Insulin-Like growth-factor 1 myocardial expression decreases in chronic alcohol consumption

Background Chronic alcohol ingestion may cause severe biochemical and pathophysiological derangements to skeletal muscle. Unfortunately, these alcohol-induced events may also prime skeletal muscle for worsened, delayed, or possibly incomplete repair following acute injury. As alcoholics may be at increased risk for skeletal muscle injury, our goals were to identify the effects of chronic alcohol ingestion on components of skeletal muscle regeneration. To accomplish this, age- and gender-matched C57Bl/6 mice were provided normal drinking water or water that contained 20% alcohol (v/v) for 1820 wk. Subgroups of mice were injected with a 1.2% barium chloride (BaCl2) solution into the tibialis anterior (TA) muscle to initiate degeneration and regeneration processes. Body weights and voluntary wheel running distances were recorded during the course of recovery. Muscles were harvested at 2, 7 or 14 days post-injection and assessed for markers of inflammation and oxidant stress, fiber cross-sectional areas, levels of growth and fibrotic factors, and fibrosis. Results Body weights of injured, alcohol-fed mice were reduced during the first week of recovery. These mice also ran significantly shorter distances over the two weeks following injury compared to uninjured, alcoholics. Injured TA muscles from alcohol-fed mice had increased TNFα and IL6 gene levels compared to controls 2 days after injury. Total protein oxidant stress and alterations to glutathione homeostasis were also evident at 7 and 14 days after injury. Ciliary neurotrophic factor (CNTF) induction was delayed in injured muscles from alcohol-fed mice which may explain, in part, why fiber cross-sectional area failed to normalize 14 days following injury. Gene levels of TGFβ1 were induced early following injury before normalizing in muscle from alcohol-fed mice compared to controls. However, TGFβ1 protein content was consistently elevated in injured muscle regardless of diet. Fibrosis was increased in injured, muscle from alcohol-fed mice at 7 and 14 days of recovery compared to injured controls. Conclusions Chronic alcohol ingestion appears to delay the normal regenerative response following significant skeletal muscle injury. This is evidenced by reduced cross-sectional areas of regenerated fibers, increased fibrosis, and altered temporal expression of well-described growth and fibrotic factors.

Insulin-Like growth-factor 1 myocardial expression decreases in chronic alcohol consumption

Background Chronic alcohol ingestion may cause severe biochemical and pathophysiological derangements to skeletal muscle. Unfortunately, these alcohol-induced events may also prime skeletal muscle for worsened, delayed, or possibly incomplete repair following acute injury. As alcoholics may be at increased risk for skeletal muscle injury, our goals were to identify the effects of chronic alcohol ingestion on components of skeletal muscle regeneration. To accomplish this, age- and gender-matched C57Bl/6 mice were provided normal drinking water or water that contained 20% alcohol (v/v) for 18-20 wk. Subgroups of mice were injected with a 1.2% barium chloride (BaCl2) solution into the tibialis anterior (TA) muscle to initiate degeneration and regeneration processes. Body weights and voluntary wheel running distances were recorded during the course of recovery. Muscles were harvested at 2, 7 or 14 days post-injection and assessed for markers of inflammation and oxidant stress, fiber cross-sectional areas, levels of growth and fibrotic factors, and fibrosis. Results Body weights of injured, alcohol-fed mice were reduced during the first week of recovery. These mice also ran significantly shorter distances over the two weeks following injury compared to uninjured, alcoholics. Injured TA muscles from alcohol-fed mice had increased TNFα and IL6 gene levels compared to controls 2 days after injury. Total protein oxidant stress and alterations to glutathione homeostasis were also evident at 7 and 14 days after injury. Ciliary neurotrophic factor (CNTF) induction was delayed in injured muscles from alcohol-fed mice which may explain, in part, why fiber cross-sectional area failed to normalize 14 days following injury. Gene levels of TGFβ1 were induced early following injury before normalizing in muscle from alcohol-fed mice compared to controls. However, TGFβ1 protein content was consistently elevated in injured muscle regardless of diet. Fibrosis was increased in injured, muscle from alcohol-fed mice at 7 and 14 days of recovery compared to injured controls. Conclusions Chronic alcohol ingestion appears to delay the normal regenerative response following significant skeletal muscle injury. This is evidenced by reduced cross-sectional areas of regenerated fibers, increased fibrosis, and altered temporal expression of well-described growth and fibrotic factors.

High amplitude contractions in the middle third of the esophagus: a manometric marker of chronic alcoholism?

