alpha-chymotrypsin and Alcoholism

Alcohol abuse is a leading cause of pancreatitis, accounting for 30% of acute cases and 70-90% of chronic cases, yet the mechanisms leading to alcohol-associated pancreatic injury are unclear. An early and critical feature of pancreatitis is the aberrant signaling of Ca(2+) within the pancreatic acinar cell. An important conductor of this Ca(2+) is the basolaterally localized, intracellular Ca(2+) channel ryanodine receptor (RYR). In this study, we examined the effect of ethanol on mediating both pathologic intra-acinar protease activation, a precursor to pancreatitis, as well as RYR Ca(2+) signals. We hypothesized that ethanol sensitizes the acinar cell to protease activation by modulating RYR Ca(2+). Acinar cells were freshly isolated from rat, pretreated with ethanol, and stimulated with the muscarinic agonist carbachol (1 μM). Ethanol caused a doubling in the carbachol-induced activation of the proteases trypsin and chymotrypsin (p < 0.02). The RYR inhibitor dantrolene abrogated the enhancement of trypsin and chymotrypsin activity by ethanol (p < 0.005 for both proteases). Further, ethanol accelerated the speed of the apical to basolateral Ca(2+) wave from 9 to 18 μm/s (p < 0.0005; n = 18-22 cells/group); an increase in Ca(2+) wave speed was also observed with a change from physiologic concentrations of carbachol (1 μM) to a supraphysiologic concentration (1 mM) that leads to protease activation. Dantrolene abrogated the ethanol-induced acceleration of wave speed (p < 0.05; n = 10-16 cells/group). Our results suggest that the enhancement of pathologic protease activation by ethanol is dependent on the RYR and that a novel mechanism for this enhancement may involve RYR-mediated acceleration of Ca(2+) waves.

Topics: Alcoholism; Animals; Calcium; Carbachol; Chymotrypsin; Dantrolene; Disease Models, Animal; Ethanol; Muscle Relaxants, Central; Pancreas; Peptide Hydrolases; Rats; Rats, Sprague-Dawley; Ryanodine Receptor Calcium Release Channel; Signal Transduction; Trypsin

187 patients were checked up over 4 years by the secretin-ceruletide test. Independently of the test results they were assigned to various disease groups on the basis of clinical assessment. 131 subjects were divided in a pilot investigation into: subjects with a healthy pancreas (n = 55); subjects with chronic pancreatitis (n = 50); subjects whose pancreatic condition could not be classified clearly (n = 26). 8 parameters were compared by univariate and multivariate statistical procedures in order to confirm or rule out the presence of chronic pancreatitis. The discriminatory power of the following parameters in duodenal fluid proved to be sufficiently high, with less than 15% frequency of misclassification: chymotrypsin (activity) and/or; lipase (activity) and/or; amylase (activity); viscosity. Under routine conditions measurement of the activity of two of these enzymes is sufficient. Their contribution to discrimination proved to be approximately equal. The diagnostic sensitivity and specificity of the parameters bicarbonate, lipase (concentration), trypsin (activity) and volume of duodenal fluid are lower. The classification rules derived from the above pilot group were confirmed by a diagnostic study under routine condition in a test group of 38 patients. Limitation to examining only volume and a maximum of 3 parameters which proved best in distinguishing between patients with chronic pancreatitis and healthy subjects, together with the omission of the first-hour samples after a secretin bolus, considerably reduced laboratory workload without altering the discriminatory power of the secretin-ceruletide test.

Topics: Adult; Alcoholism; Amylases; Ceruletide; Chronic Disease; Chymotrypsin; Duodenum; Female; Humans; Intestinal Secretions; Lipase; Male; Middle Aged; Pancreatitis; Reference Values; Secretin; Viscosity

