Study of sequential abiotic and biotic degradation of styrene butadiene rubber.

Styrene butadiene rubber is one of the main constituents of tire tread. During tire life, the tread material undergoes different stresses that impact its structure and chemical composition. Wear particles are then released into the environment as weathered material. To understand their fate, it is important to start with a better characterization of abiotic and biotic degradation of the elastomer material. A multi-disciplinary approach was implemented to study the photo- and thermo- degradation of non-vulcanized SBR films containing 15 w% styrene as well as their potential biodegradation by Rhodoccocus ruber and Gordonia polyisoprenivorans bacterial strains. Each ageing process leads to crosslinking reactions, much surface oxidation of the films and the production of hundreds of short chain compounds. These degradation products present a high level of unsaturation and oxidation and can be released into water to become potential substrates for microorganisms. Both strains were able to degrade from 0.2 to 1.2 % (% ThOD) of the aged SBR film after 30-day incubation while no biodegradation was observed on the pristine material. A 25-75 % decrease in the signal intensity of water extractable compounds was observed, suggesting that biomass production was linked to the consumption of low-molecular-weight degradation products. These results evidence the positive impact of abiotic degradation on the biodegradation process of styrene butadiene rubber.

Characteristics, fate, and impact of marine plastic debris exposed to sunlight: A review.

The increase of plastic production from the middle of the twentieth century was inevitably followed by an increase in the amount of plastic dumped in the natural environment. There, the plastic debris are exposed to sunlight, temperature, humidity, and physical stress. This can induce photo-oxidative and thermal degradation. This review discusses the mechanism of plastics UV weathering and its characteristics. Comparison of the photodegradation rate and physico-chemical properties are made according to the weathering mode (natural/accelerated) and medium (air/water). Since the photodegradation can lead to plastics fragmentation, this phenomenon is described along with the methodologies used in literature to evaluate the fragmentation. The impact of the photodegraded plastic debris on the marine environment is also presented in term of (i) photodegradation products and stabilizers leakage, (ii) organic pollutants accumulation, transfer, and leakage, and (iii) toxicity on marine organisms.

New insights into the mechanism of photodegradation of chitosan.

Chitosan films were subjected to accelerated artificial weathering at λ>300 nm and 60 °C in the presence of O2. The resulting variations in the chemical structure were characterized by IR spectroscopy and UV-vis spectroscopy, and a photooxidation mechanism was proposed based on the identified oxidation photoproducts. The formation of gluconolactone derivatives leading to chain scissions was shown. In addition, low molecular weight photoproducts, which accounted for chitosan deacetylation, were detected. Furthermore, crosslinking reactions occurred, as revealed by gel fraction characterization. Variations in the mechanical and surface properties were characterized by AFM, and the reduction in macroscopic properties was correlated with the structural changes observed at the molecular scale by a multiscale approach.

Optical calcium test for measurement of multiple permeation pathways in flexible organic optoelectronic encapsulation.

Organic photovoltaic (OPV) devices and other organic electronics have the promise to provide lightweight, flexible alternatives to traditional rigid semiconductor technologies. However, organic electronics often degrade rapidly upon exposure to oxygen, water, light, and combinations thereof, as well as upon exposure to elevated temperatures. This requires the use of high gas barrier packaging in order for devices to have operational lifetimes on the order of years. To meet the challenge of transparent high gas barrier materials which maintain the flexibility of organic optoelectronics, many different materials and encapsulation schemes have been developed including the lamination of devices between flexible multi-layer barrier films. Because of their excellent barrier properties, these materials often require specialized testing for permeation measurements which evaluate materials independently. In this work, we demonstrate the use of an optical calcium test, which uses a sample geometry that closely mimics an OPV device, to evaluate a complete encapsulation scheme and to elucidate the relative importance of different permeation pathways. Using an encapsulation scheme of laminating a device between two multi-layer barrier films using an adhesive, measurements were made for water vapor permeation through the barrier film, the bulk adhesive, and along the adhesive-to-barrier film interface. The results show that the combined lateral permeation, including through the bulk adhesive and along the adhesive-to-barrier film interface, can constitute over 50% of the total permeation for small devices (4.5 cm × 4.5 cm). The adhesive-to-barrier film interface was also found to be a very important pathway as it was deemed responsible for more permeation than the bulk adhesive. The technique was also used to evaluate encapsulation design variables such as the effects of adhesive thickness and surface treatments on the lateral water permeation. We demonstrate that decreasing the adhesive thickness leads to a decrease in the lateral water permeation.

