Hypoxic Depression of PKG-Mediated Inhibition of Serotonergic Contraction in Ovine Carotid Arteries.

Hypoxic Depression of PKG-Mediated Inhibition of Serotonergic Contraction in Ovine Carotid Arteries.

Am J Physiol Regul Integr Comp Physiol. 2013 Feb 27;
Thorpe RB, Stockman SL, Williams JM, Lincoln TM, Pearce WJ

Chronic hypoxia attenuates soluble guanylate cyclase-induced vasorelaxation in serotonin (5-HT) contracted ovine carotid arteries. Because PKG mediates many effects of soluble guanylate cyclase activation through phosphorylation of multiple kinase targets in vascular smooth muscle we tested the hypothesis that chronic hypoxia reduces the ability of PKG to phosphorylate its target proteins, which attenuates the ability of PKG to induce vasorelaxation. We also tested the hypothesis that hypoxia attenuates PKG expression and/or activity. Arteries from normoxic and chronically hypoxic (altitude of 3820m for 110 days) fetal and adult sheep were denuded of endothelium and equilibrated with 95% O2, 5% CO2 in the presence of L-NAME and L-NA to inhibit residual eNOS. Concentration-response relations for 5-HT were determined in the presence of prazosin to minimize activation of ?-adrenergic receptors. The PKG activator 8-pCPT-cGMP reduced agonist binding affinity of the 5-HT receptor in a concentration-dependent manner that was attenuated by hypoxia. Expression and activity of PKG-I was not significantly affected by chronic hypoxia in either fetal or adult arteries, although PKG-I abundance was greater in fetal arteries. Pre-treatment with the BK channel inhibitor iberiotoxin attenuated the vasorelaxation induced by 8-pCPT-cGMP in normoxic but not chronically hypoxic arteries. These results support the hypothesis that hypoxia attenuates the vasorelaxant effects of PKG through suppression of PKG’s ability to activate BK channels in arterial smooth muscle. The results also reveal that this hypoxic effect is greater in fetal than adult arteries and that chronic maternal hypoxia can profoundly affect fetal vascular function. HubMed – depression


Prospective evaluation of mental health training for occupational health practitioners.

Occup Med (Lond). 2013 Feb 27;
Madan I, Henderson M, Hashtroudi A, Hope V, Harvey SB

BackgroundOccupational health (OH) practitioners need to be confident in identifying and managing mental health problems in the workforce.AimsTo evaluate the effectiveness of a one-day workshop in improving the knowledge, attitude and confidence of OH practitioners in detecting and managing depression, anxiety, suicide risk, alcohol misuse and drug abuse.MethodsInteractive mental health workshops for 164 OH practitioners held in five regions in England were evaluated by self-administered questionnaire. Data were collected immediately prior to the workshop (T1), immediately after the workshop (T2) and 4 months following the workshop (T3).ResultsAt T1, the response rate was 97% (159/164), 90% at T2 and 63% at T3. The mean improvement in participants’ knowledge was 8% (95% CI 6-10) at T2 compared with T1. The biggest improvement was in participants with no previous training in the management of common mental health problems in the workplace, mean improvement 9% (95% CI 6-12). Participants’ confidence improved in all areas assessed at T2, and the improvement in confidence compared with that at baseline was sustained at 4 months (T3). Participants reported using the knowledge gained in clinical practice in all topic areas covered. Use of knowledge gained at the workshop was significantly higher in those who had had previous training in managing common mental health disorders.ConclusionsThis one-day interactive workshop was a feasible and effective method of improving OH professionals’ confidence, knowledge and application of skills in practice in key areas of mental health. HubMed – depression


The Phenomenology and Clinical Correlates of Suicidal Thoughts and Behaviors in Youth with Autism Spectrum Disorders.

J Autism Dev Disord. 2013 Feb 28;
Storch EA, Sulkowski ML, Nadeau J, Lewin AB, Arnold EB, Mutch PJ, Jones AM, Murphy TK

This study investigated the phenomenology and clinical correlates of suicidal thoughts and behaviors in youth with ASD (N = 102; range 7-16 years). The presence of suicidal thoughts and behavior was assessed through the Anxiety Disorders Interview Schedule-Child and Parent Versions. Children and parents completed measures of anxiety severity, functional impairment, and behavioral and emotional problems. Approximately 11 % of youth displayed suicidal thoughts and behaviors. Children with autism were more likely to have suicidal thoughts and behaviors whereas children with Asperger’s disorder were less likely. Suicidal thoughts and behaviors were associated with the presence of depression and post-traumatic stress disorder. Overall, results suggest that suicidal thoughts and behaviors are common in youth with ASD, and may be related to depression and trauma. HubMed – depression