Chronic alcohol abuse exacts a major social and medical toll in the United States and other Western countries. One of the least appreciated medical complications of alcohol abuse is altered immune regulation leading to immunodeficiency and autoimmunity. The consequences of the immunodeficiency include increased susceptibility to bacterial pneumonia, tuberculosis, and other infectious diseases. In addition, the chronic alcoholic often has circulating autoantibodies, and recent investigations indicate that the most destructive complications of alcoholism, such as liver disease and liver failure, may have a component of autoimmunity. Current research on altered cytokine balance produced by alcohol is leading to new insights on the regulation of the immune system in the chronic alcoholic. There is also recent development of exciting new techniques designed to improve or restore immune function by manipulation of cytokine balance. Although much remains to be learned, both in the abnormalities produced by alcohol and in the techniques to reverse those abnormalities, current progress reflects a rapidly improving understanding of the basic immune disorders of the alcoholic.

Alcohol Abuse, Alcoholism, and Damage to the Immune System—A Review

Alcoholic liver disease (ALD) develops as a consequence of priming and sensitizing mechanisms rendered by cross-interactions of primary mechanistic factors and secondary risk factors. This concept, albeit not novel, is becoming widely accepted by the field, and more research is directed toward identifying and characterizing the interfaces of the cross-interactions to help understand individual predisposition to the disease. Another pivotal development is the beginning of cell type-specific research to elucidate specific contributions not only of hepatocytes, but also of hepatic macrophages, liver-associated lymphocytes, sinusoidal endothelial cells, and hepatic stellate cells to sensitizing and priming mechanisms. In particular, the critical role of hepatic macrophages has been highlighted and the priming mechanisms concerning this paracrine effect have been proposed. Glutathione depletion in hepatocyte mitochondria is considered the most important sensitizing mechanism. One of the contributing factors is decreased methionine metabolism. Remaining key questions include how altered methionine metabolism contribute to the pathogenesis of ALD; how cross-talk among nonparenchymal liver cells or between nonparenchymal cells and hepatocytes leads to ALD; how dysfunctional mitochondria determine the type of cell death in ALD; and what secondary factors are critical for the development of advanced ALD such as alcoholic hepatitis and cirrhosis.

Current concepts in the pathogenesis of alcoholic liver injury

The role of the anaerobic metabolites, acetaldehyde and ethanol, in fruit ripening, enhancement of fruit quality and fruit deterioration

Measuring Alcohol Consumption

A method and apparatus for enhancing the integrity of an implantable sensor. Voids formed between an outer tubing and a sensor substrate or spacing element may be back-filled with a curable, implantable material, minimizing the extent to which unwanted fluids diffuse within the sensor. An enzyme or protein matrix pellet below the sensor window may be pre-treated with a reducing agent to enhance its bond stability, and to reduce undesired swelling that may cause the sensor window to detach or leak. The bonding between the enzyme pellet and a hydrogel layer may be reinforced by application of an intervening bonding layer of a protein material, such as human serum albumin (HSA). The size of the window may be minimized by minimizing the size of an underlying electrode, providing reduced flux and lengthening sensor. A coating may be deposited on the surface of the sensor leads, providing stiffening and lubrication.

Method and apparatus for enhancing the integrity of an implantable sensor device

The results of this study demonstrate that lysine is the major amino acid participating in the binding of acetaldehyde to proteins. The formation of both stable and unstable acetaldehyde-albumin adducts was shown to occur via the reaction of acetaldehyde with lysine residues. This conclusion was based on the following experimental evidence: (a) the ratio of stable to unstable adducts of bovine serum albumin was similar to that observed for polylysine; (b) acetylation of albumin markedly reduced acetaldehyde binding; (c) the radio-activity profiles (obtained by high-performance liquid chromatographic analysis) of [14C]acetaldehyde modified amino acids hydrolyzed from total and stable adducts of albumin were nearly identical to those of polylysine or alpha-t-boc-lysine. Analysis of stable adducts of albumin indicated two major modified lysine residues; one residue was much more acidic and the other more basic than unmodified lysine. Unstable adducts were shown to be Schiff bases since NaBH4 treatment resulted in the formation of N-ethyllysine residues. The reducing agents, NaCNBH3 and ascorbic acid, both increased stable adduct formation via increased binding to lysine residues; however, a different elution profile of modified lysine residues was observed for these reducing agents. NaCNBH3 increased the formation of N-ethyllysine residues exclusively, whereas ascorbate increased the formation of the acidic adduct of lysine and also caused the formation of an additional modified lysine residue which was present only in the ascorbate-treated polypeptides. In addition to their detection by radioactivity measurements, the acetaldehyde-lysine adducts could also be detected by the fluorescence of their ophthalaldehyde derivatives.(ABSTRACT TRUNCATED AT 250 WORDS)

Monte R. Newman

Papers

Covalent Binding of Acetaldehyde to Proteins: Participation of Lysine Residues