Serum levels of TNF-alpha, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet's disease.

AIM: Behçet's disease (BD) is asystemic immunoinflammatory disorder and the aetiopathogenesis is to be specified. Cytokines play a role in immune response and in many inflammatory diseases. The aim of this case-control study is to investigate serum pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta), soluble IL-2 receptor (sIL-2R), IL-6, and chemokine IL-8 levels in patients with BD. We also determined the end product of lipid peroxidation (malondialdehyde (MDA)) in BD patients as an index for oxidative stress. METHODS: A total of 37 patients (19 men, 18 women) with BD (active, n = 17; inactive, n = 20) and 20 age-matched and sex-matched healthy control subjects (11 men, nine women) included in this cross-sectional, blinded study. Serum TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels were determined by a spectrophotometer technique using the immulite chemiluminescent immunometric assay. Lipid peroxidation was evaluated by Wasowicz et aL The levels of cytokines and lipid peroxidation in the active period were compared with the inactive period of the disease. Results are expressed as mean +/- standard error. RESULTS: IL-1beta levels were below the detection limits of the assay (< 5 pg/ml) in all samples. Mean levels of MDA (8.1+/-0.7 micromol/l), sIL-2R (800+/-38 U/ml), IL-6 (12.6+/-1.1 pg/ml), IL-8 (7.2+/-0.4 pg/ml), and TNF-alpha (7.9+/-0.5 pg/ml) in active BD patients were significantly higher than those in inactive patients (4.3+/-0.5 micromol/l, p < 0.01; 447+/-16 U/ml, p < 0.001; 8.3+/-0.6 pg/ml, p = 0.006; 5.3+/-0.1 pg/ml, p < 0.001; and 5.1 0.2 pg/ml, p < 0.001; respectively) or control subjects (2.1+/-0.2 micromol/l, p < 0.001; 446+/-20 U/ml, p < 0.001; 6.4+/-0.2 pg/ml, p < 0.001; 5.4+/-0.1 pg/ml, p < 0.001; and 4.7+/-0.1 pg/ml, p < 0.001, respectively). On the contrary, only the mean IL-6 level was significantly different between inactive BD and control subjects (p = 0.02). All acute phase reactants were significantly higher in active BD than in inactive period (for each, p < 0.01). Conclusions: High levels of sIL-2R, IL-6, IL-8 and TNF-alpha indicate the activation of immune system in BD. Serum sIL-2R, IL-6, IL-8 and TNF-alpha seem to be related to disease activity. Increased lipid peroxidation suggests oxidative stress in BD and therefore tissue damage in such patients. Amelioration of clinical manifestations would be envisaged by targeting these cytokines, chemokines and lipid peroxidation with pharmacological agents

Adenosine deaminase enzyme activity is increased and negatively correlates with catalase, superoxide dismutase and glutathione peroxidase in patients with Behçet's disease: original contributions/clinical and laboratory investigations.

AIM: Behçet's disease (BD) is an inflammatory vasculitis with immunologic, endothelial and neutrophil alterations. Adenosine deaminase (AD) is a marker of T-cell activation and is related to the production of reactive oxygen species by neutrophils with the production of NO(*), O(2)(*-), H(2)O(2) and OH(*). We reported increased tumour necrosis factor-alpha, soluble interleukin-2 receptor, interleukin-6, interleukin-8 and NO(*) in active BD. As there is a relation between cytokines, T cells and oxidative stress in inflammatory diseases, this study further evaluated: (1) plasma AD activity and its correlation with acute phase reactants; (2) thiobarbituric acid-reactive substances (TBARS) as an indicator for lipid peroxidation; and (3) antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase in patients with BD. The effect of disease activity and correlations between the measured parameters were explored. METHODS: A total of 35 active (n=17) or inactive (n=18) patients with BD (16 men, 19 women) satisfying International Study Group criteria, and 20 age-matched and sex-matched controls (nine men, 11 women) were included in this cross-sectional case-control study. AD and TBARS were measured in plasma, catalase in red blood cells (RBC), and SOD and GSHPx in both plasma and RBC in both groups. Acute phase reactants (alpha(1)-antitrypsin, alpha(2)-macroglobulin, neutrophils, erythrocyte sedimentation rate) were used to classify patients as active or inactive. RESULTS: Plasma AD (mean+/-standard error of the mean, 36.1+/-0.7 U/l) and TBARS (4.2+/-0.1 nmol/ml) levels were significantly (for each, p<0.001) higher in BD than in controls (24.1+/-0.8 U/l and 1.6+/-0.1 nmol/ml, respectively). RBC catalase activity was significantly (p<0.001) lower in BD than in controls (120.9+/-3.8 versus 160.3+/-4.1 k/g haemoglobin). SOD and GSHPx activities were significantly lower in both plasma and erythrocytes of patients with BD than in controls (plasma SOD, 442.4+/-8.6 versus 636.4+/-9.2 U/ml, p<0.001; RBC SOD, 3719.2+/-66.0 versus 4849.7+/-49.0 U/g haemoglobin, p<0.001; plasma GSHPx, 73.1+/-1.5 versus 90.6+/-2.9 U/ml, p<0.001; RBC GSHPx, 600.7+/-8.0 versus 670.6+/-10.1 U/g haemoglobin, p<0.001). Active BD patients had significantly lower antioxidant enzymes (except RBC catalase) and higher AD and TBARS levels than inactive subjects (for each, p<0.01). When considering all BD patients, a significant positive correlation was present between AD and TBARS (p<0.001) whereas both AD and TBARS were negatively correlated with antioxidant enzymes (for each, p<0.05). CONCLUSIONS: AD and lipid peroxidation are increased and associated with defective antioxidants in BD, suggesting interactions between activated T cells and neutrophil hyperfunction. Measures of pro-oxidative stress and antioxidative defence with AD activity as an indicator of T-cell activation can be considered as significant supportive diagnostic indicators, especially in active disease. In addition, strengthening the antioxidant defence may contribute to treatment modalities