Adverse effects observed in alcoholic rats are often attributed to alcohol per se. Alcoholic liver damage, however, can be avoided by modulating nutritional factors despite high blood alcohol concentrations. Hence, we examined the effect of blood alcohol concentration on pancreatic enzyme activity and release. Three liquid diets containing 36 and 18% of total energy derived from alcohol and protein, respectively, were fed. Each alcohol diet contained 11, 21 or 31% of energy from carbohydrate, and the fat concentration was appropriately adjusted. The control groups of rats (fed an isoenergetic liquid diet without alcohol) and the alcoholic groups of rats were maintained for 2 wk. The three groups of alcoholic rats consumed 13.3 +/- 2.3, 13.3 +/- 2.2 and 13.2 +/- 1.9 g/kg of alcohol daily, and their corresponding blood alcohol levels were 41.5 +/- 4.3, 55.4 +/- 8.9 and 44.6 +/- 2.2 mmol/L. Pancreatic acinar amylase activity in alcoholic rats was proportional to carbohydrate ingested, despite high blood alcohol concentrations; chymotrypsin and trypsin activities were unchanged. Acinar enzyme activities in control rats were similar. Furthermore, cholecystokinin-octapeptide-stimulated amylase release in alcoholic rats corresponded with the amylase concentration in acini, whereas stimulated trypsin output was unaltered in both control and alcoholic rats. These results demonstrate that neither alcohol ingestion nor high blood alcohol concentration affects the activities of pancreatic proteases and that the changes in the activity and release of amylase are related to the intake of carbohydrate.

Topics: Alcoholism; Amylases; Animals; Chymotrypsin; Dietary Carbohydrates; Dietary Fats; Energy Intake; Ethanol; Kinetics; Male; Pancreas; Rats; Rats, Inbred Strains; Sincalide; Trypsin

Duodenal and jejunal absorption of a nutrient solution at two different caloric loads (1.32 and 3.96 kcal/min = 5.6 and 16.8 kJ/min) was compared in chronic alcoholics without malnutrition, liver cirrhosis, obvious small-bowel dysfunction, and exocrine pancreatic insufficiency and in an age-matched control group, by means of the intestinal perfusion technique. In chronic alcoholics duodenal net absorption of water (p < 0.025), sodium (p < 0.02), potassium (p < 0.005), total nitrogen (p < 0.02), carbohydrates (p < 0.05), and lipids (p < 0.05) was lower than in controls when both caloric loads were administered, but jejunal absorption rates were not decreased. Biliopancreatic secretion did not differ between alcoholics and controls. Higher serum protein leakage in alcoholics was indicated by an increased (p < 0.01) duodenal alpha 1-antitrypsin clearance under low caloric load infusion. It is concluded that the absorptive function of the duodenum is impaired in alcoholics, whereas the upper jejunum is not affected.

Topics: Adult; Alcoholism; alpha 1-Antitrypsin; Bile Acids and Salts; Carbohydrate Metabolism; Chymotrypsin; Duodenum; Electrolytes; Energy Intake; Female; Food, Formulated; Humans; Intestinal Absorption; Jejunum; Lipase; Lipid Metabolism; Male; Middle Aged; Nitrogen; Nutritional Status; Water

Lactoferrin, a nonenzyme protein normally secreted in small amounts in pancreatic juice, has been reported by several investigators to be secreted in large amounts in chronic pancreatitis. Whether this increased secretion first occurs at an early or late stage of alcoholic pancreatic disease is unknown. In this study we measured lactoferrin and enzyme outputs in duodenal juice from 10 healthy subjects and three groups of alcoholic subjects: asymptomatic chronic alcoholics without evidence, clinically or biochemically, of pancreatitis (10), those recovered from acute pancreatitis (8), and those with established chronic pancreatitis (8). A multilumen, marker-perfused duodenal catheter was used to aspirate basal pancreatic secretions at the ligament of Treitz. The mean ( +/-SE) lactoferrin concentration in duodenal juice for the four groups of subjects was: healthy, 0.7 +/- 0.1 micrograms/ml; asymptomatic alcoholics, 5.5 +/- 1.5 micrograms/ml; alcoholics who had recovered from acute pancreatitis, 7.4 +/- 0.8 micrograms/ml; and alcoholics with chronic pancreatitis 7.1 +/- 1.9 micrograms/ml. The three groups of alcoholics each had a greater lactoferrin concentration than the normals (P less than 0.005). The output of lactoferrin in the four groups paralleled the concentration in that the three groups of alcoholics had a significantly greater output: healthy subjects, 3.4 +/- 0.5 micrograms/kg/hr; asymptomatic alcoholics, 25.7 +/- 7.4 micrograms/kg/hr; alcoholics recovered from acute pancreatitis, 80.1 +/- 27 micrograms/kg/hr; and alcoholics with chronic pancreatitis, 90.9 +/- 32 micrograms/kg/hr. The output of chymotrypsin and trypsin in the four groups of subjects revealed increased secretory rates in the asymptomatic alcoholics and the alcoholics recovered from acute pancreatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alcoholism; Chymotrypsin; Duodenum; Humans; Intestinal Secretions; Lactoferrin; Lactoglobulins; Pancreatitis