Water as a morphological probe to study polymer-filler interfaces: an original application of thermoporosimetry.

This paper is devoted to the characterization of polymer-filler interfaces by thermoporosimetry using water as a probe. Composites of EVA filled with aluminium hydroxide with high filler content for the required fire retardant properties have been studied. After water sorption at 90 °C, the composites have been analyzed by thermoporosimetry using water as a morphological probe. This technique first allowed studying the influence of the filler content and the specific surface area on the water uptake. The study with drying steps and two molecular probes (water and cyclohexane) has highlighted that water is confined at the interface and thus thermoporosimetry is a powerful tool to characterize interfaces in EVA-ATH composites.

The European Medicines Agency approval of ingenol mebutate (Picato) for the cutaneous treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis in adults: summary of the scientific assessment of the Committee for Medicinal Products for Human Use (CHMP).

BACKGROUND: The European Commission has recently issued a marketing authorisation valid throughout the European Union for ingenol mebutate (Picato) in the cutaneous treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis in adults. OBJECTIVES: The objective of this paper is to summarise the scientific review of the application leading to regulatory approval in the EU. The full scientific assessment report and product information, including the summary of product characteristics, are available on the EMA website (www.ema.europa.eu). MATERIAL & METHODS: The application was supported by 25 clinical studies, of which 18 were performed in patients with actinic keratosis. RESULTS: The active substance is a pure ingenol angelate obtained from the aerial parts of the plant species Euphorbia peplus by extraction and purification. One tube of ingenol mebutate 150 mcg/g gel or 500 mcg/g gel should be applied once daily to the affected area for 3 or 2 consecutive days on the 'face and scalp' or 'trunk and extremities', respectively. Complete response rate is 42.2% on the 'face and scalp' and 34.1% on the 'trunk and extremities'. The most common side effects are local skin responses including erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation and erosion/ulceration at the application site. CONCLUSIONS: The benefits of ingenol mebutate are its ability to improve the complete response rate of actinic keratosis, the short duration of treatment and the ease of self-application.

FTIR and DSC studies of the thermal and photochemical stability of Balanites aegyptiaca oil (Toogga oil).

The oil extracted from the bean of Balanites aegyptiaca was characterized, and its photochemical and thermal stabilization were evaluated. The chemical composition was determined using gas chromatography (GC), revealing that the oil is very rich in unsaturated fatty acids (72% omega-6 and omega-9). The photochemical stability was assessed by subjecting it to artificially accelerated photo-aging and then examining the changes using infrared spectroscopy. The thermal stability was studied at six different temperatures ranging from 130 to 200°C and monitored in situ by differential scanning calorimetry (DSC). The kinetic parameters (EA and k) describing the thermal degradation of this oil were calculated. It has been shown that the antioxidants present in the oil delay the oxidation process (induction period). The degradation of the Toogga oil was compared with that of oleic and linoleic fatty acids. In addition, the degradation of the Toogga oil extracted with hexane was compared to that of the neat oil.

Prostate-specific antigen (PSA) concentrations in hypogonadal men during 6 years of transdermal testosterone treatment.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Hypogonadism affects an estimated 2-4 million men in the USA, but only 5% receive treatment. Testosterone replacement therapy reduces the effects of testosterone deficiency on sexual function, mood and energy in hypogonadal patients. Long-term hypogonadism management requires testosterone treatment to restore serum concentrations of testosterone and its active metabolites, within physiological ranges; a testosterone preparation that achieves physiological plasma concentrations without supra-physiological escape is a preferred option. A previous 1-year study European clinical study showed the efficacy and safety of a transdermal testosterone patch (Testopatch(®) ). The present study shows the long-term (6-year) safety and efficacy of Testopatch in patients with primary or secondary hypogonadism. We show that, over the long-term, Testopatch was associated with no relevant changes in PSA concentration and PSA velocity, or any significant prostate risks (there were no cases of prostate cancer). OBJECTIVE: To assess the change in prostate-specific antigen (PSA) concentrations in patients with primary or secondary hypogonadism, receiving transdermal testosterone. PATIENTS AND METHODS: This was an interventional, 6-year study, conducted in Urology and Endocrinology centres in Belgium, France, Germany, the Netherlands and Spain. Participants were primary (48%) or secondary (52%) hypogonadal patients who received two 60 cm(2) testosterone patches (Testopatch(®) ), delivering 4.8 mg of testosterone per day, applied every 2 days. During treatment, total testosterone (TT), dihydrotestosterone, oestradiol and, PSA concentrations were measured in a centralised laboratory every 3 months during the first year, and every 6 months thereafter. RESULTS: In all, 200 patients [mean (sd) age 41.0 (12.5) years, body weight 82.5 (13.7) kg, height 177.2 (9.3) cm, body mass index 26.2 (3.4) kg/m(2) ] were treated with transdermal testosterone patches. In all, 161 patients completed the 1-year study and 115 entered into a 5-year study extension; 51 patients completed the sixth year of the study. The mean baseline concentrations of TT and PSA were 1.4 ng/mL and 0.47 ng/mL, respectively; TT serum concentrations >3 ng/mL were achieved in 85% of patients and fluctuated between 4.4 and 6.0 ng/mL. At each successive 6-month time point, mean the PSA values were 0.60, 0.67, 0.76, 0.70, 0.61, 0.68, 0.64, 0.71, 0.75, 0.74, 1.01, 0.78, 0.80 ng/mL, respectively. The mean PSA velocity was negligible (0.00-0.03 ng/mL/year) from 30 months to the end of the trial, except for a value of 0.08 at 60 months. Seven patients had a PSA concentration of >4 ng/mL due to a sharp PSA increase. Six of these patients had prostatitis and PSA concentrations returned to previous levels with appropriate treatment. No prostate cancer was reported during the trial. CONCLUSION: These data support a strong safety profile for Testopatch, even at the highest registered dosage.

Photochemical behavior of polylactide/ZnO nanocomposite films.

This study reports the effect of light on PLA/ZnO nanocomposites films produced by melt-extrusion. The attention focused on the discrimination between the photocatalytic degradation of PLA provoked by ZnO and the UV screening effect of the ZnO nanoparticles. The chemical modifications of PLA induced by UV light irradiation were analyzed using infrared spectroscopy and completed through the analysis of the low-molecular-weight photoproducts using IC and SPME and the characterization of chain scissions with SEC. A comprehensive mechanism for the photooxidation of PLA was then proposed. The results indicated that the photocatalytic activity of ZnO nanoparticles induces the oxidation of PLA. Because ZnO limits the penetration of light inside the samples, this effect mainly concerns the first micrometers at the surface of the exposed samples. Cross-sectional analysis using micro-IR and ATR-IR spectroscopies was performed to highlight the degradation profile in the PLA/ZnO nanocomposites.

Effect of ZnO nanofillers treated with triethoxy caprylylsilane on the isothermal and non-isothermal crystallization of poly(lactic acid).

The crystallization of PLA-silane surface-treated ZnO nanocomposites was investigated by DSC and compared to that of neat PLA. Several modes of crystallization were considered: isothermal and non-isothermal cold crystallization and also isothermal and non-isothermal melt crystallization. The kinetics of cold crystallization were studied using different methods, namely the Avrami and Ozawa-Flynn-Wall models, to calculate activation energies and kinetic constants. In contrast to what is typically observed when the foreign particles are added in a polymer matrix, the silane surface-treated ZnO delayed the crystallization of PLA and made it more difficult to start. The nucleation activity of the ZnO nanoparticles, ϕ, was calculated and found to be greater than 1 (ϕ = 1.7). This indicated that ZnO played an anti-nucleating role in the crystallization of PLA nanocomposites. This effect has been linked mainly to the interactions between the silane groups onto the surface of nanoparticles and PLA macromolecules. These interactions which reduce the mobility of polymer chains have been evidenced by rheological experiments.

