Hypoxic contraction of small pulmonary arteries from normal and endotoxemic rats: fundamental role of NO.

The present study was aimed at examining the role of nitric oxide (NO) in the hypoxic contraction of isolated small pulmonary arteries (SPA) in the rat. Animals were treated with either saline (sham experiments) or Escherichia coli lipolysaccharide [LPS, to obtain expression of the inducible NO synthase (iNOS) in the lung] and killed 4 h later. SPA (300- to 600-micrometer outer diameter) were mounted as rings in organ chambers for the recording of isometric tension, precontracted with PGF2alpha, and exposed to either severe (bath PO2 8 +/- 3 mmHg) or milder (21 +/- 3 mmHg) hypoxia. In SPA from sham-treated rats, contractions elicited by severe hypoxia were completely suppressed by either endothelium removal or preincubation with an NOS inhibitor [NG-nitro-L-arginine methyl ester (L-NAME), 10(-3) M]. In SPA from LPS-treated rats, contractions elicited by severe hypoxia occurred irrespective of the presence or absence of endothelium and were largely suppressed by L-NAME. The milder hypoxia elicited no increase in vascular tone. These results indicate an essential role of NO in the hypoxic contractions of precontracted rat SPA. The endothelium independence of HPV in arteries from LPS-treated animals appears related to the extraendothelial expression of iNOS. The severe degree of hypoxia required to elicit any contraction is consistent with a mechanism of reduced NO production caused by a limited availability of O2 as a substrate for NOS.

New Strategic Direction for Alcohol and Drugs Phase 2 Update Report (March 2013) (PDF 652KB)

Update Report on NSD for Alcohol and Drugs Phase 2 - March 2013

New Strategic Direction for Alcohol and Drugs Phase 2 (2011-2016) - (December 2011) (PDF 886 KB)

New Strategic Direction for Alcohol and Drugs Phase 2 (2011-2016) - A framework for Reducing Alcohol and Drug Related Harm in Northern Ireland (December 2011)

New Strategic Direction for Alcohol & Drugs 2006-2011- NSD Update (April 2010) (PDF 611KB)

An update on the implementation and delivery of the New Strategic Direction on Alcohol and Drugs 2006-2011 (NSD)

Addressing Young People's Drinking in Northern Ireland: Action to Support the New Strategic Direction for Alcohol and Drugs

This action plan focuses on three main areas: • reducing young people’s demand for alcohol by providing information, education and training to young people and their parents; •restricting the supply of alcohol via measures to reduce accessibility to alcohol (including how alcohol is priced, marketed, and promoted); and • providing treatment and support for those who require additional help. While the emphasis of this action plan is on young people, it recognises that their drinking patterns are very much influenced by modelling the drinking patterns of adults in our society, and it therefore contains actions that will impact on the entire population. Alcohol misuse - however you measure the cost, whether to the individual, the family, the community, the health service, or society as a whole - is one of the biggest public health issues facing Northern Ireland.

Alcohol drinking and cardiovascular risk in a population with high mean alcohol consumption.

Moderate alcohol consumption has been associated with lower coronary artery disease (CAD) risk. However, data on the CAD risk associated with high alcohol consumption are conflicting. The aim of this study was to examine the impact of heavier drinking on 10-year CAD risk in a population with high mean alcohol consumption. In a population-based study of 5,769 adults (aged 35 to 75 years) without cardiovascular disease in Switzerland, 1-week alcohol consumption was categorized as 0, 1 to 6, 7 to 13, 14 to 20, 21 to 27, 28 to 34, and > or =35 drinks/week or as nondrinkers (0 drinks/week), moderate (1 to 13 drinks/week), high (14 to 34 drinks/week), and very high (> or =35 drinks/week). Blood pressure and lipids were measured, and 10-year CAD risk was calculated according to the Framingham risk score. Seventy-three percent (n = 4,214) of the participants consumed alcohol; 16% (n = 909) were high drinkers and 2% (n = 119) very high drinkers. In multivariate analysis, increasing alcohol consumption was associated with higher high-density lipoprotein cholesterol (from a mean +/- SE of 1.57 +/- 0.01 mmol/L in nondrinkers to 1.88 +/- 0.03 mmol/L in very high drinkers); triglycerides (1.17 +/- 1.01 to 1.32 +/- 1.05 mmol/L), and systolic and diastolic blood pressure (127.4 +/- 0.4 to 132.2 +/- 1.4 mm Hg and 78.7 +/- 0.3 to 81.7 +/- 0.9 mm Hg, respectively) (all p values for trend <0.001). Ten-year CAD risk increased from 4.31 +/- 0.10% to 4.90 +/- 0.37% (p = 0.03) with alcohol use, with a J-shaped relation. Increasing wine consumption was more related to high-density lipoprotein cholesterol levels, whereas beer and spirits were related to increased triglyceride levels. In conclusion, as measured by 10-year CAD risk, the protective effect of alcohol consumption disappears in very high drinkers, because the beneficial increase in high-density lipoprotein cholesterol is offset by the increases in blood pressure levels.