The present study was done to determine the effect of the interaction of ethanol and an average or high-fat diet on pancreatic acinar cell function. Weight-matched groups of Sprague-Dawley rats were fed regular rat feed or average fat and high-fat liquid diets with or without 5% (w/v) concentration of ethanol for 3 months. Trypsinogen secretion was increased by the high-fat diet but not by ethanol; chymotrypsinogen secretion was decreased by the combination of ethanol and a high-fat diet, while lipase secretion was increased by a high-fat diet. Pancreatic secretory trypsin inhibitor was not significantly altered by ethanol or fat in the diet. Ethanol feeding together with a high-fat content of the diet caused complex and nonparallel changes in the secretion of the pancreatic enzymes. These data are of interest in view of the reported positive correlation between alcoholism and a high-fat content of the diet in the causation of alcoholic pancreatitis in humans.

Topics: Alcoholism; Amylases; Animals; Chymotrypsin; Chymotrypsinogen; Dietary Fats; Female; Lipase; Pancreas; Rats; Rats, Inbred Strains; Trypsin; Trypsin Inhibitors; Trypsinogen

To study the effects of dietary composition and chronic ethanol ingestion on plasma proteinase inhibitor (PI) levels in intact animals, 192 male Wistar rats were divided into 4 groups, which received a standard diet (S), a fat-rich diet (F), a protein-rich diet (P), and a carbohydrate-rich diet (C), respectively, for 12 weeks. Half of the animals in each diet group had 15% ethanol as their drinking solution (A) during this diet period, and the rest drank tap water (W). FW and CW diets caused a significant decrease in the trypsin-inhibiting capacity (TIC) of plasma in comparison with the SW group (p less than 0.05 and p less than 0.001, respectively), and chronic ethanol ingestion in combination with P and C diets decreased plasma TIC levels significantly (p less than 0.01 and p less than 0.001) when compared with the corresponding water-drinking groups. The chymotrypsin-inhibiting capacity (CIC) of plasma behaved differently: in the FW, PW, and CW groups it was significantly higher than in the SW group (p less than 0.001). Chronic ethanol ingestion did not change plasma CIC levels significantly when compared with the corresponding water-receiving groups. In conclusion, dietary intake was found to alter plasma PI levels. Changes in the protein synthesis of the liver might be responsible for these alterations.

Topics: Alcoholism; Animals; Chymotrypsin; Diet; Endopeptidases; Liver; Male; Rats; Rats, Inbred Strains; Trypsin Inhibitors

Over the last 10 years, a series of 144 consecutive patients with alcoholic recurrent pancreatitis have been studied prospectively at regular intervals with particular regard to exocrine function, calcifications, pancreatographic ductal changes, and histopathology of the pancreas. Based upon the long-term course, the patients were classified into two groups; group A (n = 95), those with chronic pancreatitis (78 of them with calcifications); and group B (n = 49), those with acute (nonprogressive) pancreatitis. The duration of disease from onset was 2-19 years (median, 9.7 and 8.3 years, respectively, in group A and B). The two groups were comparable at onset of the disease in age, sex, number of episodes of pancreatitis, and number of pseudocysts. In group A, all 95 cases fulfilled the strict diagnostic criteria of chronic pancreatitis within the period of observation (e.g., progressive exocrine insufficiency and/or typical morphological changes, particularly calcifications). In group B, the exocrine function remained normal over the entire period of observation. No histologic evidence of chronic pancreatitis was detected in five of seven large pancreatic specimens. Marked to moderate ductal changes were found in 10 of 16 patients in group B (despite normal exocrine function). Our data suggest that about one third of patients of the present series with alcoholic (recurrent) pancreatitis did not progress toward chronic (progressive) pancreatitis, although some demonstrated morphological alterations (except calcifications) in association with normally preserved exocrine function (residual scars?). The pathogenetic factor(s) responsible for progression (or nonprogression) of alcoholic (recurrent) pancreatitis to chronic pancreatitis remain(s) to be elucidated.

