Interactive effects of venlafaxine and thermal stress on zebrafish (Danio rerio) inflammatory and heat shock responses.

Venlafaxine (VFX), a commonly prescribed antidepressant often detected in wastewater effluent, and acute temperature elevations from climate change and increased urbanization, are two environmental stressors currently placing freshwater ecosystems at risk. This study focused on understanding if exposure to VFX impacts the agitation temperature (Tag) and critical thermal maximum (CTmax) of zebrafish (Danio rerio). Additionally, we examined the interactive effects of VFX and acute thermal stress on zebrafish heat shock and inflammatory immune responses. A 96 h 1.0 µg/L VFX exposure experiment was conducted, followed by assessment of thermal tolerance via CTmax challenge. Heat shock proteins and pro-inflammatory immune cytokines were quantified through gene expression analysis by quantitative PCR (qPCR) on hsp 70, hsp 90, hsp 47, il-8, tnfα, and il-1ß within gill and liver tissue. No significant changes in agitation temperature between control and exposed fish were observed, nor were there any differences in CTmax based on treatment. Unsurprisingly, hsp 47, 70, and 90 were all upregulated in groups exposed solely to CTmax, while only hsp 47 within gill tissue showed signs of interactive effects, which was significantly decreased in fish exposed to both VFX and CTmax. No induction of an inflammatory response occurred. This study demonstrated that environmentally relevant concentrations of VFX have no impact on thermal tolerance performance in zebrafish. However, VFX can cause diminished function of protective heat shock mechanisms, which could be detrimental to freshwater fish populations and aquatic ecosystems as temperature spikes become more frequent from climate change and urbanization near watersheds.

Regulation of energy metabolism during social interactions in rainbow trout: a role for AMP-activated protein kinase.

Rainbow trout (Oncorhynchus mykiss) confined in pairs form social hierarchies in which subordinate fish typically experience fasting and high circulating cortisol levels, resulting in low growth rates. The present study investigated the role of AMP-activated protein kinase (AMPK) in mediating metabolic adjustments associated with social status in rainbow trout. After 3 days of social interaction, liver AMPK activity was significantly higher in subordinate than dominant or sham (fish handled in the same fashion as paired fish but held individually) trout. Elevated liver AMPK activity in subordinate fish likely reflected a significantly higher ratio of phosphorylated AMPK (phospho-AMPK) to total AMPK protein, which was accompanied by significantly higher AMPKα1 relative mRNA abundance. Liver ATP and creatine phosphate concentrations in subordinate fish also were elevated, perhaps as a result of AMPK activity. Sham fish that were fasted for 3 days exhibited effects parallel to those of subordinate fish, suggesting that low food intake was an important trigger of elevated AMPK activity in subordinate fish. Effects on white muscle appeared to be influenced by the physical activity associated with social interaction. Overall, muscle AMPK activity was significantly higher in dominant and subordinate than sham fish. The ratio of phospho-AMPK to total AMPK protein in muscle was highest in subordinate fish, while muscle AMPKα1 relative mRNA abundance was elevated by social dominance. Muscle ATP and creatine phosphate concentrations were high in dominant and subordinate fish at 6 h of interaction and decreased significantly thereafter. Collectively, the findings of the present study support a role for AMPK in mediating liver and white muscle metabolic adjustments associated with social hierarchy formation in rainbow trout.

Can primary care reduce inequalities in mental health?

OBJECTIVES: To explore the contributions that primary care could make to reducing and preventing inequalities in mental health through policy, local strategy and practice. STUDY DESIGN: The study used an interpretive policy analysis framework to investigate the ways in which inequalities in mental health and inequalities in health were interpreted by health and social policies, incorporated into a local strategic process in a primary care organization, and understood and acted upon by frontline primary care and mental health practitioners. The study involved analysis of nine health and social policy documents, observation of a mental health needs assessment process, and interviews with 21 frontline professionals from 14 different disciplines. METHODS: Data were collected using document analysis, observation, and interviews with frontline staff which included a vignette. Data were sorted using the Atlas-ti software programme, and a grounded theory approach guided the data collection and analysis. RESULTS: Policy documents demonstrated a disjointed picture of definitions and actions, and lacked a clear overall interpretation of inequalities in health or inequalities in mental health. The mental health needs assessment did not incorporate discussion about inequalities in mental health, despite some individual steering group members demonstrating concerns about inequalities in mental health. Frontline professionals defined inequalities as being linked to access to health services rather than social factors, and were often uncomfortable about discussing inequalities in mental health. A small minority suggested that they would explore or take action on the social circumstances of a patient presenting with potential mental health problems. CONCLUSIONS: The study found that policies were not driving practice for reducing inequalities in mental health within primary care, and the primary care organization studied was not conducive to addressing inequalities in mental health. However, some building blocks were in place at all levels that have the potential to be developed to enable primary care to address inequalities in mental health.

Helicobacter pylori secretes a chemotactic factor for monocytes and neutrophils.

Helicobacter pylori is associated with an inflammatory reaction in the stomach and duodenum, yet the mechanism of this inflammatory infiltrate is unknown. The ability of Helicobacter pylori to secrete a factor that attracts leucocytes is investigated. Helicobacter pylori conditioned supernatant attracted neutrophils and monocytes with 50-100% of the activity of control chemotactic factor, 10(-8) M formyl-methionine-leucine-phenylalanine. Strains derived from individuals with ulcer or non-ulcer associated H pylori infections displayed similar chemotactic activity. Preliminary characterisation shows that the factor has a molecular weight of less than 3000, is heat stable, is acid resistant, and can be diluted at least 10-fold. Checkerboard analysis confirmed that the activity was chemotactic rather than chemokinetic. This chemotactic activity could play a role in the pathogenesis of Helicobacter pylori gastritis.