Aiji Noda

Renal handling of amylase: evidence for reabsorption by stop-flow analysis.

Abstract Renal tubular reabsorption of amylase was demonstrated in the rat by the use of the stop-flow technique. The sequential pattern of amylase following urinary stasis was depressed around the distal portion of the nephron, suggesting that the enzyme might be transported at a more distal portion compared with the site of paraaminohippurate transport. The ratio of urinary amylase to serum amylase (UP ratio) of less than 0.2 indicated that the reabsorption of the enzyme occurred against its concentration gradient. The present results yield a hypothesis that decreased tubular clearance of amylase may be an important factor for interpreting increased clearance of the enzyme during pancreatitis.

Follow-up study of chronic pancreatitis

SummaryThe general profile of pain in the evolution of pancreatitis was analysed in relation to exocrine and endo:rine pancreatic function in 127 patients with primary chronic pancreatitis followed up over 3 years.Pain decreased or disappeared in 67.8% and 55.9% of calcifying and non-calcifying pancreatitis, respectively. While pancreatic exocrine function remained abnormal in spite of an improvement of pain in 72% of 18 patients with calcifying pancreatitis, it improved with the amelioration of pain in 64.0% of 25 patients with non-calcifying pancreatitis during the follow-up period. Alcohol abstinence seems most important for pain relief in patients with non-calcifying pancreatitis but not calcifying pancreatitis. Changes in glucose tolerance test were not related with those in pain. In calcifying pancreatitis, 69.2% of patients with calcifying pancreatitis were diabetic or became so, while 66.7% of patients with non-calcifying pancreatitis remained non-diabetic during the observation period.

Dissolution of pancreatic stones by oral trimethadione in a dog experimental model.

Experiments were conducted to develop a dissolution therapy for human pancreatic calculi in a dog experimental model of pancreatic calculi surgically prepared. On plain x-ray films of the abdomen, pancreatic calculi appeared in 19 of 39 dogs within 12 mo after operation. The antiepileptic agent trimethadione was given orally to 13 dogs at a dose of 1.0-1.5 g daily. Pancreatic calculi disappeared in 13 of 15 observations. The scanning electron microscopy, the elemental analysis, and the powder x-ray diffractometry of pancreatic calculi in this model revealed that the calculi closely resembled human pancreatic calculi, consisting mainly of a calcite of calcium carbonate. There was no histologic finding suggesting drug toxicity in the liver, the kidney, and the blood. Pancreatic calculi in 6 control dogs without the treatment neither disappeared nor diminished spontaneously. The oral treatment with trimethadione may have potential for dissolving human pancreatic calculi.

Clinical evaluation of pancreatic excretion test with dimethadione and oral BT-PABA test in chronic pancreatitis

Further evaluation of the pancreatic excretion test with 5,5-dimethyl-2,4-oxazolidinedione (dimethadione, DMO) was made in comparison with the pancreozymin-secretin (PS) test on 100 normal subjects, 79 patients with chronic pancreatitis, and 83 patients with nonpancreatic disease. The diagnostic sensitivity of the oralN-benzoyl-l-tyrosyl-PABA (BT-PABA) test was estimated in 42 patients with chronic pancreatitis, on whom both PS and DMO excretion tests were performed as test of reference for exocrine pancreatic function. Pancreatic DMO excretion after secretin injection was significantly diminished in chronic pancreatitis. The DMO excretion test was more sensitive than the PS test to detect chronic pancreatitis and to distinguish between mild to moderate and advanced noncalcific chronic pancreatitis. The specificity of the DMO excretion test was more than adequate to find out pancreatic disease. The 6-hr urinary PABA excretion was significantly reduced in chronic pancreatitis. The BT-PABA test, however, showed the low sensitivity in mild to moderate chronic pancreatitis.

The excretion of 5,5-dimethyl-2,4-oxazolidinedione from the canine pancreas and liver

With administrations of maximal and supramaximal doses of secretin, the excretion of 5,5-dimethyl-2,4-oxazolidinedione (DMO) into pancreatic juice and bile was studied in the dog. When flow rate and bicarbonate concentration in both of the digestive juices were kept relatively constant by continuous intravenous infusion of secretin (2 units/kg/hr), DMO appeared promptly in them after the intravenous administration; the concentration decreased exponentially, as it did in arterial plasma during a 30-minute period. Equilibrium was achieved within 1 hour in both plasma and pancreatic juice, and nearly attained in 1 hour in both plasma and bile. With single rapid intravenous injections of secretin (2 units/kg and 4 units/kg), pancreatic DMO excretion depended directly on flow rate, bicarbonate concentration, and even on plasma level of the compound, while biliary DMO excretion was dependent at least on flow rate.

Pancreatic excretion of 5,5-dimethyl-2,4-oxazolidinedione in narmal subjects

Pancreatic excretion of 5,5-dimethyl-2,4-oxazolidinedione (DMO) was studied in 25 normal subjects using the technique of the traditional pancreatic secretory test. The pancreozymin-secretin test was performed 4 days after the oral administration of trimethadione (3,5,5-trimethyl-2,4-oxazolidinedione, the precursor of DMO) for 3 consecutive days. When a dose of 1 unit/kg of pancreozymin was administered intravenously, both DMO concentration and output of a 10-min fractional specimen were rapidly increased and then decreased gradually. When a dose of 1 unit/kg of secretin was injected 30 min after pancreozymin, DMO concentration in duodenal aspirate showed no significant alteration, while DMO output of the aspirate was remarkably increased and then diminished in parallel to flow rate. DMO concentration in plasma varied widely from subject to subject, but was fairly constant during the course of the test in the same subject. Total DMO output in the postpancreozymin 30-min and postsecretin 60-min periods was linearly related to plasma DMO concentration. The output of DMO, when expressed as the output at a level of 10 mg/100 ml of plasma DMO, was linearly related to secretory volume and bicarbonate and amylase outputs in the postsecretin period. These results led to the conclusion that the human pancreas was capable of excreting a weak organic acid of DMO with a molecular weight of 129.1 and that the excretion of DMO in normal subjects was a function of two factors: plasma DMO concentration and pancreatic secretory volume.

