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Reproduction, Nutrition, Development 1998The secretion of zinc and the level of carboxypeptidase A and B activity in pancreatic juice were studied in three pigs fitted with a pancreatic pouch re-entrant cannula...
The secretion of zinc and the level of carboxypeptidase A and B activity in pancreatic juice were studied in three pigs fitted with a pancreatic pouch re-entrant cannula (PM pigs) and three different pigs with a catheter surgically implanted in their pancreatic duct (CM pigs). The zinc in the pancreatic juice appeared to be primarily associated with carboxypeptidase A and B. Both the concentration of zinc in pancreatic juice and the daily secretion of zinc in PM pigs were greater than in CM pigs. However, compared to the daily intake of zinc, its secretion in pancreatic juice was low. The specific activity levels of carboxypeptidase A and B in pancreatic juice collected from PM pigs were higher than in CM pigs. The total activity of carboxypeptidase A in pancreatic juice did not differ between collection methods. The total activity of carboxypeptidase B was higher in pancreatic juice collected from PM than from CM pigs. The differences in zinc and carboxypeptidase secretion between PM and CM pigs were probably due to physiological changes induced following the different surgical preparations of the animals.
Topics: Animals; Carboxypeptidase B; Carboxypeptidases; Carboxypeptidases A; Catheterization; Catheters, Indwelling; Circadian Rhythm; Male; Pancreas; Pancreatic Juice; Swine; Zinc
PubMed: 9795983
DOI: 10.1051/rnd:19980404 -
The Tohoku Journal of Experimental... Jan 1998To clarify a physiological role of endogenous peptide YY(PYY) on pancreatic exocrine secretion, gastrointestinal transit and bile flow, a hyper-PYY-emia model was...
To clarify a physiological role of endogenous peptide YY(PYY) on pancreatic exocrine secretion, gastrointestinal transit and bile flow, a hyper-PYY-emia model was constructed by performing a massive small bowel resection using rats. (1) 75% resection of the small intestine was performed at its distal side. Two weeks after surgery, these rats were fed a liquid meal, and intestinal transit of contents was observed and plasma PYY and secretin concentrations were measured by radioimmunoassay. (2) Two weeks after the same surgery, a liquid meal was infused into the duodenum, and both pancreatic juice and bile were collected separately under general anesthesia. Transit of the intestinal contents from the pyloric ring, plasma CCK concentrations, pancreatic juice flow, amylase output, and bile flow were determined. Hyper-PYY-emia occurred following surgery both at fasting and after feeding, accompanied by retardation of gastrointestinal transit, increase of pancreatic juice flow and decrease of bile flow. Plasma secretin levels were elevated slightly, while CCK levels remained unchanged. In conclusion, massive small bowel resection is a useful model to induce hyper-PYY-emia in rats. It is considered that, in a malnutritional state after small intestinal resection, a colonic regulatory mechanism, via humoral factors such as PYY, participates in the feedback regulation of proximal intestinal as well as of pancreatic function.
Topics: Animals; Bile; Cholecystokinin; Gastrointestinal Transit; Intestine, Small; Male; Osmolar Concentration; Pancreas; Pancreatic Juice; Peptide YY; Postoperative Period; Rats; Rats, Sprague-Dawley; Rats, Wistar; Secretin
PubMed: 9607398
DOI: 10.1620/tjem.184.49 -
Scientific Reports Feb 2022As oral or intestinal bacteria have been found in pancreatic cystic fluid and tumors, understanding bacterial migration from the duodenum into the pancreas via...