Genetic polymorphism in the serotonin transporter gene-linked polymorphic region and response to serotonin reuptake inhibitors in patients with premature ejaculation

OBJECTIVES: Serotonin plays a central role in ejaculation and selective serotonin reuptake inhibitors have been successfully used to treat premature ejaculation. Here, we evaluated the relationship between a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the response of patients with premature ejaculation to SSRI medication. METHODS: Sixty-nine premature ejaculation patients were treated with 20 mg/d paroxetine for three months. The Intravaginal Ejaculatory Latency Time and International Index of Erectile Function scores were compared with baseline values. The patients were scored as having responded to therapy when a 2-fold or greater increase was observed in Intravaginal Ejaculatory Latency Time compared with baseline values after three months. Three genotypes of 5-HTTLPR were studied: LL, LS and SS. The appropriateness of the allele frequencies in 5-HTTLPR were analyzed according to Hardy-Weinberg equilibrium using the χ2-test. RESULTS: The short (S) allele of 5-HTTLPR was significantly more frequent in responders than in nonresponders (

Data S1: Raw data compilation

N-Acetyl-p-Aminophenol (APAP), also known as acetaminophen, is the most commonly used over-the counter analgesic and antipyretic medication. However, its overdose leads to both liver and kidney damage. APAP-induced toxicity is considered as one of the primary causes of acute liver failure; numerous scientific reports have focused majorly on APAP hepatotoxicity. Alternatively, not many works approach APAP nephrotoxicity focusing on both its mechanisms of action and therapeutic exploration. Moringa oleifera (MO) is pervasive in nature, is reported to possess a surplus amount of nutrients, and is enriched with several bioactive candidates including trace elements that act as curatives for various clinical conditions. In this study, we evaluated the nephro-protective potential of MO leaf extract against APAP nephrotoxicity in male Balb/c mice. A single-dose acute oral toxicity design was implemented in this study. Group 2, 3, 4 and 5 received a toxic dose of APAP (400 mg/kg of bw, i.p) and after an hour, these groups were administered with saline (10 mL/kg), silymarin—positive control (100 mg/kg of bw, i.p), MO leaf extract (100 mg/kg of bw, i.p), and MO leaf extract (200 mg/kg bw, i.p) respectively. Group 1 was administered saline (10 mL/kg) during both the sessions. APAP-treated mice exhibited a significant elevation of serum creatinine, blood urea nitrogen, sodium, potassium and chloride levels. A remarkable depletion of antioxidant enzymes such as SOD, CAT and GSH-Px with elevated MDA levels has been observed in APAP treated kidney tissues. They also exhibited a significant rise in pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and decreased anti-inflammatory (IL-10) cytokine level in the kidney tissues. Disorganized glomerulus and dilated tubules with inflammatory cell infiltration were clearly observed in the histology of APAP treated mice kidneys. All these pathological changes were reversed in a dose-dependent manner after MO leaf extract treatment. Therefore, MO leaf extract has demonstrated some therapeutic effectiveness against APAP-induced nephrotoxicity through enhancement of the endogenous antioxidant system and a modulatory effect on specific inflammatory cytokines in kidney tissues

Chemical Proteomics-Based Analysis of Off-target Binding Profiles for Rosiglitazone and Pioglitazone: Clues for Assessing Potential for Cardiotoxicity

Drugs exert desired and undesired effects based on their binding interactions with protein target(s) and off-target(s), providing evidence for drug efficacy and toxicity. Pioglitazone and rosiglitazone possess a common functional core, glitazone, which is considered a privileged scaffold upon which to build a drug selective for a given target—in this case, PPARγ. Herein, we report a retrospective analysis of two variants of the glitazone scaffold, pioglitazone and rosiglitazone, in an effort to identify off-target binding events in the rat heart to explain recently reported cardiovascular risk associated with these drugs. Our results suggest that glitazone has affinity for dehydrogenases, consistent with known binding preferences for related rhodanine cores. Both drugs bound ion channels and modulators, with implications in congestive heart failure, arrhythmia, and peripheral edema. Additional proteins involved in glucose homeostasis, synaptic transduction, and mitochondrial energy production were detected and potentially contribute to drug efficacy and cardiotoxicity

L'émergence et l'évolution du cinéma documentaire de résistance en Turquie (2003-2017)

