PANCREATITIS AND CARCINOMA OF THE PANCREAS—Some Aspects of the Pathologic Physiology

The physiological phenomena accompanying pancreatic disease in adults are related to the local and generalized reaction of the body to the blockage and/or leakage of the three enzymes—amylase, lipase and trypsin. The measurements of amylase and lipase in the serum are the most reliable criteria in the diagnosis of acute disease. Related changes may include hypocalcemia, hypopotassemia, hyperlipemia, hyperglycemia and decreased renal function.In chronic pancreatitis, there is less fluctuation in the amounts of the enzymes in the blood. The presence of diabetes mellitus, demonstration of calculi by x-ray, and examination of the stools for excess fat and meat fibers are more important diagnostic guides.In cancer of the pancreas, function tests using secretin stimulation of the gland followed by an examination of the external secretion or determination of the serum amylase have been used with some success.     

Elevated Amylase and Lipase Levels in Patients Using Glucagonlike Peptide-1 Receptor Agonists or Dipeptidyl-Peptidase-4 Inhibitors In the Outpatient Setting

ObjectiveTo investigate the effects of glucagonlike peptidase-1 (GLP-1) receptor agonists and dipeptidyl-peptidase-4 (DPP-4) inhibitors on serum amylase and serum lipase levels in patients with type 2 diabetes.MethodsIn 90 patients with type 2 diabetes, treatment was initiated with a GLP-1 agonist or a DPP-4 inhibitor. A comparison group consisted of 33 patients with type2 diabetes and similar characteristics who were not prescribed these agents. Baseline serum amylase and lipase levels were measured in all patients and repeated periodically. We determined the percentage of patients with elevated levels of serum amylase or lipase (or both) in both groups.ResultsAmong all 90 patients who received a GLP-1 receptor agonist or a DPP-4 inhibitor, 32 (36%) had an increase in serum amylase or lipase (or both) in comparison with 6 of 33 patients (18%) with such increases in the comparison group. Interestingly, the serum lipase levels increased more than the serum amylase values in all groups. To ascertain that this was not a chance laboratory error, serum samples were submitted to a second independent laboratory, and the same results were obtained. Usually, use of the medication was discontinued when serum lipase or amylase values were found to be elevated at any level.ConclusionBoth GLP-1 receptor agonists and DPP-4 inhibitors are associated with increased levels of serum lipase more than serum amylase in many patients with type2 diabetes, possibly suggesting the presence of pancreatic inflammation. Whether this finding may potentially lead to acute pancreatitis or chronic pancreatitis, as reported in rat models, is currently unknown. Careful observation of patients taking these medications may be prudent. (Endocr Pract. 2012;18:472-477)     

Beneficial Effects of Trypsin Inhibitors Derived from a Spider Venom Peptide in L-Arginine-Induced Severe Acute Pancreatitis in Mice

HWTI is a 55-residue protein isolated from the venom of the spider Ornithoctonus huwena. It is a potent trypsin inhibitor and a moderate voltage-gated potassium channel blocker. Here, we designed and expressed two HWTI mutants, HWTI-mut1 and HWTI-mut2, in which the potassium channel inhibitory activity was reduced while the trypsin inhibitory activity of the wild type form (approximately 5 EPU/mg) was retained. Animal studies showed that these mutants were less toxic than HWTI. The effects of HWTI and HWTI-mut1 were examined in a mouse model of acute pancreatitis induced by intraperitoneal injection of a large dose of L-arginine (4 mg/kg, twice). Serum amylase and serum lipase activities were assessed, and pathological sections of the pancreas were examined. Treatment with HWTI and HWTI-mut1 significantly reduced serum amylase and lipase levels in a dose dependent manner. Compared with the control group, at 4 mg/kg, HWTI significantly reduced serum amylase level by 47% and serum lipase level by 73%, while HWTI-mut1 significantly reduced serum amylase level by 59% and serum lipase level by 72%. Moreover, HWTI and HWTI-mut1 effectively protected the pancreas from acinar cell damage and inflammatory cell infiltration. The trypsin inhibitory potency and lower neurotoxicity of HWTI-mut1 suggest that it could potentially be developed as a drug for the treatment of acute pancreatitis with few side effects.     

Selected enzyme activities in Mya arenaria hemolymph.

1. The activities of lysozyme, acid and alkaline phosphatases, beta-glucuronidase, amylase, lipase, glutamate-oxalacetate transaminase, and glutamate-pyruvate transaminase in the whole hemolymph and 4000 g pellets and supernatants of Mya arenaria were determined. 2. All of these enzymes, except for amylase, occurred in whole hemolymph as well as in the 4000 g pellet and supernatant. 3. Based on earlier observations, these enzymes are believed to be of cellular origin within hemolymph cells. 4. In the case of amylase, it only occurred in the whole hemolymph and/or serum and is believed to have originated from the crystalline style.     

