Senescence patterns are highly variable across the animal kingdom. However, while empirical evidence of actuarial senescence in vertebrates is accumulating in the wild and life history correlates of actuarial senescence are increasingly identified, both the extent and variation of reproductive senescence across species remain poorly studied. Here, we performed the first large-scale analysis of female reproductive senescence across 101 mammalian species that encompassed a wide range of Orders. We found evidence of reproductive senescence in 68.31 % of the species, which demonstrates that reproductive senescence is pervasive in mammals. As expected from allometric rules, the onset of reproductive senescence occurs later and the rate of reproductive senescence decreases with increasing body mass and delayed age at first reproduction. Moreover, for a given pace of life, females displaying a high level of multiple mating and/or with induced ovulation senesce earlier than females displaying a low level of multiple mating and/or with spontaneous ovulation. These results suggest that both female mating behavior and reproductive physiology shape the diversity of reproductive senescence patterns across mammals. We propose future avenues of research regarding the role played by environmental conditions or reproductive features (e.g. type of placentation) on the evolution of reproductive senescence.Ketoconazole (KZ) is broad spectrum antifungal drug, used for the treatment of fungal infections. KZ's clinical topical use has been associated with some adverse effects in healthy adults particularly local reactions, such as stinging, severe irritation, and pruritus. However, bioavailability of KZ after oral administration is low from tablets due to its low aqueous solubility. The objective of this investigation was development and characterization of KZ-containing solid lipid nanoparticles (KZ-SLNs) and SLN-containing hydrogel (KZ-SLN-H) for oral and topical delivery of KZ. KZ-SLNs were prepared using homogenization-sonication method. Optimal KZ-SLN formulation was selected based on physicochemical and in-vitro release studies. Optimized KZ-SLN converted to KZ-SLN hydrogel (KZ-SLN-H) using gelling polymers and optimized with rheological and in-vitro studies. Further, optimized KZ-SLN and KZ-SLN-H formulations evaluated for crystallinity, morphology, stability, ex-vivo and in-vivo pharmacokinetic (PK) studies in rats, comparison with KZ suspension (KZ-S) and KZ-S hydrogel (KZ-SH). Optimized KZ-SLN formulation showed desirable characters. KZ-SLN and KZ-SLN-H formulations exhibited spherical shape, converted to amorphous, sustained release behaviour and enhanced permeability (p less then 0.05). Moreover, both formulations were stable for three months at 4 °C and 25 °C. PK studies revealed 1.9 and 1.5-folds, 3.5 and 2.8-folds enhancement of bioavailability of optimized KZ-SLN and KZ-SLN-H formulations (p less then 0.05) compared with KZ-S and KZ-SH formulations, respectively. Overall, SLN and SLN-H formulations could be considered as an efficient delivery vehicles for KZ through oral and topical administration for better control over topical and systemic fungal infections.Pregnancy and lactation are reproductive processes that rely on physiological adaptations that should be timely and adequately triggered to guarantee both maternal and fetal health. Pineal melatonin is a hormone that presents daily and seasonal variations that synchronizes the organism's physiology to the different demands across time through its specific mechanisms and ways of action. The reproductive system is a notable target for melatonin as it actively participates on reproductive physiology and regulates the hypothalamus-pituitary-gonads axis, influencing gonadotropins and sexual hormones synthesis and release. For its antioxidant properties, melatonin is also vital for the oocytes and spermatozoa quality and viability, and for blastocyst development. Maternal pineal melatonin blood levels increase during pregnancy and triggers the maternal physiological alterations in energy metabolism both during pregnancy and lactation to cope with the energy demands of both periods and to promote adequate mammary gland development. Moreover, maternal melatonin freely crosses the placenta and is the only source of this hormone to the fetus.  https://www.selleckchem.com/products/GSK429286A.html  It importantly times the conceptus physiology and influences its development and programing of several functions that depend on neural and brain development, ultimately priming adult behavior and energy and glucose metabolism. The present review aims to explain the above listed melatonin functions, including the potential alterations observed in the progeny gestated under maternal chronodisruption and/or hypomelatoninemia.Trajectories of neurodevelopment and quality of life were analyzed in children with hypoplastic left heart syndrome according to socioeconomic status (SES) and maternal education. Lower SES and less maternal education were associated with greater early delays in communication and problem-solving and progressive delays in problem-solving and fine motor skills over time.Benign prostatic hyperplasia (BPH) is a common male disorder. Febuxostat is a non-purine, selective inhibitor of xanthine oxidase (XO), which has a strong antioxidant capacity and pleiotropic pharmacological properties. This study's objective was to explore the potential ameliorative effects of febuxostat against testosterone-induced BPH in rats. Febuxostat (10 mg/kg/day, per os [p.o.]) prevented increased prostate index levels, serum levels of prostate-specific antigen (PSA), and testosterone levels compared to animals treated with testosterone alone, when administered for 28 days. Histological examination indicated that febuxostat dramatically ameliorated pathological changes in the prostate architecture compared to the testosterone group. Similarly, febuxostat markedly improved testosterone-induced oxidative stress by inhibiting the increase in lipid peroxide and nitrite content, and by reducing the level of depletion of reduced glutathione (GSH) and superoxide dismutase (SOD) activity, which significantly reduced the prostate content of pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6).