The aging process.

The intricate cause of the aging process in humans and animals, at present a matter of intense speculation, has given rise to many theories. Despite its uncertain cause, aging constitutes the most significant and universal problem confronting physicians today. Age-related physiologic deterioration and age-associated diseases are of immense concern to physicians because of the "old-age boom" anticipated in the first part of the twenty-first century.

Dynamic changes of pancreatic structure and function in rats treated chronically with nicotine.

Adult, male Sprague-Dawley rats weighing initially 185-225 g, were treated with 5, 15, or 50 mg nicotine or placebo 3-week-release pellets by sc implantation, for 1.5, 3, 6 and 12 weeks. These doses of nicotine correspond to infusion rates of 9.

Proteolytic degradation of human recombinant proinsulin/insulin by sera from acute pancreatitis patients and complete inhibition by Eglin-C.

Sera from patients of biliary, alcoholic, and idiopathic acute pancreatitis with severity scored from 1 to 5 based on the Ranson criteria were tested for proinsulin/insulin degrading activity. Proinsulin degrading activity by normal controls was 8 +/- 4% as compared with 22-78 +/- 17% with a mean of 45% by the patient sera. An order of magnitude increase of proinsulin degrading activity was accompanied by an order of magnitude increase of immunoreactive pancreatic cationic trypsin(ogen) and (pro)elastase-2 as determined by radioimmunoassay with day 1 sera.

Recruiting students for medicine.

The applicant-to-acceptance ratio in the nation's 127 medical schools has slowly but steadily declined during the last decade to 1.7:1 (60.5% acceptance rate) for the 1987-1988 academic year.

Altered exocrine pancreatic function in rats treated with nicotine.

The present study investigates the effects of nicotine treatment on exocrine pancreatic function. Adult male, Sprague-Dawley rats received nicotine via a time-release pellet, at a rate of 1.65 micrograms/min for 3 weeks.

Assessment of the role of pancreatic proteases in human abdominal aortic aneurysms and occlusive disease.

Previous studies on the pathogenesis of abdominal aortic aneurysms have shown both elastase-like activity in the aortic wall and a decreased elastin content. The present study, using specific radioimmunoassays for pancreatic elastase 2 (IRE2) and cationic trypsin(ogen) (IRCT), investigates the concentrations of these proteases which are known to circulate in blood, in abdominal aortic aneurysms. Aortic specimens were obtained from 32 patients with aneurysms and 21 patients with atherosclerotic occlusive disease.

Pseudomonas aeruginosa cytotoxin stimulates secretion of amylase and protease zymogens with a concomitant decrease of mRNA levels in isolated rat pancreatic acini.

The action of Pseudomonas aeruginosa cytotoxin on isolated pancreatic acini was investigated. The release of amylase and serine protease zymogens from the isolated rat pancreatic acini was induced with increasing amounts of cytotoxin in vitro. The stimulated release of amylase reached 30% of total cellular content with 100 micrograms/mL of the purified cytotoxin.

Secretagogue-induced enzyme release from the exocrine pancreas of rats following adaptation to a high protein diet.

The mechanisms of pancreatic adaptation to dietary changes and whether these changes are reflected in the serum are not fully understood. The present study investigates secretagogue-induced release of digestive enzymes from dispersed pancreatic acini as well as the concentrations of these enzymes in serum and pancreas after adaptation to a high protein diet. Adult rats were fed an 8.

Biochemical studies in peritoneal fluid from patients with acute pancreatitis. Relationship to etiology.

The levels of pancreatic digestive enzymes, lysosomal hydrolases, and protease inhibitors were evaluated in ascites fluid from 24 patients with acute pancreatitis diagnosed as alcoholic, gallstone-induced, or idiopathic. In this group the concentrations of amylase (354 +/- 98 ng/ml), immunoreactive cationic trypsinogen (1840 +/- 238 ng/ml), and immunoreactive elastase 2 (1492 +/- 262 ng/ml) were greatly elevated in comparison to the corresponding serum values. Enzyme levels in ascites from the idiopathic pancreatitis group tended to be higher than the levels from the other two groups.

