Pesticide-related illness reported to and diagnosed in Primary Care: implications for surveillance of environmental causes of ill-health

BACKGROUND: In Great Britain (GB), data collected on pesticide associated illness focuses on acute episodes such as poisonings caused by misuse or abuse. This study aimed to investigate the extent and nature of pesticide-related illness presented and diagnosed in Primary Care and the feasibility of establishing a routine monitoring system. METHODS: A checklist, completed by General Practitioners (GP) for all patients aged 18+ who attended surgery sessions, identified patients to be interviewed in detail on exposures and events that occurred in the week before their symptoms appeared. RESULTS: The study covered 59320 patients in 43 practices across GB and 1335 detailed interviews. The annual incidence of illness reported to GPs because of concern about pesticide exposure was estimated to be 0.04%, potentially 88400 consultations annually, approximately 1700 per week. The annual incidence of consultations where symptoms were diagnosed by GPs as likely to be related to pesticide exposure was 0.003%, an annual estimate of 6630 consultations i.e. about 128 per week. 41% of interviewees reported using at least one pesticide at home in the week before symptoms occurred. The risk of having symptoms possibly related to pesticide exposure compared to unlikely was associated with home use of pesticides after adjusting for age, gender and occupational pesticide exposure (OR = 1.88, 95% CI 1.51 - 2.35). CONCLUSION: GP practices were diverse and well distributed throughout GB with similar symptom consulting patterns as in the Primary Care within the UK. Methods used in this study would not be feasible for a routine surveillance system for pesticide related illness. Incorporation of environmental health into Primary Care education and practice is needed

Adiponectin-Mediated Analgesia and AntiInflammatory Effects in Rat

The adipose tissue-derived protein, adiponectin, has significant anti-inflammatory properties in a variety of disease conditions. Recent evidence that adiponectin and its receptors (AdipoR1 and AdipoR2) are expressed in central nervous system, suggests that it may also have a central modulatory role in pain and inflammation. This study set out to investigate the effects of exogenously applied recombinant adiponectin (via intrathecal and intraplantar routes; 10–5000 ng) on the development of peripheral inflammation (paw oedema) and pain hypersensitivity in the rat carrageenan model of inflammation. Expression of adiponectin, AdipoR1 and AdipoR2 mRNA and protein was characterised in dorsal spinal cord using real-time polymerase chain reaction (PCR) and Western blotting. AdipoR1 and AdipoR2 mRNA and protein were found to be constitutively expressed in dorsal spinal cord, but no change in mRNA expression levels was detected in response to carrageenan-induced inflammation. Adiponectin mRNA, but not protein, was detected in dorsal spinal cord, although levels were very low. Intrathecal administration of adiponectin, both pre- and 3 hours post-carrageenan, significantly attenuated thermal hyperalgesia and mechanical hypersensitivity. Intrathecal administration of adiponectin post-carrageenan also reduced peripheral inflammation. Intraplantar administration of adiponectin pre-carrageenan dose-dependently reduced thermal hyperalgesia but had no effect on mechanical hypersensitivity and peripheral inflammation. These results show that adiponectin functions both peripherally and centrally at the spinal cord level, likely through activation of AdipoRs to modulate pain and peripheral inflammation. These data suggest that adiponectin receptors may be a novel therapeutic target for pain modulation

EphA2-receptor deficiency exacerbates myocardial infarction and reduces survival in hyperglycemic mice

Background We have previously shown that EphrinA1/EphA expression profile changes in response to myocardial infarction (MI), exogenous EphrinA1-Fc administration following MI positively influences wound healing, and that deletion of the EphA2 Receptor (EphA2-R) exacerbates injury and remodeling. To determine whether or not ephrinA1-Fc would be of therapeutic value in the hyperglycemic infarcted heart, it is critical to evaluate how ephrinA1/EphA signaling changes in the hyperglycemic myocardium in response to MI. Methods Streptozotocin (STZ)-induced hyperglycemia in wild type (WT) and EphA2-receptor mutant (EphA2-R-M) mice was initiated by an intraperitoneal injection of STZ (150 mg/kg) 10 days before surgery. MI was induced by permanent ligation of the left anterior descending coronary artery and analyses were performed at 4 days post-MI. ANOVAs with Student-Newman Keuls multiple comparison post-hoc analysis illustrated which groups were significantly different, with significance of at least p < 0.05. Results Both WT and EphA2-R-M mice responded adversely to STZ, but only hyperglycemic EphA2-R-M mice had lower ejection fraction (EF) and fractional shortening (FS). At 4 days post-MI, we observed greater post-MI mortality in EphA2-R-M mice compared with WT and this was greater still in the EphA2-R-M hyperglycemic mice. Although infarct size was greater in hyperglycemic WT mice vs normoglycemic mice, there was no difference between hyperglycemic EphA2-R-M mice and normoglycemic EphA2-R-M mice. The hypertrophic response that normally occurs in viable myocardium remote to the infarct was noticeably absent in epicardial cardiomyocytes and cardiac dysfunction worsened in hyperglycemic EphA2-R-M hearts post-MI. The characteristic interstitial fibrotic response in the compensating myocardium remote to the infarct also did not occur in hyperglycemic EphA2-R-M mouse hearts to the same extent as that observed in the hyperglycemic WT mouse hearts. Differences in neutrophil and pan-leukocyte infiltration and serum cytokines implicate EphA2-R in modulation of injury and the differences in ephrinA1 and EphA6-R expression in governing this are discussed. Conclusions We conclude that EphA2-mutant mice are more prone to hyperglycemia-induced increased injury, decreased survival, and worsened LV remodeling due to impaired wound healing

DAMPs and neurodegeneration

10.1016/j.arr.2014.11.003Ageing Research Reviews2417-2

Mitochondrial dysfunction and Parkinson disease: a Parkin�AMPK alliance in neuroprotection

10.1111/nyas.12820Annals of the New York Academy of Sciences1350137-4