Monthly Archives: June 2014

Exploring Structural Relationships Between Blood Alcohol Concentration and Signs and Clinical Assessment of Intoxication in Alcohol-Involved Injury Cases

Aims: Although the relationship between the Y90 (blood alcohol concentration, BAC) and Y91 (clinician intoxication assessment) ICD-10 codes has received attention recently, the role of 10 signs of intoxication in the Y91–Y90 relationship has not been studied yet. This work examines these signs in the estimation of alcohol intoxication levels of patients in medical settings. Methods: Collected and analyzed were data on 1997 injured emergency room patients from 17 countries worldwide reporting drinking prior to injury or presenting with a non-zero BAC from 17 countries worldwide. A model is estimated describing how the 10 signs inform the Y91, Y90 prediction with the goal of the use of observations on patients in place of a biological measure. Results: Signs were consistent with a single underlying construct that strongly predicted Y91. Smell of alcohol on breath predicted Y91 above its contribution through the construct and was stronger for those with tolerance to alcohol than for those without. Controlling for Y91, no sign further contributed to prediction of Y90 indicating that Y91 incorporated all intoxication sign information in predicting Y90. Variance explained was high for Y91 (R2 = 0.84) and intoxication signs (above 0.72 for all but smell on the breath, 0.57) and lower for Y90 (0.38). Conclusion: Intoxication assessments are well predicted by overall intoxication severity, which itself is well represented by intoxication signs along with differential emphasis on smell of alcohol on breath, especially for those with alcohol tolerance. However, BAC levels remain largely unexplained by intoxication signs with a clinician's assessment serving as the primary predictive measure.

Salivary Exoglycosidases as Markers of Alcohol Dependence

Background: Some salivary markers of alcohol abuse/dependence have been proposed so far: aminotransferases, gamma-glutamyltransferase, ethanol, ethyl glucuronide, ethyl sulfate, sialic acid, β-hexosaminidase A, oral peroxidase, methanol, diethylene/ethylene glycol, α-amylase, clusterin, haptoglobin, heavy/light chains of immunoglobulins and transferrin. Aim: To investigate the effect of chronic alcohol drinking and smoking on the activity (pKat/ml) and output (pKat/min) of salivary lysosomal exoglycosidases: α-fucosidase (FUC), α-mannosidase (MAN), β-galactosidase (GAL), and β-glucuronidase (GLU), and their applicability as markers of alcohol dependence. Methods: The activity of FUC, MAN, GAL and GLU was measured colorimetrically in the saliva of healthy social drinkers, alcohol-dependent non-smokers and alcohol-dependent smokers. Results: We observed an increased salivary activity of FUC, GAL, GLU and MAN, as well as an increased output of GAL and GLU, in comparison with controls. The highest increase in the activity/output was found in salivary GLU and MAN (GLU, even 7- to 18-fold), and the least in GAL. We found an excellent sensitivity and specificity and a high accuracy (measured by the area under the ROC curve) for salivary FUC, GLU and MAN activities. The salivary GLU activity positively correlated with the number of days of last alcohol intoxication. Salivary activity of FUC, GAL and MAN, but not GLU, positively correlated with the periodontal parameters such as gingival index and papilla bleeding index. Conclusions: Although we found an excellent sensitivity and specificity as well as a high accuracy for the salivary activity of FUC, GLU and MAN, the GLU activity seems to be mostly applicable as a marker of chronic alcohol drinking (alcohol dependence).

Exogenous Activation of Wnt/{beta}-Catenin Signaling Attenuates Binge Alcohol-Induced Deficient Bone Fracture Healing

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  1. Kristen L. Lauing1,2,
  2. Sumana Sundaramurthy1,3,
  3. Rachel K. Nauer2 and
  4. John J. Callaci1,2,3,*
  1. 1Alcohol Research Program, Loyola University Stritch School of Medicine, 2160 S. 1st Ave, Maywood, IL 60546, USA
  2. 2Burn and Shock Trauma Institute, Loyola University Stritch School of Medicine, 2160 S. 1st Ave, Maywood, IL 60546, USA
  3. 3Department of Orthopaedic Surgery and Rehabilitation, Loyola University Stritch School of Medicine, 2160 S. 1st Ave, Maywood, IL 60546, USA
  1. * Corresponding author: Department of Orthopaedic Surgery, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA. Tel.: +1 708 327 2461; Fax: 1 708 327 2813; E-mail: jcallaci{at}lumc.edu
  • Received October 7, 2013.
  • Revision requested December 23, 2013.
  • Revision received January 5, 2014.
  • Accepted January 21, 2014.

Abstract

Aims: Excessive alcohol consumption is associated with fracture non-union. Canonical Wnt pathway signaling activity regulates normal fracture healing. We previously demonstrated that binge alcohol exposure modulates β-catenin levels in the fracture callus of mice. Here, we sought to determine whether exogenous enhancement β-catenin signaling activity could restore normal fracture healing to binge-exposed mice. Methods: C57BL/6 male mice were exposed to episodic alcohol or saline for 6 total days of alcohol exposure over a 2-week period. Following alcohol exposure, mice were subjected to a stabilized mid-shaft tibia fracture. Beginning 4 days post-injury, mice received daily injections of either lithium chloride or saline subcutaneously. Protein levels of activated, inactivated, and total β-catenin and GSK-3β in fracture calluses were measured at post-injury day 9. Biomechanical strength testing and histology of callus tissue was assessed at post fracture day 14. Results: Binge alcohol was associated with decreased callus biomechanical strength, and reduced cartilaginous callus formation. Alcohol decreased levels of callus-associated activated β-catenin while concomitantly increasing the levels of inactive β-catenin at post-injury day 9. Alcohol also increased callus associated activated GSK-3β at post-injury day 9. Lithium chloride (an inhibitor of GSK-3β) treatment increased activated β-catenin protein levels, significantly decreased activated GSK-3β and restored cartilaginous callus formation and endochondral ossification. Conclusion: These data link alcohol-impaired fracture healing with deregulation of Canonical Wnt signaling activity in the fracture callus. Exogenous activation of the Wnt pathway using LiCl attenuated the damaging effects of binge alcohol exposure on the fracture healing process by modulating canonical Wnt signaling activity.