Topics: Acute Disease; Adult; Alcoholism; Calcinosis; Chronic Disease; Chymotrypsin; Feces; Female; Humans; Longitudinal Studies; Male; Middle Aged; Pancreas; Pancreatic Ducts; Pancreatic Pseudocyst; Pancreatitis; Prognosis; Prospective Studies; Recurrence

Topics: Adult; Alcoholism; Bicarbonates; Cholecystokinin; Chymotrypsin; Humans; Lipase; Middle Aged; Pancreas; Trypsin

We have studied the volume, protein concentration, total protein, and chymotrypsin and trypsin outputs in pure pancreatic juice (PPJ) following endoscopic cannulation of the pancreatic duct in 11 male and 2 female patients with advanced alcoholic cirrhosis (AC). Results were compared to those obtained from 21 nonalcoholic volunteers (NAV) and 26 chronic alcoholic (CA) patients without cirrhosis. Intravenous stimulation with secretin followed 10 min later by intravenous cholecystokinin-pancreozymin (CCK-PZ) resulted in highly significant increases in volumes during both phases of pancreatic stimulation in AC compared to NAV and CA. Protein concentration and total output during secretin stimulation was not different among the three groups. During CCK-PZ stimulation, CA exhibited a significant elevation in protein concentration and total output compared to NAV and AC. Although total chymotrypsin output was lower in secretin-stimulated CA than other groups, no other differences between the groups were observed in either of the hormone-stimulation phases. Marked elevations in trypsin output were observed in secretin-stimulated AC and in CCK-PZ-stimulated AC and CA. The high PPJ volume and the relatively low protein concentration observed in AC may effect a washout phenomenon resulting in a decreased tendency for ductal protein precipitation in these patients.

Topics: Adult; Aged; Alcoholism; Cholecystokinin; Chymotrypsin; Female; Humans; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Pancreas; Pancreatic Juice; Proteins; Secretin; Trypsin

Two groups of men, nonalcoholics (mean daily alcohol consumption less than 40 g) and alcoholics (mean daily alcohol consumption greater than 100 g) were compared with respect to the effects of intravenous ethanol on hormonally (secretin + CCK) submaximally stimulated pancreatic and bile secretion and chymotrypsin secretion during the basal state and after a Lundh test meal. Intravenous ethanol injection (600 mg/kg) significantly decreased pancreatic secretion of lipase (-74%), chymotrypsin (-78%), volume (-53%), and bicarbonate (-58%) in nonalcoholic but not in alcoholic men: The secretory pattern of the exocrine pancreatic response to an intravenous infusion of ethanol was therefore changes by the regular consumption of ethanol. The chymotrypsin concentration during the basal state was higher in alcoholic than in nonalcoholic men. This difference progressively disappeared after a test meal showing that chronic alcohol consumption modifies more basal than meal-stimulated pancreatic secretion.

Topics: Adult; Alcoholism; Bile; Bile Acids and Salts; Cholesterol; Chymotrypsin; Ethanol; Food; Humans; Infusions, Parenteral; Male; Middle Aged; Pancreas; Phospholipids

Not infrequently exact diagnosis of chronic pancreatitis is possible only after step by step observation. The results of examination, analyses and treatment should be communicated from a general practitioner to a specialist, further to a specialized centre and vice versa. Screening tests and special examinations should be conducted in definite order. A surgical treatment is desirable in approximately 40% of clinically pronounced chronic pancreatitis. The best results are obtained by close cooperation between different specialists and the patient himself.

Topics: 4-Aminobenzoic Acid; Alcoholism; Amylases; Chloroquine; Chronic Disease; Chymotrypsin; Diabetes Mellitus; Feces; Humans; Isoenzymes; Ligation; Lipase; Nutritional Physiological Phenomena; Pancreatic Ducts; Pancreatitis; Patient Care Team

Pancreatic ascites is a rare disease which is often misinterpreted as ascites secondary to alcoholic cirrhosis or to intraabdominal cancer. It can be diagnosed by a high protein and amylase/lipase content of the ascitic fluid. If diagnosis and subsequent surgery occur at an early stage, the prognosis is good. The natural course, therapy, prognosis, and pathogenesis of pancreatic ascites are discussed on the basis of experience with 7 patients.

