Effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system in individuals at ultra-high risk of psychosis

BACKGROUND: Oxidative stress and impaired antioxidant defenses are reported in schizophrenia and are associated with disturbed neurodevelopment, brain structural alterations, glutamatergic imbalance, increased negative symptoms, and cognitive impairment. There is evidence that oxidative stress predates the onset of acute psychotic illness. Here, we investigate the effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system (AODS). METHOD: In 64 help-seeking UHR-individuals (13-25 years of age), vitamin E levels and glutathione were investigated before and after 12 weeks of treatment with either 1.2g/d omega-3 (PUFA-E) or saturated fatty acids (SFA-E), with each condition also containing 30.4mg/d alpha-tocopherol to ensure absorption without additional oxidative risk. RESULTS: In multivariate tests, the effects on the AODS (alpha-tocopherol, total glutathione) were not significantly different (p=0.13, p=0.11, respectively) between treatment conditions. According to univariate findings, only PUFA-E caused a significant alpha-tocopherol increase, while PUFA-E and SFA-E caused a significant gamma- and delta-tocopherol decrease. Total glutathione (GSHt) was decreased by PUFA-E supplementation. CONCLUSION: Effects of the PUFA-E condition on the vitamin E and glutathione AODS could be mechanisms underlying its clinical effectiveness. In terms of the vitamin E protection system, PUFA-E seems to directly support the antioxidative defense at membrane level. The effect of PUFA-E on GSHt is not yet fully understood, but could reflect antioxidative effects, resulting in decreased demand for glutathione. It is still necessary to further clarify which type of PUFA/antioxidant combination, and in which dose, is effective at each stage of psychotic illness.

Antioxidant defense system and family environment in adolescents with family history of psychosis

[EN] Our objective was to determine antioxidant defence activity in healthy controls (HC) and healthy unaffected second-degree relatives of patients with early onset psychosis (HC-FHP),and to assess its relationship with familiar environment measured using the Family Environment Scale (FES). Methods: We included 82 HC and 14 HC-FHP aged between 9 and 17 years. Total antioxidant status,lipid peroxidation, antioxidant enzyme activities and glutathione levels were determined in blood samples. Results:There was a significant decrease in the total antioxidant level in the HC-FHP group compared with the HC group (OR = 2.94; p = 0.009), but no between-group differences in the Global Assessment of Functioning (GAF) scale scores. For the FES, the HC-FHP group had significantly higher scores in the cohesion (p = 0.007) and intellectual-cultural dimensions (p=0.025). After adjusting for these two FES dimensions, total antioxidant status remained significantly different between groups (OR = 10.86, p = 0.009).

Cellular and humoral factors involved in defense mechanisms of Fenneropenaeus indicus (H. Milne Edwards, 1837)

The present investigation revealed three types of circulating haemocytes in the haemolymph of F. indicus: hyalinocytes, small-granule haemocytes, and large-granule haemocytes. Intermediate stages indicate the maturing process of a single cell. The presence of enzymes such as peroxidase, phenoloxidase and acid phosphatase in the haemocytes, and the substantial production of oxygen radicals during phagocytosis show that the haemocytes are capable of mounting a fme cellular defense mechanism. The enzyme activities of the serum and the presence of agglutinins in the serum, which may act as opsonins, agglutinate foreign particles and augment phagocytosis, confirm the presence of a superior humoral immune system in F. indicus.Bacterial infection caused considerable variations in the cellular and humoral factors, such as the number of circulating cells and haemagglutinating activity, especially in the initial hours of infection. The total haemocyte count, haemagglutination titer and phenoloxidase enzyme showed significant reductions on bacterial presence and could be used as indicators of bacterial infection.The number of circulating cells showed drastic fluctuation on exposure to pollutants. Nuvan at low concentrations was able to produce changes in the haemolymph factors and in the tissue organization, which implies that the animal is under stress and is easily prone to infections. Exposure to nuvan resulted in significant variation in all of the cellular and humoral factors, especially, the total haemocyte count, percentage of small granule haemocytes, phagocytic activity and the haemagglutinating activity, which might be good indicators of pesticide pollution. Heavy metal exposure caused significant increase in total haemocyte count and reduction in phenoloxidase enzyme activity Even changes in the physio-chemical parameters, such as salinity caused fluctuations in the defense factors, indicating stress in this euryhaline species. The dietary incorporation of a commercial immunostimulant containing P-l,3 glucan resulted in stimulation of some of the humoral defense factors of F indicus, but was time dependent. The modulations, on exposure to various external factors, in the cellular and humoral factors, especially, total haemocyte count, phagocytic activity, haemagglutinating activity and the phenoloxidase and acid phosphatase enzymes suggest that these parameters could be used as indicators of the health status of F indicus, which assist in better monitoring and effective health management of this important cultured species.

