Life sciences
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Chronic stress-related conditions are often associated with stress-induced hyperalgesia. However, the neural circuitry responsible for producing stress-induced hyperalgesia is not well characterized. The aim of this study was to determine the contribution of mu-opioid expressing brainstem neurons to the expression of stress-induced hyperalgesia. ⋯ The finding that chronic stress produces mechanical hypersensitivity through circuitry that involves the RVM provides a potential neurobiological basis for the complex interaction between chronic stress and pain.
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We investigated the effects of in vivo intrastriatal administration of glycine (Gly), which is found at high concentrations in the brain of patients affected by nonketotic hyperglycinemia (NKH), on important parameters of oxidative stress. ⋯ The data shows that Gly in vivo administration causes lipid peroxidation, probably secondary to NMDA stimulation, induces protein oxidation and modulates the activities of important antioxidant enzymes in the striatum. In case these findings can be extrapolated to the human NKH, it is feasible that oxidative stress may be involved in the pathophysiology of the brain injury observed in patients with this neurometabolic disease.
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Cannabidiol (CBD), one of the major constituents in marijuana, has been shown to be extensively metabolized by experimental animals and humans. However, human hepatic enzymes responsible for the CBD metabolism remain to be elucidated. In this study, we examined in vitro metabolism of CBD with human liver microsomes (HLMs) to clarify cytochrome P450 (CYP) isoforms involved in the CBD oxidations. ⋯ This study indicated that CBD was extensively metabolized by HLMs. These results suggest that CYP3A4 and CYP2C19 may be major isoforms responsible for 6α-, 6β-, 7-, and/or 4″-hydroxylations of CBD in HLMs.