Rachid Koraïchi : une architecture céleste pour le soufisme

Dans cet article, nous nous proposons de présenter l'esprit dans lequel travaille Rachid Koraïchi, artiste algérien de tradition musulmane. Plus précisément, nous présentons son travail autour du fondateur de l'ordre des derviches tourneurs. Rûmî, poète mystique du XIIIe siècle, développe une conception de la fonction de l'art qui a séduit l'artiste. La musique, la danse et la poésie sont autant de moyens d'accéder à la beauté, beauté qui nous rapproche du divin. Cette métaphysique de l'art est mise en images par l'artiste. L'amour tient une place importante au sein de cette méditation. Redonner vie à la lettre de ce mystique, c'est aussi pour Koraïchi, lutter contre une image trop souvent négative de l'Islam.In this article, we intend to present the mentality informing the work of the Muslim Algerian artist Rachid Koraïchi. In particular, we will look at his work on the founder of the order of whirling dervishes. Rûmî, the mystic poet of the XIIIth century, develops a conception of the function of art which enthralled the artist. Music, dance and poetry are seen as ways of attaining beauty, a beauty which draws us towards the divine. The artist puts into images this metaphysics of art. Love occupies a central role in this meditation. Giving back life to the letter of the mystic is also for Koraïchi a way of fighting against the too frequently negative image of Islam

Determination of in vitro metabolic hepatic clearance of valproic acid (VPA) and five analogues by UPLC-MS-QTOF, applicable in alternatives to animal testing.

Abstract Laboratory measurements of intrinsic clearance support the development of TK models, with potential relevance to weight of evidence toxicity assessments of xenobiotics, including read-across, the concept of predictive estimation by data extrapolation between chemicals of similar structure (analogues). In this work a procedure with analytical method for determination of in vitro hepatic metabolic clearance, relevant to biotransformation toxicokinetic (TK) modelling, is presented. Cryopreserved primary human hepatocytes represent a suitable cells, due to their biological characteristics, for providing an in vitro model for simulating in vivo metabolic clearance. The experimental part considered an adequate sequential time-frame for collecting samples and controls for all chemicals tested, including centrifugation and aliquoting of the corresponding fractions until the instrumental session. For the first time, in vitro hepatocyte intrinsic clearance was measured for six analogue test chemicals: valproic acid, 2-ethyl caproic acid, octanoic acid, valeric acid, 2-methyl butyric acid and 2-trans pentenoic acid, during incubated cell culture exposure up to 2 h or 3.5 h. The time dependence of any metabolism was determined from analysis of the supernatant at intervals using a new developed analytical method for UPLC coupled with QTOF mass spectrometer. The chemicals could then be ranked by their relative intrinsic clearance. The analyses were reproducible, with coherence of the calculated in vitro intrinsic clearance between experiments

Neuroprotective effect of (R)-(-)-linalool on oxidative stress in PC12 cells

Background: Oxidative stress plays an important role in neurodegeneration, pain and inflammation. (R)-(-)- linalool (LIN) is endowed with neuroprotective, anti-nociceptive and anti-inflammatory properties. Purpose: The present study aims at investigating the hypothesis that LIN’s neuroprotective, antinociceptive and anti-inflammatory properties descend from its ability to act as antioxidant. The study challenges this hypothesis by verifying whether LIN may counteract hydrogen peroxide (H 2 O 2 )-induced oxidative stress in PC12 cells. Methods: In H 2 O 2 -exposed PC12 cells, LIN was tested on a) cell viability, measured by 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT), b) damage of plasma membrane, measured by lactate dehydrogenase (LDH) release, c) intracellular levels of reactive-oxygen-species (ROS), d) apoptosis and e) cell cycle distribution. Results: Under H 2 O 2 -induced cell viability reduction, LIN protects PC12 cells. Likewise, LIN protects cells from oxidative damage by preventing the H 2 O 2 -dependent increase of LDH release, counteracts intracellular ROS overproduction and reduces H 2 O 2 -induced apoptosis. Finally, the results of the cell cycle analysis from cells exposed to H 2 O 2 indicate that LIN incubation reduces the number of cells induced into quiescence by H 2 O 2 in the G2/M phase. Conclusions: These findings indicate that LIN protects PC12 cells from H 2 O 2 -induced oxidative stress. This mech- anism could justify the neuroprotective, anti-nociceptive and anti-inflammatory effects of this compound and suggest LIN as a potential therapeutic agent for the management oxidative stress-mediated pain

New perspective for an old drug: Can naloxone be considered an antioxidant agent?

