Enzyme immunoassay for human pancreatic amylase.

An enzyme immunoassay (EIA) for human pancreatic amylase has been developed for the detection of human serum amylase content. Our monoclonal antibody is highly specific for human pancreatic amylase; it cross reacted negligibly with the salivary isoenzyme. We developed a solid phase enzyme immunoassay for determination of pancreatic amylase in human serum with this antibody.

New model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats.

We examined the biological and histologic characteristics of a new experimental model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats. Rats were given a single intraperitoneal injection of 500 mg/100 g body weight of L-arginine. At 12-24 hr after the arginine injection, serum levels of amylase, lipase, and anionic trypsin(ogen) reached respective peak values 2, 5, and 20 times those of control rats without arginine and returned to control levels after 24-48 hr.

Effects of L-364,718 on pancreatic exocrine and endocrine secretion in the rat.

We examined the inhibitory effect of L-364,718, a nonpeptide cholecystokinin (CCK) antagonist, on CCK stimulation of pancreatic exocrine and endocrine secretion in both the isolated pancreatic acini and the isolated perfused pancreata of rats. In the isolated acini, L-364,718 inhibited CCK octapeptide (CCK-8)-stimulated amylase release and binding of 125I-CCK-8 in a dose-dependent manner without appreciable effects on the basal amylase secretion. L-364,718 also inhibited amylase release in response to caerulein and gastrin I, but had no effect on amylase release stimulated by other secretagogues or by agents bypassing receptors.

Beneficial effects of the synthetic trypsin inhibitor camostate in cerulein-induced acute pancreatitis in rats.

The therapeutic effect and the mechanism of action of the synthetic trypsin inhibitor camostate were studied in a rat model of acute interstitial pancreatitis induced by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Rats with acute pancreatitis were given either 100 mg/kg body weight camostate or volume- and pH-adjusted water via an orogastric tube 30 min after the last cerulein injection. The elevation of serum amylase activity was significantly reduced by camostate treatment and the peak value was seen 1 hr earlier than that observed in the rats that did not receive camostate.

[Biochemical analysis of bone and mineral metabolism in liver cirrhosis].

We investigated the disorder of bone and mineral metabolism in 29 patients with liver cirrhosis who were classified into two subgroups with (group 1, n = 13) or without (group 2, n = 13) osteopenia according to the method of Jikei. Serum levels of osteocalcin level, bone-type alkaline phosphatase activity and calcium concentration in serum and urine in these patients and 25 normal control subjects were determined. Serum osteocalcin level and bone-type alkaline phosphatase activity were elevated in group 1 compared with those in group 2 and normal control subjects.

Determination of 3 beta-hydroxylated bile acids in human serum and liver tissue.

3 beta, 7 alpha-Dihydroxy-5 beta-cholanoic acid (3 beta, 7 alpha-diOH) was detected in serum of 3 patients with intrahepatic cholestasis. 3 beta, 7 beta-dihydroxy-5 beta-cholanoic acid (3 beta, 7 beta-diOH) appeared in serum of those patients after treatment with ursodeoxycholic acid (UDC). These bile acids were also detected in only unconjugated fractions of serum of another 7 patients with chronic liver diseases, but not in liver tissue of them.

[Plasma cholecystokinin concentration in patients with chronic pancreatitis measured by bioassay].

We developed a specific and sensitive bioassay for measuring plasma cholecystokinin (CCK) in human and investigated CCK response after a test meal in patients with chronic pancreatitis. Treatment with cycloheximide increased the sensitivity and responsiveness of isolated rat pancreatic acini to CCK-octapeptide (CCK-8) and thus plasma levels of CCK-8 as low was 0.17 pM were detectable.

Hydrocortisone treatment increases the sensitivity and responsiveness to cholecystokinin in rat pancreas.

The effects of hydrocortisone treatment on the secretory abilities of pancreatic acini to various secretagogues were studied. Rats were given subcutaneous injections of hydrocortisone at doses of 1.25, 2.

[Effects of neuromedin B and neuromedin C on insulin release from isolated perfused rat pancreas].