The Emergence and Evolution of Documentary Cinema of Resistance in Turkey (2003-2017) focuses on a corpus consisting of documentaries made from the 2000s onwards. This collection of work stands out from the production of earlier decades by their independence, thematic and aesthetic diversity, and they explore social, political, and historical questions of the AKP period from the point of view of persons concerned. On one hand, based on the interviews with the filmmakers, this dissertation reveals the conditions in which this documentary cinema emancipate at the margins of the cinema industry. It examines how the filmmakers adjust to the economic, social, and political constraints due to the topics they treat, and how they adapt their strategies during the projects and over the years. On the other hand, it analyses the cinematographic language used by the filmmakers to bring up on the screen their aspiration for an inclusive and plural society. Lastly, it suggests an opening on the future of this documentary cinema which is the regular target of the state authorities and pro-government media. Structured around recurring topics such as women, LGBTI+ people, workers, ecological upheavals, Armenians, and Kurds, this dissertation provides a portrait of Turkey’s society marked, not only by various tensions, conflicts, and crises, but also questionings, oppositions, resistances, and struggles.La thèse, L’émergence et l’évolution du cinéma documentaire de résistance en Turquie (2003-2017), place au cœur de l’étude, un corpus hétérogène de documentaires réalisés à partir des années 2000, qui se démarquent de la production des décennies précédentes par leur indépendance, leur diversité thématique et esthétique, et qui abordent, du point de vue des personnes concernées, les questions sociétales, politiques et historiques de la période de l’AKP. D’une part, en s’appuyant sur les entretiens et échanges réalisés avec les cinéastes, cette thèse révèle les conditions dans lesquelles ce cinéma documentaire s’émancipe aux marges de l’industrie. Elle examine par quels moyens ces derniers s’adaptent aux contraintes économiques, sociales et politiques dues aux sujets qu’ils traitent, et comment ils ajustent leur stratégie au cours des projets et au fil des années. D’autre part, elle analyse par quels procédés cinématographiques, ils portent à l’écran leur aspiration à une société inclusive et plurielle. Enfin, elle suggère une ouverture sur l’avenir de ce cinéma documentaire, cible régulière des instances étatiques et des médias progouvernementaux. Organisée autour des thématiques récurrentes telles que les femmes, les personnes LGBTI+, les travailleurs, les bouleversements écologiques, les Arméniens et les Kurdes, cette thèse propose le portrait de la société de Turquie marquée par diverses tensions, conflits et crises mais aussi questionnements, oppositions, résistances et luttes

L'émergence et l'évolution du cinéma documentaire de résistance en Turquie (2003-2017)

The Emergence and Evolution of Documentary Cinema of Resistance in Turkey (2003-2017) focuses on a corpus consisting of documentaries made from the 2000s onwards. This collection of work stands out from the production of earlier decades by their independence, thematic and aesthetic diversity, and they explore social, political, and historical questions of the AKP period from the point of view of persons concerned. On one hand, based on the interviews with the filmmakers, this dissertation reveals the conditions in which this documentary cinema emancipate at the margins of the cinema industry. It examines how the filmmakers adjust to the economic, social, and political constraints due to the topics they treat, and how they adapt their strategies during the projects and over the years. On the other hand, it analyses the cinematographic language used by the filmmakers to bring up on the screen their aspiration for an inclusive and plural society. Lastly, it suggests an opening on the future of this documentary cinema which is the regular target of the state authorities and pro-government media. Structured around recurring topics such as women, LGBTI+ people, workers, ecological upheavals, Armenians, and Kurds, this dissertation provides a portrait of Turkey’s society marked, not only by various tensions, conflicts, and crises, but also questionings, oppositions, resistances, and struggles.La thèse, L’émergence et l’évolution du cinéma documentaire de résistance en Turquie (2003-2017), place au cœur de l’étude, un corpus hétérogène de documentaires réalisés à partir des années 2000, qui se démarquent de la production des décennies précédentes par leur indépendance, leur diversité thématique et esthétique, et qui abordent, du point de vue des personnes concernées, les questions sociétales, politiques et historiques de la période de l’AKP. D’une part, en s’appuyant sur les entretiens et échanges réalisés avec les cinéastes, cette thèse révèle les conditions dans lesquelles ce cinéma documentaire s’émancipe aux marges de l’industrie. Elle examine par quels moyens ces derniers s’adaptent aux contraintes économiques, sociales et politiques dues aux sujets qu’ils traitent, et comment ils ajustent leur stratégie au cours des projets et au fil des années. D’autre part, elle analyse par quels procédés cinématographiques, ils portent à l’écran leur aspiration à une société inclusive et plurielle. Enfin, elle suggère une ouverture sur l’avenir de ce cinéma documentaire, cible régulière des instances étatiques et des médias progouvernementaux. Organisée autour des thématiques récurrentes telles que les femmes, les personnes LGBTI+, les travailleurs, les bouleversements écologiques, les Arméniens et les Kurdes, cette thèse propose le portrait de la société de Turquie marquée par diverses tensions, conflits et crises mais aussi questionnements, oppositions, résistances et luttes