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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Randomized Controlled Trial
Ketamine spares morphine consumption after transthoracic lung and heart surgery without adverse hemodynamic effects.
Thoracotomy is associated with severe pain. Large doses of morphine can depress respiratory drive and compromise hemodynamic stability. Ketamine reduces hyperalgesia, prevents opioid tolerance and resistance and lowers morphine consumption. At sub-anesthetic (< or = 500 microg/kg) doses, ketamine rarely produces undesirable hemodynamic alterations. We hypothesized that by combining a sub-anesthetic dose of ketamine with morphine, we could effectively control pain with less morphine and minimize drowsiness, while maintaining safe hemodynamic and respiratory parameters. ⋯ The concomitant use of sub-anesthetic ketamine plus two-thirds the standard MO dose following thoracotomy, MIDCAB or OPCAB resulted in lower pain scores, reduced MO consumption and shorter postoperative IV-PCA dependence. These advantages were associated with cardiovascular stability and even better respiratory parameters.
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Myriocin, a potent inhibitor of serine palmitoyltransferase (SPT), has been shown to reduce plasma sphingolipids, cholesterol and triglycerides in hyperlipidemic apolipoprotein E knockout (apoE KO) mice. We hypothesized that the inhibition of sphingolipid biosynthesis modulates the composition of atherosclerotic plaque via its lipid-lowering effects. To test this hypothesis, the effect of myriocin on plasma lipids, sphingolipids and atherosclerosis progression, regression and lesion composition was investigated in apoE KO mice. ⋯ Compared to 24- and 36-week controls, atherosclerotic lesion area and macrophage content in the aortic root and brachiocephalic arteries of myriocin-treated ApoE KO mice were reduced but there was only a slight increase in smooth muscle content. However, the content of collagen within aortic root lesions was increased in myriocin-treated apoE KO mice. In summary, the inhibition of SPT lowers plasma sphingolipids and atherogenic plasma lipids leading to the regression of pre-existing atherosclerotic lesions and to the formation of a stable plaque phenotype.