Raised serum concentrations of pancreatic enzymes in cigarette smokers.

Circulating concentrations of digestive enzymes, certain lysosomal hydrolases and protease inhibitors were measured in 19 heavy smokers and 13 non-smokers before (basal) and at 15, 30, and 60 minutes after a single intravenous injection of secretin (75 CU). In smokers, basal serum amylase and immunoreactive pancreatic elastase 2 (IRE2) concentrations were about 100% and 25% higher respectively, than in the non-smokers, whereas, no differences were observed in basal immunoreactive cationic trypsinogen (IRCT) concentrations and in acid phosphatase and beta-glucuronidase activities between the two groups. Furthermore, a single injection of secretin to cigarette smokers significantly increased serum amylase, IRCT and IRE2 by 155%, 200%, and 100%, respectively when compared with their corresponding basal levels.

Digestive enzymes and protease inhibitors in plasma from patients with acute pancreatitis.

The plasma levels of certain digestive enzymes and protease inhibitors were determined in 40 patients with severe acute pancreatitis diagnosed as gallstone-induced (GP), alcoholic (AP), or idiopathic (IP). On admission, plasma levels of amylase and immunoreactive cationic trypsin(ogen) (IRCT) and elastase 2 (IRE 2) were found to be 50 +/- 10 ng/ml, 340 +/- 64 ng/ml, and 190 +/- 15 ng/ml, respectively, in all groups of patients. These enzymes levels remained high for the first 2 days following hospitalization and then decreased, although amylase and IRCT levels remained elevated above normal values throughout the study period (2 weeks).

Stimulation of enzyme secretion from isolated pancreatic acini by Clostridium difficile toxin B.

Exposure of isolated rat pancreatic acini to increasing concentrations (10 ng - 800 ng/ml) of toxin B from Clostridium difficile produced a biphasic effect on the rate of secretion of amylase, trypsinogen, and chymotrypsinogen. Whereas doses of toxin B from 10-30 ng/ml increased enzyme secretion by 15-20%, doses between 30 ng and 60 ng/ml showed a regression of this effect, whereafter the rate of secretion of amylase, trypsinogen, and chymotrypsinogen increased with increasing concentrations of the toxin. Toxin B concentration of 800 ng/ml enhanced amylase, trypsinogen and chymotrypsinogen secretion by 119%, 185% and 195%, respectively, when compared with the basal level.

Evaluation of the role of calcium in cytotoxic injury in isolated rat pancreatic acini.

The role of extracellular Ca2+ in pancreatic acinar membrane damage (cellular injury) by nicotine, membrane-active agents (mellitin, snake venom and Ca2+ ionophore A23187) and secretagogues (CCK-8 and secretin) was investigated. Freshly isolated dispersed pancreatic acini from 18 h fasted adult rats were incubated with one of the aforementioned agents, in the absence and presence of Ca2+. Cellular injury was assessed by measuring the release of pulse-labeled 51Cr and LDH.

Morphological and biochemical changes of the pancreas in rats treated with acetaldehyde.

Daily intraperitoneal injections of acetaldehyde for 10 days to adult rats produced distinct morphological and biochemical changes in the exocrine pancreas, without affecting the body weight, pancreatic weight, and DNA, RNA, and protein content of the pancreas. By electronmicroscopy, although the number and size of the acinar zymogen granules appeared to be the same between the saline- and acetaldehyde-treated rats, the zymogen granules of the latter group showed decreased osmiophilia. Acinar mitochondria of the acetaldehyde-treated rats were found to be slightly swollen with dense granules, and plasma membrane fragments were often seen in the acinar lumen.

Acetaldehyde inhibition of protein synthesis in isolated rat pancreatic acini.

Exposure of isolated dispersed pancreatic acini to increasing concentrations of ethanol (5 to 500 mM) or acetaldehyde (0.5 to 100 mM) produced a progressive inhibition of [3H]leucine incorporation into both "cellular" (those remaining in the cell) and "secretory" (those released into the medium) proteins. Whereas 500 mM ethanol caused 90-95% inhibition in the synthesis of "cellular" and "secretory" proteins, the concentration of acetaldehyde needed to produce a similar inhibition was found to be 50 mM.