Primary School Survey 2006 - Knowledge and use of Alcohol Cigarettes and Drugs (PDF 565 KB)

Primary School Survey 2006 - Knowledge and use of alcohol, cigarettes and drugs.

Blood, urine and vitreous isopropyl alcohol as biochemical markers in forensic investigations.

Isopropyl alcohol (IPA) is widely used as an industrial solvent and cleaning fluid. After ingestion or absorption, IPA is converted into acetone by alcohol dehydrogenase. However, in ketosis, acetone can be reduced to IPA. The aim of this study was to investigate blood IPA and acetone concentrations in a series of 400 medico-legal autopsies, including cases of diabetic ketoacidosis, hypothermia and alcohol misuse-related deaths, to illustrate the extent of ketosis at the time of death. Vitreous glucose, blood 3-β-hydroxybutyrate (3HB) and acetoacetate (AcAc) concentrations were also determined systematically. Additionally, vitreous and urine IPA, acetone, 3HB and AcAc concentrations as well as other biochemical markers, including glycated hemoglobin and carbohydrate-deficient transferrin (CDT) were also determined in selected cases. The results of this study indicate that ketosis is characterized by the presence of IPA resulting from the acetone metabolism and that IPA can be detected in several substrates. These findings confirm the importance of the systematic determination of IPA and acetone levels that is used to quantify biochemical disturbances and the importance of ketosis at the time of death.

Worm burdens in outbred and inbred laboratory rats with morphometric data on Syphacia muris (Yamaguti, 1935) Yamaguti, 1941 (Nematoda, Oxyuroidea)

Syphacia muris worm burdens were evaluated in the rat Rattus norvegicus of the strains Wistar (outbred), Low/M and AM/2/Torr (inbred), maintained conventionally in institutional animal houses in Brazil. Morphometrics and illustration data for S. muris recovered from Brazilian laboratory rats are provided for the first time since its proposition in 1935.

Changes in the vascular reactivity of the isolated tail arteries of spontaneous and renovascular hypertensive rats to endogenous and exogenous noradrenaline.

We have investigated the changes in the responses to noradrenaline of isolated tail arteries of spontaneously hypertensive (SHR) and renovascular hypertensive rats (Wistar-Kyoto: two-kidney, one-clip model, WKY:2K1C) compared with normotensive (Wistar-Kyoto, WKY) rats. Renovascular hypertension was induced by 4 weeks' unilateral renal artery clipping. Arteries were vasoconstricted with exogenous noradrenaline, electrical field stimulation or high potassium. The effects of the latter two stimuli were abolished by reserpine and so were presumably dependent on the presence of endogenous noradrenaline. In the SHR the maximal vasoconstriction produced by all three stimuli was greater than in WKY. Dose-response curves were steeper and there was no change in threshold. Vascular mass was greater. We interpret these results as showing an increase in vascular reactivity in the SHR caused by structural adaptation. The WKY:2K1C responses to noradrenaline could also be explained in terms of structural adaptation but there was no increase in vascular mass. Sensitivity to potassium and electrical stimulation was decreased, suggesting a defect in vascular neurotransmission. This was supported by the observations of a decreased arterial noradrenaline content and of decreased sensitivity to cocaine.

