Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Quantification of Diclofenac and Ibuprofen by a Vibrio Fischeri Bioluminescence Assay

We present a video-densitometric quantification method for the pain killer known as diclofenac and ibuprofen. These non-steroidal anti-inflammatory drugs were separated on cyanopropyl bonded plates using CH2Cl2, methanol, cyclohexane (95+5+40, v/v) as mobile phase. The quantification is based on a bio-effective-linked analysis using vibrio fischeri bacteria. Within 10 minutes a CCD-camera registers the white light of the light-emitting bacteria. Diclofenac and ibuprofen effectively suppress the bacterial light emission which can be used for quantification within a linear range of 10 to 2000 ng. The detection limit for ibuprofen is 20 ng and the limit of quantification 26 ng per zone. Measurements were carried out using a 16-bit ST-1603ME CCD camera with 1.56 megapixels [from Santa Barbara Instrument Group, Inc., Santa Barbara, USA]. The range of linearity covers more than two magnitudes because the extended Kubelka-Munk expression is used for data transformation [1]. The separation method is inexpensive, fast and reliable. Ibuprofen is named after its chemical description: iso-butyl-propanoic phenolic acid. Both pain killers are world-widein use and both substances are stable in aqueous solution. Both substances are mainly excreted in the urine

BioPower

Das Projekt BioPower ist eine Kooperation des Instituts für Angewandte Forschung (IAF) der Hochschule Offenburg mit dem Institut für Mikrosystemtechnik (IMTEK) der Universität Freiburg. Es handelt sich um den Versuch, die im Körper vorhandenen Energiequellen sozusagen direkt anzuzapfen, um sie für technische Zwecke zu nutzen. Von den vielen bestehenden Möglichkeiten konzentriert sich die Forschung hier auf die Nutzung der Glukose im Blut, die auch sonst als Energieträger zur Versorgung der Zellen im Körper dient

Screening of orange peel waste on valuable compounds by gradient multiple development diode-array high-performance thin-layer chromatography

High-performance thin-layer chromatography (HPTLC), as the modern form of TLC (thin-layer chromatography), is suitable for detecting pharmaceutically active compounds over a wide polarity range using the gradient multiple development (GMD) technique. Diode-array detection (DAD) in conjunction with HPTLC can simultaneously acquire ultraviolet‒visible (UV‒VIS) and fluorescence spectra directly from the plate. Visualization as a contour plot helps to identify separated zones. An orange peel extract is used as an example to show how GMD‒DAD‒HPTLC in seven different developments with seven different solvents can provide an overview of the entire sample. More than 50 compounds in the extract can be separated on a 6-cm HPTLC plate. Such separations take place in the biologically inert stationary phase of HPTLC, making it a suitable method for effect-directed analysis (EDA). HPTLC‒EDA can even be performed with living organism, as confirmed by the use of Aliivibrio fischeri bacteria to detect bioluminescence as a measure of toxicity. The combining of gradient multiple development planar chromatography with diode-array detection and effect-directed analysis (GMD‒DAD‒HPTLC‒EDA) in conjunction with specific staining methods and time-of-flight mass spectrometry (TOF‒MS) will be the method of choice to find new chemical structures from plant extracts that can serve as the basic structure for new pharmaceutically active compounds

Forensic drug analysis by means of diode-array HPTLC using RF and UV library search

Diode-array planar chromatography is a versatile tool for identification of pharmaceutical substances In this paper thirty-three compounds with benzodiazepine properties were investigated and the separating conditions for silica gel HPTLC plates and three mobile phases were optimized. Diode-array HPTLC makes it possible to identify all the compounds with high certainty down to a level of 20 ng. An algorithm for spectral recognition which is combined with R F values from the three separation steps into one fit factor is presented. This set of data is unique for each of the compounds investigated and enables unequivocal identification. The method is rapid, inexpensive, and sensitive down to a level of 20 ng mL −1

Sensitive quantification of diclofenac and ibuprofen using thin layer chromatography coupled with a vibrio fisheri bioluminescence assay

We present a video-densitometric quantification method for the pain killer known as diclofenac and ibuprofen. These non-steroidal anti-inflammatory drugs were separated on cyanopropyl bonded plates using CH2Cl2, methanol, cyclohexane (95 + 5 + 40, v/v) as mobile phase. The quantification is based on a bio-effective-linked analysis using Vibrio fisheri bacteria. Within 10 min a CCD-camera registered the white light of the light-emitting bacteria. Diclofenac and ibuprofen effectively suppressed the bacterial light emission which can be used for quantification within a linear range of 10 to 2000 ng. The detection limit for ibuprofen is 20 ng and the limit of quantification 26 ng per zone. Measurements were carried out using a 16-bit ST-1603ME CCD camera with 1.56 megapixels (from Santa Barbara Instrument Group, Inc., Santa Barbara, USA). The range of linearity covers more than two magnitudes because the extended Kubelka-Munk expression is used for data transformation. The separation method is inexpensive, fast, and reliable