Why people enter treatment for alcohol problems: Findings from UK Alcohol Treatment Trial pre‐treatment interviews

Aim: To develop a model of why people seek professional treatment for drinking problems, grounded in what clients say about the process at treatment entry.

Participants: Three sets of consecutive entrants to the UK Alcohol Treatment Trial, sets commencing at intervals during trial recruitment (total n = 98).

Location: Statutory and non‐statutory alcohol problem treatment agencies in three areas of England and Wales.

Data: Open‐ended interviews according to a brief interview guide, leading to 400–800‐word post‐interview reports used for analysis (tape recordings used for auditing the interview and analysis process).

Analysis: Reports analysed by a team according to grounded theory principles, involving an iterative process with successive refinement of interviewing and analysis with each successive set of data.

Findings: A model of professional treatment entry was developed, refined and “tested” with the last set of data. The process of seeking professional treatment was depicted in the model as involving a realization of worsening, accumulating and multiple problems related to drinking, especially in health and family domains; in conjunction with, in most cases (but not all), a trigger event and/or family or professional influence; combined with rejection of the possibility of unaided change or non‐professional help; leading to the seeking or accepting of professional help.

Conclusions: The findings support conclusions already in the literature about the process of seeking professional help for a drinking problem, but provide further refinement of existing ideas: for example regarding the accumulation of drinking‐related problems, the ways in which a realization of those problems combines with triggers or pressure, and the complex role of the family and primary care professionals in assisting motivation to seek treatment.     

Mechanism of vascular smooth muscle cells activation by hydrogen peroxide: role of phospholipase C gamma.

BACKGROUND: Hydrogen peroxide (H2O2) formation is a critical factor in processes involving ischaemia/ reperfusion. However, the precise mechanism by which reactive oxygen species (ROS) induce vascular damage are insufficiently known. Specifically, activation of phospholipase C gamma (PLCgamma) is a probable candidate pathway involved in vascular smooth muscle cells (VSMC) activation by H2O2. METHODS: The activation of human venous VSMC was measured as cytosolic free calcium mobilization, shape change and protein phosphorylation, focusing on the role of tyrosine phosphorylation-activated PLCgamma. RESULTS: The exposure of VSMC to exogenous H2O2 caused a rapid increase in cytosolic free calcium concentration ([Ca2+]i), and induced a significant VSMC shape change. Both effects were dependent on a tyrosine kinase-mediated mechanism, as determined by the blockade of short-term treatment of VSMC with the protein tyrosine kinase inhibitor, genistein. Giving further support to the putative role of phospholipase C (PLC)-dependent pathways, the [Ca2+]i and VSMC shape change response were equally inhibited by the specific PLC blocker, 1-(6-((17-beta-methoxyestra-1,3,5(10)trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). In addition, U73122 had a protective effect against the deleterious action (24 h) of H2O2 on non-confluent VSMC. As a further clarification of the specific pathway involved, the exposure to H2O2 significantly stimulated the tyrosine phosphorylation of PLCgamma with a concentration- and time-profile similar to that of [Ca(2+)](i) mobilization. CONCLUSIONS: The present study reveals that H(2)O(2) activates PLCgamma on VSMC through tyrosine phosphorylation and that this activation has a major role in rapid [Ca(2+)](i) mobilization, shape-changing actions and damage by H(2)O(2) in this type of cells. These findings have direct implications for understanding the mechanisms of the vascular actions of H(2)O(2) and may help to design pharmacologically protective strategies.     

Long-lasting changes in behavioural and neuroendocrine indices in the rat following neonatal maternal separation: gender-dependent effects

Neonatal maternal separation (MS) has been used to model long-term changes in neurochemistry and behaviour associated with exposure to early-life stress. This study characterises changes in behavioural and neuroendocrine parameters following MS. On postnatal days (PND) 3-15, male and female Long-Evans rats underwent 3 h daily MS. Non-handled (NH) control offspring remained with the dams. Starting at PND 90, behaviour was assessed at weekly intervals in the elevated plus-maze, elevated T-maze, and locomotor activity boxes, and body weight monitored throughout. At the end of the study, adrenals were weighed and blood collected for analysis of plasma corticosterone and adrenocorticotropic hormone (ACTH) under basal conditions and following restraint stress. As adults, MS weighed more than NH animals. Activity on the open arms of the plus-maze was similar between MS and NH animals. In the T-maze, MS males had shorter emergence latencies than their NH counterparts. Spontaneous ambulation in a novel environment was significantly higher in MS than in NH animals, and males exhibited overall lower activity than females. Basal plasma corticosterone was lower in MS than in NH females, but no rearing condition difference was observed following restraint stress. Females had higher corticosterone and ACTH levels than males, whereas adrenal glands of MS animals weighed less than those of NH controls. The MS paradigm caused long-term gender dependent effects on behaviour and HPA axis status. The consistent gender differences confirm and expand existing results showing altered anxiety and stress reactivity in male and female rats.