Background: Experimental evidence indicates that Naloxone (NLX) holds antioxidant properties. The present study aims at verifying the hypothesis that NLX could prevent oxidative stress induced by hydrogen peroxide (H2O2) in PC12 cells.Methods: To investigate the antioxidant effect of NLX, initially, we performed electrochemical experiments by means of platinum-based sensors in a cell-free system. Subsequently, NLX was tested in PC12 cells on H2O2induced overproduction of intracellular levels of reactive-oxygen-species (ROS), apoptosis, modification of cells' cycle distribution and damage of cells' plasma membrane.Results: This study reveals that NLX counteracts intracellular ROS production, reduces H2O2-induced apoptosis levels, and prevents the oxidative damage-dependent increases of the percentage of cells in G2/M phase. Likewise, NLX protects PC12 cells from H2O2- induced oxidative damage, by preventing the lactate dehydrogenase (LDH) release. Moreover, electrochemical experiments confirmed the antioxidant properties of NLX.Conclusion: Overall, these findings provide a starting point for studying further the protective effects of NLX on oxidative stress

Seurat-1: HepaRG, repeated and single dose exposure for Mitochondrial Health and LipidTox

The purpose of this report is to describe the experimental procedure used in order to detect changes in mitochondrial membrane potential and lipid accumulation following exposure of HepaRG cells to various chemicals both by repeated exposure as single exposure to chemicals. This procedure was created for the SEURAT-1 Project runs 15 to 18 and was developed by using live cell imaging.JRC.I.5-Systems Toxicolog

Chemical Safety Assessment Using Read-Across: Assessing the Use of Novel Testing Methods to Strengthen the Evidence Base for Decision Making

Background: Safety assessment for repeated dose toxicity is one of the largest challenges in the process to replace animal testing. This is also one of the proof of concept ambitions of SEURAT-1, the largest ever European Union research initiative on alternative testing, co-funded by the European Commission and Cosmetics Europe. This review is based on the discussion and outcome of a workshop organized on initiative of the SEURAT-1 consortium joined by a group of international experts with complementary knowledge to further develop traditional read-across and include new approach data. Objectives: The aim of the suggested strategy for chemical read-across is to show how a traditional read-across based on structural similarities between source and target substance can be strengthened with additional evidence from new approach data—for example, information from in vitro molecular screening, “-omics” assays and computational models—to reach regulatory acceptance. Methods: We identified four read-across scenarios that cover typical human health assessment situations. For each such decision context, we suggested several chemical groups as examples to prove when read-across between group members is possible, considering both chemical and biological similarities. Conclusions: We agreed to carry out the complete read-across exercise for at least one chemical category per read-across scenario in the context of SEURAT-1, and the results of this exercise will be completed and presented by the end of the research initiative in December 2015

Screening methodology to identify potential endocrine disruptors according to different options in the context of an impact assessment

Several pieces of EU legislation regulate the marketing and use of chemical substances. While several regulations, including the regulations on Plant Protection Products (PPPR), Biocidal Products (BPR) and Chemicals (REACH), include provisions for endocrine disrupting substances (EDs), objective scientific criteria are lacking. In order to evaluate the potential health, socio-economic and environmental impacts of applying four different options for criteria defining EDs across these pieces of legislation, the Commission initiated an Impact Assessment (IA). This IA has been supported by two studies, focusing on (a) selection of substances for the IA and the screening of their potential for identification as EDs according to different options for defining criteria for identification of endocrine disruptors and (b) the potential impacts of various policy options on health, environment, trade, agriculture and socio-economy. This report describes a screening methodology that has been developed by the JRC to support the first study which has assessed all pesticide and biocide active ingredients and a selection of substances falling under REACH, the Cosmetic Products Regulation and the Water Framework Directive. This screening methodology is not intended to replace an in-depth risk assessment process, and the results obtained are not intended to pre-empt regulatory conclusions that may eventually be made under different pieces of EU legislation.JRC.I.5-Systems Toxicolog

