epidermal-growth-factor and Alcoholism

Topics: Adult; Aged; Aging; Alcoholism; Amino Acids; Anesthetics, Local; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Aqueous Humor; Autonomic Nervous System; Biological Transport, Active; Brain Chemistry; Cardiac Glycosides; Catecholamines; Cell Differentiation; Central Nervous System; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Epidermal Growth Factor; Eye; Fibrinolysis; Glaucoma; Granuloma; Graves Disease; Hallucinogens; Humans; Hypertension; Immunity, Cellular; Infant; Infant, Newborn; Leukotriene B4; Metabolism, Inborn Errors; Multiple Sclerosis; Muscle Relaxation; Nutritional Physiological Phenomena; Oxygen; Oxygen Consumption; Pigment Epithelium of Eye; Pineal Gland; Prostaglandin Antagonists; Prostaglandins; Psychotropic Drugs; Retina; Retinal Degeneration; Serotonin; Smoking; SRS-A; Stress, Physiological; Water-Electrolyte Balance

To assess changes in metabolic risk factors and cancer-related growth factors associated with short-term abstinence from alcohol.. Prospective, observational study.. Single tertiary centre.. Healthy subjects were recruited based on intention to: (1) abstain from alcohol for 1 month (abstinence group), or (2) continue to drink alcohol (control group). Inclusion criteria were baseline alcohol consumption >64 g/week (men) or >48 g/week (women). Exclusion criteria were known liver disease or alcohol dependence.. The primary outcome was change in insulin resistance (homeostatic model assessment (HOMA) score). Secondary outcomes were changes in weight, blood pressure (BP), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and liver function tests. Primary and secondary outcomes were adjusted for changes in diet, exercise and cigarette smoking.. The abstinence group comprised 94 participants (mean age 45.5 years, SD ±1.2) and the control group 47 participants (mean age 48.7 years, SD ±1.8). Baseline alcohol consumption in the abstinence group was 258.2 g/week, SD ±9.4, and in the control group 233.8 g, SD ±19.0. Significant reductions from baseline in the abstinence group (all p<0.001) were found in: HOMA score (-25.9%, IQR -48.6% to +0.3%), systolic BP (-6.6%, IQR -11.8% to 0.0%), diastolic BP (-6.3%, IQR -14.1% to +1.3%), weight (-1.5%, IQR -2.9% to -0.4%), VEGF (-41.8%, IQR -64.9% to -17.9%) and EGF (-73.9%, IQR -86.1% to -36.4%). None of these changes were associated with changes in diet, exercise or cigarette smoking. No significant changes from baseline in primary or secondary outcomes were noted in the control group.. These findings demonstrate that abstinence from alcohol in moderate-heavy drinkers improves insulin resistance, weight, BP and cancer-related growth factors. These data support an independent association of alcohol consumption with cancer risk, and suggest an increased risk of metabolic diseases such as type 2 diabetes and fatty liver disease.

Topics: Adult; Alcohol Drinking; Alcoholism; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Epidermal Growth Factor; Ethanol; Fatty Liver; Female; Humans; Insulin Resistance; Liver; Liver Function Tests; Male; Middle Aged; Neoplasms; Prospective Studies; Risk Factors; Vascular Endothelial Growth Factor A

Studies of alcohol dependence (AD) have consistently found evidence of linkage on chromosome 4q21-q32. A genome-wide linkage scan in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD) sample also provided its strongest evidence of linkage on chromosome 4q22-q32 using an index of AD severity based on the count of DSM-IV AD symptoms (ADSX; LOD = 4.59). We conducted a systematic, gene-centric association study using 518 LD-tagging single nucleotide polymorphisms (SNPs) in the 65 known and predicted genes within the 1-LOD interval surrounding the linkage peak. Case-only regression analysis with the quantitative variable of ADSX was performed in the 562 genetically independent cases; nominal support for association was demonstrated by 32 tagging SNPs in 14 genes. We did not observe study-wide significance, but gene-wise correction for multiple testing with the Nyholt procedure yielded empirical evidence of association with two genes, DKK2 (dickkopf homolog 2) (P = 0.007) and EGF (epidermal growth factor) (P = 0.025) in the IASPSAD sample. Three SNPs in DKK2 (rs427983; rs419558; rs399087) demonstrated empirical significance. Assessment of possible replication in 847 cases of European descent from a large independent sample, the Collaborative Study of the Genetics of Alcoholism, yielded replication for DKK2 but not EGF. We observed genotypic and phenotypic replication for DKK2 with the three SNPs yielding significant association with ADSX in the IASPSAD sample. Haplotype-specific expression measurements in post-mortem tissue samples suggested a functional role for DKK2. This evidence notwithstanding, replication is needed before confidence can be placed in these findings.

