Notes

Ocular Manifestations: Are They Substantial within Hypertensive Ailments of Pregnancy?
Cannabis is one of the most widely used substances across the globe and its use has a substantial heritable component. However, the heritability of cannabis use varies according to substance use phenotype, suggesting that a unique profile of gene variants may contribute to the different stages of use, such as age of use onset, lifetime use, cannabis use disorder, and withdrawal and craving during abstinence. Herein, we review a subset of genes identified by candidate gene, family-based linkage, and genome-wide association studies related to these cannabis use phenotypes. We also describe their relationships with other substances, and their functions at the neurobiological, cognitive, and behavioral levels to hypothesize the role of these genes in cannabis use risk. Delineating genetic risk factors in the various stages of cannabis use will provide insight into the biological mechanisms related to cannabis use and highlight points of intervention prior to and following the development of dependence, as well as identify targets to aid drug development for treating problematic cannabis use.Several studies have demonstrated that lysophosphatidic acid (LPA) acts through its LPA receptors in multiple biological and behavioral processes, including adult hippocampal neurogenesis, hippocampal-dependent memory, and emotional regulation. However, analyses of the effects have typically involved acute treatments, and there is no information available regarding the effect of the chronic pharmacological modulation of the LPA/LPA receptors-signaling pathway. Thus, we analyzed the effect of the chronic (21 days) and continuous intracerebroventricular (ICV) infusion of C181 LPA and the LPA1-3 receptor antagonist Ki16425 in behavior and adult hippocampal neurogenesis. PFI-2 mw Twenty-one days after continuous ICV infusions, mouse behaviors in the open field test, Y-maze test and forced swimming test were assessed. In addition, the hippocampus was examined for c-Fos expression and α-CaMKII and phospho-α-CaMKII levels. The current study demonstrates that chronic C181 LPA produced antidepressant effects, improved spatial working memory, and enhanced adult hippocampal neurogenesis. In contrast, chronic LPA1-3 receptor antagonism disrupted exploratory activity and spatial working memory, induced anxiety and depression-like behaviors and produced an impairment of hippocampal neurogenesis. While these effects were accompanied by an increase in neuronal activation in the DG of C181 LPA-treated mice, Ki16425-treated mice showed reduced neuronal activation in CA3 and CA1 hippocampal subfields. Treatment with the antagonist also induced an imbalance in the expression of basal/activated α-CaMKII protein forms. These outcomes indicate that the chronic central modulation of the LPA receptors-signaling pathway in the brain regulates cognition and emotion, likely comprising hippocampal-dependent mechanisms. The use of pharmacological modulation of this pathway in the brain may potentially be targeted for the treatment of several neuropsychiatric conditions.Antipsychotics are widely used to treat psychiatric illness and insomnia. However, the etiology of insomnia is multifactorial, including disrupted circadian rhythms. Several studies show that antipsychotics might modulate even healthy circadian rhythms. The purpose of this systematic review is to integrate current knowledge about the effects of antipsychotics on the circadian rhythms in humans, and to conduct a meta- analysis with the available data. Nine electronic databases were searched. We followed the PRISMA guidelines and included randomized controlled trials (RCTs), non-RCTs, case-control studies, case series, and case reports. Of 7,217 articles, 70 were included. The available data was mainly from healthy individuals, or patients having schizophrenia, but the findings showed a transdiagnostic impact on circadian parameters. This was consistently seen as decreased amplitude of cortisol, melatonin, and body temperature. Particularly, a meta-analysis of 16 RCTs measuring cortisol rhythm showed that antipsychotics, especially atypical antipsychotics, decreased the cortisol area under the curve and morning cortisol level, compared to placebo. The data with melatonin or actigraphy was limited. Overall, this evidence about the circadian effect of antipsychotics showed a need for longitudinal, real-time monitoring of specific circadian markers to differentiate a change in amplitude from a shift in phasing, and for knowledge about optimal timing of administration of antipsychotics, according to individual baseline circadian parameters. Standardizing selection criteria and outcome methods could facilitate good quality intervention studies and evidence-based treatment guidelines. This is relevant considering the accumulating evidence of the high prevalence and unfavorable impact of disrupted circadian rhythms in psychiatric disorders.CB1 is the most abundant GPCR found in the mammalian brain. It has garnered considerable attention as a potential therapeutic drug target. CB1 is involved in a wide range of physiological and psychiatric processes and has the potential to be targeted in a wide range of disease states. However, most of the selective and non-selective synthetic CB1 agonists and antagonists/inverse agonists developed to date are primarily used as research tools. No novel synthetic cannabinoids are currently in the clinic for use in psychiatric illness; synthetic analogues of the phytocannabinoid THC are on the market to treat nausea and vomiting caused by cancer chemotherapy, along with off-label use for pain. Novel strategies are being explored to target CB1, but with emphasis on the elimination or mitigation of the potential psychiatric adverse effects that are observed by central agonism/antagonism of CB1. New pharmacological options are being pursued that may avoid these adverse effects while preserving the potential therapeutic benefits of CB1 modulation. Allosteric modulation of CB1 is one such approach. In this review, we will summarize and critically analyze both the in vitro characterization and in vivo validation of CB1 allosteric modulators developed to date, with a focus on CNS therapeutic effects.
Read More: https://www.selleckchem.com/products/pfi-2.html