Syndromic Surveillance of Health Effects Due to Summer Sun Overexposure: Construction of an Indicator Based on Drug Sales in Pharmacies-Preliminary Study within the PRISME Project.

INTRODUCTION: Solar radiation is classified as a known human carcinogen. In France, people frequently ask local pharmacies to dispense products for sunburns. In the PRISME project, studying this use can be a specific and sensitive way to assess these overexposures. OBJECTIVE: This study aims to construct an indicator for monitoring healthcare consumption in pharmacies after overexposure to solar UV. METHODS: The study, conducted between July and August 2019, covered a sample of pharmacies located in coastal communities of southern France. A list of products for sunburn was defined. When one of the products on this list was sold, the customer was asked to fill out a questionnaire to determine whether the purchase was related to UV overexposure. A positive predictive value (PPV) per active ingredient was calculated. RESULTS: Overall, nine pharmacies participated in the study, and 288 questionnaires were collected. The majority of products purchased were for women (60.7%), for people aged 15 and over (78.1%), and for people not living in the department (68.9%). The most frequently purchased products were our trolamine-containing products which accounted for 53% of sales. With the exception of three products, all PPVs were greater than 0.8. CONCLUSION: The high PPV confirms the suitability of the product selection as an indicator for monitoring healthcare consumption related to solar UV overexposure. Two indicators (one sensitive and one specific) were selected to maximise the chances of identifying UV-related remedies.

Removal Efficiency of Insoluble ß-Cyclodextrin Polymer from Water-Soluble Carcinogenic Direct Azo Dyes.

A batch system was applied to study the adsorption of three dyes (methyl violet, eriochrom black T and helianthin) from aqueous solution onto ß-cyclodextrin polymer, synthesized by using citric acid as a cross linking agent. This polymer lets to adsorb only methyl violet for this effect, several operator variables was checked only with this kind of dye, the removal efficiently increases with increase in adsorbent amount; elevation of temperature lets also to improve the dye adsorption; ionic strength has not effect on dye adsorption process, for the pH we have remarked a slight decrease in removal efficiently with increasing of pH values. Equilibrium study was investigated by applying three models (Langumir, Frendlich and Temkin), results show that Langumir isotherm is the appropriate model. FTIR spectra show the complex inclusion formation which dominates the adsorption mechanism, confirmed by the absence of characteristic peaks of methyl violet in ß-cyclodextrin after adsorption.

Effect of Autoclaving on the Physicochemical Properties and Biological Activity of Aluminum Oxyhydroxide Used as an Adjuvant in Vaccines.

The long-term biodistribution of non-biodegradable microstructures or nanostructures used in vaccinations is widely unknown. This is the case for aluminum oxyhydroxide, the most widely used vaccine adjuvant, which is a nanocrystalline compound that spontaneously forms nanoprecipitates. Although generally well-tolerated, aluminum oxyhydroxide is detected in macrophages a long time after vaccination in individuals predisposed to the development of systemic and neurological aspects of the autoimmune (inflammatory) syndrome induced by modified adjuvant. In the present study, we established that the terminal sterilization of aluminum oxyhydroxide by autoclaving in final container vials produced measurable changes in its physicochemical properties. Moreover, we found that these changes included (1) a decreasing in the pH of aluminum oxyhydroxide solutions, (2) a reduction in the adsorption capacity of bovine serum albumin, (3) a shift in the angle of X-ray diffraction, (4) a reduction in the lattice spacing, causing the crystallization and biopersistence of modified aluminum oxyhydroxide in the macrophage, as well as in muscle and the brain.

The effect of camelina oil on vascular function in essential hypertensive patients with metabolic syndrome: a randomized, placebo-controlled, double-blind study.

BACKGROUND: The effects of a dietary supplementation with the vegetable ω-3 α-linolenic acid (ALA) on cardiovascular homeostasis are unclear. In this context, it would be interesting to assess the effects of camelina oil. OBJECTIVE: This study aimed to assess the cardiovascular and metabolic effects of camelina oil in hypertensive patients with metabolic syndrome. METHODS: In a double-blind, placebo-controlled randomized study, treated essential hypertensive patients with metabolic syndrome received, during 6 mo, either cyclodextrin-complexed camelina oil containing ≈ 1.5 g ALA/d (n = 40) or an isocaloric placebo (n = 41), consisting of the same quantity of cyclodextrins and wheat starch. Anthropometric data, plasma lipids, glycemia, insulinemia, creatininemia, TBARs, high-sensitivity C-reactive protein, and n-3, n-6, and n-9 fatty acids in erythrocyte membranes were measured. Peripheral and central blood pressures, arterial stiffness, carotid intima-media thickness, and brachial artery endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation were assessed. RESULTS: Compared with placebo, camelina oil increased ALA (mean ± SD: 0 ± 0.04 compared with 0.08 ± 0.06%, P <0.001), its elongation product EPA (0 ± 0.5 compared with 0.16 ± 0.65%, P <0.05), and the n-9 gondoic acid (GA; 0 ± 0.04 compared with 0.08 ± 0.04%, P <0.001). No between-group difference was observed for cardiovascular parameters. However, changes in FMD were associated with the magnitude of changes in EPA (r = 0.26, P = 0.03). Compared with placebo, camelina oil increased fasting glycemia (-0.2 ± 0.6 compared with 0.3 ± 0.5 mmol/L, P <0.001) and HOMA-IR index (-0.8 ± 2.5 compared with 0.5 ± 0.9, P <0.01), without affecting plasma lipids, or inflammatory and oxidative stress markers. Changes in HOMA-IR index were correlated with the magnitude of changes in GA (r = 0.32, P <0.01). Nutritional intake remained similar between groups. CONCLUSION: ALA supplementation with camelina oil did not improve vascular function but adversely affected glucose metabolism in hypertensive patients with metabolic syndrome. Whether this adverse effect on insulin sensitivity is related to GA enrichment, remains to be elucidated.

