trypsinogen and Pancreatic-Diseases

Exocrine pancreatic insufficiency in children can lead to lifelong complications related to malnutrition and poor growth. The clinical presentation can be subtle in the early stages of insufficiency as the large functional capacity of the pancreas is gradually lost. The pediatrician plays a crucial role in the early identification of these children to ensure a timely referral so that a diagnosis can be made and therapy initiated. Early nutritional therapy allows for prevention and correction of deficiencies, which leads to improved outcomes and survival. When insufficiency is suspected, the workup should start with an indirect test of exocrine pancreatic function, such as fecal elastase, to establish the diagnosis. Once a diagnosis is established, further testing to delineate the etiology should be pursued, with cystic fibrosis being high on the differential list and assessed for with a sweat test. Assessment of anthropometry at every visit is key, as is monitoring of laboratory parameters and physical examination findings that are suggestive of malabsorption and malnutrition. The mainstay of management is administration of exogenous pancreatic enzymes to facilitate digestion and absorption. [Pediatr Ann. 2019;48(11):e441-e447.].

Topics: Acyl-CoA Dehydrogenase, Long-Chain; Anus, Imperforate; Child; Child Nutrition Disorders; Chymotrypsin; Congenital Bone Marrow Failure Syndromes; Cystic Fibrosis; Dietary Fats; Ectodermal Dysplasia; Enzyme Replacement Therapy; Exocrine Pancreatic Insufficiency; Feces; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Lipid Metabolism, Inborn Errors; Mitochondrial Diseases; Muscular Diseases; Nose; Nutrition Assessment; Pancreas; Pancreatic Diseases; Pancreatic Elastase; Pancreatic Function Tests; Pancreatitis, Chronic; Shwachman-Diamond Syndrome; Steatorrhea; Trypsinogen

Topics: Abdominal Pain; Adult; Age of Onset; Calculi; Child; Developing Countries; Diabetes Mellitus; Humans; Malnutrition; Manihot; Mutation; Oxidative Stress; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis, Chronic; Steatorrhea; Tropical Climate; Trypsin; Trypsinogen

Topics: DNA, Mitochondrial; Enzymes; Humans; Infant; Infant, Newborn; Mutation; Pancreas; Pancreatic Diseases; Pancreatitis; Trypsinogen

Topics: Adult; Diabetes Mellitus, Type 1; Humans; Pancreas Transplantation; Pancreatic Diseases; Pancreatitis; Protease Inhibitors; Radioimmunoassay; Trypsin; Trypsinogen

Topics: Amino Acid Metabolism, Inborn Errors; Amylases; Child, Preschool; Cholecystokinin; Cystic Fibrosis; Dicloxacillin; Humans; Infant; Infant, Newborn; Kidney Diseases; Lipase; Lipid Metabolism, Inborn Errors; Pancreas; Pancreatic Cyst; Pancreatic Diseases; Pancreatic Extracts; Prognosis; Secretin; Triglycerides; Trypsinogen; Uric Acid

Dr. Catherine Figarella is a world expert in the isolation and characterization of human exocrine pancreatic proteins (enzymatic and non-enzymatic ones). She was a pioneer in the identification and characterization of the numerous zymogens present in pancreatic juice. In particular, her discovery of a peculiar behavior of one of the main proteolytic zymogens: human trypsinogen 1, which was more readily activated into active trypsin than human trypsinogen 2 and trypsinogens of other species led her to propose that a premature intracellular activation of this zymogen may play a role in the pathogenesis of chronic pancreatitis. She demonstrated that a similar phenomenon may occur in cystic fibrosis (CF) and has applied this knowledge of pancreatic zymogens to follow the evolution of the pancreatic disease in CF. With this brief but keen biographical article Dr. Figarella shares her life experience as an innovative medical and biochemical investigator of human exocrine pancreatic function.

Topics: Gastroenterology; Humans; Mentors; Pancreas; Pancreatic Diseases; Trypsinogen

The aim of this study was to determine whether mutations in SPINK1/PRSS1 genes are associated with benign pancreatic hyperenzymemia (BPH).. Sixty-eight subjects with BPH (including 13 familial cases) were studied. In all, we sequenced germline DNA for all the exons and intro-exon boundaries of PRSS1 and SPINK1.. Nine (13.2%) of the 68 subjects harbored PRSS1 or SPINK1 mutations. As to PRSS1, no hereditary pancreatitis-associated variant was detected, whereas previously undescribed mutations (p.Ala148Val and c.40+1G>A) were respectively found in 2 subjects (2.9%). SPINK1 mutations were detected in 7 subjects (10.3%). Five of them exhibited known mutations (3 p.Asn34Ser, 1 p.Pro55Ser, and 1 c.88-23A>T), whereas 2 had a newly found variant (p.Arg67Gly and c.*32C>T, respectively). Only 2 familial BPH, belonging to 2 different families, were found to carry a mutation (1 with p.Ala148Val for PRSS1 and 1 with p.Asn34Ser for SPINK1).. No known mutations of PRSS1 have been found in BPH, whereas the frequency of known SPINK1 variants is similar to that reported in the general population. No segregation of PRSS1/SPINK1 variants occurs in BPH families. Benign pancreatic hyperenzymemia cannot be explained by mutations in genes whose variants are known to be associated with pancreatitis or by mutations in other PRSS1/SPINK1 genes.

