The study documented here was aimed to find the molecular interactions of some of the cannabinoid constituents of cannabis with acetylcholinesterase (AChE). Molecular docking and LogP determination were performed to predict the AChE inhibitory effect and lipophilicity. AChE enzyme activity was measured in the blood of cannabis addicted human subjects. Further, genetic predisposition to cannabis addiction was investigated by association analysis of cannabinoid receptor 1 (CNR1) single nucleotide polymorphism (SNP) rs806368 and ACHE rs17228602 using restriction fragment length polymorphism (RFLP) method. All the understudied cannabis constituents showed promising binding affinities with AChE and are lipophilic in nature. The AChE activity was observed to be indifferent in cannabis addicted and non-addicted healthy controls. There was no significant association with CNR1 SNP rs806368 and ACHE rs17228602. The study concludes that in silico prediction for individual biomolecules of cannabis is different from in vivo physiological action in human subjects when all are present together. However, for a deeper mechanistic insight into these interactions and association, multi-population studies are suggested. Further studies to explore the inhibitory potential of different cannabis constituents for intended AChE inhibitor-based drug are warranted.
After administration of various amounts of pralidoxime to rats, the levels in serum, brain and cerebrospinal fluid (CSF) were measured using capillary zone electrophoresis (CZE). The calibration curves were established using spiked samples. The calibration covers the ranges from 0.3 – 200 μg/mL, 0.3 – 7 μg/mL and 0.1 – 7 μg/mL for serum, brain and CSF, respectively. The CZE measurement opens the way to the fast and reliable determination of pyridinium aldoxime concentrations in serum, cerebrospinal fluid and brain, thereby monitoring blood-brain and blood-CSF penetration of pyridinium aldoximetype antidotes clinically used in organophosphate poisoning.
Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous antioxidants in kidney, liver, cerebral cortex (CC), and hippocampus after the onset of diabetes mellitus, using enzyme-linked immunosorbent assay and immunohistochemistry. Exogenous NC (aa chain 1–17; 10 µg/kg body weight) was given intraperitoneally to normal and diabetic rats for 5 days. Our results showed that catalase (CAT) is present in the proximal (PCT) and distal (DCT) convoluted tubules of kidney, hepatocytes, and neurons of CC and hippocampus. The expression of CAT was significantly (p < 0.05) reduced in the kidney of normal and diabetic rats after treatment with NC. However, NC markedly (p < 0.001) increased the expression CAT in the liver and neurons of CC of diabetic rats. Superoxide dismutase (SOD) is widely distributed in the PCT and DCT of kidney, hepatocytes, and neurons of CC and hippocampus. NC significantly (p < 0.001) increased the expression of SOD in hepatocytes and neurons of CC and the hippocampus but not in the kidney. Glutathione reductase (GRED) was observed in kidney tubules, hepatocytes and neurons of the brain. NC markedly increased (p < 0.001) the expression of GRED in PCT and DCT cells of the kidney and hepatocytes of liver and neurons of CC. In conclusion, NC is a strong inducer of CAT, SOD, and GRED expression in the kidney, liver and brain of diabetic rats.
28 March 2010 in Analytical and Bioanalytical Chemistry
Mobile phase progress in planar stationary phase can be evoked by either external or internal forces. An internal force is capillarity, while gravity, electric field, a pump and centrifugal forces belong to external forces. Overpressured layer chromatography gives a widely used special chapter of forced-flow planar chromatography, a special bridge between high-performance liquid column chromatography and thin-layer chromatography (TLC). A simple and special rule characterizes the progress of mobile phase. Optimal efficiency is composed by the doubled effect of flow resulting from the pump-forced mobile phase (convex profile of laminar flow) and capillary forces on the dry stationary phase (concave laminar flow). This review describes the most important aspects of forced-flow TLC, including how the set-ups are developed and also the progress of detection methods used.