BACKGROUND--Oesophageal motor abnormalities have been reported in alcoholism. AIM--To investigate the effects of chronic alcoholism and its withdrawal on oesophageal disease. PATIENTS--23 chronic alcoholic patients (20 men and three women; mean age 43, range 23 to 54). METHODS--Endoscopy, manometry, and 24 hour pH monitoring 7-10 days and six months after ethanol withdrawal. Tests for autonomic and peripheral neuropathy were also performed. Motility and pH tracings were compared with those of age and sex matched control groups: healthy volunteers, nutcracker oesophagus, and gastro-oesophageal reflux disease. RESULTS--14 (61%) alcoholic patients had reflux symptoms, and endoscopy with biopsy showed oesophageal inflammation in 10 patients. One patient had an asymptomatic squamous cell carcinoma. Oesophageal motility studies in the alcoholic patients showed that peristaltic amplitude in the middle third was > 150 mm Hg (95th percentile (P95) of healthy controls) in 13 (57%), the ratio lower/ middle amplitude was < 0.9 in 15 (65%) (> 0.9 in all control groups), and the lower oesophageal sphincter was hypertensive (> 23.4 mm Hg, P95 of healthy controls) in 13 (57%). All three abnormalities were present in five (22%). Abnormal reflux (per cent reflux time > 2.9, P95 of healthy controls) was shown in 12 (52%) alcoholic patients, and was unrelated to peristaltic dysfunction. Subclinical neuropathy in 10 patients did not effect oesophageal abnormalities. Oesophageal motility abnormalities persisted at six months in six patients with ongoing alcoholism, whereas they reverted towards normal in 13 who remained abstinent; reflux, however, was unaffected. CONCLUSIONS--Oesophageal peristaltic dysfunction and reflux are frequent in alcoholism. High amplitude contractions in the middle third of the oesophagus seem to be a marker of excessive alcohol consumption, and tend to improve with abstinence.

Effect of chronic ethanol feeding on glutathione and functional integrity of mitochondria in periportal and perivenous rat hepatocytes.

Chronic ethanol feeding selectively impairs the translocation of cytosol GSH into the mitochondrial matrix. Since ethanol-induced liver cell injury is preferentially localized in the centrilobular area, we examined the hepatic acinar distribution of mitochondrial GSH transport in ethanol-fed rats. Enriched periportal (PP) and perivenous (PV) hepatocytes from pair- and ethanol-fed rats were prepared as well as mitochondria from these cells. The mitochondrial pool size of GSH was decreased in both PP and PV cells from ethanol-fed rats either as expressed per 10(6) cells or per microliter of mitochondrial matrix volume. The rate of reaccumulation of mitochondrial GSH and the linear relationship of mitochondrial to cytosol GSH from ethanol-fed mitochondria were lower for both PP and PV cells, effects observed more prominently in the PV cells. Mitochondrial functional integrity was lower in both PP and PV ethanol-fed rats, which was associated with decreased cellular ATP levels and mitochondrial membrane potential, effects which were greater in the PV cells. Mitochondrial GSH depletion by ethanol feeding preceded the onset of functional changes in mitochondria, suggesting that mitochondrial GSH is critical in maintaining a functionally competent organelle and that the greater depletion of mitochondrial GSH by ethanol feeding in PV cells could contribute to the pathogenesis of alcoholic liver disease.

High amplitude contractions in the middle third of the esophagus: a manometric marker of chronic alcoholism?

BACKGROUND--Oesophageal motor abnormalities have been reported in alcoholism. AIM--To investigate the effects of chronic alcoholism and its withdrawal on oesophageal disease. PATIENTS--23 chronic alcoholic patients (20 men and three women; mean age 43, range 23 to 54). METHODS--Endoscopy, manometry, and 24 hour pH monitoring 7-10 days and six months after ethanol withdrawal. Tests for autonomic and peripheral neuropathy were also performed. Motility and pH tracings were compared with those of age and sex matched control groups: healthy volunteers, nutcracker oesophagus, and gastro-oesophageal reflux disease. RESULTS--14 (61%) alcoholic patients had reflux symptoms, and endoscopy with biopsy showed oesophageal inflammation in 10 patients. One patient had an asymptomatic squamous cell carcinoma. Oesophageal motility studies in the alcoholic patients showed that peristaltic amplitude in the middle third was > 150 mm Hg (95th percentile (P95) of healthy controls) in 13 (57%), the ratio lower/ middle amplitude was < 0.9 in 15 (65%) (> 0.9 in all control groups), and the lower oesophageal sphincter was hypertensive (> 23.4 mm Hg, P95 of healthy controls) in 13 (57%). All three abnormalities were present in five (22%). Abnormal reflux (per cent reflux time > 2.9, P95 of healthy controls) was shown in 12 (52%) alcoholic patients, and was unrelated to peristaltic dysfunction. Subclinical neuropathy in 10 patients did not effect oesophageal abnormalities. Oesophageal motility abnormalities persisted at six months in six patients with ongoing alcoholism, whereas they reverted towards normal in 13 who remained abstinent; reflux, however, was unaffected. CONCLUSIONS--Oesophageal peristaltic dysfunction and reflux are frequent in alcoholism. High amplitude contractions in the middle third of the oesophagus seem to be a marker of excessive alcohol consumption, and tend to improve with abstinence.