As oral or intestinal bacteria have been found in pancreatic cystic fluid and tumors, understanding bacterial migration from the duodenum into the pancreas via hepato-pancreatic duct is critical. Mathematical models of migration of aerobic bacteria from the duodenum to the pancreas with tumors were developed. Additionally, the bacterial distributions under the pH gradient and those under flow were measured in double-layer flow based microfluidic device and T-shaped cylinders. Migration of aerobic bacteria from the duodenum into pancreas is counteracted by bile and pancreatic juice flow but facilitated by pH-taxis from acidic duodenum fluid toward more favorable slightly alkaline pH in pancreatic juice. Additionally, the reduced flow velocity in cancer patients, due to compressed pancreatic duct by solid tumor, facilitates migration. Moreover, measured distribution of GFP E. coli under the pH gradient in a microfluidic device validated pH-tactic behaviors. Furthermore, Pseudomonas fluorescens in hydrochloride solution, but not in bicarbonate solution, migrated upstream against bicarbonate flow of > 20 μm/s, with an advancement at approximately 50 μm/s.
Topics: Bacteria, Aerobic; Cell Movement; Duodenum; Humans; Hydrogen-Ion Concentration; Pancreas; Pancreatic Juice; Pancreatic Neoplasms
PubMed: 35110595
DOI: 10.1038/s41598-022-05554-8 -
Gut Feb 1979Pure pancreatic juice was obtained from within the pancreatic duct in 54 patients after endoscopic cannulation of the papilla of Vater. In all 20 normal subjects there... (Comparative Study)
Comparative Study
Pure pancreatic juice was obtained from within the pancreatic duct in 54 patients after endoscopic cannulation of the papilla of Vater. In all 20 normal subjects there was a brisk response to intravenous injections of GIH secretin in small dosage (1 and 4 CU). Peak bicarbonate concentrations occurred after a 4 CU stimulus, whereas volumes, and bicarbonate and protein outputs were greatest after 70 CU. Total protein and amylase concentrations were highest in the first specimens collected from each patient, and fell rapidly after stimulation. Plateau levels for all indices were achieved 10-20 minutes after starting infusions of secretin and pancreozymin. When normal patients and those with chronic pancreatitis were compared, there was considerable overlap in all indices (volume, bicarbonate and total protein concentrations) after bolus injections of secretin. Most patients with chronic pancreatitis achieved a peak bicarbonate concentration in excess of 100 mmol/l. The median concentrations were not significantly different from normal after any dose of secretin when pooled 10 minute samples were analysed. However there were significant differences in peak bicarbonate concentrations (after 1 and 4 CU, but not after 70 CU), when one minute samples were compared. There were also statistically significant differences in the median 10 minute responses for volume after 1 and 70 CU, for bicarbonate output after 1, 4, and 70 CU, and for protein output after 70 CU. The results of juice studies in patients believed to have early chronic pancreatitis did not differ significantly from those in normal subjects or those with chronic pancreatitis. Endoscopic duct cannulation cannot guarantee complete recovery of pancreatic secretions, and measurements of volume and output may be inaccurate. When standard biochemical indices are used, the diagnostic role of pure juice studies is limited; further research may reveal more specific disease markers.
Topics: Bicarbonates; Chronic Disease; Humans; Pancreatic Juice; Pancreatitis; Proteins; Secretin; Time Factors
PubMed: 428831
DOI: 10.1136/gut.20.2.89 -
Seminars in Oncology Aug 2007Pancreatic cancer is the fourth most common cause of cancer death in the United States. There is a great need for better diagnostic markers of pancreatic neoplasia.... (Review)
Review
Pancreatic cancer is the fourth most common cause of cancer death in the United States. There is a great need for better diagnostic markers of pancreatic neoplasia. Better markers would improve the early diagnosis of pancreatic cancer and allow more patients to undergo curative surgical resection. Identifying individuals at high risk of developing pancreatic cancer and applying markers that could identify precancerous lesions of the pancreas in these individuals could allow such lesions to be resected before the development of pancreatic cancer. As we continue to characterize the genetic, epigenetic, and proteomics alterations that occur in pancreatic cancers and their percursors, better diagnostic markers of pancreatic cancer are expected to follow.
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Early Diagnosis; Genetic Markers; Humans; MicroRNAs; Pancreatic Juice; Pancreatic Neoplasms; Proteomics; Risk
PubMed: 17674958
DOI: 10.1053/j.seminoncol.2007.05.003 -
Pancreas Mar 2012The aims of this study were to characterize the proteome of normal pancreatic juice, to analyze the effect of secretin on the normal proteome, and to compare these...