A Psychoanalytical Reading of Emily Brontë's Wuthering Heights : An Analysis of the Defense Mechanisms of Some Characters

This essay presents a portrayal of Heathcliff, Catherine and Isabella from a psychoanalytical perspective with regard to four defense mechanisms; namely, repression, denial, sublimation and projection in order to see how these defense mechanisms have affected the characters’ decisions and behaviour, and led them to their destinations in life. It will include three major sections: repression in characters, denial in characters, and sublimation and projection in characters. These terms will be more clearly defined and explained in the subsequent sections.

Brief report : The defense mechanisms of homophobic adolescent males : a descriptive discriminant analysis

The study examined the role of defense mechanisms in homophobic attitudes of older male adolescents aged 17e18 years. A cross-sectional survey collected data from final year high school students (N ¼ 86) attending an all male school in a regional centre in Victoria, Australia. The school was identified by teachers as having a problematic culture of homophobic intolerance. Participants were divided into homophobic and non-homophobic groups based on their scores on the Homophobia Scale Questionnaire. Discriminant analysis was conducted to identify the predictors that would best categorise students into those two groups on the basis of defense styles derived from the Defense Style Questionnaire-40 (DSQ-40). The strongest predictors of homophobia amongst defense styles were idealisation, denial, somatisation and devaluation accounting for 18.31%, 17.64%, 13.10% and 11.35% of the variance, respectively. Results generally supported the larger contribution of more immature defenses to higher levels of homophobia.

Intramuscular heat shock protein 72 and heme oxygenase-1 mRNA are reduced in patients with type 2 diabetes: evidence that insulin resistance is associated with a disturbed antioxidant defense mechanism

To examine whether genes associated with cellular defense against oxidative stress are associated with insulin sensitivity, patients with type 2 diabetes (n = 7) and age-matched (n = 5) and young (n = 9) control subjects underwent a euglycemic-hyperinsulinemic clamp for 120 min. Muscle samples were obtained before and after the clamp and analyzed for heat shock protein (HSP)72 and heme oxygenase (HO)-1 mRNA, intramuscular triglyceride content, and the maximal activities of β-hyroxyacyl-CoA dehydrogenase (β-HAD) and citrate synthase (CS). Basal expression of both HSP72 and HO-1 mRNA were lower (P < 0.05) by 33 and 55%, respectively, when comparing diabetic patients with age-matched and young control subjects, with no differences between the latter groups. Both basal HSP72 (r = 0.75, P < 0.001) and HO-1 (r = 0.50, P < 0.05) mRNA expression correlated with the glucose infusion rate during the clamp. Significant correlations were also observed between HSP72 mRNA and both β-HAD (r = 0.61, P < 0.01) and CS (r = 0.65, P < 0.01). HSP72 mRNA was induced (P < 0.05) by the clamp in all groups. Although HO-1 mRNA was unaffected by the clamp in both the young and age-matched control subjects, it was increased (P < 0.05) ∼70-fold in the diabetic patients after the clamp. These data demonstrate that genes involved in providing cellular protection against oxidative stress are defective in patients with type 2 diabetes and correlate with insulin-stimulated glucose disposal and markers of muscle oxidative capacity. The data provide new evidence that the pathogenesis of type 2 diabetes involves perturbations to the antioxidant defense mechanism within skeletal muscle.