Topics: Alcoholism; Chromosomes, Human, Pair 4; Epidermal Growth Factor; Female; Genetic Linkage; Genetic Predisposition to Disease; Genome-Wide Association Study; Haplotypes; Humans; Intercellular Signaling Peptides and Proteins; Male; Polymorphism, Single Nucleotide

Alcohol abuse during pregnancy compromises fetal development not only directly but also by abnormal placental function. Therefore, hepatocyte growth factor (HGF), epidermal growth factor (EGF), and placenta growth factor (PlGF), expressed in the placenta, may play a role in alcohol-induced placental dysfunction.. Peripheral venous blood samples were collected from 40 pregnant alcohol-abusing women and 42 abstinent pregnant women from gestational weeks 4 to 41. Plasma HGF and serum PlGF were assessed by enzyme-linked immunosorbent assays and serum EGF by an immunofluorometric assay.. Plasma HGF concentrations were similar in alcohol-abusing and abstinent mothers, although in the latter women these concentrations increased with advancing pregnancy. Serum EGF concentrations were consistently higher in alcohol-abusing than in abstinent mothers. In the latter, these concentrations decreased with advancing pregnancy. Serum PlGF concentrations increased with advancing pregnancy in both groups and were higher in alcohol-abusing mothers during the second and third trimesters but not during the first.. Alcohol abuse during pregnancy is associated with changes in maternal circulating EGF and PlGF but not HGF concentrations. The observed changes may be caused by alcohol per se or may be secondary to possible alcohol-induced changes in placental physiology.

Topics: Adolescent; Adult; Alcoholism; Epidermal Growth Factor; Female; Hepatocyte Growth Factor; Humans; Placenta Growth Factor; Pregnancy; Pregnancy Proteins; Statistics, Nonparametric

Our objective was to investigate the putative role of epidermal growth factor (EGF) in esophagitis pathogenesis in both nondrinkers and chronic alcoholics. We studied the EGF serum level, the EGF salivary concentration, and the esophageal EGF receptor expression in different groups of patients with esophagitis: nondrinkers with typical symptoms of gastroesophageal reflux (N = 12) and chronic alcoholics (N = 12), and in controls: chronic alcoholics without esophagitis (N = 16) and healthy nondrinkers (N = 12). All patients had an endoscopy with esophageal biopsies, 24-hr esophageal pH-metry, and esophageal manometry. EGF serum levels and EGF salivary concentrations were determined by radioimmunoassay. EGF receptor expression was determined by immunohistochemistry. Both the EGF serum level and the EGF salivary concentration remained constant, 328 +/- 21 pg/ml and 305 +/- 48 pg/ml, respectively, regardless of alcohol intake and the presence or absence of esophagitis. In addition, the presence of esophagitis did not affect the EGF receptor expression. These results suggest that seric and salivary EGF is not involved in the pathogenesis of reflux esophagitis in nondrinkers and in chronic alcoholics.

Topics: Adult; Alcoholism; Epidermal Growth Factor; ErbB Receptors; Esophagitis; Esophagitis, Peptic; Esophagus; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Immunohistochemistry; Male; Manometry; Middle Aged; Monitoring, Physiologic; Prospective Studies; Radioimmunoassay; Saliva

We tested the hypothesis that ethanol impairs liver regeneration by abrogating receptor-mediated elevation of cytosolic free calcium ([Ca2+]i). In rats fed for 16 weeks with ethanol, hepatocellular proliferation induced by partial hepatectomy was greatly impaired. Similarly, EGF-induced DNA synthesis was reduced in cultured hepatocytes from ethanol-fed rats. There was no change in the number or affinity of EGF receptors on hepatocytes from ethanol-fed rats. Despite this, EGF-mediated production of inositol 1,4,5-trisphosphate (Ins[1,4,5]P3) was lower in hepatocytes from ethanol-fed rats, and the EGF-induced [Ca2+]i transient appeared to be abrogated. When vasopressin or phenylephrine were used as cell surface receptor ligands, hepatocytes cultured from ethanol-fed rats exhibited major reductions in Ins(1,4,5)P3 synthesis. This was associated with greatly truncated [Ca2+]i transients. These changes were not due to an effect on the Ins(1,4,5)P3 receptor on the endoplasmic reticulum or to a decrease in the size of the Ins(1,4,5)P3-mobilizable intracellular Ca+2 store. Further, mobilization of the same Ca2+ store by 2,5-di-tert-butylhydroquinone or thapsigargin restored the ability of hepatocytes from ethanol-fed rats to proliferate when exposed to EGF. It is concluded that chronic ethanol consumption inhibits liver regeneration by a mechanism that is, at least partly, the result of impaired receptor-operated [Ca2+]i signaling due to reduced generation of Ins(1,4,5)P3.

Topics: Alcoholism; Animals; Calcium; Cell Membrane; Cell Membrane Permeability; Cells, Cultured; Epidermal Growth Factor; Hepatectomy; Inositol 1,4,5-Trisphosphate; Liver; Liver Regeneration; Male; Phenylephrine; Protein Binding; Rats; Rats, Wistar; Receptors, Cell Surface; Vasopressins

Parotid saliva samples from 24 alcoholic subjects without evidence of cirrhosis were analyzed for changes in flow rate, composition, and epidermal growth factor (EGF) secretion. Mean (+/- SE) stimulated parotid saliva flow rate (ml/min/gland) was significantly (p less than 0.01) lower in alcoholic subjects than in matched control subjects. Reduction in parotid saliva flow rate was associated with significant (p less than 0.05) decrease in total protein and amylase secretion in this group of patients. In addition, secretion of immunoreactive EGF, a specific salivary protein, was also markedly reduced (p less than 0.05) in alcoholic patients. None of the parotid saliva samples from the alcoholic subjects had detectable bioactivity of EGF in saliva. These data suggest that chronic alcohol ingestion is associated with significant changes in parotid saliva secretion and its composition, which may perpetuate and compound ethanol-induced injury to the upper gastrointestinal tract.

Topics: Adult; Alcoholism; Amylases; Electrolytes; Epidermal Growth Factor; Humans; Male; Middle Aged; Parotid Gland; Radioimmunoassay; Saliva; Salivary Proteins and Peptides