Monthly Archives: October 2013

Sex-Specific Differences in the Development of Acute Alcohol-Induced Liver Steatosis in Mice

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Abstract

Aims: Results of several animal studies suggest that similar to humans, female rodents are more susceptible to chronic alcohol-induced liver disease (ALD). The aim of the present study was to determine whether female mice are more susceptible to acute alcohol-induced steatosis than male mice and to investigate possible mechanisms involved. Methods: Male and female C57BL/6J mice received one single dose of ethanol (6 g/kg bodyweight) or isocaloric maltose-dextrin solution intragastrically. Plasma alcohol concentration, markers of hepatic steatosis, activation of the TLR-4 signaling cascade and triglyceride export as well as lipid peroxidation and of iron metabolism were measured 12 h after acute alcohol intake. Results: In male and female ethanol-treated mice, plasma alcohol concentrations were still markedly increased 12 h after the alcohol challenge, which was associated with a significant accumulation of lipids in the liver and increase of transaminases in plasma; however, lipid accumulation was ∼3-fold higher in females in comparison with male animals. Expression of MyD88 was only found to be significantly induced in livers of female alcohol-exposed mice, whereas protein levels of ApoB were found to be significantly lower only in livers of female mice exposed to ethanol. Levels of 4-HNE protein adducts and ferritin were induced in livers of male and female ethanol-treated mice. Conclusion: Taken together, these data suggest that female mice are also more susceptible to acute alcohol-induced liver steatosis and that this involves an increased activation of TLR-4-dependent signaling pathways in the liver.

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.

Why Not Add Consumption Measures to Current Definitions of Substance Use Disorders? Commentary on Rehm et al. ‘Defining Substance Use Disorders: Do We Really Need More Than Heavy Use?’

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Abstract

The article by Rehm and colleagues in this issue of the Journal argues that diagnoses of substance use disorders should be based solely on measures of consumption. Although the authors provide convincing arguments for inclusion of consumption measures in the diagnostic criteria for substance use disorders, we do not agree that diagnostic criteria should be restricted to measures of consumption alone. Our clinical and research experience with alcohol use disorders suggests that use of consumption measures alone would fail to identify many patients whose alcohol or drug use is adversely impacting their health. Instead, we advocate—as others have done—that measures of consumption be added to current diagnostic criteria.

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.

The Concept of Substance Use Disorders. A Commentary on ‘Defining Substance Use Disorders: Do We Really Need More than Heavy Use’ by Rehm et al.

Substance use disorders reflect more than just substance use. At one level they are patterns of behaviour, at another level they are clusters of experiences and physiological features. Substance use disorders are strongly correlated with the level of substance use, but the importance of defining them as disorders is because this determines the need for treatment (including detoxification, agonist maintenance treatment and other pharmacotherapies). The severity of a substance disorder also strongly influences the individual's prognosis. Quantification of substance use is valuable for both clinical and epidemiological purposes, but it should be as precise as possible and notions such as “heavy use over time” are not fit for purpose.

A Commentary on Defining Substance Use Disorders: Do We Really Need More Than Heavy Use?

  1. Peter Rice*
  1. NHS Tayside, Stracathro Hospital, Brechin DD9 7QA, UK
  1. *Corresponding author: E-mail: peter.rice{at}nhs.net

Defining Substance Use Disorders as heavy use will help to reduce fruitless discussions about labeling, reduce stigma and increase the likelihood of people coming forward for help of whatever level of intensity best matches their needs. Clinicians will still need to assess propensity for withdrawal symptoms and help the heaviest drinkers to work out whether they can successfully maintain a reduced consumption level rather than abstinence.

A Radical But Flawed Proposal: Comments on Rehm et al. ‘Defining Substance Use Disorders: Do We Really Need More than Heavy Use?’

  1. Nick Heather*
  1. Department of Psychology, Northumbria University, Newcastle upon Tyne, UK
  1. *Corresponding author: Department of Psychology, Faculty of Health & Life Sciences, Northumberland Building, Northumbria University, Newcastle upon Tyne NE1 8ST, UK. Tel: +44-191-227-4521; Fax: +44-191-227-3190; E-mail: nick.heather{at}northumbria.ac.uk

Rehm et al. (2013) have given us a provocative proposal for revising the definition of substance use disorders, with radical implications for treatment, prevention and policy. They argue that, for the purposes of reducing substance-related harm, concepts of dependence and addiction are superfluous in this definition and that all we need is the concept of ‘heavy use over time’. This proposal will no doubt generate a lively and interesting debate and is to be commended for that reason. However, I believe it to be founded on deeply flawed reasoning and a short-sighted view of its topic. Owing to the prominence of its authors, their article may well be influential in the field of substance use disorders but it will be most regrettable, in my view, if it leads to the kind of changes they advocate.