Lymphocyte populations in liver biopsy specimens from patients with chronic liver disease

The characterisation of lymphocytes from liver biopsies indicates that 'activated' T lymphocytes are present in the liver in alcohol induced hepatitis, chronic active hepatitis (HBS+ve and -ve), and in primary biliary cirrhosis but not in inactive cirrhosis, chronic persistent hepatitis, extrahepatic and drug induced cholestasis. A greater percentage of lymphocytes bear Fc-receptors in chronic active hepatitis than in alcohol induced hepatitis or cholestatic liver disease. The concentration of 'activated' T cells in the peripheral blood in all groups studied was within the normal range, suggesting that the 'activated' T cells found in the liver were reacting to either native or foreign antigens within the liver. The data on Fc-receptor bearing cells are consistent with the involvement of antibody assisted K cell mediated cytotoxicity in chronic active hepatitis.

Effects of prolonged ethanol intake and malnutrition on rat pancreas

Nutritional factors, especially the protein and fat content of the diet, may change pancreatic morphology after ethanol induced injury. This study was performed to delineate the combined effects of a low fat diet and longterm ethanol ingestion on the rat pancreas. Male Sprague-Dawley rats were maintained with five different diets for 12 weeks and the pancreas removed on the day they were killed. Rats fed a very low fat diet without ethanol (5% of total calories as lipid) developed malnutrition, pancreatic steatosis, and reduction in zymogen granules content. Animals fed a 35% lipid diet with ethanol also developed pancreatic steatosis but changes in zymogen granules content were not detected. Both malnutrition and longterm ethanol consumption increased pancreatic cholesterol ester content, and their effects were additive. Pancreatic steatosis was accompanied with hypercholesterolaemia. Amylase, lipase, and cholesterol esterase content were reduced in malnourished rats; but longterm ethanol ingestion, regardless of the nutritional state, increased lipase content and decreased amylase. It is suggested that high serum cholesterol concentrations and increased pancreatic lipase activity could cause accumulation of cholesterol esters in acinar cells. Fat accumulation in the pancreas has been reported as the earliest histopathological feature in alcoholic patients and may be responsible for cytotoxic effects on the acinar cells at the level of the cell membrane. Although it is difficult to extrapolate results in this animal study to the human situation, the results presented in this work might explain the higher incidence of pancreatitis is malnourished populations as well as in alcoholic subjects that is reported in dietary surveys.

Effects of prolonged ethanol intake and malnutrition on rat pancreas

Nutritional factors, especially the protein and fat content of the diet, may change pancreatic morphology after ethanol induced injury. This study was performed to delineate the combined effects of a low fat diet and longterm ethanol ingestion on the rat pancreas. Male Sprague-Dawley rats were maintained with five different diets for 12 weeks and the pancreas removed on the day they were killed. Rats fed a very low fat diet without ethanol (5% of total calories as lipid) developed malnutrition, pancreatic steatosis, and reduction in zymogen granules content. Animals fed a 35% lipid diet with ethanol also developed pancreatic steatosis but changes in zymogen granules content were not detected. Both malnutrition and longterm ethanol consumption increased pancreatic cholesterol ester content, and their effects were additive. Pancreatic steatosis was accompanied with hypercholesterolaemia. Amylase, lipase, and cholesterol esterase content were reduced in malnourished rats; but longterm ethanol ingestion, regardless of the nutritional state, increased lipase content and decreased amylase. It is suggested that high serum cholesterol concentrations and increased pancreatic lipase activity could cause accumulation of cholesterol esters in acinar cells. Fat accumulation in the pancreas has been reported as the earliest histopathological feature in alcoholic patients and may be responsible for cytotoxic effects on the acinar cells at the level of the cell membrane. Although it is difficult to extrapolate results in this animal study to the human situation, the results presented in this work might explain the higher incidence of pancreatitis is malnourished populations as well as in alcoholic subjects that is reported in dietary surveys.