Topics: Adolescent; Adult; Aged; Amylases; Base Sequence; Carrier Proteins; Child; Exons; Female; Genetic Predisposition to Disease; Humans; Introns; Isoamylase; Lipase; Male; Middle Aged; Molecular Sequence Data; Mutation; Pancreas; Pancreatic Diseases; Pancreatitis; Syndrome; Trypsin; Trypsin Inhibitor, Kazal Pancreatic; Trypsinogen

Intracellular Ca(2+)-changes not only participate in important signaling pathways but have also been implicated in a number of disease states including acute pancreatitis. To investigate the underlying mechanisms in an experimental model mimicking human gallstone-induced pancreatitis, we ligated the pancreatic duct of Sprague-Dawley rats and NMRI mice for up to 6 h and studied intrapancreatic changes including the dynamics of [Ca(2+)](i) in isolated acini. In contrast to bile duct ligation, pancreatic duct obstruction induced intra-pancreatic trypsinogen activation, leukocytosis, hyperamylasemia, and pancreatic edema and increased lung myeloperoxidase activity. Although resting [Ca(2+)](i) in isolated acini rose by 45% to 205 +/- 7 nmol, the acetylcholine- and cholecystokinin (CCK)-stimulated calcium peaks as well as the amylase secretion declined, but neither the [Ca(2+)](i)-signaling pattern nor the amylase output in response to the Ca(2+)-ATPase inhibitor thapsigargin nor the secretin-stimulated amylase release were impaired by pancreatic duct ligation. On the single cell level pancreatic duct ligation reduced the percentage of cells in which submaximal secretagogue stimulation was followed by a physiological response (i.e. Ca(2+) oscillations) and increased the percentage of cells with a pathological response (i.e. peak plateau or absent Ca(2+) signal). Moreover, it reduced the frequency and amplitude of Ca(2+) oscillation as well as the capacitative Ca(2+) influx in response to secretagogue stimulation. Serum pancreatic enzyme elevation as well as trypsinogen activation was significantly reduced by pretreatment of animals with the calcium chelator BAPTA-AM. These experiments suggest that pancreatic duct obstruction rapidly changes the physiological response of the exocrine pancreas to a Ca(2+)-signaling pattern that has been associated with premature digestive enzyme activation and the onset of pancreatitis, both of which can be prevented by administration of an intracellular calcium chelator.

Topics: Adenosine Triphosphatases; Amylases; Animals; Calcium; Chelating Agents; Cholecystokinin; Constriction, Pathologic; Egtazic Acid; Flow Cytometry; Male; Mice; Pancreas; Pancreatic Diseases; Pancreatic Ducts; Rats; Rats, Sprague-Dawley; Signal Transduction; Thapsigargin; Time Factors; Trypsinogen

Human pancreatic secretions contain two major trypsinogen isoforms, cationic and anionic trypsinogen, normally at a ratio of 2 : 1. Pancreatitis, pancreatic cancer and chronic alcoholism lead to a characteristic reversal of the isoform ratio, and anionic trypsinogen becomes the predominant zymogen secreted. To understand the biochemical consequences of these alterations, we recombinantly expressed and purified both human trypsinogens and documented characteristics of autoactivation, autocatalytic degradation and Ca2+-dependence. Even though the two trypsinogens are approximately 90% identical in their primary structure, we found that human anionic trypsinogen and trypsin exhibited a significantly increased (10-20-fold) propensity for autocatalytic degradation, relative to cationic trypsinogen and trypsin. Furthermore, in contrast to the characteristic stimulation of the cationic proenzyme, acidic pH inhibited autoactivation of anionic trypsinogen. In mixtures of cationic and anionic trypsinogen, an increase in the proportion of the anionic proenzyme had no significant effect on the levels of trypsin generated by autoactivation or by enterokinase at pH 8.0 in 1 mm Ca2+- conditions that were characteristic of the pancreatic juice. In contrast, rates of trypsinogen activation were markedly reduced with increasing ratios of anionic trypsinogen under conditions that were typical of potential sites of pathological intra-acinar trypsinogen activation. Thus, at low Ca2+ concentrations at pH 8.0, selective degradation of anionic trypsinogen and trypsin caused diminished trypsin production; while at pH 5.0, inhibition of anionic trypsinogen activation resulted in lower trypsin yields. Taken together, the observations indicate that up-regulation of anionic trypsinogen in pancreatic diseases does not affect physiological trypsinogen activation, but significantly limits trypsin generation under potential pathological conditions.