Neuromedin B and neuromedin C are novel decapeptides that have recently been isolated from porcine spinal cord and canine intestinal mucosa. We have studied the effects of neuromedin B and neuromedin C on insulin release from the isolated perfused rat pancreas. The effect of neuromedin B was detectable at a concentration of 10mM, and that of neuromedin C was detectable at a concentration of 1nM.

Increased beta-cell secretory responsiveness to ceruletide and TPA in streptozocin-induced mildly diabetic rats.

We examined the effects of various stimuli on immunoreactive insulin (IRI) and glucagon (IRG) release from perfused pancreases isolated from control and streptozocin-induced diabetic (STZ-D) rats. Diabetes was induced by injecting 30 mg/kg STZ into rats fasted for 16-18 h 12-17 days before our experiments. Glucose (11.

Effect of a new cholinergic agonist, aclatonium napadisilate, on exocrine and endocrine rat pancreas.

The effect of aclatonium napadisilate, a choline sulfonate derivative, on exocrine and endocrine pancreatic functions was compared with that of carbamylcholine in both isolated pancreatic acini and the isolated perfused pancreas of rats. In the isolated acini, aclatonium napadisilate and carbamylcholine stimulated amylase release. While the relative efficacy of aclatonium napadisilate was the same as that of carbamylcholine, aclatonium napadisilate was about 20-fold less potent.

Non-septic endotoxemia in cirrhotic patients.

We have found that endotoxemia detected by conventional LCT (limulus colorimetric test) in patients with liver diseases could not be detected by endotoxin-specific LCT at all, and proposed that this beta-glucan like activity (BGLA) should be termed as non-septic endotoxemia, distinguishing it from septic endotoxemia seen in gram-negative sepsis. In this study, we investigated non-septic endotoxemia through the clinical course of 8 cirrhotic patients. Non-septic endotoxemia appeared at the onset of DIC but tended to decline in level in the late terminal stage.

Loxiglumide. A new proglumide analog with potent cholecystokinin antagonistic activity in the rat pancreas.

D,L-4-(3,4-dichlorobenzoylamino)-5-(N-3-methoxypropyl-pentylami no)-5- oxopentanoic acid (CR 1505; loxiglumide) is a newly developed analog of proglumide. We examined the inhibitory effects of loxiglumide on pancreatic exocrine function in the isolated pancreatic acini and the isolated perfused pancreata of rats. Loxiglumide inhibited cholecystokinin octapeptide (CCK-8)-stimulated amylase release and, similarly, binding of [125I]CCK-8 to isolated rat pancreatic acini.

Cholecystokinin in the entero-insular axis.

Cholecystokinin (CCK) is a well-characterized gastrointestinal hormone which is released into the general circulation after meals. Targets for CCK include not only the gallbladder and the exocrine pancreas but also the endocrine pancreas. In this paper, we review the role of CCK from the perspective of the entero-insular axis, where CCK seems to function as one component of incretin and can raise insulin release synergistically with other incretin components.

Effects of a new proglumide analogue CR 1392 on pancreatic exocrine secretion in the rat.

The effects of proglumide analogue. CR 1392, on pancreatic exocrine secretion were studied in the isolated pancreatic acini and the isolated perfused pancreata of rats. In the isolated acini, CR 1392 caused a parallel rightward shift of the dose-response curve for amylase secretion stimulated by cholecystokinin octapeptide (CCK-8).

Bioassay of plasma cholecystokinin in rat and human: inhibition of protein synthesis prevents the decrease in the sensitivity and responsiveness of isolated rat pancreatic acini to CCK-8.

Isolated rat pancreatic acini were most sensitive and responsive when stimulated directly with cholecystokinin octapeptide (CCK-8) without preincubation. Both the responsiveness and sensitivity of acini to CCK-8 decreased time dependently with prolonged preincubation. When acini were stimulated with CCK-8 following pulse labeling with radioactive leucine, old protein was discharged together with newly synthesized (labeled) protein.

Effect of a new cholecystokinin receptor antagonist CR 1392 on caerulein-induced acute pancreatitis in rats.