Hypotrypsinemia as a possible factor in the activation of motor function of the duodenum in pancreatic atrophy in rats]

The effect of pancreas atrophy on myoelectrical activity of the duodenum and serum trypsin, trypsin inhibitor, amylase, lipase activity has been described. The activation of the duodenum motor activity has been established. The changes in the motor activity were connected with trypsin and trypsin inhibitor activity of serum. The motor activity changes were compensated by trypsin therapy.     

The Pancreozymin-Secretin Test After Partial Gastrectomy

The administration of pancreozymin and secretin to eight control patients and 18 patients after partial gastrectomy caused no rise in serum amylase levels above normal. Four postgastrectomy patients had unexplained elevations of basal serum lipase levels but in only one did the lipase increase above the basal level after stimulation.Duodenal aspirates from the control group and from one patient with a Billroth I gastrectomy showed a wide range of values for volume, bicarbonate and amylase content. This would appear to limit the diagnostic value of the test. The two-tube method used for collecting duodenal contents proved difficult.     

Stability of methylnicotinate in aqueous solution as utilized in the 'niacin patch test'

Background

Animal models and observations in human neonates suggest fetal exocrine pancreas vulnerability to reduced maternofetal blood flow. We investigated the relationship between superior mesenteric artery blood flow velocity (sma bfv) and exocrine pancreatic function, in a cohort of very low birth weight (VLBW) babies. Group 1: 9 babies < 3rd percentile for birth weight. Antenatally, all had absent or reversed diastolic flow on Doppler ultrasound of the umbilical artery (UA). Group2: 18 babies > 10th percentile for birth weight.

Findings

All had Doppler ultrasound scan of the superior mesenteric artery (sma), by same operator (RMN), on day 1 of life before commencement of enteral feeding. Stool samples assayed for faecal chymotrypsin and weekly serum samples assayed for amylase and lipase (kinetic colorimetric assay) from days 1 to 14 of life. Growth restricted babies had significantly lower sma bfv values compared with appropriately grown preterm babies. Faecal chymotrypsin levels were also lower but this difference did not achieve statistical significance. Both groups had serum lipase levels detectable in adult concentrations. Serum amylase was undetectable in either group.

Conclusion

Babies with previous in-utero blood flow redistribution may exhibit altered gut ontogeny with re-setting of mesenteric blood flow velocities and altered exocrine pancreatic function.     

Recovery of exocrine pancreas six months following pancreatitis induction with L-arginine in streptozotocin-diabetic rats.

The aim of the present work was to investigate the laboratory and morphologic alterations in the pancreas 6 months after pancreatitis induction with L-arginine (Arg) in normal and streptozotocin (STZ)-diabetic rats. The amylase content of the pancreas was significantly decreased in the Arg-treated groups vs. the control group. No significant changes were observed in the DNA, soluble protein and lipase contents of the pancreas. In the STZ-treated groups, the serum glucose level was significantly elevated, whereas the serum immunoreactive insulin (IRI) level was significantly decreased vs. the control group. In these treated groups, the amylase content of the pancreas was also significantly decreased, but that of trypsinogen was significantly elevated vs. the control group. Histologic sections revealed periductal fibroses, adipose tissue and tubular complexes in the Arg-treated rats, but centroacinar hyperplasia was not observed in these groups. No alterations were observed on histological examination in the diabetic rats vs. normal rats 6 months following pancreatitis induction. In conclusion, a major restitution of the pancreatic enzyme content, but moderate histologic alterations were detected 6 months following pancreatitis induction with Arg. The diabetic state appeared to shift the normal pancreatic enzyme content (decreased amylase and increased trypsinogen) in this long-term study, but not to modify the recovery of the exocrine pancreas 6 months following Arg-induced pancreatitis.     