Topics: Animals; Calcium; Enzyme Activation; Humans; Hydrogen-Ion Concentration; Mutation; Pancreatic Diseases; Protein Isoforms; Recombinant Proteins; Trypsin; Trypsinogen

To explore relationships between malnutrition and pancreatic damage in hospitalised aboriginal children.. Immunoreactive trypsinogen (IRT) concentrations were measured in two populations of hospitalised aboriginal children in Australia: 472 children aged 0-3 years, in Alice Springs (Northern Territory); and 187 children aged 0-16 years in Mount Isa (Queensland). Correlation of whole blood IRT with height and weight z-scores, four-site skinfold thickness and upper arm circumference was sought.. In Mount Isa, the geometric mean IRT concentration rose with decreasing weight z-score. The IRT concentration was otherwise unrelated to nutritional indices. Sixty percent of the 39 Mount Isa patients with gastroenteritis and 24.5% of the 358 Alice Springs patients with gastroenteritis had an IRT concentration in the upper quartile for their population, compared with 16% for patients with other diagnoses in both populations.. A high IRT concentration in patients with low weight z-scores is a confounding effect of gastroenteritis, and may result from subclinical pancreatic disease in gastroenteritis.

Topics: Adolescent; Analysis of Variance; Anthropometry; Australia; Child; Child Nutrition Disorders; Child, Preschool; Gastroenteritis; Hospitalization; Humans; Infant; Infant Nutrition Disorders; Native Hawaiian or Other Pacific Islander; Pancreatic Diseases; Trypsinogen

A 71-year-old woman was admitted with the suspected diagnosis of pancreatic carcinoma. As a child she had had repeated attacks of abdominal pain of undetermined cause. When aged 48 years she had developed diabetes mellitus. Her now 42-year-old daughter had from the age of 9 years suffered from repeated attacks of acute pancreatitis that had finally led to chronic pancreatitis. The patient's 15-year-old grandchild was having recurrent bouts of abdominal pain.. Imaging procedures revealed calcifications in the pancreas and an infiltrating space-occupying lesion, about 3 cm in diameter, in the head of the pancreas with lymph node and liver metastases. Cytological analysis of material aspirated from the space-occupying mass showed typical findings of ductal pancreatic carcinoma. FURTHER TESTS, TREATMENT AND COURSE: At first the patient's course was not typical for a genetically-determined disease, but the family history raised the suspicion of hereditary pancreatitis. A genetic test (Afl-III-RFLP test) demonstrated the mutation Arg 117 His in the cationic trypsinogen gene in all diseased or symptomatic family members. The patient died of the complications of the pancreatic cancer.. Genetic tests are valuable in the diagnosis of hereditary pancreatitis, because the increased cancer risk can be met by frequent examinations in affected family members.

Topics: Abdominal Pain; Acute Disease; Adolescent; Adult; Aged; Calcinosis; Chronic Disease; Family; Fatal Outcome; Female; Humans; Pancreas; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Point Mutation; Polymorphism, Restriction Fragment Length; Recurrence; Risk Factors; Tomography, X-Ray Computed; Trypsinogen; Ultrasonography

Trypsins have been purified and characterized in a multitude of mammalian and nonmammalian species, but not in the domestic cat (Felis catus). In several species two or more isoforms of trypsin have been isolated. Feline trypsin was purified from feline pancrease by sulfuric acid extraction, ammonium sulfate fractionation, gel filtration and affinity chromatography on a benzamidine-activated sepharose gel. Feline trypsinogen was purified by sulfuric acid extraction, SDS-PAGE and electroelution. Only one isoform of feline trypsin and its zymogen could be demonstrated. Isoelectric focusing on agarose gel revealed an isoelectric point of greater than 10.0 for both feline trypsinogen and trypsin. The molecular weight of feline trysinogen was estimated at 22,600, while the molecular weight of feline trypsin was estimated at 21,000. The N-terminal amino acid sequence of feline trypsinogen was Phe-Pro-Ile-Asp-Asp-Asp-Asp-Lys-Ile-Val-Gly-Gly-Tyr-Thr-Asn-Arg. We conclude that cats either have only one isoform of trypsin or that other isoforms are present in minute quantities, undetectable by commonly used methods. We further conclude that feline trypsinogen and trypsin are cationic. Finally, the N-terminal amino acid sequence of the last 16 amino acid residues of feline trypsinogen is closely related to that of other mammalian species and the final 8 amino acid residues (termed trypsinogen activation peptide) are identical to those of canine cationic trypsinogen.

