Role of oxidative stress in plasticity of Dendritic cells

Dendritic cells (DCs) are antigen presenting cells with an unique ability to induce primary immune responses. Different DCs subsets with an intrinsic capacity to polarise Tcells have been described: myeloid (Th1) and lymphoid (Th2). Plasticity is defined as DCs capacity to polarise T cells independent of the DCs origin. We investigated the potential role played by oxidants such as superoxide anion (·O2-), in the plasticity of DCs, measured by the induction of a specific DCs subset, cytokine release and antigen presentation. Furthermore, we are interested in the amplification of immune response analysed by the exosomes production after oxidative stress and LPS stimulation. Recently, we have demonstrated that exposure of cells to superoxide anions resulted in the activation of DC2 profile. To analyse the role of oxidative stress in DCs subsets, we used BDCA-1 and BDCA-2 antibodies, which identify myeloid and plasmacytoid DCs respectively. Freshly isolated monocytes have shown to be BDCA-1-, but BDCA-2+ populations. During 6 days culture up-regulation of BDCA-1, but a down-regulation of BDCA-2 were observed, giving a clear myeloid population. When DC were stimulated with superoxide anions or LPS, we have observed that both down regulate the expression of BDCA-1 when compared to immature DC. Antigen presentation was markedly altered according to the periodicity used, and antigens and oxidants exposures. Using DCs trapped in collagen "matrix" after LPS activation we were able to quantify DCs-exosomes (small membrane vesicles ~50-100 nm in diameter) by reconstruction pictures in three dimensions. Using double vital staining we have found that exosomes from activated DCs can fuse with the membrane of resting DCs. Understanding the capacity of DCs to integrate external signals we will be able to unravel and control Tcells-polarisation triggering a specific immune response or tolerance. We will be able also to understand the amplification role of DCs-exosomes in remote not yet activated DCs.

Building Evidence for Dementia Prevention

As was the case in 2010 when the National Institutes of Health issued a consensus statement on the prevention of Alzheimer’s and other dementias, there remains a lack of firm evidence for dementia prevention. Because of the difficulties in studying this phenomenon, no modifiable risk factors for dementia have been definitively established, and no pharmaceutical or nutritional supplements been proven to prevent Alzheimer’s disease or cognitive decline. However, longitudinal observational studies have identified several factors associated with dementia. A recent review article summarizes the current epidemiological evidence about Alzheimer’s and other dementias, and presents three ongoing large scale randomized control trials (RCTs) that focus on preventing dementia. The review argues that there is substantial evidence for many factors that, in combination, might reduce the risk of, or delay the onset of, dementia. Although no specific cure for dementia exists, and no specific pathway between risk factor and disease onset has been identified, several cardiovascular, stress, toxicity, and psychosocial variables have been repeatedly associated with dementia. Protective factors, such as high education, physical exercise, and not smoking cigarettes, have been identified as well. Intervention studies that account for these multiple factors may well identify strategies for preventing or delaying dementia. However, the protective effects and risk factors suggested by observational data have yet to be assessed in RCT research. The role of such factors in reducing or increasing the risk for dementia needs to be more specifically defined. Three ongoing RCT studies in Europe show promise in this area, as they target multiple risk and protective factors by promoting healthy lifestyle changes and medical treatment of vascular diseases. These are: FINGER, a Finnish trial involving 1,200 older adults at risk for dementia. This intervention features nutritional guidance, physical activity, cognitive and social engagement, and medical management of risk factors. Participants were involved in previous, intensive observational studies of vascular health and health behavior, so FINGER will provide a level of relevant information about its research subjects that is normally impossible for clinical RCTs to attain;MAPT, a multicenter study of 1,680 frail older adults in France. This study will compare the efficacy of omega-3 dietary supplementation with a multidomain training intervention that involves physical and cognitive training. The study will include follow-up assessments after five years;PreDIVA, a Dutch study of 3,534 community dwelling participants between 70 and 78 years old, recruited from primary care clinics. This study will compare standard medical care with a multicomponent vascular health intervention. The study will last for six years and measure both dementia and disability outcomes. These studies are an important step in dementia research, using earlier observational studies as the basis for rigorously assessed interventions. Although a cure for dementia has not been identified, this new research may identify preventive strategies against dementia. �� Source: Mangialasche F, Kivipelto M, et al. (2012). Dementia prevention: current epidemiological evidence and future perspective. Alzheimer’s Research and Therapy 4:6.

