Pharmacol Rep
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The functional single nucleotide polymorphism (SNP) C3435T in exon 26 of the ABCB1 gene encoding the xenobiotic transporter P-glycoprotein (P-gp) may influence susceptibility to several diseases, as well as the clinical outcome of treatment with P-gp substrates. Exposure to environmental chemicals is thought to be involved in peptic ulcer pathogenesis and then later in stomach cancer development. About 80% of ulcers are associated with Helicobacter pylori infection, one of the risk factors of stomach cancer. ⋯ In addition, the CT genotype was associated with 1.56 times and the TT with 2.45 times higher prevalence of infection compared to the CC genotype. Asimilar association was present in a subgroup of peptic ulcer men (p = 0.0090). The isolated C3435T ABCB1 SNP is not a major factor for genetic susceptibility to peptic ulcer, but in a group of men who suffered from peptic ulcer, this polymorphism seemed to be a risk factor for H. pylori infection development.
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Resveratrol (RSV), a polyphenolic phytoestrogen, has been shown to activate the serine/threonine kinase 5'-adenosine monophosphate-activated protein kinase (AMPK) and to stimulate insulin signaling and glucose uptake in skeletal muscle cells. A direct effect of RSV on neuronal insulin signaling, however, has not been demonstrated. ⋯ Compound C abrogates RSV-induced Akt and GSK-3β phosphorylation and glucose uptake. Thus, we demonstrate that RSV potentiates insulin signaling and glucose uptake via AMPK activation in neuronal cells.
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A conditioned place preference paradigm was used to assess potential rewarding properties of melatonin. The conditioning with melatonin was carried out at two periods of the 12-h light/dark cycle: in the morning (08.30-10.00) and in the evening (18.30-20.00). Morning administration of melatonin (2.5, 5 and 10 mg/kg) did not support conditioned place preference. ⋯ In chronic experiment, melatonin (10 mg/kg) caused similar increase of the time spent on conditioned side both in animals administered vehicle for 7 days and in rats receiving 10 mg/kg of melatonin for the same period of time. Potent activity in the conditioned preference model suggests that melatonin may have rewarding properties, which moreover, is not tolerated following repeated pre-exposure to the drug. These findings may indicate potential abuse liability of melatonin, and therefore, its use by humans should require a careful monitoring for abuse and/or dependency.
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The aim of this study was to determine the analgesic effects of pregabalin (a third-generation antiepileptic drug) using the acute thermal pain model (hot-plate test) in mice. Linear regression analysis was used to evaluate a dose-response relationship between logarithms of pregabalin doses and their resultant maximum possible antinociceptive effects (MPAE) using the hot-plate test in mice. From the linear equation of the dose-response relationship, doses of pregabalin that increased antinociceptive effects by 20%, 30%, 40%, and 50% were calculated and amounted to 9.33, 24.80, 65.93, and 175.26 mg/kg, respectively. In conclusion, pregabalin produces analgesic effects in a dose-dependent manner, as demonstrated using the hot-plate test in mice.
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The results of recent studies suggest that metformin, in addition to its efficacy in treating type 2 diabetes, may also have therapeutic potential for the treatment of neuroinflammatory diseases in which reactive microglia play an essential role. However, the molecular mechanisms by which metformin exerts its anti-inflammatory effects remain largely unknown. Adenosine-monophosphate-activated protein kinase (AMPK) activation is the most well-known mechanism of metformin action; however, some of the biological responses to metformin are not limited to AMPK activation but are mediated by AMPK-independent mechanisms. ⋯ The presented evidence supports the conclusion that metformin-activated AMPK participates in regulating the release of TNF-α. Furthermore, the effects of metformin on the release of IL-1β, IL-6, IL-10, TGF-β, NO, and ROS as well as on the expression of arginase I, iNOS, NF-κB p65 and PGC-1α were not AMPK-dependent, because pretreatment of LPS-activated microglia with compound C, a pharmacological inhibitor of AMPK, did not reverse the effect of metformin. Based on the present findings, we propose that the shift of microglia toward alternative activation may underlie the beneficial effects of metformin observed in animal models of neurological disorders.