Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism for acute hypercalcaemia increasing pancreatic enzyme secretion is unknown. To determine if raised extracellular calcium concentrations can directly stimulate pancreatic enzyme output, we measured discharges of pulse labelled protein and chymotrypsin from isolated cat pancreatic lobules in the presence of normal and raised calcium concentrations. Incubation in 5.0 mmol/l calcium increased discharges of pulse labelled protein (four fold), chymotrypsin (2.5 fold) and amylase (2.2 fold), compared with control experiments with 2.5 mmol/l calcium (p less than 0.001). This effect was similar to the maximal effect of carbachol or caerulein. Compared with 5.0 mmol/l calcium, incubation at the higher calcium concentration of 10.0 mmol/l induced similar discharges of chymotrypsin and amylase, whereas the increase in discharge of pulse labelled protein was smaller (p less than 0.01). The effects of raised calcium were not altered by atropine. Incubation in a high calcium medium did not impair pancreatic acinar response to subsequent stimulation with carbachol, but incubation in hypothermia abolished the effects of high calcium concentrations, suggesting that increased enzyme discharge is caused by stimulation of secretion not to cell damage. These data are consistent with a direct stimulatory effect of raised extracellular calcium concentrations on pancreatic acinar cell function.
 ...
PMID:In vitro stimulation of pancreatic enzyme discharge by calcium. 367 49

Chronic pancreatitis has been reported to be associated with an increased secretion of calcium in pancreatic juice. To determine whether estimation of duodenal calcium may be useful for diagnosing chronic pancreatitis, we compared duodenal calcium output in patients with chronic pancreatitis and in subjects without pancreatic disease, during intravenous infusion of secretion alone, with calcium, or with cholecystokinin-pancreozymin (CCK-PZ). Duodenal calcium output increased during infusion of both calcium and CCK-PZ to a similar extent in chronic pancreatitis and controls. Overall, duodenal output of chymotrypsin was markedly lower in chronic pancreatitis; however, chymotrypsin output increased in response to both intravenous calcium and CCK-PZ in both groups. Bilirubin output increased in both groups during calcium infusion, but this increase was significantly reduced in chronic pancreatitis; in contrast, CCK-PZ caused a similar increase in both groups. The high calcium output observed in hypercalcemia in the presence of low enzyme output suggests increased pancreatic secretion of enzyme-independent calcium in chronic pancreatitis. However, the difference is obscured by biliary calcium, which is secreted in much higher concentrations. Thus, duodenal calcium determination does not appear to be a useful diagnostic test in chronic pancreatitis.
 ...
PMID:Duodenal calcium in chronic pancreatitis: is it of diagnostic value? 370 99

In healthy subjects, the 3 known pancreatic trypsinogens, which are endopeptidases belonging to the chymotrypsin superfamily, are activated by enterokinase and partial autoactivation in the duodenum. The premature activation of trypsinogen in the pancreatic interstitium, with the subsequent activation of other pancreatic zymogens, is believed to lead to the autodigestion of the gland, this being the first event in acute pancreatitis. The mechanisms that lead to trypsinogen, activation in acute pancreatitis are largely unknown. However, ischemia, hypercalcemia and the activation of cathepsin B (by cholecystokinin) are thought to be of importance. The easiest and most reliable way to assess trypsinogen activation is the measurement of the activation peptide, TAP, in urine, plasma, pancreatic tissue or ascitic fluid. In the animal model of acute pancreatitis, TAP in ascites and pancreatic tissue has been shown to correlate with the presence and extent of necroses. It has proven to be a good marker for the severity of pancreatitis and is a useful marker in examining the pathophysiology and possible treatment modalities in the animal model of acute pancreatitis. Studies on TAP in human acute pancreatitis were most commonly focused on urinary TAP. Within a 48-hour time frame after the onset of the disease, TAP was a good predictor of the severity of acute pancreatitis. The main advantage over other markers, such as CRP, is that TAP is the earliest marker of necrosis to be increased. Also, increased levels of TAP in ascitic fluid were shown to correlate well with pancreatic necroses. In our experience, plasma TAP was found to have a "diagnostic window" within the first 3 days predicting pancreatic necroses. Positive TAP gave a very good positive prediction and a high specificity towards the development of pancreatic necroses, but did not differ between necrotizing pancreatitis with systemic complications or uncomplicated necrotizing pancreatitis. We therefore think that plasma TAP is a very good marker for local complication in acute pancreatitis and its routine measurements may help to identify patients at a high risk within the first days of the disease.
 ...
PMID:Mechanism and role of trypsinogen activation in acute pancreatitis. 1057 41