The perceptual and anti-Inflammatory effects of oleocanthal, an olive oil phenolic

 Oleocanthal a virgin olive oil phenolic produces varying intensities of irritation in the oropharanx in individuals and is also a naturally occuring NSAID effective in reducing inflammatory markers and increasing protein synthesis in skeletal muscle cells. There may be a link between the variation in throat sensitivity to oleocanthal and its effects on muscle growth processes and inflammation.

Youth Depression Alleviation-Augmentation with an anti-inflammatory agent (YoDA-A): protocol and rationale for a placebo-controlled randomized trial of rosuvastatin and aspirin

AIM: There is growing support for the role of inflammation and oxidative stress in the pathophysiology of major depressive disorder (MDD). This has led to the development of novel strategies targeting inflammation in the treatment of depression. Rosuvastatin and aspirin have well-documented, anti-inflammatory and antioxidant properties. The aim of the Youth Depression Alleviation: Augmentation with an anti-inflammatory agent (YoDA-A) study is to determine whether individuals receiving adjunctive anti-inflammatory agents, aspirin and rosuvastatin experience a reduction in the severity of MDD compared with individuals receiving placebo. METHODS: YoDA-A is a 12-week triple-blind, randomized controlled trial funded by the National Health and Medical Research Council, Australia. Participants aged 15-25, with moderate-to-severe MDD, are allocated to receive either 10 mg/day rosuvastatin, 100 mg/day aspirin, or placebo, in addition to treatment as usual. Participants are assessed at baseline and at weeks 4, 8, 12 and 26. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. RESULTS: The study is planned to be completed in 2017. At date of publication, 85 participants have been recruited. CONCLUSION: Timely and targeted intervention for youth MDD is crucial. Given the paucity of new agents to treat youth MDD, adjunctive trials are not only pragmatic and 'real-world', but additionally aim to target shortfalls in conventional medications. This study has the potential to first provide two new adjunctive treatment options for youth MDD; aspirin and rosuvastatin. Second, this study will serve as proof of principle of the role of inflammation in MDD.

Acute psychophysiological relationships between mood, inflammatory and cortisol changes in response to simulated physical firefighting work and sleep restriction

This study examined how changes in wildland firefighters' mood relate to cytokine and cortisol levels in response to simulated physical firefighting work and sleep restriction. Firefighters completed 3 days of simulated wildfire suppression work separated by an 8-h (control condition; n = 18) or 4-h sleep opportunity (sleep restriction condition; n = 17) each night. Firefighters' mood was assessed daily using the Mood Scale II and Samn-Perelli fatigue scale. Participants also provided samples for the determination of salivary cortisol and pro- (IL-6, IL-8, IL-1β, TNF-α) and anti-inflammatory (IL-4, IL-10) cytokine levels. An increase in the positive mood dimension Happiness was related to a rise in IL-8 and TNF-α in the sleep restriction condition. A rise in the positive mood dimension Activation among sleep restricted firefighters was also related to higher IL-6 levels. An increase in the negative mood dimension Fatigue in the sleep restriction condition was associated with increased IL-6, TNF-α, IL-10 and cortisol levels. In addition, an increase in Fear among sleep restricted firefighters was associated with a rise in TNF-α. Elevated positive mood and immune activation may reflect an appropriate response by the firefighters to these stressors. To further understand this relationship, subsequent firefighting-based research is needed that investigates whether immune changes are a function of affective arousal linked to the expression of positive moods. Positive associations between negative mood and inflammatory and cortisol levels to physical work and restricted sleep provide useful information to fire agencies about subjective fire-ground indicators of physiological changes.

Relationships between inflammatory cytokine and cortisol responses in firefighters exposed to simulated wildfire suppression work and sleep restriction