Multiscale investigation of the poly(N-vinylcarbazole) photoageing mechanism.

During the past decade, the development of polymeric solar cells has received a great deal of attention from both academic and industrial laboratories. In order to enhance the device performances both in terms of power conversion efficiency stability in use conditions, Polycarbazole copolymers have attracted increasing attention. In this paper, the photodegradation of poly(N-vinylcarbazole) (PVK) was investigated from the molecular scale to the nanomechanical properties. It was shown irradiation provoked chain scissions, homolysis of the C-N bond and formation of new covalent bonds between the macromolecular chains. To fully understand the mechanism of the degradation of PVK provoked by exposure to UV radiation, mechanical analyses were performed. The consequences of the cross-linking reactions on the surface modifications were analyzed. Roughness and stiffness measurements were obtained through surface analysis and nanoindentation by atomic force microscopy (AFM), and depth-profiling experiments were also performed. The surface modifications and the shape of the profiles of the degradation photoproducts were explained in light of the chemical modifications of the PVK structure. Quantitative correlations were successfully obtained between the main relevant criteria of degradation, from the chemical structure to the mechanical properties. It was found that cross-linking reactions were prevalent.

Comparison of oral versus transdermal testosterone supplementation in hypogonadal men.

OBJECTIVE: To compare mean serum total testosterone, bioavailable-testosterone, and dihydrotestosterone levels between transdermal testosterone and oral testosterone undecanoate treatment. METHODS: Multicentre, randomized, cross-over study; 44 men >18 years, testosterone ≤2.5 ng/mL. Two patches (Testopatch®) every other day in the morning or two capsules Pantestone® 40 mg bid in each 22-day period. Hormone serum levels of four blood samples over the first and last 48 h of each treatment period. RESULTS: Mean age 49 years. Mean testosterone before inclusion 1.99 ng/mL. Mean testosterone serum levels over the last 48 h of Testopatch treatment were superior to Pantestone (4.64 vs. 2.58 ng/mL, p<0.001). Testosterone trough levels at the end of each treatment period were significantly higher for Testopatch (3.15 vs. 2.45 ng/mL, p<0.01). Bioavailable-testosterone levels over the first and last 48 h of treatment were significantly greater with Testopatch than with Pantestone (p=0.001 and p<0.01). Dihydrotestosterone levels over the first and last 48 h of treatment (0.71 vs. 1.05 ng/mL and 0.68 vs. 0.89 ng/mL) as well as at trough (0.59 vs. 0.96 ng/mL) were significantly lower with Testopatch than with Pantestone (p<0.001, p<0.05, and p<0.001). SHBG levels decreased by Pantestone but not by Testopatch (p<0.001). CONCLUSIONS: Testopatch was superior to Pantestone to increase testosterone and bioavailable-testosterone levels in hypogonadal men from the first days and throughout the three weeks of treatment. Pantestone increased dihydrotestosterone to a larger extent and decreased SHBG.

Direct protective effects of poly-unsaturated fatty acids, DHA and EPA, against activation of cardiac late sodium current: a mechanism for ischemia selectivity.

Polyunsaturated fatty acids (PUFAs) such as docosahexaenoic and eicosapentaenoic acids (DHA, EPA) exert ischemic anti-arrhythmic effects. However, their mechanism of action remains unknown. The present study was designed to investigate their potential effect on the regulation of the late sodium current as the basis for their ischemic anti-arrhythmic activity. Human isoforms of wild-type SCN5A and DeltaKPQ-mutated cardiac sodium channels were stably transfected in HEK 293 cells and, the resulting currents were recorded using the patch clamp technique in whole cell configuration. In addition to their effect to inhibit peak I(Na), acute application of DHA and EPA blocked veratridine-induced late sodium current (late I(Na-Verat)) in a concentration--dependent manner with IC(50) values of 2.1 +/- 0.5 microM and 5.2 +/- 0.8 microM,for DHA and EPA, respectively. Channels availability was reduced, resulting in a significant leftward shift of the steadystate inactivation curve by -10.0 +/- 2.1 mV and -8.5 +/- 0.2 mV for DHA and EPA, respectively. Similar inhibitory effects of DHA and EPA were also observed on late I(Na-KPQ). In addition to their role as blocking agents of peak I(Na), DHA and EPA reduced human late I(Na). These results could explain the antiarrhythmic properties of DHA and EPA during ischemia or following ischemia-reperfusion.

