Evaluating the inhibitory potential of Withania somnifera on platelet aggregation and inflammation enzymes: An in vitro and in silico study

Context Withania somnifera (L.) Dunal is traditionally used for treating various ailments, but lacks scientific evaluation.

Objective This study evaluates Withania somnifera (WS) for its effect on platelet activity and inflammatory enzymes.

Materials and methods Aqueous and ethanolic (1:1) leaf extracts were subjected to in vitro indirect haemolytic activity using Naja naja venom, human platelet aggregation was quantified for lipid peroxidation using arachidonic acid (AA) as agonist and 5-lipoxygenase (5-LOX) levels were determined using standard spectrometric assays. Further, molecular docking was performed by the ligand fit method using molegro software package (Molegro ApS, Aarhus, Denmark).

Results The study found that aqueous and ethanol extracts have very negligible effect (15%) with an IC₅₀ value of 13.8?mg/mL on PLA₂ from Naja naja venom. Further, extracts of WS also had very little effect (18%) with an IC₅₀ value of 16.6?mg/mL on malondialdehyde (MDA) formation. However, a 65% inhibition of 5-LOX with an IC₅₀ value of 0.92?mg/mL was observed in 1:1 ethanol extracts. The same was evident from SAR model with the active ingredient withaferin A binding predominantly on Phe 77, Tyr 98, Arg 99, Asp 164, Leu 168, Ser 382, Arg 395, Tyr 396 and Tyr 614 with an atomic contact energy value of??128.96 compared to standard phenidone (?103.61). Thus, the current study validates the application of WS for inflammatory diseases.

Conclusion This study reveals the inhibitory potential of W. somnifera on inflammatory enzymes and platelet aggregation. Thus, WS can serve as a newer, safer and affordable medicine for inflammatory diseases.     

A critical evaluation of the electronic surgical logbook

Background  

The Association of Surgeons of Great Britain and Ireland (ASGBI) devised the electronic surgical logbook (version 2.4) for higher trainees in General Surgery enabling trainees to compile a uniform data set of their operative and training experience. This is in use by higher surgical trainees (HST) in the United Kingdom. This logbook permits trainees to submit data centrally into a Regional Analysis Database (RAD). With the implementation of the European Working Time Directive (EWTD) there is need for reliable data to assess the effects of the directive on training. In order to draw meaningful conclusions from the database the quality of data needs to be validated. We critically analysed the RAD in the Yorkshire region for a one-year period.     

Development of the New Lung Allocation System in the United States

This article reviews the development of the new U.S. lung allocation system that took effect in spring 2005. In 1998, the Health Resources and Services Administration of the U.S. Department of Health and Human Services published the Organ Procurement and Transplantation Network (OPTN) Final Rule. Under the rule, which became effective in 2000, the OPTN had to demonstrate that existing allocation policies met certain conditions or change the policies to meet a range of criteria, including broader geographic sharing of organs, reducing the use of waiting time as an allocation criterion and creating equitable organ allocation systems using objective medical criteria and medical urgency to allocate donor organs for transplant. This mandate resulted in reviews of all organ allocation policies, and led to the creation of the Lung Allocation Subcommittee of the OPTN Thoracic Organ Transplantation Committee. This paper reviews the deliberations of the Subcommittee in identifying priorities for a new lung allocation system, the analyses undertaken by the OPTN and the Scientific Registry for Transplant Recipients and the evolution of a new lung allocation system that ranks candidates for lungs based on a Lung Allocation Score, incorporating waiting list and posttransplant survival probabilities.     

Metabolism of the bay-region diol-epoxide of chrysene to a triol-epoxide and the enzyme-catalysed conjugation of these epoxides with glutathione

Metabolic activation of chrysene in mouse skin appears to involver-1,t-2-dihydroxy-t-3,4-oxy-1,2,3,4-tetrahydrochrysene (anti-chrysene-1,2-diol 3, 4-oxide) and 9-hydroxy-r-1,t-2-dihydroxy-t-3, 4-oxy-1,2, 3, 4-tetrahydrochrysene (anti-9-OH-chrysene-1, 2-diol 3,4-oxide). The enzyme-catalysed conjugation of these epoxideswith [³⁵S]glutathione has been studied in experiments in whichthe glutathione conjugates were separated by h.p.l.c. and examinedby fluorescence spectrophotometry. Both anti-chrysene-1, 2-diol3, 4-oxide and anti-9-OH-chrysene-1, 2-diol 3, 4-oxide formedconjugates nonenzymically and both were shown to be substratesfor rat liver glutathione transferases. When anti-chrysene-1,2-diol 3, 4-oxide was incubated with [³⁵S]glutathione and arat liver microsomal metabolizing system, glutathione conjugateswith h.p.l.c. and fluorescence spectral characteristics identicalto those of conjugates formed from both anti-chrysene-1, 2-diol3,4-oxide and anti-9-OH-chrysene-1, 2-diol 3, 4-oxide were detected.This finding provides evidence that anti-chrysene-1, 2-diol3, 4-oxide can be further metabolized to the triolepoxide, anti-9-OH-chrysene-1,2-diol 3, 4-oxide by rat liver microsomal systems.