OBJECTIVES
The aims of this study were to characterize the proteome of normal pancreatic juice, to analyze the effect of secretin on the normal proteome, and to compare these results with published data from patients with pancreatic cancer.
METHODS
Paired pancreatic fluid specimens (before and after intravenous secretin stimulation) were obtained during endoscopic pancreatography from 3 patients without significant pancreatic pathology. Proteins were identified and quantified by mass spectrometry-based protein quantification technology. The human RefSeq (NCBI) database was used to compare the data in samples from patients without pancreatic disease with published data from 3 patients with pancreatic cancer.
RESULTS
A total of 285 proteins were identified in normal pancreatic juice. Ninety had sufficient amino acid sequences identified to characterize the protein with a high level of confidence. All 90 proteins were present before and after secretin administration but with altered relative concentrations, usually by 1 to 2 folds, after stimulation. Comparison with 170 published pancreatic cancer proteins yielded an overlap of only 42 proteins.
CONCLUSIONS
Normal pancreatic juice contains multiple proteins related to many biological processes. Secretin alters the concentration but not the spectrum of these proteins. The pancreatic juice proteome of patients without pancreatic disease and that of patients with pancreatic cancer differ markedly.
Topics: Adult; Biomarkers, Tumor; Cholangiopancreatography, Endoscopic Retrograde; Chromatography, Liquid; Computational Biology; Female; Humans; Indiana; Pancreatic Diseases; Pancreatic Juice; Pancreatic Neoplasms; Predictive Value of Tests; Proteins; Proteomics; Secretin; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 22129531
DOI: 10.1097/MPA.0b013e31822862f6 -
Cancer Epidemiology, Biomarkers &... May 2007Differentiating between periampullary carcinoma and chronic pancreatitis with an inflammatory mass is difficult. Consequently, 6% to 9% of pancreatic resections for...
Differentiating between periampullary carcinoma and chronic pancreatitis with an inflammatory mass is difficult. Consequently, 6% to 9% of pancreatic resections for suspected carcinoma are done inappropriately for chronic pancreatitis. Here, we test if matrix metalloproteinase 7 (MMP-7), a secreted protease frequently expressed in pancreatic carcinoma, can be measured in plasma, pancreatic, and duodenal juice, and if it can distinguish between periampullary carcinoma and chronic pancreatitis. Ninety-four patients who underwent pancreatic surgery for a (peri)pancreatic neoplasm (n = 63) or chronic pancreatitis (n = 31) were analyzed. Median plasma MMP-7 levels were significantly higher in carcinoma (1.95 ng/mL; interquartile range, 0.81-3.22 ng/mL) compared with chronic pancreatitis and benign disease (0.83 ng/mL; interquartile range, 0.25-1.21 ng/mL; P < 0.01). MMP-7 levels in pancreatic juice were higher, although not significantly, in carcinoma (62 ng/mg protein; interquartile range, 18-241 ng/mg protein) compared with chronic pancreatitis and benign disease (23 ng/mg protein; interquartile range, 8.5-99 ng/mg protein; P = 0.17). MMP-7 levels in duodenal juice were universally low. At an arbitrary cutoff of 1.5 ng/mL in plasma, positive and negative predictive values were 83% and 57%, respectively, values comparable to those of today's most common pancreatic tumor marker, carbohydrate antigen 19-9 (CA19-9; 83% and 53%, respectively). Positive and negative likelihood ratios for plasma MMP-7 were 3.35 and 0.52, respectively. The area under the receiver operating characteristic curve for MMP-7 was 0.73 (95% confidence interval, 0.63-0.84) and for CA19-9, 0.75 (95% confidence interval, 0.64-0.85). Combined MMP-7 and CA19-9 assessment gave a positive predictive value of 100%. Thus, plasma MMP-7 levels discriminated between patients with carcinoma and those with chronic pancreatitis or benign disease. The diagnostic accuracy of plasma MMP-7 alone is not sufficient to determine treatment strategy in patients with a periampullary mass, but combined evaluation of plasma MMP-7 with CA19-9 and other markers may be clinically useful.
Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoma; Diagnosis, Differential; Female; Humans; Male; Matrix Metalloproteinase 7; Middle Aged; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis, Chronic; ROC Curve
PubMed: 17507610
DOI: 10.1158/1055-9965.EPI-06-0779 -
Journal of Applied Physiology... Jul 2018Pancreatic ductular epithelial cells comprise the majority of duct cells in pancreas, control cystic fibrosis transmembrane conductance regulator (CFTR)-dependent...
Pancreatic ductular epithelial cells comprise the majority of duct cells in pancreas, control cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate ([Formula: see text]) secretion, but are difficult to grow as a polarized monolayer. Using NIH-3T3-J2 fibroblast feeder cells and a Rho-associated kinase inhibitor, we produced well-differentiated and polarized porcine pancreatic ductular epithelial cells. Cells grown on semipermeable filters at the air-liquid interface developed typical epithelial cell morphology and stable transepithelial resistance and expressed epithelial cell markers (zona occludens-1 and β-catenin), duct cell markers (SOX-9 and CFTR), but no acinar (amylase) or islet cell (chromogranin) markers. Polarized cells were studied in Ussing chambers bathed in Krebs-Ringer [Formula: see text] solution at 37°C gassed with 5% CO to measure short-circuit currents ( I). Ratiometric measurement of extracellular pH was performed with fluorescent SNARF-conjugated dextran at 5% CO. Cells demonstrated a baseline I (12.2 ± 3.2 μA/cm) that increased significantly in response to apical forskolin-IBMX (∆ I: 35.4 ± 3.8 μA/cm, P < 0.001) or basolateral secretin (∆ I: 31.4 ± 2.5 μA/cm, P < 0.001), both of which increase cellular levels of cAMP. Subsequent addition of apical GlyH-101, a CFTR inhibitor, decreased the current (∆ I: 20.4 ± 3.8 μA/cm, P < 0.01). Extracellular pH and [Formula: see text] concentration increased significantly after forskolin-IBMX (pH: 7.18 ± 0.23 vs. 7.53 ± 0.19; [Formula: see text] concentration, 14.5 ± 5.9 vs. 31.8 ± 13.4 mM; P < 0.05 for both). We demonstrate the development of a polarized pancreatic ductular epithelial cell epithelium with CFTR-dependent [Formula: see text] secretion in response to secretin and cAMP. This model is highly relevant, as porcine pancreas physiology is very similar to humans and pancreatic damage in the cystic fibrosis pig model recapitulates that of humans. NEW & NOTEWORTHY Pancreas ductular epithelial cells control cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate secretion. Their function is critical because when CFTR is deficient in cystic fibrosis bicarbonate secretion is lost and the pancreas is damaged. Mechanisms that control pancreatic bicarbonate secretion are incompletely understood. We generated well-differentiated and polarized porcine pancreatic ductular epithelial cells and demonstrated feasibility of bicarbonate secretion. This novel method will advance our understanding of pancreas physiology and mechanisms of bicarbonate secretion.
Topics: Animals; Bicarbonates; Cell Line; Colforsin; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Cells; Epithelium; Humans; Mice; NIH 3T3 Cells; Pancreatic Ducts; Pancreatic Juice; Signal Transduction; Swine
PubMed: 29517421
DOI: 10.1152/japplphysiol.00043.2018 -
Pancreas Jan 2018Secretin-stimulated pancreatic juice is collected from the duodenum and analyzed to identify biomarkers of pancreatic neoplasia, but the optimal duration of pancreatic...
OBJECTIVE
Secretin-stimulated pancreatic juice is collected from the duodenum and analyzed to identify biomarkers of pancreatic neoplasia, but the optimal duration of pancreatic juice collection is not known.
