Species differences in CYP enzymes

Species differences in CYP enzymes

Neuromuscular training and the risk of leg injuries in female floorball players: cluster randomised controlled study

Objective To investigate whether a neuromuscular training programme is effective in preventing non-contact leg injuries in female floorball players

Environmental Intolerance, Symptoms and Disability Among Fertile-Aged Women

The purpose was to study the prevalence of environmental intolerance (EI) and its different manifestations, including behavioral changes and disability. Fertile-aged women (n = 680) of the Kuopio Birth Cohort Study were asked about annoyance to 12 environmental factors, symptoms and behavioral changes. We asked how much the intolerance had disrupted their work, household responsibilities or social life. We chose intolerance attributed to chemicals, indoor molds, and electromagnetic fields to represent typical intolerance entities. Of the respondents, 46% reported annoyance to chemicals, molds, or electromagnetic fields. Thirty-three percent reported symptoms relating to at least one of these three EIs, 18% reported symptoms that included central nervous system symptoms, and 15% reported behavioral changes. Indicating disability, 8.4% reported their experience relating to any of the three EIs as at least "somewhat difficult", 2.2% "very difficult" or "extremely difficult", and 0.9% "extremely difficult". Of the latter 2.2%, all attributed their intolerance to indoor molds, and two thirds also to chemicals. As the number of difficulties increased, the number of organ systems, behavioral changes and overlaps of the three EIs also grew. EI is a heterogeneous phenomenon and its prevalence depends on its definition. The manifestations of EI form a continuum, ranging from annoyance to severe disability.Peer reviewe

Liver safety assessment: required data elements and best practices for data collection and standardization in clinical trials.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and standards for the accurate measurement of DILI risk associated with new therapeutic agents in clinical trials. There was agreement that in order to achieve this goal the systematic acquisition of protocol-specified clinical measures and lab specimens from all study subjects is crucial. In addition, standard DILI terms that address the diverse clinical and pathologic signatures of DILI were considered essential. There was a strong consensus that clinical and lab analyses necessary for the evaluation of cases of acute liver injury should be consistent with the US Food and Drug Administration (FDA) guidance on pre-marketing risk assessment of DILI in clinical trials issued in 2009. A recommendation that liver injury case review and management be guided by clinicians with hepatologic expertise was made. Of note, there was agreement that emerging DILI signals should prompt the systematic collection of candidate pharmacogenomic, proteomic and/or metabonomic biomarkers from all study subjects. The use of emerging standardized clinical terminology, CRFs and graphic tools for data review to enable harmonization across clinical trials was strongly encouraged. Many of the recommendations made in the breakout session are in alignment with those made in the other parallel sessions on methodology to assess clinical liver safety data, causality assessment for suspected DILI, and liver safety assessment in special populations (hepatitis B, C, and oncology trials). Nonetheless, a few outstanding issues remain for future consideration

In vitro human metabolism and inhibition potency of verbascoside for CYP enzymes

Verbascoside is found in many medicinal plant families such as Verbenaceae. Important biological activities have been ascribed to verbascoside. Investigated in this study is the potential of verbascoside as an adjuvant during tuberculosis treatment. The present study reports on the in vitro metabolism in human hepatic microsomes and cytosol incubations as well as the presence and quantity of verbascoside within Lippia scaberrima. Additionally, studied are the inhibitory properties on human hepatic CYP enzymes together with antioxidant and cytotoxic properties. The results yielded no metabolites in the hydrolysis or cytochrome P450 (CYP) oxidation incubations. However, five different methylated conjugates of verbascoside could be found in S-adenosylmethionine incubation, three different sulphate conjugates with 30 -phosphoadenosine 50 -phosphosulfate (PAPS) incubation with human liver samples, and very low levels of glucuronide metabolites after incubation with recombinant human uridine 5’-diphospho-glucuronosyltransferase (UGT) 1A7, UGT1A8, and UGT1A10. Additionally, verbascoside showed weak inhibitory potency against CYP1A2 and CYP1B1 with IC50 values of 83 µM and 86 µM, respectively. Potent antioxidant and low cytotoxic potential were observed. Based on these data, verbascoside does not possess any clinically relevant CYP-mediated interaction potential, but it has effective biological activity. Therefore, verbascoside could be considered as a lead compound for further drug development and as an adjuvant during tuberculosis treatment.National Research Foundationhttps://www.mdpi.com/journal/moleculespm2020Plant Production and Soil Scienc

Longitudinal Analyses of Diet Quality and Maternal Depressive Symptoms During Pregnancy : The Kuopio Birth Cohort Study

Publisher Copyright: © 2022 Academy of Nutrition and DieteticsBackground: Depression and diet quality appear to be associated in the general population. Nevertheless, little is known about their relationship among pregnant females. Objective: The aims of this study were first, to investigate longitudinally whether or not diet quality is associated with depressive symptoms during pregnancy; second, to examine whether or not variation in diet quality during pregnancy predicts variation in depressive symptoms; and third, to explore how individual dietary components are associated with depressive symptoms. Design: A longitudinal secondary analysis of the Kuopio Birth Cohort Study in eastern Finland was conducted. Data were collected from pregnant females during the first and third trimesters of pregnancy. Participants/setting: The participants were 1,362 pregnant females who entered the study between 2012 and 2017. Main outcome measures: Depressive symptoms, as measured with the Edinburgh Postnatal Depressive Scale during the first and third trimesters of pregnancy were used as continuous variables. Statistical analyses performed: The main analyses consisted of linear mixed model analyses adjusted for potential confounders to longitudinally assess the association between diet quality as measured by the Healthy Eating Index-2015, calculated using data from a food frequency questionnaire completed during the first trimester and third trimester, and depressive symptoms during the study period. An exploratory set of linear mixed models was also used to longitudinally assess the associations between selected individual food frequency questionnaire food groups and depressive symptoms. Results: Descriptive analyses revealed that 12.3% of the participants had clinically relevant levels of depressive symptoms (ie, Edinburgh Postnatal Depressive Scale score ≥10) during either the first or third trimester. Longitudinal modeling suggested that depressive symptoms in pregnant females tend to remain stable throughout pregnancy. Females with a poorer quality diet already displayed higher levels of depressive symptoms during the first trimester of pregnancy (β = –.038 ± .016; P = 0.022). Variation in diet quality did not predict variation in depressive symptoms over the course of pregnancy (β = –9.741 × 10–5 ± .001; P = 0.869). Conclusions: Females entering pregnancy with a poorer quality diet also displayed higher levels of depressive symptoms compared with females with a higher quality diet at the beginning of pregnancy, and this association remained constant throughout pregnancy. Further research is needed to assess the direction and the potential causality of the observed associations between diet quality and depressive symptoms.Peer reviewe