Alcoholism, clinical and experimental research
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Alcohol. Clin. Exp. Res. · Aug 2005
Mechanical ventilation exacerbates alveolar macrophage dysfunction in the lungs of ethanol-fed rats.
Patients with alcohol abuse have a two- to three-fold increased risk of acute lung injury and respiratory failure after sepsis or trauma but are also at increased risk of nosocomial pneumonia. Mechanical ventilation exacerbates lung injury during critical illnesses. In this study we tested whether mechanical ventilation of the alcoholic lung promotes on balance a proinflammatory phenotype favoring ventilator-induced lung injury or an immunosuppressive phenotype favoring ventilator-associated pneumonia. ⋯ Ethanol ingestion dampens ventilator-induced inflammation but exacerbates macrophage immune dysfunction. These findings could explain at least in part why alcoholic patients are at increased risk of ventilator-associated pneumonia.
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Alcohol. Clin. Exp. Res. · Aug 2005
Comparative StudyAdolescent rats exposed to repeated ethanol treatment show lingering behavioral impairments.
Repeated ethanol treatment has been reported to differentially affect water maze performance in adolescent and adult rats. The present study was undertaken to determine the age-specific reversal of ethanol-induced deficit in water maze performance. ⋯ Adolescent rats exposed to ethanol showed deficits in water maze performance, had increased hug time, and failed to catch up with control rats during the weeks after the ethanol treatment period was over. Adult alcohol rats showed some behavioral dysfunction (increased latency and distance to find the hidden platform) but had problems swimming, and in the probe trial they performed as well as control rats. Also, in adult rats, ethanol-induced impairments were quickly reversed after the ethanol treatment was over, a finding that suggests impaired motor coordination more than a true learning deficit. Together, these data indicate that repeated ethanol treatment in adolescent rats, but not adult rats, show long-term impairments in maze performance.
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Alcohol. Clin. Exp. Res. · Jul 2005
Temporal differences in the ability of ethanol to modulate endotoxin-induced increases in inflammatory cytokines in muscle under in vivo conditions.
Acute alcohol (EtOH) intoxication may both antagonize and potentiate the ability of monocytes/macrophages to respond to endotoxin (lipopolysaccharide [LPS]). The suppressive effects of EtOH predominate when the duration between EtOH and LPS administration is relatively short, whereas sensitization is observed under conditions when there is a relatively longer delay between EtOH and LPS exposure. Striated muscle is now recognized to possess components of both the afferent and efferent limbs of the innate immune system. The aim of the present study was to determine whether the interval between EtOH and LPS administration differentially affects the mRNA content for selected elements of the innate immune response in skeletal and cardiac muscle and to compare such changes with those occurring in liver and spleen. ⋯ Under in vivo conditions, the interval between EtOH exposure and LPS differentially affected the synthesis of various cytokines. In this regard, EtOH administered within two hr of LPS generally suppressed IL-6, IL-1beta, and TNF-alpha mRNAs in muscle, heart, liver, and spleen. Delaying the exposure of animals to LPS for 24 hr after EtOH, however, accentuated the increase in IL-6 and HMGB1, and for IL-6, this increased sensitivity appeared localized to striated muscle.
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Alcohol. Clin. Exp. Res. · Jun 2005
Ethanol-induced activation of myosin light chain kinase leads to dysfunction of tight junctions and blood-brain barrier compromise.
Brain endothelial cells form the blood-brain barrier (BBB) that regulates solute and macromolecule flux in and out of the brain, leukocyte migration, and maintains the homeostasis of the central nervous system. BBB dysfunction is associated with disruption of tight junctions (TJ) in the brain endothelium. We propose that alcohol abuse may impair BBB permeability through TJ modification. ⋯ These results suggest that EtOH activates MLCK leading to phosphorylation of MLC, occludin and claudin-5. Cytoskeletal alterations (MLC) and TJ changes (occludin and claudin-5 phosphorylation) result in BBB impairment (decrease in TEER). TJ compromise is associated with increased monocyte migration across the BBB.
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Alcohol. Clin. Exp. Res. · May 2005
Effectiveness of the derived Alcohol Use Disorders Identification Test (AUDIT-C) in screening for alcohol use disorders and risk drinking in the US general population.
The three consumption questions from the Alcohol Use Disorders Identification Test (AUDIT-C) are increasingly used as a screener for alcohol use disorders (AUDs) and risk drinking. ⋯ The derived AUDIT-C performs well in screening for AUDs and risk drinking. The use of variable cut points for men and women improves its sensitivity and specificity. Validation in a realistic screening situation, in which the AUDIT-C questions are asked as stand-alone and not embedded items, is a critical future step.