The interplay between inflammatory and cortisol responses modulates an appropriate response to a stressor. Exposure to severe stressors, however, may alter the actions and relationships of these responses and contribute to negative health outcomes. Physical work and sleep restriction are two stressors faced by wildland firefighters, yet their influence on the relationship between inflammatory and cortisol responses is unknown. The aim of the present study was to quantify the relationship between the cytokine and cortisol responses to sleep restriction while performing simulated physical wildfire suppression work. Firefighters completed 3 days of simulated physical firefighting work separated by either an 8-h (Control condition; n = 18) or 4-h sleep (Sleep restriction condition; n = 17) opportunity on each of the two nights. Salivary cortisol and inflammatory cytokines (IL-6, IL-8, IL-1β, TNF-α, IL-4, and IL-10) were measured throughout each day. An increase in morning IL-6 was related to a rise (6.2%, P = 0.043) in evening cortisol among firefighters in the sleep restriction condition. Higher morning IL-6 levels were related to increased (5.3%, P = 0.048) daily cortisol levels, but this relationship was not different between conditions. Less pronounced relationships were demonstrated between TNF-α, IL-10, IL-4, and cortisol independent of the sleep opportunity, but relationships did not persist after adjusting for demographic factors and other cytokines. These findings quantify the relationship between cytokine and cortisol responses among wildland firefighters exposed to simulated occupational stressors. Potential disturbances to the IL-6 and cortisol relationship among sleep-restricted firefighters' supports further investigations into the negative health effects related to possible imbalances between these systems.

Pro-inflammatory dietary intake as a risk factor for CVD in men: a 5-year longitudinal study

Convincing evidence has identified inflammation as an initiator of atherosclerosis, underpinning CVD. We investigated (i) whether dietary inflammation, as measured by the 'dietary inflammatory index (DII)', was predictive of 5-year CVD in men and (ii) its predictive ability compared with that of SFA intake alone. The sample consisted of 1363 men enrolled in the Geelong Osteoporosis Study who completed an FFQ at baseline (2001-2006) (excluding participants who were identified as having previous CVD). DII scores were computed from participants' reported intakes of carbohydrate, micronutrients and glycaemic load. DII scores were dichotomised into a pro-inflammatory diet (positive values) or an anti-inflammatory diet (negative values). The primary outcome was a formal diagnosis of CVD resulting in hospitalisation over the 5-year study period. In total, seventy-six events were observed during the 5-year follow-up period. Men with a pro-inflammatory diet at baseline were twice as likely to experience a CVD event over the study period (OR 2·07; 95 % CI 1·20, 3·55). This association held following adjustment for traditional CVD risk factors and total energy intake (adjusted OR 2·00; 95 % CI 1·03, 3·96). This effect appeared to be stronger with the inclusion of an age-by-DII score interaction. In contrast, SFA intake alone did not predict 5-year CVD events after adjustment for covariates (adjusted OR 1·40; 95 % CI 0·73, 2·70). We conclude that an association exists between a pro-inflammatory diet and CVD in Australian men. CVD clinical guidelines and public health recommendations may have to expand to include dietary patterns in the context of vascular inflammation.

The Glutathione System: a new drug target in neuroimmune disorders

Glutathione (GSH) has a crucial role in cellular signaling and antioxidant defenses either by reacting directly with reactive oxygen or nitrogen species or by acting as an essential cofactor for GSH S-transferases and glutathione peroxidases. GSH acting in concert with its dependent enzymes, known as the glutathione system, is responsible for the detoxification of reactive oxygen and nitrogen species (ROS/RNS) and electrophiles produced by xenobiotics. Adequate levels of GSH are essential for the optimal functioning of the immune system in general and T cell activation and differentiation in particular. GSH is a ubiquitous regulator of the cell cycle per se. GSH also has crucial functions in the brain as an antioxidant, neuromodulator, neurotransmitter, and enabler of neuron survival. Depletion of GSH leads to exacerbation of damage by oxidative and nitrosative stress; hypernitrosylation; increased levels of proinflammatory mediators and inflammatory potential; dysfunctions of intracellular signaling networks, e.g., p53, nuclear factor-κB, and Janus kinases; decreased cell proliferation and DNA synthesis; inactivation of complex I of the electron transport chain; activation of cytochrome c and the apoptotic machinery; blockade of the methionine cycle; and compromised epigenetic regulation of gene expression. As such, GSH depletion has marked consequences for the homeostatic control of the immune system, oxidative and nitrosative stress (O&NS) pathways, regulation of energy production, and mitochondrial survival as well. GSH depletion and concomitant increase in O&NS and mitochondrial dysfunctions play a role in the pathophysiology of diverse neuroimmune disorders, including depression, myalgic encephalomyelitis/chronic fatigue syndrome and Parkinson’s disease, suggesting that depleted GSH is an integral part of these diseases. Therapeutical interventions that aim to increase GSH concentrations in vivo include N-acetyl cysteine; Nrf-2 activation via hyperbaric oxygen therapy; dimethyl fumarate; phytochemicals, including curcumin, resveratrol, and cinnamon; and folate supplementation.

