Lysosomal dysfunction produces distinct alterations in synaptic alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid and N-methyl-D-aspartate receptor currents in hippocampus

The early processes that lead to synaptic dysfunction during aging are not clearly understood. Dysregulation of alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors may cause age-related cognitive decline. Using hippocampal slice cultures exhibiting lysosomal dysfunction, an early marker of brain aging that is linked to protein accumulation, we identified alterations to AMPA and NMDA receptor-mediated synaptic currents. The miniature and spontaneous excitatory postsynaptic currents that were examined after 3, 6, and 9 days of lysosomal disruption showed progressive changes in amplitude, frequency, and rise and decay kinetics. To investigate whether modifications in specific channel properties of single synaptic receptors contributed to changes in the amplitude and time course of synaptic currents, we examined the single channel properties of synaptic AMPA and NMDA receptors. The channel open probability and the mean open times showed decreases in both receptor populations, whereas the closed times were increased without any change in the channel conductance. The Western blot analysis revealed a progressive decline in synaptic markers including glutamate receptor subunits. These results indicate that lysosomal dysfunction leads to progressive functional perturbation of AMPA and NMDA receptors in this slice model of protein accumulation, suggesting that age-related cognitive decline could result from altered glutamate receptor function before reductions in synaptic density.     

Pharmacogenomics for the forensic toxicologist

Pharmacogenomics is the study of the linkage between an individual's genotype and the disposition of drugs in the body. The first association between adverse drug reactions and inherited variations was recognized in the 1950s, and since then, pharmacogenomics has come a long way. The importance of pharmacogenomics is accentuated by the incidence of adverse drug reactions, which may account for hospital expenditures of up to 5.6 billion dollars annually. Interindividual variations in drug metabolism are often the result of genetic variants or genetic polymorphisms, and polymorphisms have been known to alter the relationship between dose and plasma drug concentration. Drug disposition can be affected by polymorphisms in drug metabolizing enzymes, drug transport proteins, and drug targets. The cytochrome P450 (CYP) enzymes are responsible for the metabolism of a large number of drugs. Polymorphisms of the CYP enzymes have been well documented, and CYP2D6 is the most polymorphic CYP enzyme. However, there is a relative dearth of research on the role of transport proteins and drug targets. This review attempts to provide a brief synopsis of the pharmacogenomics of some common drug-metabolizing enzymes, transport proteins, and targets. The examples of tramadol, methadone, and oxycodone are used to illustrate the potential role of pharmacogenomics in forensic toxicology. Pharmacogenomics may present a practicable hypothesis in cases of incongruence between dose and plasma drug concentration, and the possibility of genotype-mediated drug plasma levels needs to be considered.     

Food safety knowledge, attitudes and practices of mothers: findings from focus group studies in South India

In India, most of the diarrhoeal deaths among children (<5 years) are attributed to food and water contamination. Mothers are usually the final line of defence against food borne illnesses. Thus, the role of mothers in ensuring food safety at homes is well accepted. There are hardly any studies in India to understand their knowledge, attitudes and practices on food safety. The present study was an attempt in this direction. A total of 32 Focus Group Discussions were carried out with mothers of children <5 years in 16 districts from all the four South Indian states. The findings reveal that food safety awareness and practices are good among mothers perhaps due to the Indian food ethos passed on to them through generations. Home cooked foods are considered to be safer than prepared foods bought from outside. Many mothers were aware of the common food adulterants but do not bother to complain or take action. There is a need to create enabling environment with improved access to potable water, sanitation and cooking fuel. Spreading awareness about checking food labels and reporting to the health authorities in case of food poisoning or adulteration is also the need of the hour. The Anganwadi Centres can be the focal points for imparting food safety education to the mothers.     

Atrial ECG as a guide to the placement of central venous catheter in patients undergoing Open Heart Surgery

Hundred adults undergoing open heart surgery were randomized into two equal groups. In group I (n=50), surface anatomical landmarks and in group II (n=50) atrial ECG was used as a guide for correct placement of the central venous catheter (within 1 cm of superior vena cava - right atrial junction). The position of the catheter tip was confirmed by direct palpation by the surgeon on the operating table and by radiological examination in the post operative period. Surgeon's assessment revealed that the catheter was successfully placed in 32 (69.6%) patients in group II and 25 (50%) patients in group I (p=NS). Radiological examination revealed that the catheter was successfully placed in 31 (67.4%) patients in group II and in 28 (57.1%) patients in group I (p=NS). Amongst the unsuccessful placements right atrial placement was present in 5 patients (10%) in group I and 7 patients (15.2%) in group II by surgeon's assessment and 8 patients (16.3%) in group I and 9 patients (9.6%) in group II by radiological examination (p=NS) No complications related to intracardiac placement occurred in any of the patients. We conclude that atrial ECG is a promising technique for central venous catheter placement, although it did not significantly increase the correct placement in this study. This may be due to alteration in the relationship of sino-atrial node and superior vena cava - right atrial junction in patients with cardiac disease. Further studies defining the correct technique of insertion, (especially in cardiac patients) are necessary to improve the success rate.     

Formulation and evaluation of chitosan solid lipid nanoparticles of carbamazepine

ABSTRACT: The present work aims at preparing aqueous suspension of Solid lipid Nanoparticles containing Chitosan (CT) which is a biopolymer that exhibits a number of interesting properties which include controlled drug delivery. Carbamezapine (CBZ) is a lipophilic drug which shows it antiepileptic activity by inactivating sodium channels. The solid lipid Nanoparticles (SLN) of Chitosan-CBZ were prepared by using solvent injection method using ethanol as organic solvent. The prepared SLN formulations exhibited high encapsulation efficiency, high physical stability. The drug incorporated SLNs have demonstrated that the controlled release patterns of the drug for prolonged period. The prepared SLNs were characterized for surface morphology by SEM analysis, entrapment efficiency, zeta potential, FTIR, DSC and in-vitro diffusion studies. The hydrodynamic mean diameter and zeta potential were 168.7 +/-1.8 nm and 28.9 +/-2.0 mV for SLN-chitosan-CBZ respectively. Therefore chitosan-SLN can be good candidates to encapsulate CBZ and to increase its therapeutic efficacy in the treatment of Epilepsy.