Moderate exercise blunts oxidative stress induced by normobaric hypoxic confinement

PURPOSE: Both acute hypoxia and physical exercise are known to increase oxidative stress. This randomized prospective trial investigated whether the addition of moderate exercise can alter oxidative stress induced by continuous hypoxic exposure. METHODS: Fourteen male participants were confined to 10-d continuous normobaric hypoxia (FIO2 = 0.139 +/- 0.003, PIO2 = 88.2 +/- 0.6 mm Hg, approximately 4000-m simulated altitude) either with (HCE, n = 8, two training sessions per day at 50% of hypoxic maximal aerobic power) or without exercise (HCS, n = 6). Plasma levels of oxidative stress markers (advanced oxidation protein products [AOPP], nitrotyrosine, and malondialdehyde), antioxidant markers (ferric-reducing antioxidant power, superoxide dismutase, glutathione peroxidase, and catalase), nitric oxide end-products, and erythropoietin were measured before the exposure (Pre), after the first 24 h of exposure (D1), after the exposure (Post) and after the 24-h reoxygenation (Post + 1). In addition, graded exercise test in hypoxia was performed before and after the protocol. RESULTS: Maximal aerobic power increased after the protocol in HCE only (+6.8%, P < 0.05). Compared with baseline, AOPP was higher at Post + 1 (+28%, P < 0.05) and nitrotyrosine at Post (+81%, P < 0.05) in HCS only. Superoxide dismutase (+30%, P < 0.05) and catalase (+53%, P < 0.05) increased at Post in HCE only. Higher levels of ferric-reducing antioxidant power (+41%, P < 0.05) at Post and lower levels of AOPP (-47%, P < 0.01) at Post + 1 were measured in HCE versus HCS. Glutathione peroxidase (+31%, P < 0.01) increased in both groups at Post + 1. Similar erythropoietin kinetics was noted in both groups with an increase at D1 (+143%, P < 0.01), a return to baseline at Post, and a decrease at Post + 1 (-56%, P < 0.05). CONCLUSIONS: These data provide evidence that 2 h of moderate daily exercise training can attenuate the oxidative stress induced by continuous hypoxic exposure.

Insufficient coping behavior under chronic stress and vulnerability to psychiatric disorders

Epidemiological data indicate that 75% of subjects with major psychiatric disorders have their onset in the age range of 17-24 years. An estimated 35-50% of college and university students drop out prematurely due to insufficient coping skills under chronic stress, while 85% of students receiving a psychiatric diagnosis withdraw from college/university prior to the completion of their education. In this study we aimed at developing standardized means for identifying students with insufficient coping skills under chronic stress and at risk for mental health problems. A sample of 1,217 college students from 3 different sites in the U.S. and Switzerland completed 2 self-report questionnaires: the Coping Strategies Inventory "COPE" and the Zurich Health Questionnaire "ZHQ" which assesses "regular exercises", "consumption behavior", "impaired physical health", "psychosomatic disturbances", and "impaired mental health". The data were subjected to structure analyses by means of a Neural Network approach. We found 2 highly stable and reproducible COPE scales that explained the observed inter-individual variation in coping behavior sufficiently well and in a socio-culturally independent way. The scales reflected basic coping behavior in terms of "activity-passivity" and "defeatism-resilience", and in the sense of stable, socio-culturally independent personality traits. Correlation analyses carried out for external validation revealed a close relationship between high scores on the defeatism scale and impaired physical and mental health. This underlined the role of insufficient coping behavior as a risk factor for physical and mental health problems. The combined COPE and ZHQ instruments appear to constitute powerful screening tools for insufficient coping skills under chronic stress and for risks of mental health problems.

Stress au travail et santé : situation chez les indépendants : synthèse et recommandations

Dans le cadre de l'activité professionnelle, des facteurs de stress d'ordre psychologique, social, et liés à l'organisation du travail, peuvent induire des réponses physiologiques et comportementales impliquées dans la survenue de pathologies comme les maladies cardiovasculaires, les troubles de la santé mentale et les troubles musculosquelettiques.Le Régime social des indépendants (RSI) a sollicité l'Inserm afin de disposer d'un bilan des connaissances sur le stress d'origine professionnelle chez les travailleurs indépendants et ses répercussions sur la santé.Regroupant à la fois des compétences en biologie, psychologie, sociologie et économie de la santé, cette expertise collective présente les modèles et les mécanismes explicatifs mettant en relation le stress au travail et les principales pathologies.Les stratégies de prévention individuelle et collective qui se développent dans le milieu des travailleurs salariés peuvent-elles être adaptées aux travailleurs indépendants ? [Ed.]

