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.     

Cyclodextrin complexes of valdecoxib: properties and anti-inflammatory activity in rat.

The influence of natural beta-cyclodextrin and its hydrophilic derivatives (HPbetaCd and SBE7betaCd) on the in vitro dissolution rate, in vivo absorption and oral bioavailability of a poorly water soluble anti-inflammatory agent, valdecoxib (VALD) was studied. Equimolar drug-cyclodextrin solid complexes were prepared by kneading and coevaporation methods and characterized by infrared spectroscopy, differential scanning calorimetry, X-ray diffraction. In the liquid state, the cyclodextrin complexes were studied using phase solubility analysis, (1)H nuclear magnetic resonance and circular dichroism spectroscopy. Drug solubility and dissolution rate in distilled water were notably improved by employing the betaCds. The DP(15) (i.e. percent of dissolved VALD at 15 min) was 10.5% for the pure drug and 50, 91 and 93% for VALD-betaCd, VALD-HPbetaCd and VALD-SBE7betaCd complexes, respectively. Moreover, it was found that in the, the cyclodextrin complexes of drug showed significant improvement in the anti-inflammatory activity.     

Double‐Chambered Right Ventricle with Pulmonary Valve Endocarditis

We describe a rare case of pulmonary valve endocarditis associated with a double‐chambered right ventricle in an adolescent male highlighting the two‐dimensional and three‐dimensional transthoracic echocardiographic findings. He was managed with aggressive antibiotic therapy followed by surgery. The echocardiographic findings were confirmed during surgery.     

Clinical scale electroloading of mature dendritic cells with melanoma whole tumor cell lysate is superior to conventional lysate co-incubation in triggering robust in vitro expansion of functional antigen-specific CTL

Recent commercial approval of cancer vaccine, demonstrating statistically significant improvement in overall survival of prostate cancer patients has spurred renewed interest in active immunotherapies; specifically, strategies that lead to enhanced biological activity and robust efficacy for dendritic cell vaccines. A simple, widely used approach to generating multivalent cancer vaccines is to load tumor whole cell lysates into dendritic cells (DCs). Current DC vaccine manufacturing processes require co-incubation of tumor lysate antigens with immature DCs and their subsequent maturation. We compared electroloading of tumor cell lysates directly into mature DCs with the traditional method of lysate co-incubation with immature DCs. Electroloaded mature DCs were more potent in vitro, as judged by their ability to elicit significantly (p < 0.05) greater expansion of peptide antigen-specific CD8⁺ T cells, than either lysate-electroloaded immature DCs or lysate-co-incubated immature DCs, both of which must be subsequently matured. Expanded CD8⁺ T cells were functional as judged by their ability to produce IFN-γ upon antigen-specific re-stimulation. The electroloading technology used herein is an automated, scalable, functionally closed cGMP-compliant manufacturing technology supported by a Master File at CBER, FDA and represents an opportunity for translation of enhanced potency DC vaccines at clinical/commercial scale.     

Predictors of metformin failure in gestational diabetes mellitus (GDM)

Introduction and objective

The role of metformin in gestational diabetes mellitus (GDM) is also increasing. However, almost half of metformin-treated women required additional insulin. Therefore, identifying the characteristics of these women may help define optimal therapeutic strategy.

Development and Evaluation of Probioticated Cucumber Juice Using <Emphasis Type="Italic">Lactobacillus plantarum</Emphasis>

The aim of the present study was to develop a probioticated cucumber juice by optimizing the concentration of prebiotic (inulin), stevia (Stevia rebudiana) and inoculum (Lactobacillus plantarum) by varying one factor at a time. Cucumber juice with 2% prebiotic had a pH 3.76, acidity 0.239%, total sugars 198.2 μg/mL, reducing sugars 102.3 μg/mL and microbial viability of 1.36 × 10⁸ colony forming units (CFU)/mL, respectively. The juice with 3% stevia had a pH 3.59, acidity 0.388%, total sugars 214 μg/mL, reducing sugars 156.7 μg/mL and microbial viability of 6.7 × 10⁷ CFU/mL, respectively. The juice with 3% inoculum size had a pH 3.82, acidity 0.39%, total sugars 128.3 μg/mL, reducing sugars 198.6 μg/mL and microbial viability of 3.5 × 10⁸ CFU/mL, respectively. Maximum growth of the probiotic (L. plantarum) in the cucumber juice was obtained at the end of 48 h of fermentation for 2% prebiotic, 3% stevia and 3% inoculum size without much changes in nutritional and organoleptic properties. The probiotic strain namely L. plantarum proved its ability and suitability to ferment cucumber juice. The growth of the probiotic in the cucumber juice was found maximum with 2% prebiotic, 3% stevia and 3% inoculum size at the end of 48 h of fermentation with minimal changes in nutritional value and organoleptic characteristics with a good shelf life at 4 °C in polyethylene terephthalate bottles.     

Unruptured sinus of Valsalva aneurysm with right ventricular outflow obstruction

The recommended operative management of unruptured sinus of Valsalva aneurysm consists of closure of the mouth of the aneurysm with or without aortic valve surgery. We report a case of unruptured aneurysm producing right ventricular outflow tract obstruction. Closure of the mouth of the aneurysm failed to relieve the obstruction, which was subsequently achieved by excising the aneurysmal wall overlying the outflow tract.