Pancreatic excretion of 5,5-dimethyl-2,4-oxazolidinedione in patients with chronic pancreatitis

Abnormal pancreatic excretion of 5,5-dimethyl-2,4-oxazolidinedione (DMO) was demonstrated in 44 patients with chronic pancreatitis (14 with calcification and 30 without calcification). Pancreatic excretion of DMO in patients with chronic pancreatitis, as well as in normal subjects, depended on plasma DMO concentration and secretory volume. In the postsecretin 60-min period, almost all patients showed a decrease in total DMO output of duodenal aspirate over the observed range of plasma DMO concentration. More than half the patients without calcification gave a discordant pattern between the DMO output and volume, ie, decreased DMO output with normal volume secretion, while most of patients with calcification had low DMO output with decreased volume flow. The data of the pancreozymin-secretin test suggested that chronic pancreatic inflammation was moderate or minimal in patients without calcification and far advanced in those with calcification. From these results the hypothesis was advanced that DMO diffusion into the pancreatic ducts might be primarily impaired in the relatively early stage of chronic pancretitis, and as the inflammation progressed to the final stage, DMO outflow from the ducts to the duodenum would be disturbed with evolving diffusion impairment of the compound. Total DMO output, when expressed as the output at a level of 10 mg/100 ml of plasma DMO (standard DMO output), was significantly reduced in chronic pancreatitis during a 60-min period after secretin stimulation. DMO in duodenal content, when expressed in terms of maximal concentration ratio of duodenal juice/plasma for the compound (maximalJ/P ratio), was significantly low in chronic pancreatitis during the last 40-min period after secretin stimulation. These two parameters can therefore be used as indices of pancreatic excretion of DMO. The present technique may well become an effective diagnostic tool for early detection of chronic pancreatitis.

Chronic pancreatitis at early age of onset presenting interesting findings through endoscopic retrograde pancreatography and chemical analysis of nonopaque pancreatic concretion.

SummaryThis case concerns a 20-year-old male patient with an approximate 10-year history of recurrent and severe abdominal pain radiating to the back. Endoscopic retrograde cholangiopancreatography revealed a short obstructing stenosis of the main pancreatic duct in the head of the pancreas, marked and tortuous dilatation of the prestenotic portion of the main pancreatic duct and its side branches, and a filling defect in the side branch in the body of the gland. Pancreaticojejunostomy was performed to induce decompression of the pancreatic duct. Histology of the pancreas showed advanced chronic pancreatitis. Three nonopaque concretions were obtained at operation. The largest one, which was milky white in appearance and elastic and soft in consistency, proved to be made up of protein. The concretion was rich in acidic amino acids, but poor in basic or aromatic residues. The molar composition of amino acids in the concretion was, in decreasing order, aspartic acid, serine, valine, glycine, and glutamic acid. Powder x-ray diffractometry revealed no crystalline structures.

Isoamylase analysis using an amylase inhibitor comparison with an electrophoretic method

Serum amylase increases in non-pancreatic diseases as well as in pancreatic diseases [l]. Isoamylase analysis is useful in the differential diagnosis of hyperamylasemia. The existence of isoenzymes of amylase has been established through electrophoresis, isoelectric focusing and chromatography [ 11. However, these analytical procedures are either technically too complex or time consuming for ready clinical use. A commercial kit using an amylase inhibitor, following the principle of O’Donnell’s method [2], has been available from Pharmacia, Sweden, and has made prompt analysis of isoamylase possible. This paper evaluates the correlation of pancreatic-type isoamylase levels in serum and urine obtained by the inhibitor and electrophoretic methods, and describes its clinical application in two cases of hyperamylasemia.

Secretory characteristics of pancreatic ?-glutamyl transpeptidase

SummaryIn an attempt to identify the secretory mechanism of pancreatic γ-glutamyl transpeptidase (γ-GTP), constant intravenous infusions of secretin alone and in combination with caerulein were performed in anesthetized dogs prepared with a pancreatic fistula. Caerulein produced a marked increase in amylase concentration and only a slight increase in γ-GTP. γ-GTP concentration of the pancreatic juice varied from 12 to 490 mU per ml which ranged up to 188-fold higher than that of the serum. The enzyme concentration depended largely on the flow rate, revealing 3 characteristic curvlinear relationship, regardless of whether caerulein was added to the secretin infusion. No significant relation was demonstrated between amylase concentration and flow rate, amylase and γ-GTP concentrations, and γ-GTP and protein concentration. An inverse linear correlation between γ-GTP and chloride concentrations was obtained when flow rate was below 2.5 ml per 15 min. A significant linear relationship was demonstrated between γ-GTP and leucine aminopeptidase concentrations, and amylase and protein concentrations. The results presented clearly demonstrate that the mechanism of pancreatic secretion of γ-GTP is quite distinct from that of amylase.