Topics: Adolescent; Adult; Alcoholism; Amylases; Ascites; Ascitic Fluid; Chymotrypsin; Feces; Female; Humans; Male; Pancreatic Diseases; Pancreatitis; Proteins

Topics: Alanine Transaminase; Alcoholism; Amylases; Animals; Aspartate Aminotransferases; Chymotrypsin; Chymotrypsinogen; Humans; Male; Pancreas; Rats; Time Factors; Trypsin; Trypsin Inhibitors; Trypsinogen

97 chronic alcoholic patients were investigated with regard to exocrine pancreatic function. Chronic calcifying pancreatitis was radiologically established in 7.2% of the cases. Secretin-pancreozymin tests were performed in 30 patients. Pancreatic insufficiency was found in 8 patients, while 8 patients showed marked hypersection. The daily faecal fat excretion in 10 other patients with partial gastrectomy and Billroth II operation was 5.3 g. Pancreatic disorders were, thus, detected in 53.2% cases of chronic alcoholism. This is higher than expected for Austria.

Topics: Adult; Alcoholism; Austria; Bicarbonates; Chronic Disease; Chymotrypsin; Female; Humans; Male; Middle Aged; Pancreas; Pancreatic Juice; Pancreatitis; Trypsin

Topics: Aged; Alcoholism; Biopsy, Needle; Cholecystokinin; Chymotrypsin; Drainage; Duodenum; Eating; Fatty Liver; Feces; Female; Humans; Lipid Metabolism; Lipids; Liver; Liver Cirrhosis; Malabsorption Syndromes; Male; Middle Aged; Pancreas; Pancreatic Diseases; Secretin

Topics: Aged; Alcoholism; Bicarbonates; Cholecystokinin; Chymotrypsin; Female; Humans; Liver Cirrhosis; Malabsorption Syndromes; Male; Middle Aged; Pancreas; Secretin

Topics: Alcoholism; Blood Protein Disorders; Cachexia; Carbohydrate Metabolism; Chymotrypsin; Deficiency Diseases; Dietary Proteins; Gastrectomy; Humans; Jejunum; Lipase; Male; Middle Aged; Nutrition Disorders; Pancreas; Pancreatin; Trypsin

Trypsin and chymotrypsin concentrations were determined in 180 spot stool specimens from 110 control patients in hospital. The lower limit of normality for each enzyme was placed at the 5% level: 95% of this population excreted feces containing more than 100 mug. of chymotrypsin and 30 mug. of trypsin per g. of feces. Chymotrypsin concentrations appeared to be a more reliable guide to pancreatic function than trypsin concentrations.Fecal chymotrypsin concentrations were subnormal in five patients with chronic pancreatitis, borderline in one patient with relapsing pancreatitis, subnormal in one patient after pancreatectomy, and subnormal in five of nine with carcinoma of the pancreas. Subnormal concentrations of fecal chymotrypsin were found in seven of 21 patients with chronic liver disease related to alcoholism, eight of 32 with a partial gastrectomy, three of 10 with adult celiac disease and five of 16 with psoriasis.It appears that the determination of fecal chymotrypsin concentrations provides a valuable screening test for pancreatic exocrine deficiency. However, normal results may be found in some patients with pancreatic disease and subnormal values may occur in some patients with other conditions.

Topics: Alcoholism; Chymotrypsin; Feces; Humans; Liver Cirrhosis; Malabsorption Syndromes; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Skin Diseases; Trypsin

Topics: Acute Disease; Adult; Alcoholism; Amylases; Chronic Disease; Chymotrypsin; Clinical Enzyme Tests; Crohn Disease; Diagnosis, Differential; Feces; Humans; Male; Pancreas; Pancreatitis

Topics: Alcoholism; Amylases; Anemia, Hemolytic; Cholecystokinin; Chymotrypsin; Clinical Enzyme Tests; Fatty Liver; Humans; Hyperlipidemias; Jaundice; Pancreas; Secretin; Trypsin