Alcohol abuse and glycoconjugate metabolism

The relationship between alcohol consumption and glycoconjugate metabolism is complex and multidimensional. This review summarizes the advances in basic and clinical research on the molecular and cellular events involved in the metabolic effects of alcohol on glycoconjugates (glycoproteins, glycolipids, and proteoglycans). We summarize the action of ethanol, acetaldehyde, reactive oxygen species (ROS), nonoxidative metabolite of alcohol — fatty acid ethyl esters (FAEEs), and the ethanol-water competition mechanism, on glycoconjugate biosynthesis, modification, transport and secretion, as well as on elimination and catabolism processes. As the majority of changes in the cellular metabolism of glycoconjugates are generally ascribed to alterations in synthesis, transport, glycosylation and secretion, the degradation and elimination processes, of which the former occurs also in extracellular matrix, seem to be underappreciated. The pathomechanisms are additionally complicated by the fact that the effect of alcohol intoxication on the glycoconjugate metabolism depends not only on the duration of ethanol exposure, but also demonstrates dose- and regional-sensitivity. Further research is needed to bridge the gap in transdisciplinary research and enhance our understanding of alcohol- and glycoconjugate-related diseases

Salivary lysozyme in smoking alcohol dependent persons

The purpose of the study was evaluation the effect of chronic alcohol intoxication and smoking, on the concentration and output of salivary lysozyme. In the study participated 37 persons, consisted of 17 male smoking patients after chronic alcohol intoxication (AS), and 20 control nonsmoking male social drinkers (CNS) with no history of alcohol abuse or smoking. For all participants the DMFT index (decayed, missing, or filled teeth), gingival index (GI) and papilla bleeding index (PBI) were assessed. Resting whole saliva was collected 24 to 48 hours after chronic alcohol intoxication period. Level of lysozyme was assessed by radial immunodiffusion method. The differences between groups were evaluated using Mann-Whitney “U” test. Salivary flow (SF) was significantly lower in smoking alcohol dependent persons than in the control group. It was found a tendency to increase in the concentration of lysozyme and significantly lower lysozyme output in smoking persons chronically intoxicated by alcohol, as compared to the control group. Gingival index was significantly higher in smoking alcohol dependent persons than in the control group, whereas there were no significant differences in PBI and DMFT indexes between these groups. There were no significant correlations between the amount/number and length of alcohol consumption as well as cigarette smoking, and the concentration as well as the output of lysozyme. There were also no significant correlations between salivary lysozyme output/concentration and SF. In conclusion, reduced salivary flow and salivary lysozyme output may impair innate immunity of the oral cavity. Reduced levels of salivary flow and salivary lysozyme output seem to be more likely to be the result of ethanol action than smoking. We confirmed that persons addicted to alcohol and cigarettes have worse periodontal condition than general population, which partially may be due to the decreased protective effect of reduced salivary flow and lysozyme output

The effect of chronic alcohol intoxication and smoking on the output of salivary immunoglobulin A

It was investigated the effect of chronic alcohol intoxication and smoking, on the output of salivary immunoglobulin A (IgA). In the study participated 37 volunteers: 17 male smoking patients after chronic alcohol intoxication (AS) and 20 control nonsmoking male social drinkers (CNS). The DMFT index (decayed, missing, or filled teeth), gingival index (GI) and papilla bleeding index (PBI) were assessed. Levels of IgA were determined by the enzyme-linked immunosorbent method. There were significantly decreased salivary flow (SF) and IgA output in AS, when compared to the CNS. There were no significant correlations between amount of alcohol/cigarettes as well as  duration of alcohol intoxication/smoking, and SF or IgA output, and between IgA and SF. Gingival index was significantly higher in AS than in CNS, and inversely correlated with IgA. It is more probable that SF and IgA decrease, are the result of ethanol action than smoking. Worse periodontal state in smoking alcohol dependent persons than in controls, may be the result of lower IgA protection of the oral cavity due to its decreased output

Decrease in salivary lactoferrin output in chronically intoxicated alcohol-dependent patients

