NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder of uncertain pathogenesis characterized by a loss of substantia nigra pars compacta (SNpc) dopaminergic (DA) neurons, and can be modeled by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Both inflammatory processes and oxidative stress may contribute to MPTP- and PD-related neurodegeneration. However, whether inflammation may cause oxidative damage in MPTP and PD is unknown. Here we show that NADPH-oxidase, the main reactive oxygen species (ROS)-producing enzyme during inflammation, is up-regulated in SNpc of human PD and MPTP mice. These changes coincide with the local production of ROS, microglial activation, and DA neuronal loss seen after MPTP injections. Mutant mice defective in NADPH-oxidase exhibit less SNpc DA neuronal loss and protein oxidation than their WT littermates after MPTP injections. We show that extracellular ROS are a main determinant in inflammation-mediated DA neurotoxicity in the MPTP model of PD. This study supports a critical role for NADPH-oxidase in the pathogenesis of PD and suggests that targeting this enzyme or enhancing extracellular antioxidants may provide novel therapies for PD.     

Relationship of lipid oxidation with subclinical atherosclerosis and 10-year coronary events in general population

Objectives

To assess 1) the association of lipid oxidation biomarkers with 10-year coronary artery disease (CAD) events and subclinical atherosclerosis, and 2) the reclassification capacity of these biomarkers over Framingham-derived CAD risk functions, in a general population.

Methods

Within the framework of the REGICOR study, 4782 individuals aged between 25 and 74 years were recruited in a population-based cohort study. Follow-up of the 4042 who met the eligibility criteria was carried out. Plasma, circulating oxidized low-density lipoprotein (oxLDL) and oxLDL antibodies (OLAB) were measured in a random sample of 2793 participants.End-points included fatal and non-fatal acute myocardial infarction (AMI) and angina. Carotid intima-media thickness (IMT) in the highest quintile and ankle-brachial index <0.9 were considered indicators of subclinical atherosclerosis.

Results

Mean age was 50.0 (13.4) years, and 52.4% were women. There were 103 CAD events (34 myocardial infarction, 43 angina, 26 coronary deaths), and 306 subclinical atherosclerosis cases. Oxidized LDL was independently associated with higher incidence of CAD events (HR = 1.70; 95% Confidence Interval: 1.02–2.84), but not with subclinical atherosclerosis. The net classification index of the Framingham-derived CAD risk function was significantly improved when ox-LDL was included (NRI = 14.67% [4.90; 24.45], P = 0.003). No associations were found between OLAB and clinical or subclinical events. The reference values for oxLDL and OLAB are also provided (percentiles).

Conclusions

OxLDL was independently associated with 10-year CAD events but not subclinical atherosclerosis in a general population, and improved the reclassification capacity of Framingham-derived CAD risk functions.     

Experiencia de colaboración entre atención primaria y salud mental en el Departamento de Salud La Ribera, 7 años después

Despite the high prevalence of mental health problems among patients attending primary care, diagnosis and treatment of these disorders remain inadequate. Sound training of primary care physicians in how to manage mental health problems is needed to reduce the health, economic and social impact associated with these disorders. Among other elements, there is a need for cooperation between primary care physicians and mental health services. Distinct models are available for such collaboration. In 2006, our health department started a collaboration between these two levels of heath care, using a liaison model. Delays until the first specialist visit were reduced and satisfaction among health professionals increased, although these results should be interpreted with caution. Evidence has recently accumulated on the usefulness of the collaborative model, but evaluation of this model and extrapolation of its results are complex. We intend to evaluate our model more thoroughly, similar to other projects in our environment.     