The effects of cholecystokinin receptor antagonist CR 1392 was studied in a model of mild acute pancreatitis induced in rats by four subcutaneous injections of the secretagogue caerulein. A single subcutaneous injection of 50 mg/kg body weight of CR 1392 caused a dramatic reduction in serum amylase concentration and pancreatic wet weight as well as histologic improvement of the caerulein-induced acute pancreatitis when given 30 min before the first caerulein injection. CR 1392 was also effective in reducing the elevated serum amylase activity, pancreatic weight, and histologic alterations even when administered after the pancreatitis had been induced.

[Inhibitory effect of a new proglumide derivative, loxiglumide, on CCK action in isolated rat pancreatic acini].

The effect of a new proglumide derivative, loxiglumide (DL-4-(3,4-dichloro-benzoyl-amino)-5-(N-3-methoxy-propyl-pentylamino+ ++)-5-oxo-pentanic acid; CR 1505), on binding of 125I-CCK-8 and amylase release stimulated by CCK-8 was investigated in isolated rat pancreatic acini. Loxiglumide inhibited CCK-8-stimulated amylase release and binding of 125I-CCK-8 to rat pancreatic acini in a dose-dependent manner. Loxiglumide caused a concentration-dependent rightward shift of the dose-response curve for CCK-8-stimulated amylase release without altering the maximal response.

Effect of alpha-glucosidase inhibitor on exocrine and endocrine pancreatic function in rats fed a high-carbohydrate diet consisting of sucrose or glucose.

The effect of the alpha-glucosidase inhibitor acarbose on pancreatic exocrine and endocrine function was studied using the isolated perfused pancreata prepared from rats fed a normal (control diet) or an acarbose-containing sucrose- (ACS diet) or glucose-supplemented diet (ACG diet) for 10 days. Pancreatic amylase and insulin contents in rats fed the ACS diet were significantly decreased compared with those in rats with the control diet. Rats fed the ACG diet, however, had normal enzyme and hormone contents.

Pancreatic endocrine function in cirrhotic rats.

Pancreatic endocrine function in liver cirrhosis was examined in rats both in vivo and in vitro. Experimental liver cirrhosis was induced by subcutaneous injections of 50% carbon tetrachloride in a dose of 2 mL/kg body weight twice a week for 16 weeks. Control rats received a similar dose of olive oil during the same period.

Secretin-induced exocrine secretion in perfused pancreas isolated from diabetic rats.

Exocrine secretory function in response to 10 pM to 10 nM synthetic secretin was evaluated in perfused pancreas isolated from control, streptozocin-induced diabetic (STZ-D), alloxan-induced diabetic (ALX-D), and insulin-treated STZ-D rats. In STZ-D rats, the basal rate of pancreatic juice flow was significantly increased (10.3 +/- 1.

Severe acute exacerbation in chronic hepatitis B virus infection in Sendai, Japan.

In order to examine the clinical features of severe acute exacerbation in chronic hepatitis B virus (HBV) infection, 297 hepatitis B surface antigen (HBsAg) carriers were followed for 35 +/- 22 months (mean +/- S.D.) in Tohoku University Hospital from 1976 to 1987.

In-vitro and in-vivo activities of T-3262, a new pyridone carboxylic acid.

T-3262[p-toluenesulfonic acid salt of dl-7-(3-amino-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-1, 4-dihydro-4-oxo-1, 8-naphthyridine-3-carboxylic acid monohydrate] is a new pyridone carboxylic acid with a broad spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria. The activity of T-3262 against most Enterobacteriaceae was comparable with that of ciprofloxacin except Proteus spp. and Providencia rettgeri and exceeded that of ofloxacin and norfloxacin.

Effect of diabetes mellitus on pancreatic exocrine secretion from isolated perfused pancreas in rats.

We studied pancreatic exocrine function in response to cerulein and carbamylcholine in isolated perfused pancreas obtained from control, streptozotocin-induced diabetic, and insulin-treated diabetic rats. The time course of pancreatic juice, protein, amylase, and trypsinogen secretion in response to cerulein or carbamylcholine in diabetic rats was similar to that in control rats. Basal as well as cerulein- or carbamylcholine-stimulated output of amylase from diabetic rat pancreas was significantly reduced, whereas that of trypsinogen was similar to the control.