Prevalence of mental health disorders in inflammatory bowel disease: an Australian outpatient cohort

BACKGROUND: This study aimed to characterize prevalence of anxiety and depressive conditions and uptake of mental health services in an Australian inflammatory bowel disease (IBD) outpatient setting.

METHODS: Eighty-one IBD patients (39 males, mean age 35 years) attending a tertiary hospital IBD outpatient clinic participated in this study. Disease severity was evaluated according to the Manitoba Index. Diagnosis of an anxiety or depressive condition was based upon the Mini-International Neuropsychiatric Interview and the Hospital Anxiety and Depression Scale.

RESULTS: Based on Hospital Anxiety and Depression Scale subscale scores >8 and meeting Mini-International Neuropsychiatric Interview criteria, 16 (19.8%) participants had at least one anxiety condition, while nine (11.1%) had a depressive disorder present. Active IBD status was associated with higher prevalence rates across all anxiety and depressive conditions. Generalized anxiety was the most common (12 participants, 14.8%) anxiety condition, and major depressive disorder (recurrent) was the most common depressive condition reported (five participants, 6.2%). Seventeen participants (21%) reported currently seeking help for mental health issues while 12.4% were identified has having at least one psychological condition but not seeking treatment.

CONCLUSION: We conclude that rates of anxiety and depression are high in this cohort, and that IBD-focused psychological services should be a key component of any holistic IBD service, especially for those identified as having active IBD.

PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications

Protein kinase R (PKR) has previously been suggested to mediate many of the deleterious consequences of a high-fat diet (HFD). However, previous studies have observed substantial phenotypic variability when examining the metabolic consequences of PKR deletion. Accordingly, herein, we have re-examined the role of PKR in the development of obesity and its associated metabolic complications in vivo as well as its putative lipid-sensing role in vitro. Here we show that the deletion of PKR does not affect HFD-induced obesity, hepatic steatosis or glucose metabolism, and only modestly affects adipose tissue inflammation. Treatment with the saturated fatty acid palmitate in vitro induced comparable levels of inflammation in WT and PKR KO macrophages, demonstrating that PKR is not necessary for the sensing of pro-inflammatory lipids. These results challenge the proposed role for PKR in obesity, its associated metabolic complications and its role in lipid-induced inflammation.

Assessing mediators between discrimination, health behaviours and physical health outcomes: a representative cross-sectional study

PURPOSE: Discrimination is a social determinant of health; however, the pathways linking discrimination to ill-health are under-researched. This study investigated the mediators through which discrimination affects health behaviours and physical health outcomes, as well as assessed whether sex moderated these mechanisms. METHODS: Data from a representative survey (n = 1023) of undergraduate students enrolled in a Brazilian university in 2012 were used. Structural equation models were applied to assess the following mediation mechanisms--(1) discrimination influences self-rated health and body mass index via anxiety/depression; (2) discrimination affects behaviours (alcohol consumption, problem drinking, smoking, fruit/vegetable consumption, and physical activity) through discomfort associated with discriminatory experiences. The potential of sex to act as an effect-modifying variable was also explored in each of the postulated pathways. RESULTS: The effect of discrimination on self-rated poor health was totally (100.0%) mediated by anxiety/depression, while body mass index was not correlated with discrimination. Self-reported discrimination was associated with some behaviours via discomfort. Particularly, discomfort partially mediated the positive association between discrimination, leisure time physical activity (43.3%), and fruit/vegetable consumption (52.2%). Sex modified the association between discrimination, discomfort and physical activity in that such mechanism (more discrimination → more discomfort → more physical activity) was statistically significant in the entire sample and among females, but not among males. CONCLUSIONS: This is one of the first studies to demonstrate that discrimination is associated with physical health outcomes and behaviours via distinct pathways. Future investigations should further explicate the mediational pathways between discrimination and key health outcomes.

Role of phospholipase A(2) and tyrosine kinase in Clostridium difficile toxin A-induced disruption of epithelial integrity, histologic inflammatory damage and intestinal secretion

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Evaluation of anti-inflammatory activity of derivatives from aerial parts of Baccharis uncinella

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Inhibition of Neurotoxic Secretory Phospholipases A(2) Enzymatic, Edematogenic, and Myotoxic Activities by Harpalycin 2, an Isoflavone Isolated from Harpalyce brasiliana Benth

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)