New Strategic Direction for Alcohol and Drugs (2006-2011) (Online Publication)

Executive Summary and Strategy Document (May 2006) The New Strategic Direction has a set of overarching long-term aims to: • Provide accessible and effective treatment and support for people who are consuming alcohol and/or using drugs in a potentially hazardous, harmful or dependent way. • Reduce the level, breadth and depth of alcohol and drug-related harm to users, their families and/or their carers and the wider community. • Increase awareness on all aspects of alcohol and drug-related harm in all settings and for all age groups. • Integrate those policies which contribute to the reduction of alcohol and drug-related harm into all Government Department strategies. • Develop a competent skilled workforce across all sectors that can respond to the complexities of alcohol and drug use and misuse. • Promote opportunities for those under the age of 18 years to develop appropriate skills, attitudes and behaviours to enable them to resist societal pressures to drink alcohol and/or use illicit drugs, with a particular emphasis on those identified as potentially vulnerable. • Reduce the availability of illicit drugs in Northern Ireland åÊ

New Strategic Direction for Alcohol and Drugs (2006-2011) Executive Summary

Executive Summary and Strategy Document (May 2006) The New Strategic Direction has a set of overarching long-term aims to: • Provide accessible and effective treatment and support for people who are consuming alcohol and/or using drugs in a potentially hazardous, harmful or dependent way. • Reduce the level, breadth and depth of alcohol and drug-related harm to users, their families and/or their carers and the wider community. • Increase awareness on all aspects of alcohol and drug-related harm in all settings and for all age groups. • Integrate those policies which contribute to the reduction of alcohol and drug-related harm into all Government Department strategies. • Develop a competent skilled workforce across all sectors that can respond to the complexities of alcohol and drug use and misuse. • Promote opportunities for those under the age of 18 years to develop appropriate skills, attitudes and behaviours to enable them to resist societal pressures to drink alcohol and/or use illicit drugs, with a particular emphasis on those identified as potentially vulnerable. • Reduce the availability of illicit drugs in Northern Ireland

New Strategic Direction for Alcohol and Drugs (2006-2011) (PDF 976 KB)

Strategy Document - May 2006

D-JNKi, a peptide inhibitor of c-Jun N-terminal kinase, promotes functional recovery after transient focal cerebral ischemia in rats

The c-Jun-N-terminal kinase (JNK) pathway has been shown to play an important role in excitotoxic neuronal death and several studies have demonstrated a neuroprotective effect of D-JNKi, a peptide inhibitor of JNK, in various models of cerebral ischemia. We have now investigated the effect of D-JNKi in a model of transient focal cerebral ischemia (90 min) induced by middle cerebral artery occlusion (MCAo) in adult male rats. D-JNKi (0.1 mg/kg), significantly decreased the volume of infarct, 3 days after cerebral ischemia. Sensorimotor and cognitive deficits were then evaluated over a period of 6 or 10 days after ischemia and infarct volumes were measured after behavioral testing. In behavioral studies, D-JNKi improved the general state of the animals as demonstrated by the attenuation of body weight loss and improvement in neurological score, as compared with animals receiving the vehicle. Moreover, D-JNKi decreased sensorimotor deficits in the adhesive removal test and improved cognitive function in the object recognition test. In contrast, D-JNKi did not significantly affect the infarct volume at day 6 and at day 10. This study shows that D-JNKi can improve functional recovery after transient focal cerebral ischemia in the rat and therefore supports the use of this molecule as a potential therapy for stroke.

Workplace Drugs and Alcohol Policies - Example of a Model Policy (PDF 113 KB)

The Workplace Drugs and Alcohol Policy aims to contribute to a safe, healthy and productive work environment by: • Preventing drugs and alcohol problems through awareness raising; • Identifying problems at the earliest stage; • Offering support to those who have a problem. The policy has been developed in conjunction with our employees, their representatives and management and applies equally to all staff including all levels of management. åÊ