METHODS
We compared the yield of KRAS mutations detected in pancreatic juice samples aspirated from near the duodenal papilla at 1 to 5, 6 to 10, and 11 to 15 minutes after secretin infusion, and from the third part of the duodenum (at 15 minutes) from 45 patients undergoing endoscopic ultrasound pancreatic surveillance. KRAS mutation concentrations were measured by using droplet digital polymerase chain reaction.
RESULTS
Forty of 45 patients had KRAS mutations detected in their pancreatic juice, and most patients' juice samples had more than 1 KRAS mutation. Of 106 KRAS mutations detected in 171 pancreatic juice samples, 58 were detected in the 5-minute samples, 70 mutations were detected in the 10-minute samples, and 65 were detected in the 15-minute samples. Nine patients who did not have KRAS mutations detected in their 5-minute sample had mutations detected in samples collected at later time points. Ninety-percent of all pancreatic juice mutations detected in any sample were detected in the 5- or 10-minute samples.
CONCLUSIONS
Collecting pancreatic juice for 10 minutes after secretin infusion increases the likelihood of detecting pancreatic juice mutations over shorter collections.
Topics: Aged; DNA Mutational Analysis; Female; Humans; Male; Middle Aged; Mutation; Pancreatic Juice; Pancreatic Neoplasms; Proto-Oncogene Proteins p21(ras); Time Factors
PubMed: 29200129
DOI: 10.1097/MPA.0000000000000956 -
Pancreas Apr 2013Pancreatic diseases pose significant diagnostic challenge as signs and symptoms often overlap. We investigated the potential of pancreatic juice neutrophil...
Neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1, and carbohydrate antigen 19-9 in pancreatic juice: pathobiologic implications in diagnosing benign and malignant disease of the pancreas.
OBJECTIVE
Pancreatic diseases pose significant diagnostic challenge as signs and symptoms often overlap. We investigated the potential of pancreatic juice neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1 (MIC-1), and carbohydrate antigen 19-9 (CA19-9) to aid in the diagnosis of patients with symptoms suggestive of pancreatic diseases.
METHODS
A total of 105 chronic pancreatitis (CP), pancreatic cancer (PC), and nonpancreatic nonhealthy (patients with symptoms mimicking pancreatic disease but found to be free of any pancreatic disease) patients underwent endoscopic pancreatic juice collection after secretin stimulation. Neutrophil gelatinase-associated lipocalin and MIC-1 levels were measured by enzyme-linked immunosorbent assay, whereas CA19-9 was measured by radioimmunoassay.
RESULTS
Neutrophil gelatinase-associated lipocalin, MIC-1, and CA19-9 were significantly elevated in the pancreatic juice of patients with CP and patients with PC as compared with nonpancreatic nonhealthy controls (P ≤ 0.034). Neutrophil gelatinase-associated lipocalin seemed most promising in differentiating diseased versus nondiseased pancreata (areas under the curve, 0.88-0.91), whereas MIC-1 was found to be higher in patients with PC than in patients with CP (P = 0.043). Interestingly, MIC-1 levels in diabetic patients with PC were higher than in nondiabetic patients with PC (P = 0.030) and diabetic patients with CP (P = 0.087). Carbohydrate antigen 19-9 showed the least ability to distinguish patient groups (areas under the curve, 0.61-0.76).
CONCLUSIONS
Pancreatic juice neutrophil gelatinase-associated lipocalin shows potential utility in establishing pancreatic etiology in the context of nonspecific symptoms, whereas MIC-1 may aid in differentiating PC from CP.
Topics: Acute-Phase Proteins; Aged; Biomarkers; CA-19-9 Antigen; Diabetes Mellitus, Type 2; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Growth Differentiation Factor 15; Humans; Lipocalin-2; Lipocalins; Male; Middle Aged; Pancreas; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis, Chronic; Prospective Studies; Proto-Oncogene Proteins; Radioimmunoassay; Sensitivity and Specificity
PubMed: 23146921
DOI: 10.1097/MPA.0b013e31826a8597