Soluble epoxide hydrolase inhibition improves myocardial perfusion and function in experimental heart failure.

The study addressed the hypothesis that soluble epoxide hydrolase (sEH) inhibition, which increases cardiovascular protective epoxyeicosatrienoic acids (EETs), exerts beneficial effects in an established chronic heart failure (CHF) model. In CHF rats, left ventricular (LV) function, perfusion and remodeling were assessed using MRI and invasive hemodynamics after 42-day (starting 8 days after coronary ligation) and delayed 3-day (starting 47 days after coronary ligation) treatments with the sEH inhibitor AUDA (twice 0.25 mg/day). Delayed 3-day and 42-day AUDA increased plasma EETs demonstrating the effective inhibition of sEH. Delayed 3-day and 42-day AUDA enhanced cardiac output without change in arterial pressure, thus reducing total peripheral resistance. Both treatment periods increased the slope of the LV end-systolic pressure-volume relation, but only 42-day AUDA decreased LV end-diastolic pressure, relaxation constant Tau and the slope of the LV end-diastolic pressure-volume relation, associated with a reduced LV diastolic volume and collagen density. Delayed 3-day and, to a larger extent, 42-day AUDA increased LV perfusion associated with a decreased LV hypoxia-inducible factor-1alpha. Both treatment periods decreased reactive oxygen species level and increased reduced-oxidized glutathione ratio. Finally, MSPPOH, an inhibitor of the EET-synthesizing enzyme cytochrome epoxygenases, abolished the beneficial effects of 3-day AUDA on LV function and perfusion. Augmentation of EET availability by pharmacological inhibition of sEH increases LV diastolic and systolic functions in established CHF. This notably results from short-term processes, i.e. increased LV perfusion, reduced LV oxidative stress and peripheral vasodilatation, but also from long-term effects, i.e. reduced LV remodeling.

Soluble epoxide hydrolase inhibition prevents coronary endothelial dysfunction in mice with renovascular hypertension.

OBJECTIVES: The study addresses the hypothesis that endothelial dysfunction in experimental arterial hypertension can be related to an alteration in epoxyeicosatrienoic acids (EETs) pathway and can be prevented by the inhibition of EETs degradation by soluble epoxide hydrolase (sEH). METHODS AND RESULTS: Arterial hypertension was induced in FVB/N mice by renal artery stenosis ('two-kidney-one-clip', 2K1C). Seven weeks after surgery, increased aortic pressures (Millar tonometer; Millar Instruments, Houston, Texas, USA) and cardiac hypertrophy (echocardiography) were present in 2K1C mice as compared with control mice. Left coronary artery endothelium-dependent relaxations to acetylcholine were decreased in 2K1C mice without modification in the relaxing responses to NS309 and NS1619, the openers of calcium-activated potassium channels mediating the hyperpolarizing effect of EETs. The inhibitors of the EET-synthesizing enzymes cytochrome P450 epoxygenases, fluconazole and N-methylsulfonyl-6-(2-propargyloxyphenyl)-hexanamide (MSPPOH), reduced the coronary relaxations to acetylcholine in control but not in 2K1C mice. The sEH expression was increased in 2K1C mice. The sEH inhibitor 12-(3-adamantan-1-yl-ureido)dodecanoic acid administered for 2 weeks starting 5 weeks after surgery in 2K1C mice (25 mg/l in drinking water) reduced aortic pressures and cardiac hypertrophy, improved the coronary relaxations to acetylcholine and restored the inhibitory effect of fluconazole and MSPPOH on acetylcholine-induced relaxations, without modifying the relaxations to NS309 and NS1619. CONCLUSION: These results demonstrate that a reduced EET-mediated relaxations related to an increased degradation by sEH contributes to coronary endothelial dysfunction in 2K1C hypertensive mice. Inhibiting sEH prevents endothelial dysfunction by restoring EET-mediated relaxations and thus, could represent a promising pharmacological intervention to limit cardiovascular morbidity and mortality in arterial hypertension.