Topics: Amino Acid Sequence; Animals; Cats; Chromatography, Affinity; Chromatography, Gel; Dogs; Electrophoresis, Agar Gel; Electrophoresis, Polyacrylamide Gel; Isoelectric Focusing; Molecular Sequence Data; Molecular Weight; Pancreas; Pancreatic Diseases; Sequence Analysis; Sequence Homology, Amino Acid; Trypsin; Trypsinogen

Acute pancreatitis is characterized by hyperamylasemia, pancreatic edema, and the presence of activated digestive enzymes within the pancreas. The secretagogue-induced model of acute pancreatitis is also characterized by pancreatic acinar cell vacuolation, subcellular redistribution of lysosomal hydrolases, and a fall in pancreatic glutathione levels. We have performed time-dependence studies to determine the sequence with which these phenomena appear and to establish their cause-and-effect relationship. Evidence of lysosomal enzyme redistribution and trypsinogen activation within the pancreas could be detected within 10-15 min of the onset of supramaximal secretagogue stimulation, while hyperamylasemia (30 min), pancreatic edema (60 min), and acinar cell vacuolation (60 min) occurred at later times. Pancreatic glutathione levels were either unchanged (15 and 30 min) or elevated (60 min) during the early times of supramaximal stimulation and were only noted to be decreased at a later time. These results support the conclusion that intrapancreatic digestive enzyme activation, possibly occurring by a mechanism involving lysosomal hydrolase redistribution, is an early and likely a critical event in the evolution of secretagogue-induced pancreatitis but that glutathione depletion is neither early nor critical to the evolution of this model of pancreatitis.

Topics: Amylases; Animals; Cathepsin B; Ceruletide; Edema; Enzyme Activation; Glutathione; Male; Pancreas; Pancreatic Diseases; Pancreatitis; Rats; Rats, Wistar; Subcellular Fractions; Trypsinogen

Topics: Alcohol Drinking; Biomarkers; Enzyme-Linked Immunosorbent Assay; Humans; Pancreatic Diseases; Pancreatic Neoplasms; Trypsin; Trypsinogen

Calcium infusion and hypotension have been described as the most important risk factors for pancreatic injury after cardiopulmonary bypass.. Rats were randomly allocated to three experimental groups undergoing either sham operation and saline infusion (Control, n = 30), hemorrhagic reduction of mean arterial pressure to 30 mmHg for 30 min alone (hypotension, n = 51), or hypovolemic hypotension followed by bolus infusion of CaCl2 (200 mg.kg-1; hypercalcemia, n = 85). Serum ionized calcium, amylase activity, trypsinogen activation peptide in pancreatic tissue homogenates, pancreatic wet/dry weight ratio, histologic changes, and mortality were assessed for 24 h.. Control rats showed no significant changes of any parameter throughout the experiments. In contrast, hypotension significantly increased serum amylase (P < 0.001), tissue trypsinogen activation peptide (P < 0.01), wet/dry weight ratio (P < 0.001), and histologic scores for edema (P < 0.001) and pancreatic necrosis (P < 0.05). Subsequent CaCl2 administration transiently increased [Ca2+] (P < 0.001) with the concentration rapidly returning to baseline within 3 h. That infusion of CaCl2 further increased amylase (P < 0.05), tissue trypsinogen activation peptide (P < 0.05), wet/dry weight ratio (P < 0.001), and histologic evidence of pancreatic edema (P < 0.05) and acinar necrosis (P < 0.05) when compared with hypotension alone. Whereas all Control animals survived the experiments, 22% (P < 0.05) and 47% (P < 0.05 vs. hypotension) of animals died in the hypotension and hypercalcemia groups, respectively.. Temporary hypotension alone causes ectopic trypsinogen activation and lethal acute pancreatitis. Super-imposed hypercalcemia significantly aggravates hypotension-induced pancreatic injury and mortality in rats.

Topics: Animals; Blood Volume; Calcium; Cardiopulmonary Bypass; Enzyme Activation; Hemorrhage; Hypotension; Male; Pancreatic Diseases; Rats; Rats, Sprague-Dawley; Trypsinogen

We compared pancreatic acinar and ductal secretion in two patients with Johanson-Blizzard syndrome, age-matched control subjects, and patients with other primary pancreatic diseases. Patients with Johanson-Blizzard syndrome had preservation of ductular output of fluid and electrolytes, as in patients with Shwachman syndrome but differing from those with cystic fibrosis, who have a primary ductular defect. They also had decreased acinar secretion of trypsin, colipase and total lipase, and low serum immunoreactive trypsinogen levels, consistent with a primary acinar cell defect.

Topics: Case-Control Studies; Colipases; Consanguinity; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Female; Humans; Infant; Infant, Newborn; Lipase; Malabsorption Syndromes; Male; Pancreas; Pancreatic Diseases; Pancreatic Ducts; Syndrome; Trypsin; Trypsinogen

Protein analysis of intraductal precipitates and calculi is important to elucidate the mechanism of stone formation in chronic pancreatitis. We revealed human cationic trypsin immunoreactivity in protein extracts of pancreatic stones from 11 of 13 patients with chronic calcified pancreatitis, ranging from 0 to 42.3 ng/micrograms protein. On gel filtration the immunoreactivity eluted as one peak, which is identical to that of human cationic trypsinogen. On immunostaining of pancreatic stone, using an immunogold technic and scanning electron microscopy, the immunoreactivity was observed more densely in the amorphous portion of the center of the stones than in the concentric laminar layer of the periphery. Only negligible activity was detected for elastase 1 or amylase in the stone extracts. These results suggest that the presence of trypsinogen in pancreatic stone is not due to coprecipitation or adsorption of pancreatic enzymes but that trypsinogen is more likely involved in an initial step of intraductal precipitate formation than in a subsequent step of stone formation. However, the absence of trypsinogen in the stones from two of the 13 patients also suggests that trypsinogen is not the sole protein initiating precipitate formation.