The underlying mistake in their argument is to identify the concepts of dependence and addiction with definitions in the International Classification of Diseases and the Diagnostic and Statistical Manual of Mental Disorders. (There may be differences between the terms ‘dependence’ and ‘addiction’ but for present purposes I see no advantages in using the former and will therefore confine myself to the latter in this commentary. I will also illustrate my own argument, where appropriate, by the example of alcohol use rather than substance use in general.) These definitions were developed mainly for bureaucratic purposes and, as the authors themselves recognize, to respond to socio-political influences on diagnostic practice; this tick-box approach to definition does not help us to think clearly about what addiction means and what part it plays in the production of substance-related harm. If these were the only or the most useful definitions of addiction available, some of the claimed benefits for switching to heavy use over time may be justified. But …

Defining Substance Use Disorders: Do We Really Need More Than Heavy Use?

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  1. J. Rehm1,2,3,4,5,*,
  2. S. Marmet6,
  3. P. Anderson7,8,
  4. A. Gual9,
  5. L. Kraus10,11,
  6. D.J. Nutt12,
  7. R. Room11,13,14,
  8. A.V. Samokhvalov2,5,
  9. E. Scafato15,
  10. M. Trapencieris16,
  11. R.W. Wiers17 and
  12. G. Gmel2,6,18,19
  1. 1Institute for Clinical Psychology and Psychotherapy, TU Dresden, Dresden Germany
  2. 2Centre for Addiction and Mental Health (CAMH), Toronto, Canada
  3. 3Institute of Medical Science, University of Toronto, Toronto, Canada
  4. 4Dalla Lana School of Public Health (DLSPH), University of Toronto, Toronto, Canada
  5. 5Department of Psychiatry, University of Toronto, Toronto, Canada
  6. 6Addiction Switzerland, Lausanne, Switzerland
  7. 7Institute of Health and Society, Newcastle University, Newcastle Upon Tyne, UK
  8. 8Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
  9. 9Addictions Unit, Psychiatry Department, Neurosciences institute, Hospital Clínic, IDIBAPS, Barcelona, Spain
  10. 10IFT Institut für Therapieforschung, Munich, Germany
  11. 11Centre for Social Research on Alcohol and Drugs, Stockholm University, Stockholm, Sweden
  12. 12Centre for Neuropsychopharmacology, Imperial College London, London, UK
  13. 13Melbourne School of Population and Global Health, University of Melbourne, Parkville, Australia
  14. 14Centre for Alcohol Policy Research, Turning Point Alcohol & Drug Centre, Fitzroy, VIC, Australia
  15. 15Population's Health and Health Determinants Units, National Observatory on Alcohol – CNESPS, National Centre for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanita, Rome, Italy
  16. 16Institute of Philosophy and Sociology, University of Latvia, Riga, Latvia
  17. 17Addiction, Development and Psychopathology (ADAPT) Lab, Psychology, University of Amsterdam, Amsterdam, The Netherlands
  18. 18University of the West of England, Frenchay Campus, Coldharbour Lane, Bristol BS16 1QY, UK
  19. 19Alcohol Treatment Center, Lausanne University Hospital, CH-1011 Lausanne, Switzerland
  1. *Corresponding author: E-mail: jtrehm{at}gmail.com
  • Received April 27, 2013.
  • Revision requested June 3, 2013.
  • Revision received June 16, 2013.
  • Accepted July 10, 2013.

Abstract

Aims: The aim of the study was to explore whether the concept of heavy substance use over time can be used as definition of substance use disorder. Methods: Narrative review. Results: Heavy use over time clearly underlies the neurobiological changes associated with current thinking of substance use disorders. In addition, there is evidence that heavy use over time can explain the majority of social problems and of burden of disease (morbidity and mortality). A definition of substance use disorders via heavy use over time would avoid some of the problems of current conceptualizations, for instance the cultural specificity of concepts such as loss of control. Finally, stressing the continuum of use may avoid the high level of stigmatization currently associated with substance use disorders. Conclusion: ‘Heavy substance use over time’ seems to be a definition of substance use disorders in line with results of basic research and epidemiology. Additionally, it reduces stigmatization. This approach should thus be further explored.

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.