One function of the blood-brain barrier (BBB) is the efflux of xenobiotics by breast cancer resistance protein (BCRP), and inhibition of BCRP can cause unexpected central nervous system toxicity. Despite the importance of BCRP inhibition and the associated risk of BBB penetration in vivo, there has been little investigation of it to date. In this study, inhibition of BCRP-mediated transport was assessed by in vitro assay in the presence of bovine serum albumin (BSA) to change the unbound inhibitor concentrations, and the in vitro-in vivo correlation (IVIVC) at the BBB was evaluated. The IC values of BCRP inhibitors were determined in vitro with and without BSA and the inhibitors were categorized into two groups. One group of compounds had little risk of inhibiting BCRP because of their low unbound concentrations. https://www.selleckchem.com/products/ziftomenib.html In contrast, the other group has the potential to facilitate BBB penetration by inhibiting BCRP. In the IVIVC approach, brain concentrations and the brain-to-plasma ratio were better correlated with the ratio of the unbound plasma concentration at steady-state to the unbound-fraction-adjusted IC . We have found a way to obtain a better in vitro-in vivo correlation for BCRP-mediated transport. We have found a way to obtain a better in vitro-in vivo correlation for BCRP-mediated transport. The non-homogenous flow of the cerebrospinal fluid within the ventricular catheter is one of the causative factors in shunt obstructions during the treatment of hydrocephalus. Previously, we studied the flow in ventricular catheters under the steady and pulsatile boundary conditions by means of computational fluid dynamics (CFD) in three-dimensional paradigms. Subsequently, several catheter designs with homogeneous flow patterns were developed out of which one prototype was chosen after a validation study. To test the effectiveness of the flow ventricular catheter in a prospective, multicenter, comparative study. Eligible centers were three pediatric hospitals two with sole adult practice and one a mixed pediatric-adult. Standard silicone material was used to develop a parametric catheter model with homogenous flow characteristics. The flow catheters were inserted in pediatric (n = 30) and adult (n = 10) patients with all types of hydrocephalus. Simultaneously, regular ventricular catheters were inserteomparative study showed a possible obstruction-free functionality. This prototype model represents the next generation of ventricular catheters with a homogeneous flow pattern. The flow catheter can be inserted safely in hydrocephalic patients, and this preliminary prospective comparative study showed a possible obstruction-free functionality. The widespread deficits in cognitive flexibility observed across psychiatric disorders call for improved rodent tests to understand the biology of cognitive flexibility and development of better psychotherapeutics. Current reversal learning paradigms have a forced-choice setup that challenges the interpretation of results. We aimed at developing a free-choice reversal learning test, where images are presented sequentially and animals are free to move, to enable investigation of the cognitive sub-processes that occur during reversal. Behavior in female C57BL/6JOlaHsd mice was characterized using chronic fluoxetine as a reference compound. Additional tests were included to support the interpretation of results and exclude confounding pharmacological effects. Behaviors in vehicle-treated mice were furthermore analyzed for relatedness to deepen the understanding of parameters measured. We found that exploitation of the previously rewarded image was independent of exploration and acquisition of the new reward contingency and could be differentially modulated by fluoxetine, supporting recent theories that these processes are not mutually exclusive. Specifically, fluoxetine reduced mistake rate, premature and perseverative responses, and promoted conservative strategies during reversal without affecting hit rate. These effects appeared to be most prominent during the late stage of reversal learning, where accuracy was above chance level. Analysis of behaviors in vehicle-treated mice suggested that exploitation was related to an impulsive-like deficit in response inhibition, while exploration was more related to motivation. This new schedule was feasible, easy to implement, and can provide a deeper understanding of the cognitive sub-processes during reversal. This new schedule was feasible, easy to implement, and can provide a deeper understanding of the cognitive sub-processes during reversal.Caffeine has been demonstrated to enhance olfactory function in rodents, but to date, the sparse research in humans has not shown any equivalent effects. However, due to the methodological nature of those human studies, a number of questions remain unanswered, which the present study aimed to investigate. Using a double-blind experimental design, participants (n = 40) completed baseline mood measures, standardised threshold and identification tests and were then randomly allocated to receive a capsule containing either 100 mg of caffeine or placebo, followed by the same olfactory tests and mood measures. Results revealed that despite a trend toward elevated arousal following caffeine for habitual caffeine consumers, there were no changes in odour function. In contrast, for non-caffeine consumers, caffeine acted to enhance odour (threshold) sensitivity but reduce odour identification. Overall, these findings demonstrate a complex profile of effects of caffeine on odour function and, given the evidence from the wider caffeine literature, it is proposed that the effects of caffeine might be limited to older populations. Nicotine is initially anxiogenic and becomes anxiolytic after prolonged exposure. The mechanisms that facilitate the shift in anxiety-like behaviour produced by nicotine are unclear. We investigated the change in time spent in the centre of an open field (as a measure anxiety-like behaviour) produced by three intermittent injections of nicotine as part of experiments of locomotor sensitization to nicotine. Rats were injected with nicotine (0.4 mg/kg) or saline and immediately placed in the open field arena for 1 h on two consecutive days and again 9 days later. When given saline, time spent in the centre of the arena did not change, whereas repeated nicotine injections increased in time spent in the centre beyond the increase produced by an acute injection of nicotine. Repeated nicotine (and not acute nicotine) also increased time in the centre in a drug-free state when tested 24 h after the last injection. Repeated nicotine sensitized the time spent in the centre of an open field with the long-lasting sensitization of this measure of anxiety-like behaviour evident in a drug-free state, in contrast to locomotor sensitization which does not persist in the drug-free state.