Genetic loci linked to Type 1 Diabetes and Multiple Sclerosis families in Sardinia

<p>Abstract</p> <p>Background</p> <p>The Mediterranean island of Sardinia has a strikingly high incidence of the autoimmune disorders Type 1 Diabetes (T1D) and Multiple Sclerosis (MS). Furthermore, the two diseases tend to be co-inherited in the same individuals and in the same families. These observations suggest that some unknown autoimmunity variant with relevant effect size could be fairly common in this founder population and could be detected using linkage analysis.</p> <p>Methods</p> <p>To search for T1D and MS loci as well as any that predispose to both diseases, we performed a whole genome linkage scan, sequentially genotyping 593 microsatellite marker loci in 954 individuals distributed in 175 Sardinian families. In total, 413 patients were studied; 285 with T1D, 116 with MS and 12 with both disorders. Model-free linkage analysis was performed on the genotyped samples using the Kong and Cox logarithm of odds (LOD) score statistic.</p> <p>Results</p> <p>In T1D, aside from the HLA locus, we found four regions showing a lod-score ≥1; 1p31.1, 6q26, 10q21.2 and 22q11.22. In MS we found three regions showing a lod-score ≥1; 1q42.2, 18p11.21 and 20p12.3. In the combined T1D-MS scan for shared autoimmunity loci, four regions showed a LOD >1, including 6q26, 10q21.2, 20p12.3 and 22q11.22. When we typed more markers in these intervals we obtained suggestive evidence of linkage in the T1D scan at 10q21.2 (LOD = 2.1), in the MS scan at 1q42.2 (LOD = 2.5) and at 18p11.22 (LOD = 2.6). When all T1D and MS families were analysed jointly we obtained suggestive evidence in two regions: at 10q21.1 (LOD score = 2.3) and at 20p12.3 (LOD score = 2.5).</p> <p>Conclusion</p> <p>This suggestive evidence of linkage with T1D, MS and both diseases indicates critical chromosome intervals to be followed up in downstream association studies.</p

Insight in cognitive impairment assessed with the Cognitive Assessment Interview in a large sample of patients with schizophrenia

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). The present study aimed at assessing, in a large sample of SCZ (n = 601), the agreement between patients and their informants on CAI ratings, to explore patients' insight in their cognitive deficits and its relationships with clinical and functional indices. Agreement between patient- and informant-based ratings was assessed by the Gwet's agreement coefficient. Predictors of insight in cognitive deficits were explored by stepwise multiple regression analyses. Patients reported lower severity of cognitive impairment vs. informants. A substantial to almost perfect agreement was observed between patients' and informants' ratings. Lower insight in cognitive deficits was associated to greater severity of neurocognitive impairment and positive symptoms, lower severity of depressive symptoms, and older age. Worse real-life functioning was associated to lower insight in cognitive deficit, worse neurocognitive performance, and worse functional capacity. Our findings indicate that the CAI is a valid co-primary measure with the interview to patients providing a reliable assessment of their cognitive deficits. In the absence of informants with good knowledge of the subject, the interview to the patient may represent a valid alternative

The association between insight and depressive symptoms in schizophrenia: Undirected and Bayesian network analyses

Background. Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions. Methods. Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination). Bayesian network analysis was used to estimate a directed acyclic graph (DAG) while investigating the most likely direction of the putative causal association between insight and depression. Results. After adjusting for confounders, better levels of insight were associated with greater self-depreciation, pathological guilt, morning depression and suicidal ideation. No difference in global network structure was detected for socioeconomic status, service engagement or illness severity. The DAG confirmed the presence of an association between greater insight and self-depreciation, suggesting the more probable causal direction was from insight to depressive symptoms. Conclusions. In schizophrenia, better levels of insight may cause self-depreciation and, possibly, other depressive symptoms. Person-centered and narrative psychotherapeutic approaches may be particularly fit to improve patient insight without dampening self-esteem