Action potential experiments complete hERG assay and QT-interval measurements in cardiac preclinical studies.

INTRODUCTION: The ICHS7B guideline focused on hERG and QT assays, although other factors have also been linked with the induction of severe arrhythmias. Thus, the aim of the present study was to demonstrate that two in vitro action potential recordings constitute convincing models of predictive drug-induced Torsades de pointes (TdP) and re-entry arrhythmias. METHODS: The effects of D,L-sotalol, flecainide and quinidine were investigated on potassium (hERG) and sodium (Na(V)1.5) currents transfected in HEK-293 cells to determine the repercussion of the blockade of these currents on rabbit Purkinje fibre (PF) and atrial action potentials. Atrial conduction velocity was also investigated as a model of re-entry arrhythmias. RESULTS: hERG channels were blocked by D,L-sotalol, quinidine and flecainide (IC(50): 69, 0.33 and 0.74 micromol/L, respectively). D,L-sotalol (30 micromol/L) induced reverse-use dependent increases in action potential duration (APD(90): +31.7% and +81.2% at 1 and 0.2 Hz) and triangulation (APD(90-40): +34.7% and +73.6% at 1 and 0.2 Hz) in PF but not in atria. Quinidine (10 micromol/L) also increased APD(90) (+14.5% and +68.5% at 1 and 0.2 Hz) and APD(90-40) (+73.3% and +152.1% at 1 and 0.2 Hz) in PF. Flecainide (10 micromol/L) shortened APD(90) in PF (-26.0% and - 22.2% at 1 and 0.2 Hz). Quinidine and flecainide blocked Na(V)1.5 channels by 32.3% and 73.1%, respectively, and produced decreases in dV/dt(max) which were more marked in atria (-20.4% and -31.9%) compared to PF (-12.8% and 22.4%) at 1 Hz. Finally, quinidine and flecainide decreased atrial conduction speed by 14.6% and 30.8%, respectively. CONCLUSION: Results obtained with flecainide demonstrate that use of the hERG channel alone should not be considered as a useful single assay. Rabbit Purkinje fiber action potentials can be considered as a comparable model for detection of reverse-use dependent APD prolongation and triangulation whereas the rabbit atria can be considered as a useful model for detection of sodium channel blockade associated with decreases in dV/dt(max) and conduction velocity.

Longchain n-3 polyunsaturated fatty acids and microvascular reactivity: observation in the hamster cheek pouch.

Previous experiments in our laboratory, using the hamster cheek pouch microcirculation, have shown that precapillary vessels exhibit spontaneous rhythmic luminal variations, termed vasomotion, a myogenic activity sustained by a balance between membrane currents among which polarizing K(+) currents play an important role. In these microvessels, endothelium-derived relaxing factors (EDRFs) seem to regulate arteriolar diameter [via nitric oxide (NO) and cyclic GMP] and vasomotion [probably via endothelium-derived hyperpolarizing factor (EDHF)]. Fish or fish oil diet can decrease the risk of cardiovascular diseases, probably by modifying the conductance of selective ion channels, such as K(+) and/or Ca(++), and/or increasing the production of vasodilators, such as NO. To investigate its effect on microvascular reactivity, using the same preparation and an intravital microscope coupled to a closed circuit TV system, male hamsters were treated for 14 days, twice a day, with 0.4 mL/100 g body weight with fish or olive oil. An attempt was also undertaken to record in arterioles, in vivo, the membrane potential of smooth muscle cells during their vasomotor activity combining conventional microelectrode and intravital microscopy techniques. The effects of topical application of two vasodilators, acetylcholine [endothelium-dependent one, NO release and membrane hyperpolarization via Ca(++)-activated K(+) channels (K(Ca))] and sodium nitroprusside (endothelium-independent, NO donor and no change on membrane potential) and two vasoconstrictors which elicited membrane depolarization via Ca(++) channels, phenylephrine (alpha(1)-adrenergic receptor agonist) and serotonin (5-hydroxi-tryptamine) on mean internal diameter of arterioles and venules, arteriolar blood flows, spontaneous arteriolar vasomotion frequency and amplitude and functional capillary density (FCD, number of capillaries with flowing red blood cells per unit area of tissue) were determined. Anesthesia was induced by sodium pentobarbital (i.p.) and maintained with alpha-chloralose through the femoral vein. In the presence of vasomotion, the membrane potentials are slowly oscillating by about 20 mV around values of approximately -50 mV in perfect synchrony with vasomotor movements and depolarizing phases coincide with vasoconstrictions while polarizing ones with vasodilatations. Comparing all parameters, in control conditions, only the spontaneous vasomotion frequency was significantly higher (2.37 times higher) on the group treated with fish oil and persisted as such throughout all experiments. With topical application of the drugs mentioned above, the group treated with fish oil showed, for each drug concentration, a balance towards vasodilatation with consequent increase on arteriolar blood flow and on FCD, compared with the olive oil treated one. No significant changes on mean arterial pressure, spontaneous arteriolar vasomotion amplitude or venular diameter could be detected in the two groups. Our results support the concept that, in the hamster cheek pouch microcirculation, fish oil supplementation activates K(+) channels which act as the EDHF and might also increase the production of vasodilators, probably NO.

Reduction in triglyceride level with N-3 polyunsaturated fatty acids in HIV-infected patients taking potent antiretroviral therapy: a randomized prospective study.

To assess the evolution of triglyceride (TG) levels in HIV-infected patients receiving stable potent antiretroviral therapy treated with N-3 polyunsaturated fatty acids (PUFAs), a prospective double-blind randomized design for a reliable assessment of TG evolution was performed. One hundred twenty-two patients with TG levels >2 g/L and < or =10 g/L after a 4-week diet (baseline TG: 4.5 +/- 1.9 g/L) were randomized for 8 weeks to N-3 PUFAs (2 capsules containing 1 g of fish oil 3 times daily, n = 60), or placebo (1 g of paraffin oil capsules, n = 62). An 8-week open-label phase of N-3 PUFAs followed. Evaluation criteria were TG percent change at week 8, percentage of responders (normalization or > or =20% TG decrease), and safety issues. Ten patients with baseline TG levels >10 g/L were not randomized and received N-3 PUFAs as open treatment. The difference (PUFA - placebo) in TG percent change at week 8 was -24.6% (range: -40.9% to -8.4%; P = 0.0033), the median was -25.5% in the PUFA group versus 1% in the placebo group, and mean TG levels at week 8 were 3.4 +/- 1.8 g/L and 4.8 +/- 3.1 g/L, respectively. TG levels were normalized in 22.4% (PUFA) versus 6.5% (placebo) of patients (P = 0.013) with a > or =20% reduction in 58.6% (PUFA) versus 33.9% (placebo) of patients (P = 0.007). Under the open-label phase of N-3 PUFAs, the decrease in TG levels was sustained at week 16 for patients in the PUFA group (mean TG: 3.4 +/- 1.7 g/L), whereas a 21.2% decrease in TG levels occurred for patients in the placebo group (mean TG: 3.3 +/- 1.4 g/L). No significant differences were observed between groups in the occurrence of adverse events. The median TG change at week 8 was -43.6% (range: Q1-Q3; 95% CI: -66.5% to -4.6%) for patients with baseline TG levels >10 g/L. The difference in mean total cholesterol between groups (PUFA - placebo) at week 8 was -8.5% (P = 0.0117). This study demonstrated the efficacy of PUFAs to lower elevated TG levels in treated HIV-infected hypertriglyceridemic patients. N-3 PUFAs have a good safety profile.