云斑尖塘鳢消化酶活力的研究

本文采用酶学分析方法研究了云斑尖塘鳢在正常摄食状态与饥饿的状态下胃、肠及肝胰脏组织中蛋白酶、淀粉酶和脂肪酶的活性。结果显示,在30℃的条件下,正常摄食组样本在酸性条件下的蛋白酶活力表现为:胃后肠肝胰脏前肠,中性和碱性条件下:后肠肝胰脏前肠及胃;饥饿组样本仅有胃表现出较高的酸性蛋白酶活性,其他器官的蛋白酶活性均很低。在正常和饥饿实验组中肝胰脏的淀粉酶活性均高于其他器官,胃肠的淀粉酶活性均较低。正常摄食组中脂肪酶活力后肠肝胰脏;而在饥饿组中仅有肝胰脏检测到脂肪酶活性。结果表明,云斑尖塘鳢适度饥饿组较正常摄食组消化酶活性大幅降低;其高蛋白酶活力及中等脂肪酶活力与其肉食性相一致;此外云斑尖塘鳢也具备少量的淀粉消化能力。     

Changes in mRNA levels of rat pancreatic lipase in the early days of consumption of a high-lipid diet

The time-course response of rat pancreatic enzymes to a diet containing 25% sunflower oil was investigated. A 1.2-fold enhancement in lipase specific activity was observed as early as the first day of diet consumption and was further increased up to 1.9-fold on the 5th day. On the other hand, colipase activity was slightly decreased during the first two days of high-lipid diet intake and then increased. An immediate and direct effect was also exerted by the 25% lipid diet on lipase biosynthesis. Both fractional synthetic rate and specific activity of lipase were comparably induced. Due to a 1.6-fold increase in the overall protein synthesis following 5 days of lipid diet consumption, the absolute synthesis of lipase and amylase was increased by 3.5-fold and 0.98-fold, respectively, as compared to control animals. By contrast, the synthesis of procarboxypeptidases and serine proteases did not increase before day 5, probably as the result of a distinct adaptive mechanism. The pancreatic mRNA levels in control and adapted animals, which were determined by dot-blot hybridization with amylase and lipase cDNAs, were consistent with a biphasic induction of lipase synthesis since a first increase in the level of the enzyme-specific mRNA during the first two days of diet intake (4-fold on day 1) was followed by a second increase after the fourth day (6.5-fold on day 5). On the other hand, amylase mRNA level was unchanged during the dietary manipulation. Thus, hyperlipidic diets exerted an both lipase activity and synthesis but a delayed effect on procarboxypeptidase and serine protease synthesis. In a similar manner, the immediate induction of lipase mRNA level by dietary fat, followed by another increase a few days later, suggested that at least two different mechanisms are involved in lipase mRNA induction.     

pH值对中国龙虾消化酶活力的影响

采用酶学分析方法研究了pH对中国龙虾胃蛋白酶、类胰蛋白酶、淀粉酶、纤维素酶和脂肪酶活力的影响。结果表明,在设定的pH范围内,中国龙虾各消化酶的活力均随着pH的升高呈现先升后降的变化趋势。其中,胃、肠、肝胰腺内胃蛋白酶最适pH均为2.2,类胰蛋白酶最适pH分别为8.8-9.2、8.4、8.8,淀粉酶最适pH分别为7.0、7.0、7.4,纤维素酶最适pH分别为4.2、4.2-4.6、5.4,脂肪酶最适pH分别为7.2-7.6、7.2、6.8-7.2。同时测得中国龙虾胃、肠、肝胰腺内的生理pH分别为5.33、6.93、6.60。中国龙虾的消化酶活力存在器官特异性。在最适pH下,胃蛋白酶活力顺序为胃>肠>肝胰腺,类胰蛋白酶、纤维素酶、脂肪酶的活力顺序均为肝胰腺>肠>胃,淀粉酶的活力顺序为肠>肝胰腺>胃。     

Influence of dietary aflatoxin on certain serum enzyme levels in broiler chickens

Experimental aflatoxicosis was produd in Cobb broiler chickens by feeding them with dietary aflatoxin at concentrations of 1 and 3 ppm for a poriod of four weeks from 0 to 28 days. Twelve birds in triplicate were used for each treatment of which three from each replicate were sacrificed at weekly intervals for enzymatic estimations of SGPT, SGOT, Serum amylase and serum lipase. Thus each treatment contained nine weekly observations and 36 observations in total. The SGPT activity was not found in appreciable amounts either in control or in toxin treated birds. However, the SGOT levels were in measurable amounts and elevated levels were observed in toxin treated birds from first week onwards at both levels of toxin and was dose related. The treatment means of SGOT differed significantly (P<0.05). The serum lipase levels increased from first week onwards and the treatment means showed significant difference (P<0.01). Serum lipase changes in toxin treated birds occurred to about the same extent. But the serum amylase levels decreased from first week onwards and their treatment means differed significantly (P<0.01) at both levels of toxin treated birds. Serum amylase concentrations decreased as the aflatoxin level increased in the diet.Presented in X Annual Poultry Symposium of the Indian Poultry Science Association held at Madras Veterinary College, Madras-600 007, 15th to 17th December, 1983.     