Antioxidant defense in rat brain regions after developmental lead exposure

Oxidative stress is considered a possible molecular mechanism involved in Pb neurotoxicity. Considering the vulnerability of the developing brain to Pb neurotoxicity, this study was carried out to investigate the effects of low-level developmental Pb exposure on brain regions antioxidant enzymes activities. Wister dams were exposed to 500 ppm of Pb, as Pb acetate, or to 660 ppm Na acetate in the drinking water during pregnancy and lactation. The activities of superoxide dismutase (SOD), glutathione peroxidase and glutathione reductase were determined in the hypothalamus, hippocampus and striatum of male pups at 23 (weaned) or 70 days (adult) of age. In the Pb-exposed 23-day-old pups, the activity of SOD was decreased in the hypothalamus. Regarding adults, there was no significant treatment effect in any of the enzymes and regions evaluated. Based on the present results, it seems that oxidative stress due to decreased antioxidant function may occur in weaned rats but it is suggested that this should not be the main mechanism involved in the neurotoxicity of low-level Pb exposure. (C) 2001 Elsevier B.V. Ireland Ltd. All rights reserved.

SET protein accumulates in HNSCC and contributes to cell survival: Antioxidant defense, Akt phosphorylation and AVOs acidification

Objectives: Determination of the SET protein levels in head and neck squamous cell carcinoma (HNSCC) tissue samples and the SET role in cell survival and response to oxidative stress in HNSCC cell lineages. Materials and Methods: SET protein was analyzed in 372 HNSCC tissue samples by immunohistochemistry using tissue microarray and HNSCC cell lineages. Oxidative stress was induced with the pro-oxidant tert-butylhydroperoxide (50 and 250 mu M) in the HNSCC HN13 cell lineage either with (siSET) or without (siNC) SET knockdown. Cell viability was evaluated by trypan blue exclusion and annexin V/propidium iodide assays. It was assessed caspase-3 and -9, PARP-1, DNA fragmentation, NM23-H1, SET, Akt and phosphorylated Akt (p-Akt) status. Acidic vesicular organelles (AVOs) were assessed by the acridine orange assay. Glutathione levels and transcripts of antioxidant genes were assayed by fluorometry and real time PCR, respectively. Results: SET levels were up-regulated in 97% tumor tissue samples and in HNSCC cell lineages. SiSET in HN13 cells (i) promoted cell death but did not induced caspases, PARP-1 cleavage or DNA fragmentation, and (ii) decreased resistance to death induced by oxidative stress, indicating SET involvement through caspase-independent mechanism. The red fluorescence induced by siSET in HN13 cells in the acridine orange assay suggests SET-dependent prevention of AVOs acidification. NM23-H1 protein was restricted to the cytoplasm of siSET/siNC HN13 cells under oxidative stress, in association with decrease of cleaved SET levels. In the presence of oxidative stress, siNC HN13 cells showed lower GSH antioxidant defense (GSH/GSSG ratio) but higher expression of the antioxidant genes PRDX6, SOD2 and TXN compared to siSET HN13 cells. Still under oxidative stress, p-Akt levels were increased in siNC HN13 cells but not in siSET HN13, indicating its involvement in HN13 cell survival. Similar results for the main SET effects were observed in HN12 and CAL 27 cell lineages, except that HN13 cells were more resistant to death. Conclusion: SET is potential (i) marker for HNSCC associated with cancer cell resistance and (ii) new target in cancer therapy. (C) 2012 Elsevier Ltd. All rights reserved.

Roles of social pain and defense mechanisms in response to social exclusion: Reply to Panksepp (2005) and Coff (2005)

In comments on G. MacDonald and M. R. Leary (2005), J. Panksepp (2005) argued for more emphasis on social pain mechanisms, whereas P. J. Corr (2005) argued for more emphasis on physical defense mechanisms. In response to the former, the authors clarify their positions on the topics of anger, the usefulness of rat models, the role of analgesic mechanisms, and basic motivational processes. In response to the latter, the authors clarify their positions on the topics of the relation of social exclusion to fear, the value of the pain affect construct, and the nature of the social pain experience. The authors conclude that consideration of the roles of both social pain and defense mechanisms is essential to best understand human response to social exclusion.

Role of mitochondrial antioxidant defense systems in fatty acid β-oxidation defects

Mitochondrial fatty acid oxidation (FAO) plays a pivotal role in energy homeostasis, namely during periods of fasting or metabolic stress. FAO defects are a group of inherited metabolic disorders that encompass at least twelve distinct enzyme or transporter deficiencies, and can present with a wide range of clinical symptoms with various degrees of severity. Besides recent advances, many doubts still remain on the degree and characteristics of mitochondrial dysfunction on FAOD and its contribution to the clinical phenotype.