Topics: Adult; Aged; Calculi; Chronic Disease; Female; Humans; Immunohistochemistry; Male; Microscopy, Electron, Scanning; Middle Aged; Pancreatic Diseases; Pancreatitis; Proteins; Trypsin; Trypsinogen

We studied the effect of short-term (3 hours) pancreatic duct obstruction (PDO) on the exocrine pancreas and on the secretion of lysosomal enzymes into the pancreatic juice of rabbits during stimulation by pancreatic secretagogues. The following evaluations were made: serum amylase levels, pancreatic water content, pancreatic amylase, trypsinogen and cathepsin B content, and output of pancreatic enzymes and lysosomal hydrolases when stimulated by secretin and caerulein as well as the distribution of cathepsin B in subcellular fraction. PDO for 3 hours plus secretin infusion caused a significant rise in serum amylase levels, pancreatic water content, and pancreatic amylase and trypsinogen content due to congestion of digestive enzymes during PDO. There was also a redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction. In normal rabbits and in those with only secretin infusion, caerulein stimulated the secretion of cathepsin B, into pancreatic juice. Just after PDO, the secretion of cathepsin B, amylase and trypsinogen significantly decreased. By 24 hours after PDO, the output of cathepsin B stimulated by caerulein and secretin had increased significantly. Amylase and trypsinogen output were also significantly increased at this stage, in both the secretin and caerulein fractions. These results indicate that the secretion of lysosomal enzymes into pancreatic juice is stimulated by gut hormones, such as caerulein, in the normal physiological state and in pathological states, such as PDO. These results also show augmented secretion of both lysosomal enzymes and pancreatic digestive enzymes in the recovery stage after PDO and their important roles at this stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amylases; Animals; Cathepsin B; Constriction; Lysosomes; Male; Pancreas; Pancreatic Diseases; Pancreatic Ducts; Pancreatic Juice; Rabbits; Trypsinogen

The serum behavior of amylase, pancreatic isoamylase, lipase, trypsinogen, and elastase 1 was studied in 145 patients with pancreatic disease and in 66 patients with abdominal pain of nonpancreatic origin, for the purpose of evaluating the relative diagnostic utility of their assays. In 34 patients with acute pancreatitis, serum lipase, trypsinogen, and elastase 1 were elevated in all 34, pancreatic isoamylase in 33 (97%) and amylase in 30 (88%). Ten of these acute pancreatitis patients were followed sequentially for seven days: the variations in their serum enzyme levels were parallel, although the lipase, trypsinogen, and particularly the elastase 1 elevations persisted longer than did those of amylase and pancreatic isoamylase. Among the patients with chronic pancreatitis, either in painful relapse (N = 19) or with pancreatic cysts (N = 15), the respective percentages of enzymes elevations were: 79 and 80% for elastase 1, 68 and 67% for trypsinogen, 63 and 73% for pancreatic isoamylase, 58 and 60% for lipase, 53 and 60% for amylase. In the 52 chronic pancreatitis patients studied during clinical remission, serum enzyme behavior varied greatly, and a majority of the assays (60%) were normal; even in the case of severe pancreatic exocrine insufficiency, normal as well as abnormally high and low enzyme values were seen. Highly variable enzyme behavior was also seen in the 40 patients with pancreatic cancer, and elastase I was the most frequently (35%) elevated enzyme in this group as well. Among the patients with abdominal pain of nonpancreatic origin, abnormally high enzyme levels were present in percentages ranging from 6% for lipase to 21% for trypsinogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adult; Aged; Amylases; Chronic Disease; Clinical Enzyme Tests; Female; Humans; Isoamylase; Lipase; Male; Middle Aged; Pancreatic Diseases; Pancreatic Elastase; Pancreatic Neoplasms; Trypsinogen

In order to investigate the role of renal factors in affecting trypsinogen 1 metabolism and excretion in chronic pancreatic disease, serum immunoreactive trypsin (IRT), urinary IRT, gamma-glutamyltransferase (GGT), alpha-glucosidase (AGL) and RNase outputs and the molecular size distribution of serum and urine IRT were studied in 8 control subjects, 18 cases with pancreatic cancer, and 23 cases with chronic pancreatitis. Serum chromatography demonstrated that most immunoreactivity eluted as trypsinogen 1. Smaller amounts of immunoreactivity at higher molecular weights were also observed. Urine chromatography displayed both trypsinogen 1 and heavier molecular forms. An inverse linear correlation was noticed between creatinine clearance and serum trypsinogen 1 levels. Multiple regression analysis (urinary IRT output dependent and GGT, AGL, and RNase predictor variables) showed a significant linear correlation. RNase was found to be the most important parameter in explaining urinary IRT output. Mild variations in the glomerular function seem to be able to influence serum trypsinogen 1 levels. Urinary IRT excretion is principally explained by a disturbance in the tubular reabsorption of low molecular weight proteins, such as RNase.