Chronic fatigue syndrome and personality: A case-control study using the alternative five factor model

Neuroticism is the personality dimension most frequently associated with chronic fatigue syndrome (CFS). Most studies have also shown that CFS patients are less extraverted than non-CFS patients, but results have been inconsistent, possibly because the facets of the extraversion dimension have not been separately analyzed. This study has the following aims: to assess the personality profile of adults with CFS using the Alternative Five-Factor Model (AFFM), which considers Activity and Sociability as two separate factors of Extraversion, and to test the discriminant validity of a measure of the AFFM, the Zuckerman–Kuhlman Personality Questionnaire, in differentiating CFS subjects from normal-range matched controls. The CFS sample consisted of 132 consecutive patients referred for persistent fatigue or pain to the Department of Medicine of a university hospital. These were compared with 132 matched normal population controls. Significantly lower levels of Activity and significantly higher levels of Neuroticism-Anxiety best discriminated CFS patients from controls. The results are consistent with existing data on the relationship between Neuroticism and CFS, and clarify the relationship between Extraversion and CFS by providing new data on the relationship of Activity to CFS.     

The Spanish version of the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) is valid for use in the general population

Purpose

Mental well-being has aroused interest in Europe as an indicator of population health. The Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) was developed in the United Kingdom showing good face validity and has been previously adapted into Spanish. The aim of this study is to assess the validity and reliability of the Spanish version of WEMWBS in the general population.

Methods

Cross-sectional home face-to-face interview survey with computer-assisted personal interviewing was administered with the 2011 Catalan Health Interview Survey Wave 3, which is representative of the non-institutionalized general population of Catalonia, Spain. A total of 1,900 participants 15+ years of age were interviewed. The Spanish version of WEMWBS was administered together with socioeconomic and health-related variables, with a hypothesized level of association.

Results

Similar to the original, confirmatory factor analysis fits a one-factor model adequately (CFI = 0.974; TLI = 0.970; RMSEA = 0.059; χ ² = 584.82; df = 77; p < .001) and has a high internal consistency (Cronbach’s alpha = 0.930; Guttman’s lambda 2 = 0.932). The WEMWBS discriminated between population groups in all health-related and socioeconomic variables, except in gender (p = 0.119), with a magnitude similar to that hypothesized. Overall, mental well-being was higher for the general population of Catalonia (average and whole distribution) than that for Scotland general population.

Conclusions

The Spanish version of WEMWBS showed good psychometric properties similar to the UK original scale. Whether better mental well-being in Catalonia is due to methodological or substantive cultural, social, or environmental factors should be further researched.     

Total mercury and selenium concentrations in Sarpa salpa and Balistes capriscus and in their respective Digenean endoparasites Robphildollfusium fractum and Neoapocreadium chabaudi from Tunisia

The present study reports the levels of mercury and selenium in Sarpa salpa and Balistes capriscus collected along the coast of Mahdia and Sfax (Tunisia). The systems constituted by S. salpa and Robphildollfusium fractum and by B. capriscus and Neoapocreadium chabaudi were tested as potential bioindicators to monitor environmental Hg pollution in marine ecosystems. Mercury and selenium concentrations were assessed in kidney, liver and muscle of 51 S. salpa and of 45 B. capriscus as well as in their respective endoparasites R. fractum and N. chabaudi. The Se:Hg molar ratios were evaluated for both species across the study areas. Surprisingly, the Se:Hg molar ratio in B. capriscus muscle from Mahdia is significantly lower than in Sfax. Our results indicate that some parasites may also be implicated in the amount of Se and Hg available in tissues and therefore contribute to oscillations of the Se:Hg molar ratios. In the model involving the carnivorous species (B. capriscus), the 5.1-times higher levels of mercury in N. chabaudi than in B. capriscus muscle in Sfax enable this fluke to be a sensitive biomonitoring tool for Hg pollution. The present results confirm that the habitual consumption of S. salpa should not suppose any potential health risk for Tunisian people. On the other hand, the consumption of B. capriscus may be of concern and further monitoring is advisable, since the Hg average concentration in Mahdia was above the maximum allowed Hg concentration in the edible portion of fish fixed by the European Union.