  1. Alcohol and Alcoholism

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.

Effects of Ceftriaxone on Systemic and Central Expression of Anti- and Pro-inflammatory Cytokines in Alcohol-Preferring (P) Rats Exposed to Ethanol

  1. P.S.S. Rao,
  2. S. Ahmed and
  3. Y. Sari*
  1. Department of Pharmacology, University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH, USA
  1. *Corresponding author: Department of Pharmacology, University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA. E-mail: youssef.sari{at}utoledo.edu
  • Received December 13, 2013.
  • Revision requested January 21, 2014.
  • Revision received February 25, 2014.
  • Accepted March 20, 2014.

Aims: Determine the effect of reduction in ethanol consumption by alcohol-preferring (P) rats, following ceftriaxone treatment, on the cytokines levels in prefrontal cortex (PFC) and plasma. Methods: Following 5 weeks of free access to ethanol (15 and 30%), P rats were treated daily with ceftriaxone or saline vehicle for either 2 or 5 consecutive days. Plasma and PFC were collected from ceftriaxone- and saline vehicle-treated groups, and assayed for the levels of pro- and anti-inflammatory cytokines. Results: A significant increase in the plasma level of anti-inflammatory cytokine IL-10 was observed in the ceftriaxone-treated group when compared with the saline-treated group in both the 2-day and 5-day treatments. Furthermore, ceftriaxone treatment for 2 days induced reduction in TNFα level in both plasma and PFC. Additionally, ceftriaxone treatment for 2 days significantly reduced the IFNγ level in PFC. Conclusion: These findings show the ability of ceftriaxone to reduce alcohol consumption and induce modulation of the anti-inflammatory and pro-inflammatory cytokines levels in P rats.

Chronic Ethanol Consumption Increases Myocardial Mitochondrial DNA Mutations: A Potential Contribution by Mitochondrial Topoisomerases

  1. D. Laurent,
  2. J.E. Mathew,
  3. M. Mitry,
  4. M. Taft,
  5. A. Force and
  6. J.G. Edwards*
  1. Department of Physiology, New York Medical College, Valhalla, NY, USA
  1. *Corresponding author: Department of Physiology, New York Medical College, 15 Dana Road, Valhalla, NY, USA. Tel.: +1-914-594-4166; Fax: +1-914-594-4018; E-mail: j_edwards{at}nymc.edu
  • Received February 17, 2014.
  • Revision received March 26, 2014.
  • Accepted March 27, 2014.

Aims: Alcoholic cardiomyopathy (ACM) presents as decreased myocardial contractility, arrhythmias and secondary non-ischemic dilated cardiomyopathy leading to heart failure. Mitochondrial dysfunction is known to have a significant role in the development and complications of ACM. This study investigated if chronic ethanol feeding promoted myocardial mitochondrial topoisomerase dysfunction as one underlying cause of mitochondrial DNA (mtDNA) damage and mitochondrial dysfunction in ACM. Methods: The impact of chronic ethanol exposure on the myocardial mitochondria was examined in both neonatal cardiomyocytes using 50 mM ethanol for 6 days and in rats assigned to control or ethanol feeding groups for 4 months. Results: Chronic ethanol feeding led to significant (P < 0.05) decreases in M-mode Fractional Shortening, ejection fraction, and the cardiac output index as well as increases in Tau. Ethanol feeding promoted mitochondrial dysfunction as evidenced by significantly decreased left ventricle cytochrome oxidase activity and decreases in mitochondrial protein content. Both in rats and in cultured cardiomyocytes, chronic ethanol presentation significantly increased mtDNA damage. Using isolated myocardial mitochondria, both mitochondrial topoisomerase-dependent DNA cleavage and DNA relaxation were significantly altered by ethanol feeding. Conclusion: Chronic ethanol feeding compromised cardiovascular and mitochondrial function as a result of a decline in mtDNA integrity that was in part the consequence of mitochondrial topoisomerase dysfunction. Understanding the regulation of the mitochondrial topoisomerases is critical for protection of mtDNA, not only for the management of alcoholic cardiomyopathy, but also for the many other clinical treatments that targets the topoisomerases in the alcoholic patient.

Alcoholic Liver Disease: A Synopsis of the Charles Lieber’s Memorial Symposia 2009-2012

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Abstract

This paper is based upon the ‘Charles Lieber Satellite Symposia’ organized by Manuela G. Neuman at each of the 2009–2012 Research Society on Alcoholism (RSA) Annual Meetings. The presentations represent a broad spectrum dealing with alcoholic liver disease (ALD). In addition, a literature search (2008–2013) in the discussed area was performed in order to obtain updated data. The presentations are focused on genetic polymorphisms of ethanol metabolizing enzymes and the role of cytochrome P4502E1 (CYP2E1) in ALD. In addition, alcohol-mediated hepatocarcinogenesis, immune response to alcohol and fibrogenesis in alcoholic hepatitis as well as its co-morbidities with chronic viral hepatitis infections in the presence or absence of human deficiency virus are discussed. Finally, emphasis was led on alcohol and drug interactions as well as liver transplantation for end-stage ALD.

  1. Alcohol and Alcoholism

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.