.
Reaction between monoclonal antibodies to porcine zona pellucida (LPD8, LPC4) and human and porcine ovaries was studied by ABC immunohistochemistry technique in vitro. When slices of human and porcine ovaries were stained with ABC, not only the zona pellucida but also the ovum cytoplasm was stained. Other regions of the ovary, such as granulosa cell, theca cell and connective tissue, could not be stained. These results suggest that the monoclonal antibodies to porcine zona pellucida probably have no direct effect on the endocrine function of ovary, but they may combine with ovum cytoplasm and inhibit follicular growth, so that the number of follicles reduces and endocrine function of the ovary decreases. We do not think that the prospects of continual study on LPD8, LPC4 are good.
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The functional interactions between supraspinal mu and delta receptors were characterized in the mouse using mu receptor-selective antagonists. The effects of pretreatment with the mu opioid antagonists, beta-funaltrexamine (beta-FNA) and naloxonazine on the modulation of morphine antinociception by the delta agonists [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2,Met5]enkephalinamide (DAMA) were studied. When co-administered in the same i.c.v. injection, a sub-antinociceptive dose of DPDPE consistently and significantly increased the antinociceptive potency of morphine in control animals, while a sub-effective dose of DAMA decreased morphine antinociception; both the respective increase and the decrease of morphine potency by DPDPE and DAMA had been previously shown to be blocked by ICI 174,864, a delta antagonist. Pretreatment of mice with the non-equilibrium mu antagonist beta-FNA 4 h prior to testing, a pretreatment which had no effect on i.c.v. DPDPE or DAMA antinociception, prevented the modulation of morphine antinociception by both DPDPE and DAMA. Pretreatment with the long acting mu 1 antagonist naloxonazine, 24 h prior to testing, failed to affect the modulation of morphine antinociception by either DPDPE or DAMA; such a pretreatment had no effect on the antinociceptive effects of DPDPE or DAMA when given alone. These results provide further support for the concept of a functionally coupled mu-delta receptor complex which is sensitive to antagonism by beta-FNA, but not naloxonazine, and support the notion that subtypes of opioid mu and delta (i.e. complexed and non-complexed) receptors may exist.
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The role of central (supraspinal and spinal) and peripheral alpha-adrenoceptors in the regulation of gastrointestinal propulsion in the mouse was studied using clonidine, an alpha 2-adrenoceptor agonist. Clonidine produced a dose-dependent inhibition of propulsion when given intracerebroventricularly, intrathecally, or subcutaneously, but was most potent when given intracerebroventricularly. The antitransit effects of centrally given clonidine were antagonized by intracerebroventricular (i.c.v.) yohimbine, but higher doses were required when this antagonist was given peripherally. Whereas i.c.v. and s.c. administration of clonidine were effective in inhibiting gut transit in spinally transected mice, intrathecal (i.th.) administration of this agonist was not. A supraspinal site of clonidine action is suggested based upon (a) the higher central to peripheral potency of clonidine; (b) the greater potency of i.c.v., compared with s.c., administration of yohimbine in blocking i.c.v. clonidine; (c) the lack of effect of i.th. administration of clonidine in spinally transected mice; and (d) the reduced potency of i.c.v., but not s.c., administration of clonidine in spinally transected mice. Additionally, a peripheral site of clonidine action is suggested by (a) the lower potency of i.c.v. yohimbine in blocking s.c., compared with i.c.v., clonidine; (b) the lower potency of i.c.v. yohimbine in blocking i.c.v. clonidine in transected mice (compared with normal mice); (c) the equal potency of s.c. clonidine in slowing propulsion in normal and spinally transected mice; and (d) the equal potency of i.c.v. yohimbine in blocking s.c. clonidine in normal and spinally transected mice. These data in mice would thus support the concept that normal (peripheral) therapeutic administration of clonidine would affect gut motor function by interactions within the brain and directly at the level of the gut.
The gastrointestinal motor effects of centrally-given morphine and bombesin were compared in mice. Both compounds produced a dose-related decrease in the propulsion of a marker along the gut when given by the intracerebroventricular (i.c.v.) or intrathecal (i.th.) routes. Co-administration of the same compound by both routes was found to produce a marked increase in potency for morphine, but only a slight increase in potency for bombesin. Isobolographic analysis of the gut effects of these compounds revealed a multiplicative brain-spinal cord interaction for morphine, but an additive interaction for bombesin. These results are consistent with the interpretation that morphine can act at either the level of the brain or the spinal cord, activating independent pathways which ultimately converge to alter gut propulsion. In contrast, spinal bombesin requires communication to supraspinal sites in order for its gut effects to occur, suggesting activation of a common outflow pathway from the central nervous system.
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The dual properties of two human retinoblastoma cell lines, WERI-Rb1 and Y79, were investigated with immunohistochemistry. Two neuron-specific markers, dopamine-B-hydroxylase (DBH) and tetanus toxin, and an astrocyte-specific marker, the glial fibrillary acid protein (GFAP), were applied for immunohistochemical reactions. With peroxidase-antiperoxidase (PAP) and immunofluorescence techniques, all of the WERI-Rb1 and Y79 cells showed consistently positive results with both neuronal and glial markers. The findings demonstrate that cultured retinoblastoma cells WERI-Rb1 and Y79 have both neuronal and glial properties.
Perceptual sensitivity to a visual target presented in a random continuous sequence of targets and nontargets decreased rapidly over time when stimuli were highly degraded visually but not when moderately degraded or undegraded. Large declines in sensitivity, independent of changes in response criterion, were found after only 5 minutes of observation. These rapid decrements of sensitivity to degraded targets seem to result from demands on the limited capacity of visual attention.