Topics: Adult; Aged; Chronic Disease; Female; Humans; Kidney; Male; Middle Aged; Pancreatic Diseases; Pancreatic Neoplasms; Trypsin; Trypsinogen

Ultrasonic monitoring of the pancreas following secretin stimulation has shown to cause a marked dilatation of Wirsung duct; whether this phenomenon is due to the stimulation of pancreatic secretion and/or to the effect of secretin on the sphincter of Oddi (SO) motility is unknown. In the present study pancreatic scan after secretin was performed in 11 patients with nonpancreatic diseases after premedication with glucagon (inhibition of both pancreatic secretion and SO motility) or tyropramide (inhibition of SO motor function) and in patients with different degrees of pancreatic insufficiency. Serum immunoreactive trypsinogen (IRT) levels were measured in all the subjects during the test. Premedication with glucagon completely abolished both Wirsung enlargement and serum IRT increase, while tyropramide significantly reduced, but did not abolish, the response to secretin. These results suggest that both stimulation of pancreatic secretion and the increase of SO pressure are prerequisites for a full-blown occurrence of the secretin-induced modifications of Wirsung. Within chronic pancreatitis patients, the response to secretin was exaggerated in those with a still preserved pancreatic function and it was lacking in those with severe pancreatic insufficiency.

Topics: Chronic Disease; Common Bile Duct Diseases; Dilatation, Pathologic; Humans; Pancreas; Pancreatic Diseases; Pancreatic Ducts; Pancreatitis; Secretin; Sphincter of Oddi; Trypsinogen; Ultrasonography

Pancreatic insufficiency was induced in rats by a single injection of 50 microliter oleic acid into the pancreatic duct over a period of 3 min. Exocrine tissue was destroyed within 3-6 days, and after 6 weeks the remaining pancreas equaled 2.7% of the original organ. The rats showed retardation of body weight in spite of normal food intake. After 7 weeks the fecal weight increased by 23%, and the fecal chymotrypsin activity decreased by 90% compared to controls. At this time plasma cholecystokinin (CCK) concentrations were significantly elevated. The amylase content in the remaining pancreas was reduced by 99%, and trypsin content was reduced by 93%. Unstimulated protein discharge from the remnant pancreas in vitro was threefold higher compared to secretion from control tissue. Thus a simple, reproducible model for inducing persistent pancreatic insufficiency was developed. To compensate for the loss of exocrine tissue, the remaining acinar cells adapt by a CCK-mediated increase in protein secretion.

Topics: Adaptation, Physiological; Amylases; Animals; Cholecystokinin; Digestive System; Disease Models, Animal; Male; Oleic Acid; Oleic Acids; Pancreatic Diseases; Rats; Rats, Inbred Strains; Trypsinogen

A procedure to collect pure pancreatic juice endoscopically is described which allows an instant estimation of the protein content of the secretion by measuring its absorption at 280 nm. By this the kinetics of protein secretion can already be read from a curve during the collecting procedure, thus avoiding a multitude of small fractions otherwise necessary. Timing and size of the samples are adjusted individually according to the course of protein secretion and not to a rigid regimen. The method described is especially apt to investigations of pancreatic proteins and substances the secretion of which parallels that of protein; e. g. trypsinogen, calcium and zinc, however not sodium and potassium.

Topics: Cholecystokinin; Electrolytes; Endoscopy; Humans; Pancreatic Diseases; Pancreatic Function Tests; Pancreatic Juice; Proteins; Trypsinogen