Salivary lactoferrin is a glycoprotein involved in the elimination of pathogens and the prevention of massive overgrowth of microorganisms that affect oral and general health. A high concentration of lactoferrin in saliva is often considered to be a marker of damage to the salivary glands, gingivitis, or leakage through inflamed or damaged oral mucosa, infiltrated particularly by neutrophils. We conducted a study to determine the effect of chronic alcohol intoxication on salivary lactoferrin concentration and output. The study included 30 volunteers consisting of ten non-smoking male patients after chronic alcohol intoxication (group A), and 20 control nonsmoking male social drinkers (group C) with no history of alcohol abuse. Resting whole saliva was collected 24 to 48 hours after a chronic alcohol intoxication period. Lactoferrin was assessed by enzyme-linked immunosorbent assay. For all participants, the DMFT index (decayed, missing, or filled teeth), gingival index (GI) and papilla bleeding index (PBI) were assessed. The differences between groups were evaluated using the Mann–Whitney U test. We noticed significantly decreased salivary flow (SF) in alcohol dependent patients after chronic alcohol intoxication (A), compared to the control group (C). Although there was no significant difference in salivary lactoferrin concentration between the alcohol dependent group A and the control group C, we found significantly decreased lactoferrin output in group A compared to group C. We found a significant correlation between the amount of daily alcohol use and a decrease in lactoferrin output. There was a significant increase in GI and a tendency of PBI to increase in group A compared to group C. We demonstrated that chronic alcohol intoxication decreases SF and lactoferrin output. The decreased lactoferrin output in persons chronically intoxicated by alcohol may be the result of lactoferrin exhaustion during drinking (due to its alcohol-related lower biosynthesis or higher catabolism) or to decreased function of neutrophils affected by the ethanol. The poorer periodontal state in alcohol dependent persons compared to controls may be a result of lower salivary flow and decreased protection of the oral cavity by lactoferrin

Time to Osteoporosis and Major Fracture in Older Men

For older men who undergo bone mineral density (BMD) testing, the optimal osteoporosis screening schedule is unknown. Time-to-disease estimates are necessary to inform screening intervals

Time to Osteoporosis and Major Fracture in Older Men

For older men who undergo bone mineral density (BMD) testing, the optimal osteoporosis screening schedule is unknown. Time-to-disease estimates are necessary to inform screening intervals

Epigenetic Dysregulation in Mesenchymal Stem Cell Aging and Spontaneous Differentiation

BACKGROUND: Mesenchymal stem cells (MSCs) hold great promise for the treatment of difficult diseases. As MSCs represent a rare cell population, ex vivo expansion of MSCs is indispensable to obtain sufficient amounts of cells for therapies and tissue engineering. However, spontaneous differentiation and aging of MSCs occur during expansion and the molecular mechanisms involved have been poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Human MSCs in early and late passages were examined for their expression of genes involved in osteogenesis to determine their spontaneous differentiation towards osteoblasts in vitro, and of genes involved in self-renewal and proliferation for multipotent differentiation potential. In parallel, promoter DNA methylation and hostone H3 acetylation levels were determined. We found that MSCs underwent aging and spontaneous osteogenic differentiation upon regular culture expansion, with progressive downregulation of TERT and upregulation of osteogenic genes such as Runx2 and ALP. Meanwhile, the expression of genes associated with stem cell self-renewal such as Oct4 and Sox2 declined markedly. Notably, the altered expression of these genes were closely associated with epigenetic dysregulation of histone H3 acetylation in K9 and K14, but not with methylation of CpG islands in the promoter regions of most of these genes. bFGF promoted MSC proliferation and suppressed its spontaneous osteogenic differentiation, with corresponding changes in histone H3 acetylation in TERT, Oct4, Sox2, Runx2 and ALP genes. CONCLUSIONS/SIGNIFICANCE: Our results indicate that histone H3 acetylation, which can be modulated by extrinsic signals, plays a key role in regulating MSC aging and differentiation