PHARMACOKINETIC STUDIES OF A CHRONOTHERAPEUTIC DRUG DELIVERY SYSTEM OF LORNOXICAM BY LC-MS/MS METHOD

Objective: The objective of this study was to investigate differences in pharmacokinetic patterns of immediate release tablet (IR) and compression coated tablet (CCT) of lornoxicam, proposed for the chronotherapeutic treatment of rheumatoid arthritis.Methods: The dosage forms were administered to two groups of white New Zealand rabbits (n=3), and the plasma drug levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters like maximum concentration (Cmax), time is taken to reach maximum concentration (Tmax), area under the curve (AUC), elimination half-life (t1/2) and Mean Residence Time (MRT) were determined.Results: In the case of IR tablets, the drug was detected within 15 min after oral administration and a Cmax of 1269.57±4.04 ng/ml were attained at 2±0.15 h. With CCT, the drug was detected only after 5 h and a Cmax of 1279.24±12.76 ng/ml were attained at 8±0.10 h. The CCT showed maximum drug release at the eighth hour in comparison to IR tablet which showed maximum release at the second hour of study.Conclusion: The predominant lag time prior to drug release from CCT is an indication that it is consistent with the requirements of chronopharmaceutical drug delivery. The results suggest that the compression coated tablet is a promising approach for chronotherapeutic management of rheumatoid arthritis

A High Fidelity Transmural Anisotropic Ventricular Tissue Model Function to Investigate the Interaction Mechanisms of Drug: An In-Silico Model for Pharmacotherapy

A high fidelity transmural anisotropic ventricular tissue model consisting of endocardial, mid myocardial, and epicardial myocytes were configured to investigate drug interaction, such as Hydroxychloroquine (HCQ), under hypoxia conditions without and with pro-arrhythmic comorbidity like hypokalemia in (a) ventricular tissue b) its arrhythmogenesis for different dosages and (b) two different pacing sequences (Normal and tachycardiac). In-silico ventricular modeling indicates HCQ has an insignificant effect on hypoxia with and without comorbidities, except in the combination of mild hypoxia with moderate hypokalemia condition and severe hypoxia with mild hypokalemia where it initiated a re-entrant arrhythmia. Secondly, incorporating drug dosage variations indicates the 10 μM HCQ created PVCs for all settings except in severe hypoxia conditions where re-entrant arrhythmia occurred. In addition to the dosage of HCQ utilized for treatment, the pacing protocol also influences the appearance of re-entrant arrhythmia only for severe hypoxia with 10 μM HCQ dosage alone. For all other conditions, including tachycardiac pacing protocol, no arrhythmia occurred. These findings infer that the arrhythmic fatality rate due to HCQ treatment for hypoxia can be effectively alleviated by subtly altering or personalizing the dosage of HCQ and aid in the treatment of hypoxia-induced symptoms caused by COVID

N,N′-Dibenzyl-N,N,N′,N′-tetra­methyl­ethylenediammonium dibromide dihydrate

In the title compound, C20H30N2 2+·2Br−·2H2O, the asymmetric unit consists of half of the N,N′-dibenzyl-N,N,N′,N′-tetra­methyl­ethylenediammonium cation lying across an inversion center, a bromide ion and a water mol­ecule of solvation. There is an eight-membered dibromide dihydrate ring, which is formed via hydrogen bonds of the type O—H⋯Br

Cognitive Workload Analysis of Fighter Aircraft Pilots in Flight Simulator Environment

Maintaining and balancing an optimal level of workload is essential for completing the task productively. Fighter aircraft is one such example, where the pilot is loaded heavily both physically (due to G manoeuvering) and cognitively (handling multiple sensors, perceiving, processing and multi-tasking including communications and handling weapons) to fulfill the combat mission requirements. This cognitive demand needs to be analysed to understand the workload of fighter pilot. Objective of this study is to analyse dynamic workload of fighter pilots in a realistic high-fidelity flight simulator environment during different flying workload conditions. The various workload conditions are (a) normal visibility, (b) low visibility, (c) normal visibility with secondary task, and (d) low visibility with secondary task. Though, pilot’s flying performance score was good, the physiological measure like heart rate variability (HRV) features and subjective assessment (NASA-TLX) components are found to be statistically significant (p<0.05) between tasks. HRV features such as SD2, SDNN, VLF and total power are found to be significant at all task load conditions. The features LFnu and HFnu are able to differentiate the effect of low visibility and secondary cognitive task, which was imposed as increased task in this study. This result benefits to understand the pilot’s task and performance at each flying phase and their cognitive demands during dynamic workload using HRV, which could assist pilot’s training schedule in optimal way on simulators as well as in actual flight conditions

Quantitative Description of Glycan-Receptor Binding of Influenza A Virus H7 Hemagglutinin

In the context of recently emerged novel influenza strains through reassortment, avian influenza subtypes such as H5N1, H7N7, H7N2, H7N3 and H9N2 pose a constant threat in terms of their adaptation to the human host. Among these subtypes, it was recently demonstrated that mutations in H5 and H9 hemagglutinin (HA) in the context of lab-generated reassorted viruses conferred aerosol transmissibility in ferrets (a property shared by human adapted viruses). We previously demonstrated that the quantitative binding affinity of HA to α2→6 sialylated glycans (human receptors) is one of the important factors governing human adaptation of HA. Although the H7 subtype has infected humans causing varied clinical outcomes from mild conjunctivitis to severe respiratory illnesses, it is not clear where the HA of these subtypes stand in regard to human adaptation since its binding affinity to glycan receptors has not yet been quantified. In this study, we have quantitatively characterized the glycan receptor-binding specificity of HAs from representative strains of Eurasian (H7N7) and North American (H7N2) lineages that have caused human infection. Furthermore, we have demonstrated for the first time that two specific mutations; Gln226→Leu and Gly228→Ser in glycan receptor-binding site of H7 HA substantially increase its binding affinity to human receptor. Our findings contribute to a framework for monitoring the evolution of H7 HA to be able to adapt to human host.National Institutes of Health (U.S.) (GM R37 GM057073-13)Singapore-MIT Alliance for Research and Technolog

Glycosylation at Asn91 of H1N1 haemagglutinin affects binding to glycan receptors

The glycoprotein HA (haemagglutinin) on the surface of influenza A virus plays a central role in recognition and binding to specific host cell-surface glycan receptors and in fusion of viral membrane to the host nuclear membrane during viral replication. Given the abundance of HA on the viral surface, this protein is also the primary target for host innate and adaptive immune responses. Although addition of glycosylation sites on HA are a part of viral evolution to evade the host immune responses, there are specific glycosylation sites that are conserved during most of the evolution of the virus. In the present study, it was demonstrated that one such conserved glycosylation site at Asn91 in H1N1 HA critically governs the glycan receptor-binding specificity and hence would potentially impinge on the host adaptation of the virus