We evaluated serum cationic trypsinogen as a marker of exocrine pancreatic function in children without cystic fibrosis. The ability of this test to determine steatorrhoea of pancreatic origin, and its relationship to a wide range of exocrine pancreatic function were assessed. Serum trypsinogen was measured in 32 children with steatorrhoea, 10 with pancreatic and 22 with non-pancreatic causes. In patients with pancreatic steatorrhoea, serum cationic trypsinogen was 4.9 +/- 4.9 micrograms/l (mean +/- SD), significantly below values in patients with non-pancreatic steatorrhoea (47.0 +/- 22.1 micrograms/l, p less than 0.001) and 50 control subjects (31.4 +/- 7.4 micrograms/l, p less than 0.001). Serum cationic trypsinogen values in patients with pancreatic steatorrhoea all fell below the lower limit of our control range and below all values for patients with non-pancreatic steatorrhoea. Serum cationic trypsinogen was also evaluated against pancreatic trypsin output in 47 patients (range 0.2-17.0 yr who underwent a hormonal pancreatic stimulation test. In 17 patients, serum cationic trypsinogen was low (less than -2SD or less than 16.6 micrograms/l), and associated with greatly impaired pancreatic trypsin output, ranging from 0-8% of mean normal trypsin output. Five of these 17 patients did not have steatorrhoea. In 30 patients with normal or raised serum cationic trypsinogen (greater than or equal to 16.6 micrograms/l), pancreatic trypsin output ranged from 15-183% of mean normal values. In conclusion, low serum cationic trypsinogen suggests severely impaired exocrine pancreatic function, with sensitivity extending above the steatorrhoeic threshold. In the presence of steatorrhoea, low serum cationic trypsinogen indicates a pancreatic aetiology. Normal serum cationic trypsinogen, however, does not exclude impaired pancreatic function, above the steatorrhoeic threshold.

Topics: Adolescent; Celiac Disease; Child; Child, Preschool; Humans; Infant; Pancreas; Pancreatic Diseases; Trypsin; Trypsinogen

Previous studies, in selected populations, have determined that a low serum trypsinogen can be seen in chronic exocrine pancreatic disorders (CP) and primary diabetes mellitus (DM). In this study, we investigated the predictive value of a low serum trypsinogen. The study population consisted of 488 consecutive emergency room patients admitted to our hospital on whom a serum amylase was drawn by the emergency room staff. Of the sera drawn, 418 were saved and tested for immunoassayable trypsinogen. Ten of 418 (2.4%), had a low level of this marker (less than 10 ng/ml). Of these 10, four had obvious historical or clinical evidence of CP during their initial hospitalization. Six patients, however, had no initial evidence of CP. Follow-up was obtained in three of the six, and all three had evidence of CP despite absence of symptoms. Of the 418 patients, 37 had DM. A low trypsinogen was found in three of these 37, and all three had concomitant CP. We conclude that this new assay has excellent predictive value in diagnosing chronic exocrine pancreatic disorders.

Topics: Adult; Aged; Chronic Disease; Diabetes Mellitus; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Trypsinogen

Topics: Acute Disease; Humans; Pancreatic Diseases; Trypsinogen

Topics: Celiac Disease; Humans; Pancreatic Diseases; Trypsinogen

Serological tests used in pancreatic diseases, especially isoamylase analysis and trypsin radioimmunoassay are presented. The results show that these markers are helpful in the diagnosis of chronic pancreatic diseases.

Topics: Adolescent; Amylases; Child; Child, Preschool; Chronic Disease; Cystic Fibrosis; Humans; Infant; Isoenzymes; Lipase; Pancreatic Diseases; Trypsinogen

Topics: Adult; Aged; Female; Gallstones; Hepatitis, Alcoholic; Humans; Male; Middle Aged; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Radioimmunoassay; Trypsin; Trypsinogen

Serum immunoreactive trypsinogen (IT) levels were measured in 479 normal controls and in 604 patients (510 with nonpancreatic diseases and 94 with pancreatic diseases) in order to evaluate the distribution of IT values in the control population and the accuracy of the assay in the diagnosis of pancreatic diseases. It concentrations were normally distributed in the healthy population; children showed mean IT values significantly lower than adults. The sensitivity, specificity, and predictive value of a positive and negative result in diagnosing acute or chronic pancreatitis were evaluated vs normals and vs normals plus all patients. With an IT value higher than 80 ng/ml, the likelihood that a patient is not affected by acute pancreatitis is less than 5%. An IT value lower than 9 ng/ml detected 44% of chronic pancreatitis and was related to a 52% probability of such a condition. The 48% false positive results also include patients with pancreatic tumor (31% of cases), so that the chance of finding reduced IT levels in subjects without pancreatic damage drops to 17%. In view of the low prevalence of pancreatic diseases, IT assay should not be taken into consideration as a diagnostic screening test in the general population and its use should be limited to a hospitalized population.

Topics: Adolescent; Adult; Aged; Cations; Child; Child, Preschool; False Positive Reactions; Female; Humans; Infant; Male; Middle Aged; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Radioimmunoassay; Trypsinogen

The concentration in serum of cathodal trypsinogen has been studied in certain clinical and experimental situations. The concentration correlated with pancreatic amylase activity. Low levels were found in patients with malabsorption due to exocrine pancreatic insufficiency. The concentration rose after endoscopic retrograde cholangiopancreatographic examinations (ERCP). After ERCP, however, no trypsin was detected complexed with protease inhibitors, as is generally found in acute pancreatitis. The trypsinogen concentration in serum also rose in renal failure indicating a renal elimination route for the endogenous trypsinogen.