Biochemical changes in the pancreas of rats with chronic renal failure.

Chronic renal failure (CRF) was produced in female Sprague-Dawley rats by 7/8 nephrectomy. Creatinine clearance was depressed significantly (P less than 0.005) and blood urea nitrogen (BUN) increased in CRF rats when compared with the sham-operated (S) controls.

Irreversible inhibition by acetaldehyde of cholecystokinin-induced amylase secretion from isolated rat pancreatic acini.

Acetaldehyde inhibited both amylase secretion induced by maximal concentrations (300 pM) of cholecystokinin octapeptide and the binding of radioiodinated cholecystokinin to receptors on isolated rat pancreatic acini. This inhibition was concentration dependent (10 mM to 1 M for amylase secretion and 100 mM to 1 M for binding). However, a correlation between the two inhibitory effects could not be obtained.

Acute pancreatitis.

The exocrine pancreas secretes into the gut on demand more than 20 proteins that are indispensable for digestion. In-vivo autodigestion is prevented by an array of natural safeguards. In acute pancreatitis, inappropriate intrapancreatic activation and release of pancreatic hydrolases occur, but the pathogenetic mechanism of autodigestion is unclear.

Nonparallel discharge of digestive enzymes from isolated pancreatic acini.

The secretion of amylase, trypsinogen, chymotrypsinogen and proelastase from isolated rat dispersed pancreatic acini was investigated in the absence (basal) and presence of two concentrations of CCK8 (50 and 500 pM), carbachol (2.5 and 7.5 microM) and secretin (10 nM and 1 microM).

Effect of Pseudomonas aeruginosa exotoxin-A on the synthesis and secretion of proteins in isolated rat pancreatic acini.

Exposure of isolated rat dispersed pancreatic acini to increasing concentrations (10 to 1000 ng/ml) of purified exotoxin-A from Pseudomonas aeruginosa resulted in a progressive inhibition of 3H-leucine incorporation into "cellular" (those remaining in the cells) and "secretory" (those released into the medium) proteins. With each concentration of exotoxin-A, magnitude of reduction was found to be greater for the "secretory" proteins than that observed for the "cellular" proteins. Thus, in the presence of 250 ng/ml of exotoxin-A, a dose that produced maximal inhibition in protein synthesis, 3H-leucine incorporation into "cellular" and "secretory" proteins was found to be decreased by about 19 and 50%, respectively, when compared with the corresponding basal controls.

The aging gastrointestinal tract, liver, and pancreas.

This article summarizes the age-related structural and functional alterations in the esophagus, stomach, small and large intestines, liver, pancreas, and vermiform appendix. Also considered are the possible relationships of these changes with the disturbance of homeostatic mechanisms and proneness to certain diseases in the aged.

Nicotine stimulation of protein secretion from isolated rat pancreatic acini.

The secretion of amylase and trypsinogen from isolated rat pancreatic acini was greatly stimulated by 3-25 mM nicotine. In the presence of 12.5 mM nicotine, a concentration used in the study, amylase and trypsinogen release was increased by 95 and 400%, respectively, when compared with the corresponding control and showed further a preferential release of trypsinogen.

Effect of ethanol on cholecystokinin-induced enzyme secretion from isolated rat pancreatic acini.

Cholecystokinin octapeptide (CCK8)-stimulated amylase release in isolated rat pancreatic acini was inhibited over 30% by 600 mM ethanol. The configuration of the dose-response curve for CCK8, however, in the presence of ethanol was similar to that of the control. Amylase release elicited by maximal concentrations of CCK8 (300 pM) was inhibited by increasing concentrations of ethanol (0.

Effects of food intake and cholecystokinin on plasma trypsinogen levels in dogs.

Concentrations of plasma immunoreactive anionic and cationic trypsin(ogen) were monitored in unanesthetized dogs to investigate diurnal variation, response to food intake, and effects of cholecystokinin octapeptide (CCK-8) plus secretin administration. Identical meals were consumed at the beginning and end of a 24-h period. Plasma levels of both trypsin(ogen)s increased significantly within 30 min of feeding.