Individualiser la thérapie d'exposition pour le stress post-traumatique: le cas de Caroline

Dans la thérapie de l'état de stress post-traumatique chronique (PTSD), l'Exposition Prolongée (PE) à des stimuli associes à une expérience d'origine traumatique est considérée comme une méthode de traitement de pointe. Notre étude de cas, basée sur l'utilisation du manuel de Foa et Rothbaum (1998), concerne Caroline, une patiente adulte victime d'abus sexuels dans l'enfance, traitée en 40 séances, sur une durée d'une année. En complément, nous avons la technique de l'«Analyse des Plans» de Caspar (1995, 2007) pour la formulation de cas individualisée et la planification du traitement, selon le concept de Caspar de la Relation Thérapeutique Orientée sur les Motifs (MOTR). Le traitement a été très efficace, comme l'attestent les mesures quantitatives standardisées, les changements dans les schémas de comportements, ainsi que son compte rendu subjectif. Une analyse du processus thérapeutique illustre l'importance d'une combinaison de procédures basées sur un manuel avec des formulations et interventions de cas individuels. Le cas est discute dans le contexte de l'amélioration du traitement cognitivo-comportemental du PTSD.

Steps to deal with stress - A simple guide to stressing less and enjoying life more

The Steps to deal with stress booklet provides tips and practical advice on coping with stress in your life and covers recognizing stress, getting ready, coping better, learning from bad experiences and taking action now. Simple steps such as relaxation exercises and talking to someone can help you feel better and put you in a better frame of mind for dealing with your problems.

The cost-effectiveness and public health benefit of nalmefene added to psychosocial support for the reduction of alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels: a Markov model.

OBJECTIVES: To determine whether nalmefene combined with psychosocial support is cost-effective compared with psychosocial support alone for reducing alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels (DRLs) as defined by the WHO, and to evaluate the public health benefit of reducing harmful alcohol-attributable diseases, injuries and deaths. DESIGN: Decision modelling using Markov chains compared costs and effects over 5 years. SETTING: The analysis was from the perspective of the National Health Service (NHS) in England and Wales. PARTICIPANTS: The model considered the licensed population for nalmefene, specifically adults with both alcohol dependence and high/very high DRLs, who do not require immediate detoxification and who continue to have high/very high DRLs after initial assessment. DATA SOURCES: We modelled treatment effect using data from three clinical trials for nalmefene (ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941)). Baseline characteristics of the model population, treatment resource utilisation and utilities were from these trials. We estimated the number of alcohol-attributable events occurring at different levels of alcohol consumption based on published epidemiological risk-relation studies. Health-related costs were from UK sources. MAIN OUTCOME MEASURES: We measured incremental cost per quality-adjusted life year (QALY) gained and number of alcohol-attributable harmful events avoided. RESULTS: Nalmefene in combination with psychosocial support had an incremental cost-effectiveness ratio (ICER) of £5204 per QALY gained, and was therefore cost-effective at the £20,000 per QALY gained decision threshold. Sensitivity analyses showed that the conclusion was robust. Nalmefene plus psychosocial support led to the avoidance of 7179 alcohol-attributable diseases/injuries and 309 deaths per 100,000 patients compared to psychosocial support alone over the course of 5 years. CONCLUSIONS: Nalmefene can be seen as a cost-effective treatment for alcohol dependence, with substantial public health benefits. TRIAL REGISTRATION NUMBERS: This cost-effectiveness analysis was developed based on data from three randomised clinical trials: ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941).

Self-reported health needs and use of primary health care services by adolescents enrolled in post-mandatory schools or vocational training programmes in Switzerland.

BACKGROUND: The second Swiss Multicenter Adolescent Survey on Health (SMASH02) was conducted among a representative sample (n = 7428) of students and apprentices aged 16 to 20 from the three language areas of Switzerland during the year 2002. This paper reports on health needs expressed by adolescents and their use of health care services over the 12 months preceding the survey. METHODS: Nineteen cantons representing 80% of the resident population agreed to participate. A complex iterative random cluster sample of 600 classes was drawn with classes as primary sampling unit. The participation rate was 97.7% for the classes and 99.8% for the youths in attendance. The self-administered questionnaire included 565 items. The median rate of item non-response was 1.8%. Ethical and legal requirements applying to surveys of adolescent populations were respected. RESULTS: Overall more than 90% of adolescents felt in good to excellent health. Suffering often or very often from different physical complaints or pain was also reported such as headache (boys: 15.9%, girls: 37.4%), stomach-ache (boys: 9.7%, girls: 30.0%), joint pain (boys: 24.7%, girls: 29.5%) or back pain (boys: 24.3%, girls: 34.7%). Many adolescents reported a need for help on psychosocial and lifestyle issues, such as stress (boys: 28.5%, girls: 47.7%) or depression (boys: 18.9%, girls: 34.4%). Although about 75% of adolescents reported having consulted a general practitioner and about one-third having seen another specialist, reported reasons for visits do not correspond to the expressed needs. Less than 10% of adolescents had visited a psychiatrist, a family planning centre or a social worker. CONCLUSIONS: The reported rates of health services utilisation by adolescents does not match the substantial reported needs for help in various areas. This may indicate that the corresponding problems are not adequately detected and/or addressed by professionals from the health and social sectors.