Topics: Amylases; Endoscopy; Humans; Kidney Failure, Chronic; Malabsorption Syndromes; Pancreas; Pancreatic Diseases; Pancreatic Juice; Pancreatitis; Radiography; Trypsinogen

Premature activation of proteolytic zymogens (trypsinogen, chymotrypsinogen) as an early step in the pathogenesis of exocrine pancreatic insufficency (EPI) syndrome in CBA/J mice was investigated in electrophoresed pancreatic homogenates. Polyacrylamide gels containing extracts from control pancreas required prior activation of trypsinogen and chymotrypsinogen (with exogenously added enterokinase and trypsin, respectively) to produce activity staining with specific synthetic substrates. On the contrary, bands of activity staining in gels containing homogenates from mice with EPI syndrome could be readily detected without trypsin or enterokinase preincubation. Subcellular fractionation of control and diseased pancreas revealed that the premature intracellular proteolysis was confined to the zymogren granule fraction, which, even in very moderately affected pancreases (10 to 30% acinar cell autolysis), was very labile in vitro. These proteolytic events reflect the biochemical consequences of zymogen granule destabilization that were observed at the ultrastructural level.

Topics: Animals; Chemical Fractionation; Chymotrypsin; Chymotrypsinogen; Cytoplasmic Granules; Electrophoresis, Polyacrylamide Gel; Enzyme Precursors; Female; Male; Mice; Mice, Inbred CBA; Pancreatic Diseases; Rodent Diseases; Staining and Labeling; Trypsin; Trypsinogen

Topics: Amylases; Child; Cystic Fibrosis; Enteropeptidase; Humans; Infant; Methods; Neutropenia; Pancreas; Pancreatic Cyst; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Peptide Hydrolases; Syndrome; Trypsinogen

Effects of age and long-term nutritional treatment on pancreas composition and digestive function were determined in rats fed a cereal-type chow after weaning (experiment 1) or diets with 30% casein and 34% butterfat, 54% starch, or 54% sucrose after 9 mo (experiment 2). The rats were adapted for 1-2 wk to a 15% whole-egg protein diet before killing. In experiment 1, pancreas size, nucleic acid, and digestive enzyme content increased significantly with age up to 3 mo. Values for pancreatic weight and DNA were significantly greater in 28-mo-old rats than in 12-mo-old rats. Pancreatic digestive enzyme content was 65-100% lower in rats with and without gross pathologic lesions. In experiment 2, mortality was higher and pathologic changes were more pronounced by 24 mo in rats fed the butterfat or sucrose diet. Usually, pancreatic enzymes were not reduced as much as in experiment 1, although chymotrypsinogen and trypsinogen concentrations were significantly and negatively correlated with the degree of pathologic change. Apparent digestibility of dietary nitrogen and food energy content was not reduced in rats with reduced enzyme reserves. The rate of incorporation in vitro of label into pancreatic protein and RNA did not differ significantly among aged and control rats.

Topics: Age Factors; Aging; Animals; Caseins; Chymotrypsinogen; Diet; Digestion; DNA; Edible Grain; Eggs; Fats; Male; Nutritional Physiological Phenomena; Organ Size; Pancreas; Pancreatic Diseases; Proteins; Rats; RNA; Starch; Sucrose; Trypsinogen

Topics: Amylases; Drug Evaluation, Preclinical; Humans; In Vitro Techniques; Lipase; Pancreatic Diseases; Pancreatic Extracts; Peptide Hydrolases; Trypsin; Trypsinogen

Topics: Amylases; Autopsy; Bone Marrow Diseases; Child, Preschool; Clinical Enzyme Tests; Copper; Endopeptidases; Female; Humans; Infant; Kwashiorkor; Lipase; Male; Metabolism, Inborn Errors; Pancreas; Pancreatic Diseases; Pancreatitis; Trypsinogen; Zinc

Topics: Amylases; Animals; Clinical Enzyme Tests; Dogs; Endopeptidases; Enzyme Activation; Injections, Intravenous; Pancreatic Diseases; Pancreatic Juice; Time Factors; Trypsin; Trypsinogen

Topics: Anilides; Animals; Cattle; Child; Child, Preschool; Duodenum; Humans; Immunoassay; Immunodiffusion; Immunoelectrophoresis; Intestinal Secretions; Methods; Pancreatic Diseases; Rabbits; Trypsin; Trypsin Inhibitors; Trypsinogen

Topics: Adolescent; Amylases; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Lipase; Lipomatosis; Male; Metabolism, Inborn Errors; Pancreas; Pancreatic Diseases; Trypsinogen

Topics: Amylases; Animals; Cell Membrane; Chymotrypsin; Enzyme Precursors; Hypertrophy; Male; Nucleic Acids; Pancreas; Pancreatic Diseases; Proteins; Rats; Trypsin Inhibitors; Trypsinogen

Topics: Diagnosis, Differential; Duodenum; Endopeptidases; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Intestinal Diseases; Male; Metabolism, Inborn Errors; Pancreatic Diseases; Pancreatic Juice; Trypsinogen