Effects of prolonged ethanol intake and malnutrition on rat pancreas

Nutritional factors, especially the protein and fat content of the diet, may change pancreatic morphology after ethanol induced injury. This study was performed to delineate the combined effects of a low fat diet and longterm ethanol ingestion on the rat pancreas. Male Sprague-Dawley rats were maintained with five different diets for 12 weeks and the pancreas removed on the day they were killed. Rats fed a very low fat diet without ethanol (5% of total calories as lipid) developed malnutrition, pancreatic steatosis, and reduction in zymogen granules content. Animals fed a 35% lipid diet with ethanol also developed pancreatic steatosis but changes in zymogen granules content were not detected. Both malnutrition and longterm ethanol consumption increased pancreatic cholesterol ester content, and their effects were additive. Pancreatic steatosis was accompanied with hypercholesterolaemia. Amylase, lipase, and cholesterol esterase content were reduced in malnourished rats; but longterm ethanol ingestion, regardless of the nutritional state, increased lipase content and decreased amylase. It is suggested that high serum cholesterol concentrations and increased pancreatic lipase activity could cause accumulation of cholesterol esters in acinar cells. Fat accumulation in the pancreas has been reported as the earliest histopathological feature in alcoholic patients and may be responsible for cytotoxic effects on the acinar cells at the level of the cell membrane. Although it is difficult to extrapolate results in this animal study to the human situation, the results presented in this work might explain the higher incidence of pancreatitis is malnourished populations as well as in alcoholic subjects that is reported in dietary surveys.

Effects of prolonged ethanol intake and malnutrition on rat pancreas

Nutritional factors, especially the protein and fat content of the diet, may change pancreatic morphology after ethanol induced injury. This study was performed to delineate the combined effects of a low fat diet and longterm ethanol ingestion on the rat pancreas. Male Sprague-Dawley rats were maintained with five different diets for 12 weeks and the pancreas removed on the day they were killed. Rats fed a very low fat diet without ethanol (5% of total calories as lipid) developed malnutrition, pancreatic steatosis, and reduction in zymogen granules content. Animals fed a 35% lipid diet with ethanol also developed pancreatic steatosis but changes in zymogen granules content were not detected. Both malnutrition and longterm ethanol consumption increased pancreatic cholesterol ester content, and their effects were additive. Pancreatic steatosis was accompanied with hypercholesterolaemia. Amylase, lipase, and cholesterol esterase content were reduced in malnourished rats; but longterm ethanol ingestion, regardless of the nutritional state, increased lipase content and decreased amylase. It is suggested that high serum cholesterol concentrations and increased pancreatic lipase activity could cause accumulation of cholesterol esters in acinar cells. Fat accumulation in the pancreas has been reported as the earliest histopathological feature in alcoholic patients and may be responsible for cytotoxic effects on the acinar cells at the level of the cell membrane. Although it is difficult to extrapolate results in this animal study to the human situation, the results presented in this work might explain the higher incidence of pancreatitis is malnourished populations as well as in alcoholic subjects that is reported in dietary surveys.

Wine, beer, alcohol and polyphenols on cardiovascular disease and cancer

Abstract: Since ancient times, people have attributed a variety of health benefits to moderate consumption of fermented beverages such as wine and beer, often without any scientific basis. There is evidence that excessive or binge alcohol consumption is associated with increased morbidity and mortality, as well as with work related and traffic accidents. On the contrary, at the moment, several epidemiological studies have suggested that moderate consumption of alcohol reduces overall mortality, mainly from coronary diseases. However, there are discrepancies regarding the specific effects of different types of beverages (wine, beer and spirits) on the cardiovascular system and cancer, and also whether the possible protective effects of alcoholic beverages are due to their alcoholic content (ethanol) or to their non-alcoholic components (mainly polyphenols). Epidemiological and clinical studies have pointed out that regular and moderate wine consumption (one to two glasses a day) is associated with decreased incidence of cardiovascular disease (CVD), hypertension, diabetes, and certain types of cancer, including colon, basal cell, ovarian, and prostate carcinoma. Moderate beer consumption has also been associated with these effects, but to a lesser degree, probably because of beer"s lower phenolic content. These health benefits have mainly been attributed to an increase in antioxidant capacity, changes in lipid profiles, and the anti-inflammatory effects produced by these alcoholic beverages. This review summarizes the main protective effects on the cardiovascular system and cancer resulting from moderate wine and beer intake due mainly to their common components, alcohol and polyphenols.

Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial

Background: Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods: We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results: Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality.