Hyaluronic acid combined with mannitol to improve protection against free-radical endothelial damage: Experimental Model

Purpose: To evaluate the protective properties of combined sodium hyaluronate2% and mannitol 0.5% (Visiol) on the corneal endothelium in the presence of oxidative stress induced by hydrogen peroxide (H2O2). Setting: Instituto Oftalmolo´ gico de Alicante, Universidad Miguel Herna´ ndez, Alicante, Spain. Methods: This was an exploratory randomized controlled parallel-group, maskedassessor study of 3 sodium hyaluronate-based ophthalmic viscosurgical devices (OVDs): Visiol, Healon (sodium hyaluronate 1%), and Viscoat (sodium hyaluronate 3%–chondroitin sodium 4%). The OVDs were tested for protective effects on the endothelium following oxidative stress induced by H2O2 at increased concentrations: control (lactated Ringer’s solution), 1mM, 10mM, and 100 mM. Groups without OVD were used as controls at the same concentrations of peroxide. Each animal received the same treatment in both eyes (10 eyes per group). Endothelial cell lesion was assessed using the Janus green photometry absorbance technique. Results: At 10 mM peroxide concentration, the value of endothelial cell lesion was significantly lower in the Visiol (16.8%, P Z .0056), Healon (22.2%, P Z .0302), and Viscoat (21.6%, PZ .0336) groups than in the control group (29.4%, no OVD). There was a trend in favor of Visiol to more efficiently reduce cell lesions of the endothelium, than Healon (PZ .055) and Viscoat (P Z .1013). Values of endothelial cell lesion at peroxide concentrations of 1 mM and 100 mM showed the same trends than those observed at 10 mM. Conclusions: All of the OVDs tested efficiently reduced endothelial lesions against free radicals compared with the control group in which no OVD was used. The following sequence for the efficacy of endothelial cell protection was established: Visiol O Viscoat O Healon O no OVD

Visceral and somatic pain modalities reveal NaV 1.7-independent visceral nociceptive pathways.

KEY POINTS: Voltage-gated sodium channels play a fundamental role in determining neuronal excitability. Specifically, voltage-gated sodium channel subtype NaV 1.7 is required for sensing acute and inflammatory somatic pain in mice and humans but its significance in pain originating from the viscera is unknown. Using comparative behavioural models evoking somatic and visceral pain pathways, we identify the requirement for NaV 1.7 in regulating somatic (noxious heat pain threshold) but not in visceral pain signalling. These results enable us to better understand the mechanisms underlying the transduction of noxious stimuli from the viscera, suggest that the investigation of pain pathways should be undertaken in a modality-specific manner and help to direct drug discovery efforts towards novel visceral analgesics. ABSTRACT: Voltage-gated sodium channel NaV 1.7 is required for acute and inflammatory pain in mice and humans but its significance for visceral pain is unknown. Here we examine the role of NaV 1.7 in visceral pain processing and the development of referred hyperalgesia using a conditional nociceptor-specific NaV 1.7 knockout mouse (NaV 1.7Nav1.8 ) and selective small-molecule NaV 1.7 antagonist PF-5198007. NaV 1.7Nav1.8 mice showed normal nociceptive behaviours in response to intracolonic application of either capsaicin or mustard oil, stimuli known to evoke sustained nociceptor activity and sensitization following tissue damage, respectively. Normal responses following induction of cystitis by cyclophosphamide were also observed in both NaV 1.7Nav1.8 and littermate controls. Loss, or blockade, of NaV 1.7 did not affect afferent responses to noxious mechanical and chemical stimuli in nerve-gut preparations in mouse, or following antagonism of NaV 1.7 in resected human appendix stimulated by noxious distending pressures. However, expression analysis of voltage-gated sodium channel α subunits revealed NaV 1.7 mRNA transcripts in nearly all retrogradely labelled colonic neurons, suggesting redundancy in function. By contrast, using comparative somatic behavioural models we identify that genetic deletion of NaV 1.7 (in NaV 1.8-expressing neurons) regulates noxious heat pain threshold and that this can be recapitulated by the selective NaV 1.7 antagonist PF-5198007. Our data demonstrate that NaV 1.7 (in NaV 1.8-expressing neurons) contributes to defined pain pathways in a modality-dependent manner, modulating somatic noxious heat pain, but is not required for visceral pain processing, and advocate that pharmacological block of NaV 1.7 alone in the viscera may be insufficient in targeting chronic visceral pain.University of Granada Dr Hadwen Trust for Humane Researc

Enabling planetary science across light-years. Ariel Definition Study Report

Ariel, the Atmospheric Remote-sensing Infrared Exoplanet Large-survey, was adopted as the fourth medium-class mission in ESA's Cosmic Vision programme to be launched in 2029. During its 4-year mission, Ariel will study what exoplanets are made of, how they formed and how they evolve, by surveying a diverse sample of about 1000 extrasolar planets, simultaneously in visible and infrared wavelengths. It is the first mission dedicated to measuring the chemical composition and thermal structures of hundreds of transiting exoplanets, enabling planetary science far beyond the boundaries of the Solar System. The payload consists of an off-axis Cassegrain telescope (primary mirror 1100 mm x 730 mm ellipse) and two separate instruments (FGS and AIRS) covering simultaneously 0.5-7.8 micron spectral range. The satellite is best placed into an L2 orbit to maximise the thermal stability and the field of regard. The payload module is passively cooled via a series of V-Groove radiators; the detectors for the AIRS are the only items that require active cooling via an active Ne JT cooler. The Ariel payload is developed by a consortium of more than 50 institutes from 16 ESA countries, which include the UK, France, Italy, Belgium, Poland, Spain, Austria, Denmark, Ireland, Portugal, Czech Republic, Hungary, the Netherlands, Sweden, Norway, Estonia, and a NASA contribution

Cent scientifiques répliquent à SEA (Suppression des Expériences sur l’Animal vivant) et dénoncent sa désinformation

La lutte contre la maltraitance animale est sans conteste une cause moralement juste. Mais elle ne justifie en rien la désinformation à laquelle certaines associations qui s’en réclament ont recours pour remettre en question l’usage de l’expérimentation animale en recherche

Chemical and physical parameters of tears relevant for the design of ocular drug delivery formulations

This paper provides a summary of the most important chemical and physical parameters of tears that can help the formulator in the development of new ocular formulations and in the conception of innovative ophthalmic delivery approaches. For each physiological parameter, the relevance in ocular drug delivery is discussed in detail and the analytical tools that are used for the determination of these parameters are described and summarized. The aim of this review is also to give a description of the main analytical techniques available in ophthalmology that can be used for pharmacokinetic studies of active compounds. The importance of tear sampling techniques used in the determination of the parameters is also discussed

Delivery of antibiotics to the eye using a positively charged polysaccharide as vehicle

The positively charged polysaccharide chitosan is able to increase precorneal residence time of ophthalmic formulations containing active compounds when compared with simple aqueous solutions. The purpose of the study was to evaluate tear concentration of tobramycin and ofloxacin after topical application of chitosan-based formulations containing 0.3% wt/vol of antibiotic and to compare them with 2 commercial solutions: Tobrex® and Floxal®, respectively. The influence of the molecular weight, deacetylation degree, and concentration of 4 different samples of chitosan on pharmacokinetic parameters (area under the curve values [AUCeff] and time of efficacy [teff]) of tobramycin and ofloxacin in tears was investigated over time. It was demonstrated that the 2 chitosan products of high molecular weight (1350 and 1930 kd) and low deacetylation degree (50%) significantly increased antibiotic availability when compared to the controls, with AUCeff showing a 2-to 3-fold improvement. The time of efficacy of ofloxacin was significantly increased from about 25 minutes to 46 minutes by the chitosan of higher Mw (1930 kd) at a concentration of 0.5% wt/vol, whereas a similar performance was achieved by a chitosan of low Mw (580 kd) at a concentration of 1.5% wt/vol in the case of tobramycin

Application à un cas clinique d’un protocole d’évaluation des processus pour les troubles anxio-dépressifs

Cet article présente l’application à un cas clinique de la procédure d’évaluation des processus pour les troubles anxiodépressifs développée dans l’article de Philippot et al., 2015 (dans ce numéro). Sept classes de processus ont été identifiées par questionnaire chez Marie, une jeune femme de 28 ans souffrant d’une anxiété importante de ne pas pouvoir aller aux toilettes lorsqu’elle est anxieuse. Les résultats aux questionnaires ainsi que la discussion des résultats avec Marie mettent en évidence plusieurs processus psychologiques : évitements, mode de pensée abstrait-analytique, métacognitions, écarts entre les sois, et faible sentiment d’efficacité personnel dans la régulation des émotions et la gestion du quotidien. La mise en évidence de ces processus implique plusieurs pistes thérapeutiques : exposition ciblant la honte avec débriefing des significations, activation comportementale, identification et détachement par rapport aux pensées critiques, identification de la fonction des ruminations, réengagement attentionnel vers l’ici et maintenant et test comportemental des croyances métacognitives. Au bout de 12 séances, les questionnaires ont été complétés une nouvelle fois afin d’évaluer les changements. Les résultats mettent en évidence des modifications importantes sur certaines des dimensions évaluées et permettent de fixer de nouveaux objectifs pour la suite de la thérapie.This article presents a clinical case study of the process evaluation procedure for anxious and depressive disorders developed in the article of Philippot et al., 2015 (in this issue). Seven types of process have been evaluated via self-reported scales by Marie, a woman aged 28 years suffering from an intense anxiety of not being able to find a bathroom and having involuntary urine leakage. Any biological explanation of the problem has been excluded by a physician. Marie also suffers from stress in regard to managing daily activities. Those problems seem to increase over time. The questionnaire results and subsequent discussion with Marie evidence several psychological processes which we have articulated in a global modelization. Self-discrepancies or perfectionism were inspired by the models of Higgins, 1987 as well as Shafran et al., 2002. Marie suffers from a discrepancy between high standards for herself mainly on the intellectual dimension and the perception of herself as being uneducated. This discrepancy is a source of intense shame that she represses, resulting in a secondary emotion of anxiety (Greenberg, 2002). Marie also displays low self-efficacy (Bandura, 1988) in the regulation of emotion as well as in the management of daily activities. Meta-cognitive factors (Wells, 1995), such as positive beliefs about worrying and a lack of cognitive confidence, induce persistent worrying and an abstract-analytic thinking style (Watkins, 2008). Avoidance is present through the avoidance of shame, resulting in the secondary emotion of anxiety, through worries as a way of avoiding negative self-image, as well as through intense efforts to meet high standards. The questionnaires and the resulting discussion brought to light some important processes that were not evidenced through anamnesis, concretization and holistic conceptualization. The identification of processes implies several therapeutic approaches. Firstly, the target of exposure must be carefully chosen. In regard to the recommendations of Greenberg (2002), the exposure should be undertaken in targeting not only the anxiety of having a urinary leakage (secondary emotion) but also the emotion of shame (primary emotion). This could be done though the reactivation in imagery of shame memories with an attitude of acceptance of the induced emotion. Moreover, whereas shame is strongly related to self-image, the debriefing of these exposures should be oriented to the actualization of the meanings associated to these memories (Hackmann et al., 2011). Self-discrepancies and perfectionism should be addressed by highlighting the fact that Marie's self-evaluation is too closely focused on failures and does not take into account important qualities she possesses. Behavioral activation in the sense of engaging in activities that fulfil important values (Jacobson et al., 2001), as well as the identification and detached observation of self-criticisms (Egan and Shafran, 2010) could also address self-discrepancies. Ruminations and meta-cognitive factors could be addressed through the rumination function identification, information about the distinction between concrete and abstract thinking style (Watkins, 2008), refocusing on the present moment (Segal et al., 2002), and behavioral testing of meta-cognitive beliefs (Fisher and Wells, 2009). Twelve sessions of therapy following these guidelines were conducted. The questionnaires were completed again by Marie. From a symptomatic point of view, we observed a decline in distress. In regard to processes, the results display changes that are consistent with the targets of intervention: a decrease in behavioral avoidance, in distraction/suppression, in negative meta-cognitive beliefs, in lack of cognitive confidence, in abstract thinking, in self-discrepancies and associated distress, as well as an increase in self-efficacy in daily activities. However, some processes targeted did not change: self-efficacy in regard to work, hobbies and emotion regulation, distress aversion, positive beliefs. These results allowed us to highlight the effective changes and define new intervention targets. In conclusion, whereas the case was initially seen as relatively simple, the proposed tool offered a comprehensive and more complex view of the process involved and oriented the intervention. This tool also provided an important resource for discussion with the client and offered an evaluation of changes throughout therapy

Validation of the Self-Discrepancies Scale (S-DS). A tool to investigate the self in clinical and research settings

International audienceIntroductionSelf-discrepancies (the distances between the perceived self and the ideal or the socially prescribed selves) are a hallmark in psychological distress. However, a clinical tool evaluating these discrepancies is lacking.ObjectiveTo investigate the validity, the psychometric characteristics and the clinical relevance of the Self-Discrepancy Scale, an instrument designed to assess with multiple indices discrepancies between mental representations of the self: the actual self, on the one hand and ideal or socially-prescribed selves, on the other hand.MethodThe Self-Discrepancy Scale has been administered to a large community sample, together with measures of depression, anxiety, self-esteem, and self-efficacy. It was also proposed to an additional clinical sample composed of clients with a diagnosis of mood or anxiety disorders seeking psychotherapeutic help.ResultsA factor analysis evidenced three underlying dimensions to self-discrepancies: the size of the discrepancies, the resulting distress and the presence to unwanted traits. Test-retest consistency is in the acceptable range. Different profiles of self-discrepancies distinguished clinical groups suffering from different disorders.ConclusionsThe data suggest that the Self-Discrepancy Scale is a valid measure of self-discrepancies and a valuable predictor of emotional vulnerability, especially with regards to abstract global judgments of discrepancies and of discrepancy induced distress. It is concluded that the Self-Discrepancy Scale offers a valuable help in clinical settings