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Biomedical subjects

M O'Rourke

Publications and source records attributed to M O'Rourke.

At least 91 records · Page 5Linked to original sources

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. Second-meal responses were much larger than those following the first meal. Plasma cationic trypsin(ogen) was also elevated during the normal feeding period when food was withheld and dogs in adjacent cages were fed. Small, irregular variations in plasma trypsin(ogen)s occurred during the interdigestive period when blood was sampled every 2 h. CCK-8 plus secretin, in doses shown previously to stimulate exocrine secretion of enzymes submaximally, increased plasma levels of both trypsin(ogen)s dose dependently. Most (greater than 80%) of the immunoreactive cationic trypsin(ogen) in plasma before and after feeding and following CCK-8 was in proenzyme form. We conclude that plasma levels of pancreatic trypsinogens are increased by food intake and low doses of CCK-8. Furthermore, cephalic mechanisms appear to play an important role in mediating the response to food intake.

Animals↗

Plasma immunoreactive anionic pancreatic trypsin in cystic fibrosis.

Previous data from this laboratory have shown good correlation between plasma cationic trypsin(ogen) and levels of pancreatic function in older cystic fibrosis (CF) patients with and without malabsorption. In the present study a radioimmunoassay for human anionic trypsin(ogen) has been employed in the assessment of pancreatic function in older patients with CF. Immunoreactive anionic trypsin(ogen) levels correlated poorly with pancreatic function due to an apparent elevation of this enzyme in many older CF patients with malabsorption (CF + M). When plasma from three older CF + M patients is examined for the molecular size of the apparent immunoreactive material detected, no free anionic trypsinogen is observed. Instead, a broad peak of apparent immunoreactive material appears in the gammaglobulin region. However, only free anionic trypsinogen could be detected in plasma from two CF patients without malabsorption (CF - M), who had not received pancreatic enzyme supplements. It appears possible that a human plasma immunoglobulin G (IgG) to porcine pancreatic enzyme in the CF + M patients might interfere in the assay by binding TLCK--anionic trypsin tracer. It is unclear why such an effect does not appear to occur in the cationic trypsin(ogen) assay. The results of the current study suggest that, for assessment of pancreatic insufficiency in CF, the radioimmunoassay for cationic trypsin(ogen) is more useful than the presently available radioimmunoassay for the anionic form.

Adolescent↗

Plasma pancreatic trypsinogens in chronic renal failure and after nephrectomy.

The kidney has previously been shown to be a major site for the plasma clearance of pancreatic trypsinogens in the rat. This study investigated plasma concentrations of anionic and cationic trypsinogen in chronic renal failure and anephric patients. Plasma concentrations were significantly elevated in both groups of patients. Hemodialysis did not change their plasma levels. The plasma levels of anionic and cationic trypsinogens were highly correlated in patients and normal subjects; however, the relative concentrations of anionic trypsinogen were significantly higher in renal failure patients. This suggests that in patients with renal failure the secondary clearance mechanisms for these plasma proteins more efficiently clear cationic molecules. In normal dogs, intravenous infusion of synthetic octapeptide of cholecystokinin (CCK-8) resulted in small transitory increases in plasma trypsinogen levels. After nephrectomy, basal levels of anionic and cationic trypsinogen were elevated, and intravenous infusion of CCK-8 resulted in prolonged, high levels of plasma trypsinogens.

Animals↗

Immunoreactive forms of cationic trypsin in plasma and ascitic fluid of dogs in experimental pancreatitis.

A canine model of bile-induced pancreatitis has been employed to investigate time-dependent changes in the molecular forms of trypsin in blood and ascitic fluid in this disease. The distribution of immunoreactive trypsin as trypsinogen and trypsin bound to plasma inhibitors in ascitic fluid and plasma during the course of the disease has been investigated by means of a radioimmunoassay for canine pancreatic cationic trypsin. In addition, trypsinlike amidase activity was determined in plasma and ascitic fluid using Z-Gly-Gly-Arg-beta-Nap as substrate. Early plasma and ascitic fluid samples in four dogs that died contained primarily trypsinogen, while extensive activation of trypsinogen to alpha 2-macroglobulin and alpha 1-protease inhibitor-bound trypsin occurred in the course of the disease. A fifth dog survived and showed little activation of trypsinogen. In the four dogs that died, the levels of trypsinlike amidase activity in the ascitic fluid were substantial throughout the course of the disease. The plasma levels of trypsinlike activity in these animals were much lower, but increased during the disease process. The dog that survived had lower concentrations of trypsinlike activity in ascitic fluid and plasma. These results suggest that activation of trypsinogen resulting in inhibitor-bound forms of trypsin in ascitic fluid and plasma is important in the pathogenesis of acute pancreatitis.

Amidohydrolases↗

Clearance of circulating anionic and cationic pancreatic trypsinogens in the rat.

The kinetics and mechanism of clearance of pancreatic cationic and anionic trypsinogens from the circulation have been investigated in a rat model. 125I-labeled rat cationic trypsinogen is cleared from the bloodstream with a half-life of approximately 4 min. In contrast, 125I-labeled rat anionic trypsinogen has a half-life in the circulation of approximately 55-60 min. The major site of clearance for both enzymes is the kidney. Neither zymogen binds to plasma proteins to a significant extent over a period of three half-lives. The relative rates of clearance of these zymogens from the circulation appears to correlate with their respective isoelectric points.

Animals↗

The role of long term beta-blockade after myocardial infarction: Paper 1.

The opinion is emerging that beta-blocking drugs have an important role in management of patients following acute myocardial infarction. Already beta-blocking drugs are accepted as the treatment of choice in hypertension and in angina pectoris--in the major risk factor and consequence respectively of coronary atherosclerosis, and both commonly recognized in patients who survive acute myocardial infarction. But beta-blocking drugs also may be of benefit in reducing the incidence and risk of subsequent infarction, and so may be of value for long term treatment of patients who have no symptoms whatever following acute infarction.

Acute Disease↗