An α-linolenic acid-rich formula reduces oxidative stress and inflammation by regulating NF-κB in rats with TNBS-induced colitis.

We have previously shown that α-linolenic acid (ALA), a (n-3) PUFA exerts in vitro antiinflammatory effects in the intestine. In this study, we aimed to evaluate its effect on inflammatory and oxidative stress in a colitis model. Colitis was induced in 2 groups at d 0 by intrarectal injection of 2-4-6-trinitrobenzen sulfonic acid (TNBS), whereas the control group received the vehicle. Rats we fed 450 mg . kg(-1) . d(-1) of ALA (TNBS+ALA) while the other colitic group (TNBS) and the control group were fed an isocaloric corn oil formula for 14 d (from d -7 to d 7). RBC fatty acid composition was assessed. Oxidative stress was studied by measuring urinary 8-isoprostanes (8-IP) and colon glutathione (GSH) concentration and inducible nitric oxide synthase (iNOS) expression. Colitis was assessed histologically, by production of proinflammatory mediators, including cytokines, leukotrienes B(4) (LTB(4)), and cyclooxygenase-2 (COX-2) and by nuclear factor-κB (NF-κB) activation. The ALA-rich diet significantly increased the RBC levels of ALA, eicosapentaenoic acid, and docosapentaenoic acid (n-3) compared with the TNBS group (P < 0.01 for all). The beneficial effect of ALA supplementation on oxidative stress was reflected by lower urinary 8-IP levels (P < 0.05), a normalized colon GSH concentration (P < 0.01), and reduced colon iNOS expression (P < 0.05) compared with the TNBS group. ALA also protected against colon inflammation as assessed by lower tumor necrosis factor-α secretion and mRNA level (P < 0.05), reduced NF-κB activation (P = 0.01), and lower colon lipid mediator concentrations such as LTB(4) and COX-2 (P < 0.05) compared with the TNBS group. These findings show that an ALA-rich formula is beneficial to TNBS-induced colitic rats via inhibition of oxidative and inflammatory stress.

Solubility and dissolution rate of progesterone-cyclodextrin-polymer systems.

This contribution focused on the solubility improvement of the poorly water-soluble steroid hormone progesterone which, in its natural state, presents a reduced oral bioavailability. In the first part of this study, two simple, reproducible methods that were candidates for use in the preparation of inclusion complexes with cyclodextrins were investigated. Solubility capacities of the progesterone complex with hydroxypropyl-beta-CD (HPbeta-CD), hydoxypropyl-gamma-CD (HPgamma-CD), permethyl-beta-CD (PMbeta-CD), and sulfobutylether-beta-CD (SBEbeta-CD), prepared by the freeze-drying and precipitation methods, were evaluated by Higuchi phase solubility studies. The results showed that HPbeta-CD and PMbeta-CD were the most efficient among the four cyclodextrins for the solubilization of progesterone, with the highest apparent stability constants. Therefore, dissolution studies were conducted on these latest progesterone/cyclodextrin complexes and physical mixtures. Two additional natural cyclodextrins, beta-CD and gamma-CD, were taken as references. Hence, the influence of more highly soluble derivatives of beta-CD (HPbeta-CD, PMbeta-CD) on the progesterone dissolution rate, in comparison to pristine beta-CD, alongside an increase in the cavity width for gamma-CD versus beta-CD, were investigated. The dissolution kinetics of progesterone dissolved from HPbeta-CD, PMbeta-CD, and gamma-CD revealed higher constant rates in comparison to beta-CD. Therefore, the aim of the second part of this study was to investigate the possibility of improving the dissolution rate of progesterone/beta-CD binary systems upon formation of ternary complexes with the hydrophilic polymer, PEG 6000, as beta-CD had the smallest progesterone solubility and dissolution capacity among the four cyclodextrins studied (beta-CD, HPbeta-CD, HPgamma-CD and PMbeta-CD). The results indicated that dissolution constant rates were considerably enhanced for the 5% and 10% progesterone/beta-CD complexes in PEG 6000. The interaction of progesterone with the cyclodextrins of interest on the form of the binary physical mixtures, complexes, or ternary complexes were investigated by differential scanning calorimetry (DSC) and Fourier transformed-infrared spectroscopy (FT-IR). The results proved that progesterone was diffused into the cyclodextrin cavity, replacing the water molecules and, in case of ternary systems, that the progesterone beta-cyclodextrin was well dispersed into PEG, thus improving progesterone bioavailability for subsequent oral delivery in the same way as derivatized cyclodextrins. The present work proves that ternary complexes are promising systems for drug encapsulation.