Digestive protease,lipase and amylase activities in stage i larvae of the american lobster,Homarus americanus

• 1.1. Digestive protease, lipase, and amylase of Stage I larvae of the American lobster Homarus americanus are characterized.
• 2.2. A sensitive method for detection of crustacean lipase was developed using an latroscan which combines thin-layer chromatography and flame ionization detection to quantify free fatty acids generated by lipase digestion.
• 3.3. pH optima of the three enzymes occurred at or near the pH of gastric fluid.
• 4.4. A time course study demonstrated slight increases in protease and amylase activities during the first larval stage, regardless of whether the lobsters were fed or not, whereas lipase activity was constant.

     

Effects of secretin and caerulein on enzymes of cultured pancreatic acinar cells

Summary We examined the effects of secretin (0 to 200 nM) and caerulein (0 to 100 nM) on rat pancreatic acinar cells cultured 0 to 48 h in serum-free medium. The effects of 100 nM secretin with 1 nM caerulein were also studied because secretin may potentiate the effects of caerulein. Cellular and media (secreted) lipase and amylase were analyzed as were cellular DNA and protein content. Cellular lipase and amylase activities significantly decreased (P<0.0001) over time in all treatment groups, whereas media amylase and lipase significantly increased (P<0.0001). Neither secretin nor caerulein affected cellular lipase or media amylase. However, secretin significantly increased (P<0.04) and caerulein tended to increase (P<0.08) media lipase in a dose-dependent manner. At 12 h, 10 nM secretin maximally increased media lipase (58%), suggesting that cultured acinar cells remain responsive to secretin in vitro. Caerulein, at all concentrations, significantly decreased (P<0.001) cellular amylase but exhibited a dose-dependent effect only at 24 h when 100 nM caerulein maximally decreased cellular amylase (34%). Secretin (100 nM) did not alter these effects of caerulein. These results support the proposed role of caerulein in the regulation of amylase but not a direct role of secretin in the regulation of lipase. This study was supported in part by grant RO1 DK32690 from the National Institutes of Health, Bethesda, MD.     

Renal handling of amylase and immunoreactive trypsin in pancreatic cancer and chronic pancreatitis.

In order to evaluate the renal metabolism of amylase and immunoreactive trypsin (IRT) in chronic pancreatic disease, we assayed amylase, IRT and creatinine in serum and urine and gamma-glutamyl transferase (GGT) in dialyzed urine as well as alpha-glucosidase (AGL) and ribonuclease (RNase) in 24 control subjects, 34 patients with pancreatic cancer, 52 with chronic pancreatitis and 32 with extra-pancreatic diseases. Urinary amylase and IRT outputs were found to be more elevated in chronic pancreatitis than in control subjects. The levels of serum amylase, its renal inputs and outputs were correlated with the corresponding IRT values. Multiple regression analyses (dependent on amylase or IRT urinary outputs, circulating levels of the two enzymes, creatinine clearance and the excretion of GGT, AGL and RNase predictor variables) showed significant correlations. The standardized partial regression coefficients found to be significant were: GGT, RNase and serum amylase for amylase, and GGT and RNase for IRT. No difference was found between amylase and IRT outputs in patients with chronic pancreatitis, taking the presence or the absence of alcohol abuse, exocrine insufficiency and pancreatic pseudocysts into consideration. Urinary GGT excretion correlated with serum amylase and IRT levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activity of Ligustrum vulgare L extracts against acute pancreatitis in murine models by regulation of p38 MAPK and NF-κB signaling pathways

Pancreatitis is a fatal disease associated with significant mortality and morbidity. At present, no specific treatment is available for pancreatitis and the patients are mainly treated with supportive medication. The need for specific antipancreatitic chemotherapy is an urgent medical obligation. In the current study, protective effects of the methanolic extract of the Ligustrum vulgare berries were investigated in the rat model of acute pancreatitis. Acute pancreatitis (AP) was induced in the male Sprague-Dawley (SD) rats by cerulein injection. Fruit extract of L. vulgare L extract was prepared using the methanol. Treatment effects of L. vulgare were evaluated in AP rats. Serum levels of lipase, amylase, proinflamatory cytokines (TNF-α, IL-6, TL-1β), lipid peroxidase (LPO), myeloperoxidase (MPO) were determined. Histological changes in the pancreas were assessed. L. vulgare treatment prevented the increase in serum amylase and lipase levels, reduced the disease progression in pancreas, and reduced the serum levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in AP rats. Moreover, L. vulgare significantly suppressed pancreatic edema, inhibited oxidative damage (MPO activity and SOD activity), and inhibited the expression of NF-κB/p65 and activation (phosphorylation) of the inhibitor of NF-κB (IκBα) and p38 MAPKs. Histological examinations showed that L. vulgare significantly reduced the inflammatory and fibrotic changes. The results indicated the potent pancreato-protective effects of L. vulgare in AP.     

