Pharmacological research : the official journal of the Italian Pharmacological Society
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Glycyrrhizin is a triterpene glycoside, a major active constituent of licorice (Glycyrrhiza glabra) root and numerous pharmacological effects like anti-inflammatory, anti-viral, anti-tumour and hepatoprotective activities has been attributed to it. In this study we evaluated the anti-inflammatory activities of glycyrrhizin in mice model of acute inflammation, carrageenan-induced pleurisy. We report here that glycyrrhizin (given at 10 mg/kg i.p. 5 min prior to carrageenan) exerts potent anti-inflammatory effects in this model. ⋯ Additionally, we demonstrate that these inflammatory events were associated with the activation of nuclear factor-kappaB (NF-kappaB) and signal transducer and activator transcription-3 (STAT-3) activation in the lung. NF-kappaB and STAT-3 activation were significantly reduced by glycyrrhizin treatment. Taken together, our results indicate that prevention of the activation of NF-kappaB and STAT-3 by glycyrrhizin reduces the development of acute inflammation.
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Previous studies indicate that rapid eye movement (REM) sleep deprivation facilitates pain sensitivity. Since serotoninergic raphe neurons are involved both in regulation of sleep and descending pain modulation, we studied whether spinal 5-HT receptors have a role in sleep deprivation-induced facilitation of pain-related behavior. REM sleep deprivation of 48h was induced by the flower pot method in the rat. ⋯ The results indicate that serotoninergic receptors in the spinal cord have a complex role in the control of sleep-deprivation induced cutaneous hypersensitivity as well as baseline sensitivity in control conditions. While endogenous serotonin acting on 5-HT(1A) and 5-HT(2C) receptors may facilitate mechanical sensitivity in animals with a sleep deprivation-induced hypersensitivity as well as in controls, increased activation of spinal 5-HT(1A) receptors by an exogenous agonist leads to suppression of mechanical sensitivity in both conditions. Spinal 5-HT(3) receptors do not contribute to cutaneous hypersensitivity induced by sleep deprivation.
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The association of erectile dysfunction (ED) with cardiovascular diseases is so common. This study was carried out to investigate possible impact of sildenafil; the prototype phosphodiesterase 5 inhibitor used for treatment of ED, on the beneficial hemodynamic and histopathological effects of the prototype third generation calcium antagonist, amlodipine, in nitric oxide (NO)-deficient hypertensive rats. Hypertension was induced by 4-weeks treatment with N(omega)-nitro-l-arginine-methyl ester (l-NAME). ⋯ When combined with sildenafil, both hemodynamic and histopathological effects of amlodipine were augmented with an underlying enhanced elevation of both plasma NO(x) and cGMP levels to statistically higher values than amlodipine alone. These results show that sildenafil augments the beneficial hemodynamic and histopathological effects of amlodipine in NO-deficient hypertensive rats with a pivotal role being played by NO-cGMP pathway. Whether this pharmacodynamic interaction could exist in other models of hypertension that do not share such biochemical derangement warrants further investigations.
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A number of studies support the notion that lithium interacts with the protein kinase C (PKC) pathway, an important mediator of several intracellular responses to neurotransmitter signaling. PDLIM5 (PDZ and LIM domain 5; LIM) is an adaptor protein that selectively binds the isozyme PKC(epsilon) to N-type Ca(2+) channels in neurons. We tested for an association between three single nucleotide polymorphisms (SNPs) at the PDLIM5 gene and lithium prophylaxis in a Sardinian sample comprised of 155 bipolar patients treated with lithium. ⋯ No association was shown between PDLIM5 polymorphisms and lithium response. When PDLIM5 expression was evaluated, no significant differences were detected between Full Responders to lithium (total score>or=7) and other patients (total score
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The effect of the non-selective, 1-aminoindan-1,5-dicarboxylic acid (AIDA), and selective (3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl) methanone (JNJ16259685), metabotropic glutamate subtype 1 (mGlu1) receptor antagonists, on rat sciatic nerve chronic constrictive injury (CCI)-induced hyperalgesia, allodynia, spinal dorsal horn apoptosis, and gliosis was examined at 3 and 7 days post-injury. RT-PCR analysis showed increased expression of bax, apoptotic protease-activating factor-1 (apaf-1), nestin, GFAP, and caspase-7 mRNA in the dorsal horn spinal cord by 3 days post-CCI. At 7 days post-CCI, only over-expression of bcl-2, nestin and GFAP mRNA was observed. ⋯ We report here that despite inhibiting CCI-induced over-expression of pro-apoptotic genes in the spinal cord dorsal horn, the selective mGlu1 receptor antagonist JNJ16259685 exerted only a slight and transient allodynic effect. Moreover, JNJ16259685, but not the non-selective AIDA, increased astrogliosis which may account for its decreased analgesic efficacy. This study provides evidence that the contemporary and partial blockade of group I and likely ionotropic glutamate receptors may be a more suitable therapy than selective blockade of mGlu1 subtype receptors condition to decrease neuropathic pain symptoms.