The Journal of pharmacy and pharmacology
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J. Pharm. Pharmacol. · May 2009
Comparative StudyThe importance of brain PGE2 inhibition versus paw PGE2 inhibition as a mechanism for the separation of analgesic and antipyretic effects of lornoxicam in rats with paw inflammation.
Lornoxicam is a non-selective cyclooxygenase inhibitor that exhibits strong analgesic and anti-inflammatory effects but a weak antipyretic effect in rat models. Our aim was to investigate the mechanism of separation of potencies or analgesic and antipyretic effects of lornoxicam in relation to its effect on prostaglandin E2 (PGE2) production in the inflammatory paw and the brain. ⋯ Lornoxicam exhibits strong analgesic but weak antipyretic effects in rats with paw inflammation. Such a separation of effects is related to its efficacy in the reduction of PGE2 levels in the paw and brain hypothalamus.
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J. Pharm. Pharmacol. · Apr 2009
Bis-(3-hydroxyphenyl) diselenide inhibits LPS-stimulated iNOS and COX-2 expression in RAW 264.7 macrophage cells through the NF-kappaB inactivation.
Previously, we reported that diaryl diselenide compounds have strong inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophages. In this study, we investigated the molecular mechanisms underlying NO suppression and prostaglandin E(2) (PGE(2)) production by diaryl diselenide compounds, bis-(2-hydroxyphenyl) diselenide (DSE-A), bis-(3-hydroxyphenyl) diselenide (DSE-B), bis-(4-hydroxyphenyl) diselenide (DSE-C), dipyridyl diselenide (DSE-D) and diphenyl diselenide (DSE-E). ⋯ Taken together, our data suggest that the anti-inflammatory properties of DSE-B are due to reduction in the expression of iNOS, COX-2, TNF-alpha, IL-1beta and IL-6 through the down-regulation of NF-kappaB binding activity.
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J. Pharm. Pharmacol. · Nov 2008
Comparative StudyPharmacological and local toxicity studies of a liposomal formulation for the novel local anaesthetic ropivacaine.
This study reports an investigation of the pharmacological activity, cytotoxicity and local effects of a liposomal formulation of the novel local anaesthetic ropivacaine (RVC) compared with its plain solution. RVC was encapsulated into large unilamellar vesicles (LUVs) composed of egg phosphatidylcholine, cholesterol and alpha-tocopherol (4:3:0.07, mole %). Particle size, partition coefficient determination and in-vitro release studies were used to characterize the encapsulation process. ⋯ Treatment with RVC(LUV) increased the duration (P < 0.001) and intensity of the analgesic effects either on sciatic nerve blockade (1.4-1.6 fold) and infraorbital nerve blockade tests (1.5 fold), in relation to RVC(PLAIN). Regarding histological analysis, no morphological tissue changes were detected in the area of injection and sparse inflammatory cells were observed in only one of the animals treated with RVC(PLAIN) or RVC(luv) at 0.5%. Despite the differences between these preclinical studies and clinical conditions, we suggest RVC(LUV) as a potential new formulation, since RVC is a new and safe local anaesthetic agent.
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J. Pharm. Pharmacol. · Oct 2008
Suppressive potencies of calcineurin inhibitors against the mitogen-induced blastogenesis of peripheral-blood mononuclear cells of myasthenia gravis patients.
The calcineurin inhibitors, tacrolimus and ciclosporin, are two useful immunosuppressive drugs for the treatment of myasthenia gravis (MG), for patients who have low responses to glucocorticoids. We have studied the suppressive potencies of tacrolimus and ciclosporin on concanavalin A-induced blastogenesis of peripheral-blood mononuclear cells (PBMCs) obtained from 38 MG patients and 26 healthy volunteers. Differences in the IC50 values of the two calcineurin inhibitors between the patients and the healthy subjects were evaluated. ⋯ Furthermore, the ciclosporin IC50 values significantly correlated with the periods of glucocorticoid administration for MG treatment (r = 0.42, P = 0.038). Such correlations were not observed with the tacrolimus IC50 values. These results suggested that glucocorticoid administration had an influence on PBMC response to the suppressive efficacy of ciclosporin in MG.
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J. Pharm. Pharmacol. · Oct 2008
Microinjection of morphine into thalamic nucleus submedius depresses bee venom-induced inflammatory pain in the rat.
Previous studies have provided evidence of the existence of a pain modulatory feedback pathway consisting of thalamic nucleus submedius (Sm)-ventrolateral orbital cortex-periaqueductal grey pathway, which is activated during acute pain and leads to depression of transmission of nociceptive information in the spinal dorsal horn. The aim of this study was to test the hypothesis that morphine microinjection into the Sm decreased spontaneous pain and bilateral thermal hyperalgesia, as well as ipsilateral mechanical allodynia, induced by subcutaneous injections of bee venom into the rat hind paw. ⋯ These morphine-induced effects were antagonized by 1.0 microg naloxone (an opioid antagonist) microinjected into the Sm 5 min before morphine administration. The results provided further support for the important role of the Sm and Sm-opioid receptors in inhibiting nociceptive behaviour and indicated for the first time that Sm opioid receptors were also effective in inhibiting the hypersensitivity provoked by bee venom-induced inflammation.