Patients presenting with somatic complaints in general practice: depression, anxiety and somatoform disorders are frequent and associated with psychosocial stressors.

BACKGROUND: Mental disorders in primary care patients are frequently associated with physical complaints that can mask the disorder. There is insufficient knowledge concerning the role of anxiety, depression, and somatoform disorders in patients presenting with physical symptoms. Our primary objective was to determine the prevalence of depression, anxiety, and somatoform disorders among primary care patients with a physical complaint. We also investigated the relationship between cumulated psychosocial stressors and mental disorders. METHODS: We conducted a multicentre cross-sectional study in twenty-one private practices and in one academic primary care centre in Western Switzerland. Randomly selected patients presenting with a spontaneous physical complaint were asked to complete the self-administered Patient Health Questionnaire (PHQ) between November 2004 and July 2005. The validated French version of the PHQ allowed the diagnosis of mental disorders (DSM-IV criteria) and the analyses of exposure to psychosocial stressors. RESULTS: There were 917 patients exhibiting at least one physical symptom included. The rate of depression, anxiety, and somatoform disorders was 20.0% (95% confidence interval [CI] = 17.4% to 22.7%), 15.5% (95% CI = 13.2% to 18.0%), and 15.1% (95% CI = 12.8% to 17.5%), respectively. Psychosocial stressors were significantly associated with mental disorders. Patients with an accumulation of psychosocial stressors were more likely to present anxiety, depression, or somatoform disorders, with an increase of 2.2 fold (95% CI = 2.0 to 2.5) for each additional stressor. CONCLUSIONS: The investigation of mental disorders and psychosocial stressors among patients with physical complaints is relevant in primary care. Psychosocial stressors should be explored as potential epidemiological causes of mental disorders.

Stress et satisfaction au travail des cadres intermédiaires dans les hôpitaux de Suisse romande dans un contexte de réformes

L'article vise à identifier les déterminants du stress et de la satisfaction au travail parmi une population de cadres intermédiaires exerçant dans des établissements hospitaliers de Suisse romande. Il vise également à combler un vide dans les études sur les administrations publiques suisses: mieux saisir, au moyen d'une enquête par questionnaires, quels sont les principales variables qui se trouvent à l'origine de la satisfaction au travail et qui peuvent être des ressources pour les acteurs afin de faire face au stress. L'étude confirme des résultats de recherches internationales, montrant que des facteurs relationnels et des caractéristiques du travail sont les principaux déterminants du stress et de la satisfaction. Elle souligne dès lors l'importance d'adopter une lecture « structurelle » et « organisationnelle » du stress et de la satisfaction, soulignant aussi que les caractéristiques individuelles de la population étudiée n'expliquent qu'une très infime variance de ces phénomènes.

The role of platelet and plasma markers of antioxidant status and oxidative stress in thrombocytopenia among patients with vivax malaria

Malaria remains an important health problem in tropical countries like Brazil. Thrombocytopenia is the most common hematological disturbance seen in malarial infection. Oxidative stress (OS) has been implicated as a possible mediator of thrombocytopenia in patients with malaria. This study aimed to investigate the role of OS in the thrombocytopenia of Plasmodium vivax malaria through the measurement of oxidant and antioxidant biochemical markers in plasma and in isolated platelets. Eighty-six patients with P. vivax malaria were enrolled. Blood samples were analyzed for total antioxidant and oxidant status, albumin, total protein, uric acid, zinc, magnesium, bilirubin, total thiols, glutathione peroxidase (GPx), malondialdehyde (MDA), antibodies against mildly oxidized low-density lipoproteins (LDL-/nLDL ratio) and nitrite/nitrate levels in blood plasma and GPx and MDA in isolated platelets. Plasma MDA levels were higher in thrombocytopenic (TCP) (median 3.47; range 1.55-12.90 µmol/L) compared with the non-thrombocytopenic (NTCP) patients (median 2.57; range 1.95-8.60 µmol/L). Moreover, the LDL-/nLDL autoantibody ratio was lower in TCP (median 3.0; range 1.5-14.8) than in NTCP patients (median 4.0; range 1.9-35.5). Finally, GPx and MDA were higher in the platelets of TPC patients. These results suggest that oxidative damage of platelets might be important in the pathogenesis of thrombocytopenia found in P. vivax malaria as indicated by alterations of GPx and MDA.

Trypanosoma cruzi: a stage-specific calpain-like protein is induced after various kinds of stress

Calpains are calcium-dependent cysteine proteinases found in all living organisms and are involved in diverse cellular processes. Calpain-like proteins have been reported after in silico analysis of the Tritryps genome and are believed to play important roles in cell functions of trypanosomatids. We describe the characterization of a member of this family, which is differentially expressed during the life-cycle of Trypanosoma cruzi.