Life sciences
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The effects of L-buthionine sulfoximine (L-BSO), 2-cyclohexene-1-one and diethylmaleate (DEM) on the concentration of rat brain glutathione (GSH) were investigated. Both DEM and 2-cyclohexene-1-one, administered subcutaneously, produced marked and rapid reduction of brain GSH, but 2-cyclohexene-1-one appeared less toxic than DEM. Six hours after 2-cyclohexene-1-one (100 microliters/kg) the striatal GSH concentration was 35% of control values, whereas the level was 55% of controls at 24 h and 80% of controls at 48 h. ⋯ The disappearance rate of GSH after L-BSO alone gives an estimate of the turn-over of GSH. We found the turn-over of GSH to be higher in the substantia nigra pars compacta than in the striatum. The present work suggest that L-BSO and 2-cyclohexene-1-one would be very useful for evaluation of the biological role of GSH in the central nervous system.
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Randomized Controlled Trial Clinical Trial
Objective assessment of clonidine analgesia in man and influence of naloxone.
Experimental data indicate that clonidine can induce marked analgesia. We characterized this effect in healthy volunteers and investigated possible links with the opioid peptide system by means of naloxone antagonism. According to a cross-over, double-blind, placebo-controlled design, 10 subjects received oral and i.v. placebo or clonidine (0.2 mg p.o.) or clonidine and naloxone (2.8 mg i.v. in 5 h). ⋯ Oral clonidine alone or with naloxone increased subjective and objective pain thresholds for at least 4 hours (p less than 0.01, ANOVA). Naloxone tended to reinforce clonidine analgesia. Only moderate and well tolerated side-effects were observed.
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Capsaicin, the pungent constituent of chili peppers, represents the paradigm for the capsaicinoids or vanilloids, a family of compounds shown to stimulate and then desensitize specific subpopulations of sensory receptors, including C-polymodal nociceptors, A-delta mechanoheat nociceptors and warm receptors of the skin, as well as enteroceptors of thin afferent fibers. An exciting recent advance in the field has been the finding that resiniferatoxin (RTX), a naturally occurring diterpene containing a homovanillic acid ester, a key structural motif of capsaicin, functions as an ultrapotent capsaicin analog. ⋯ Specific [3H]RTX binding provides the first direct proof for the existence of vanilloid receptors. We expect that the RTX class of vanilloids will promote rapid progress in understanding of vanilloid structure/activity requirements and mechanism.
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When inflammation is induced in rats following injection of Freund's complete adjuvant, steady state levels of T-I and T-II kininogen mRNAs increase markedly as do plasma levels of T-I and T-II kininogens. When rats are additionally treated with dexamethasone, T-I and T-II steady state mRNA levels and plasma levels of T-kininogens are reduced. The results suggest that dexamethasone may affect the magnitude of T-kininogen gene induction caused by inflammation.
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Comparative Study
Spinal antinociceptive synergy between clonidine and morphine, U69593, and DPDPE: isobolographic analysis.
The spinal antinociceptive interaction between the opiate receptor subtype agonists morphine (mu), U69593 (kappa) and [D-Pen2,5]-enkephalin (DPDPE; delta) with clonidine (alpha 2 adrenergic) was examined. Male SD rats received fixed ratios of clonidine to morphine (10:1), U69593 (1:3), or DPDPE (10:1) through catheters terminating at the lumbar cord. ⋯ Synergy was determined by isobolographic analysis. The ED50 values for the mixtures were significantly less than the theoretical additive ED50 values, indicating synergy between clonidine and morphine, U69593, or DPDPE.