The use of OTC medication during exams was more among high school and university students. Gender, age and educational institution were found significantly affecting the use of OTC medicines during exams.

Epilepsy is a complex neurological condition characterized by repeated spontaneous seizures and can be induced by initiating seizures known as status epilepticus (SE). Elaborating the critical molecular mechanisms following SE are central to understanding the establishment of chronic seizures. Here, we identify a transient program of molecular and metabolic signaling in the early epileptogenic period, centered on day five following SE in the pre-clinical kainate or pilocarpine models of temporal lobe epilepsy. Our work now elaborates a new molecular mechanism centered around Wnt signaling and a growing network comprised of metabolic reprogramming and mTOR activation. Biochemical, metabolomic, confocal microscopy and mouse genetics experiments all demonstrate coordinated activation of Wnt signaling, predominantly in neurons, and the ensuing induction of an overall aerobic glycolysis (Warburg-like phenomenon) and an altered TCA cycle in early epileptogenesis. A centerpiece of the mechanism is the regulation of pyruvate dehydrogenase (PDH) through its kinase and Wnt target genes PDK4. Intriguingly, PDH is a central gene in certain genetic epilepsies, underscoring the relevance of our elaborated mechanisms. While sharing some features with cancers, the Warburg-like metabolism in early epileptogenesis is uniquely split between neurons and astrocytes to achieve an overall novel metabolic reprogramming. This split Warburg metabolic reprogramming triggers an inhibition of AMPK and subsequent activation of mTOR, which is a signature event of epileptogenesis. Interrogation of the mechanism with the metabolic inhibitor 2-deoxyglucose surprisingly demonstrated that Wnt signaling and the resulting metabolic reprogramming lies upstream of mTOR activation in epileptogenesis. To augment the pre-clinical pilocarpine and kainate models, aspects of the proposed mechanisms were also investigated and correlated in a genetic model of constitutive Wnt signaling (deletion of the transcriptional repressor and Wnt pathway inhibitor HBP1). The results from the HBP1-/- mice provide a genetic evidence that Wnt signaling may set the threshold of acquired seizure susceptibility with a similar molecular framework. Using biochemistry and genetics, this paper outlines a new molecular framework of early epileptogenesis and advances a potential molecular platform for refining therapeutic strategies in attenuating recurrent seizures.

Canagliflozin, used to treat type 2 diabetes mellitus (T2DM), is commonly co-administered with sulfonylureas. The objective of the present study was to evaluate the possible inhibitory effect of sulfonylureas and non-steroidal anti-inflammatory drugs (NSAIDs) on canagliflozin metabolism in vitro. Three sulfonylurea derivatives were evaluated as inhibitors: chlorpropamide, glimepiride and gliclazide. Two other NSAIDs were used as positive control inhibitors: niflumic acid and diclofenac. The rate of formation of canagliflozin metabolites was determined by HPLC analysis of in vitro incubations of canagliflozin as a substrate with and without inhibitors, using human liver microsomes (HLMs). Among sulfonylureas, glimepiride showed the most potent inhibitory effect against canagliflozin M7 metabolite formation, with an IC value of 88 μm, compared to chlorpropamide and gliclazide with IC values of more than 500 μm. Diclofenac inhibited M5 metabolite formation more than M7, with IC values of 32 μm for M5 and 80 μm for M7. Niflumic acid showed no inhibition activity against M5 formation, but had relatively selective inhibitory potency against M7 formation, which is catalysed by UGT1A9, with an IC value of 1.9 μm and an inhibition constant value of 0.8 μm. A clinical pharmacokinetic interaction between canagliflozin and sulfonylureas is unlikely. However, a possible clinically important drug interaction between niflumic acid and canagliflozin has been identified.

The use of cannabis has led to a dramatic increase in cannabinoid (CB) abuse during the past decade, presenting a major public health challenge. Despite significant research there is a lack of full understanding on how cannabinoids that vary and efficacy and affinity at CB 1 receptors alter key neurotransmitters like dopamine (DA) in reward-related brain regions to impact behavior. Mounting evidence suggests that actions at CB 1 receptors modulate DA within the nucleus accumbens shell-a key brain region involved in the abuse-related neurobiological actions of most drugs of abuse. Here, we utilized in vivo microdialysis and liquid chromatography-mass spectrometry (LC-MS/MS) to quantify changes in DA within the nucleus accumbens shell of mice administered (i.p.) the synthetic full CB 1 agonist AM8936 (0.01-1.0 mg/kg), the synthetic partial CB 1 agonist AM11101 (0.1-3.2 mg/kg), or the phytocannabinoid partial CB 1 agonist D 9 -THC (0.1-3.2 mg/kg). At lower doses, AM8936, AM11101, and D 9 -THC administration increased extracellular levels of DA within the nucleus accumbens shell reaching a maximum of 134%, 140%, and 161% of baseline levels after 0.032, 0.32, and 0.32 mg/kg, respectively. AM11101 and D 9 -THC produced peak increases in DA at 20 minutes post-injection, which remained elevated for approximately 2 hours and then returned toward baseline levels. Conversely, the peak increases in DA after administration of 0.032 mg/kg AM8936 was observed at about 140 minutes post-injection, and DA remained elevated until the end of the experiment (5 hours post injection). At 10-fold higher doses, AM8936, AM11101, and D 9 -THC decreased DA to 62%, 72%, and 62% of baseline levels after 0.32, 3.2, and 3.2 mg/kg, respectively; for all drugs these decreases persisted until the end of the experiment. The calculated area under the curve for a 100-minute window centered around the peak DA increase for each agonist showed that low doses of AM8936 (0.01-0.032 mg/kg) AM11101 (0.1-0.32 mg/kg) and D 9 -THC (0.1-0.32 mg/kg) increased DA levels, whereas higher doses of AM8936 (0.1-1.0 mg/kg) AM11101 (1.0-3.2 mg/kg) and D 9 -THC (1.0-3.2 mg/kg) decreased extracellular levels of DA. Together, these results demonstrate that while AM11101 and D 9 -THC DA effects have quicker onset and shorter duration compared to AM8936, CB 1 partial and full agonists have similar, biphasic effects on DA within the nucleus accumbens shell.