Notes

Retrospective analysis involving skin photosensitivity induced simply by pirfenidone.
The reduction of sleep hours is a public health problem in contemporary society. It is estimated that humans sleep between 1.5 and 2 h less, per night, than 100 years ago. The reduction of sleep hours is a risk factor for developing cardiovascular, metabolic, and psychiatric problems. Previous studies have shown that low sleep quality is a factor that favors relapse in addicted patients. In rodents, sleep deprivation increases the preference for methylphenidate and the self-administration of cocaine. However, it is unknown whether chronic sleep restriction induces voluntary alcohol consumption in rats and whether alcohol intake is associated with delta FosB expression in the brain reward circuit. Potentially, chronic sleep restriction could make the brain vulnerable and consequently promote addictive behavior. Therefore, the present study's objective was to evaluate alcohol consumption in a chronic sleep restriction model and determine the expression of delta FosB in brains of adult rats. FICZ cell line For this purpose, male Wistar rats (300-350 g body weight) were divided into four experimental groups (n = 6 each group) control (without manipulation), sleep restriction (SR) for 7 days, SR and ethanol exposure (Ethanol + SR), and a group with just ethanol exposure (Ethanol). At the end of the management, rats were sacrificed, and the brains were dissected and processed for immunohistochemical detection of delta FosB. The results showed that SR stimulates alcohol consumption compared to unrestricted-sleep rats and induces a significant increase in the number of delta FosB-positive cells in brain nuclei within the motivation/brain reward circuit. These results suggest that chronic reduction of sleep hours is a risk factor for developing a preference for alcohol consumption.Osteoporosis is characterized by reduced bone mineral density (BMD) and increased bone fragility, which may be modified by lifestyle behaviors. In observational studies, chronic moderate ethanol consumption is associated with higher BMD, but results are inconsistent and underlying mechanisms are unknown. To understand the influence of chronic ethanol consumption on true bone density (Archimedes principal), bone mechanical properties (Young's Modulus of bend), and osteogenic gene expression, 12-month-old male Wistar rats were randomly assigned to a control group or ethanol intervention (20% ethanol in drinking water on alternate days) group for 13 weeks and tibiae and femurs were collected. Blood was collected to assess alcohol content and antioxidant enzyme activities. We hypothesized that chronic ethanol consumption would increase true bone density and mechanical properties and increase osteoblastic gene expression and serum antioxidant enzyme activity. Ethanol consumption did not influence femoral or tibial true bone density but did result in lower tibial Young's modulus of bend (p = 0.0002). However, there was no influence of ethanol on other measures of mechanical properties. Femoral pro-osteoclastic gene expression of Dkk1 was lower (p = 0.0006) and pro-osteoblastic gene expression of Ctnnb1 was higher (p = 0.02) with ethanol consumption. We observed no differences in circulating antioxidant activities between groups, other than a tendency for greater (p = 0.08) glutathione peroxidase in the ethanol group. Results showed chronic ethanol consumption did not influence true bone density, only modestly reduced tibial mechanical properties (lower Young's modulus of bend), and moderately impacted expression of genes within the femur known to regulate both osteoblast and osteoclast activities.Nominal effect concentrations from in vitro toxicity assays may lead to inaccurate estimations of in vivo toxic doses because the nominal concentration poorly reflects the concentration at the molecular target in cells in vitro, which is responsible for initiating effects and can be referred to as the biologically effective dose. Chemicals can differentially distribute between in vitro assay compartments, including serum constituents in exposure medium, microtitre plate plastic, headspace and extracellular matrices. The partitioning of test chemicals to these extracellular compartments reduces the concentration at the molecular target. Free concentrations in medium and cell-associated concentrations are considered better proxies of the biologically effective dose. This paper reviews the mechanisms by which test chemicals distribute between in vitro assay compartments, and also lists the physicochemical properties driving the extent of this distribution. The mechanisms and physicochemical properties driving the distribution of test chemical in vitro help explain the makeup of mass balance models that estimate free concentrations and cell-associated concentrations in in vitro toxicity assays. A thorough understanding of the distribution processes and assumptions underlying these mass balance models helps define chemical and biological applicability domains of individual models, as well as provide a perspective on how to improve model predictivity and quantitative in vitro-in vivo extrapolations.Next Generation Risk Assessment (NGRA) can use the so-called Dietary Comparator Ratio (DCR) to evaluate the safety of a defined exposure to a compound of interest. The DCR compares the Exposure Activity Ratio (EAR) for the compound of interest, to the EAR of an established safe level of human exposure to a comparator compound with the same putative mode of action. A DCR ≤ 1 indicates the exposure evaluated is safe. The present study aimed at defining adequate and safe comparator compound exposures for evaluation of anti-androgenic effects, using 3,3-diindolylmethane (DIM), from cruciferous vegetables, and the anti-androgenic drug bicalutamide (BIC). EAR values for these comparator compounds were defined using the AR-CALUX assay. The adequacy of the new comparator EAR values was evaluated using PBK modelling and by comparing the generated DCRs of a series of test compound exposures to actual knowledge on their safety regarding in vivo anti-androgenicity. Results obtained supported the use of AR-CALUX-based comparator EARs for DCR-based NGRA for putative anti-androgenic compounds.
Homepage: https://www.selleckchem.com/products/ficz.html