Ebselen reduces hyperglycemia temporarily-induced by diazinon: a compound with insulin-mimetic properties

The present study investigated the effect of ebselen (EB) against hyperglycemia induced by the organophosphate (OPI) diazinon (DI) in rats. The insulin-mimetic properties of EB were investigated in vitro with the aim of better understanding the hypoglycemic effect of this compound. The protective effect of EB against pancreatic and hepatic damage caused by DI in rats was also appraised. In the in vivo experiments, rats were pre-treated with a single injection of EB (50mg/kg, intraperitoneal, i.p.). Afterward, animals were treated with a single injection of DI (200 mg/kg, i.p.). The parameters indicative of pancreatic and hepatic damage such as, serum amylase, lipase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities as well as serum glucose levels, hepatic glycogen content and glucose-6-phosphatase (G6Pase) activity were determined. EB pre-treatment was effective in reducing serum amylase, lipase, AST, ALT, ALP, and LDH activities, protecting against pancreatic and hepatic damage. EB reduced hyperglycemia and increased hepatic glycogen content in animals exposed to DI. In the in vitro assays, EB (150 μM) or insulin (IN 10 μM, positive control) was incubated with either skeletal muscle or hepatic tissue with the aim of measuring glucose uptake, glycogen synthesis and glycogen breakdown. EB increased the glucose uptake in skeletal muscle, stimulated hepatic glycogen synthesis and inhibited glycogen breakdown in a similar way to IN. In conclusion, EB, possibly through its insulin-mimetic action, protected against pancreatic and hepatic damage caused by DI in rats.     

The protective effect of erdosteine on vancomycin-induced pancreatic damage in rats

Objective The goal of this study was to investigate whether vancomycin (VCM) has a negative effect on pancreatic tissue and to elucidate the role of erdosteine (ERD), an expectorant and an antioxidant agent, on possible VCM-induced pancreas impairment in rats. Materials and methods A total of 21 male Wistar albino rats were included in this study. All animals were equally divided into three groups as follows: Controls (n = 7), VCM treated group (200 mg/kg twice daily for 7 days intraperitoneally, n = 7) and VCM (200 mg/kg) + ERD treated group (10 mg/kg day orally ERD, n = 7). The first dose of ERD administration was performed 24 h prior to VCM injection and the study was continued for 7 days. At the end of the study, all animals were sacrificed. Blood and pancreas tissue samples were collected. For biochemical analysis, serum amylase, lipase, alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT) activities were measured. For histopathological examination, pancreas tissue samples were investigated under the light microscope. Results VCM administration has significantly increased the serum amylase, lipase, ALP, and GGT activities, when compared with the controls. VCM + ERD administration significantly decreased the serum lipase, amylase, and GGT activities. There was no statistically significant difference between the VCM + ERD treated group and only VCM treated group by means of serum ALP levels. It has been observed that there was a prominent pancreatic tissue damage in only VCM given group. However, ERD exhibited structural protection against VCM-induced pancreatic damage and this effect was statistically significant. ERD has also obtained a marked reduction in the extent of pancreatic damage. Conclusion Erdosteine may play an important role in the VCM-induced pancreatic damage and may reduce the pancreatic damage both in biochemical and histopathological aspects.     

Piperine ameliorates the severity of cerulein-induced acute pancreatitis by inhibiting the activation of mitogen activated protein kinases

Piperine is a phenolic component of black pepper (Piper nigrum) and long pepper (Piper longum), fruits used in traditional Asian medicine. Our previous study showed that piperine inhibits lipopolysaccharide-induced inflammatory responses. In this study, we investigated whether piperine reduces the severity of cerulein-induced acute pancreatitis (AP). Administration of piperine reduced histologic damage and myeloperoxidase (MPO) activity in the pancreas and ameliorated many of the examined laboratory parameters, including the pancreatic weight (PW) to body weight (BW) ratio, as well as serum levels of amylase and lipase and trypsin activity. Furthermore, piperine pretreatment reduced the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 during cerulein-induced AP. In accordance with in vivo results, piperine reduced cell death, amylase and lipase activity, and cytokine production in isolated cerulein-treated pancreatic acinar cells. In addition, piperine inhibited the activation of mitogen-activated protein kinases (MAPKs). These findings suggest that the anti-inflammatory effect of piperine in cerulein-induced AP is mediated by inhibiting the activation of MAPKs. Thus, piperine may have a protective effect against AP.