Pancreas In Acute Pancreatitis Research Articles

The Interaction of Microbiome and Pancreas in Acute Pancreatitis.

Acute pancreatitis (AP) is a common acute abdomen disease characterized by the pathological activation of digestive enzymes and the self-digestion of pancreatic acinar cells. Secondary infection and sepsis are independent prognosticators for AP progression and increased mortality. Accumulating anatomical and epidemiological evidence suggests that the dysbiosis of gut microbiota affects the etiology and severity of AP through intestinal barrier disruption, local or systemic inflammatory response, bacterial translocation, and the regulatory role of microbial metabolites in AP patients and animal models. Recent studies discussing the interactions between gut microbiota and the pancreas have opened new scopes for AP, and new therapeutic interventions that target the bacteria community have received substantial attention. This review concentrates on the alterations of gut microbiota and its roles in modulating gut-pancreas axis in AP. The potential therapies of targeting microbes as well as the major challenges of applying those interventions are explored. We expect to understand the roles of microbes in AP diagnosis and treatment.

The combination of ulinastatin and somatostatin reduces complication rates in acute pancreatitis: a systematic review and meta-analysis of randomized controlled trials

Currently, there is no specific pharmaceutical agent for treating acute pancreatitis (AP). Somatostatin and its analogues have been used to prevent the autolysis of the pancreas in AP, however, their effectiveness has not been confirmed. This investigation aimed to examine the efficacy of ulinastatin, a protease inhibitor, combined with somatostatin analogues in the treatment of AP. We conducted a systematic database search in 4 databases to identify randomized controlled trials in which the efficacy of ulinastatin in combination with somatostatin analogue was compared to somatostatin analogue alone in patients with AP. Since the patient populations of analysed papers were slightly different, we used random effect models to pool odds ratios (OR) and mean differences (MD) and the corresponding 95% confidence intervals (CI). A total of 9 articles comprising 1037 patients were included in the meta-analysis. The combination therapy significantly reduced the complication rates for acute respiratory distress syndrome, acute kidney injury, and multiple organ dysfunction. Symptoms were relieved threefold with the combination therapy compared to somatostatin alone, and combination therapy significantly shortened the length of hospital stay. The decrease in mortality was not statistically significant.

Ultrasonography based imaging criterion to ascertain pancreatic enlargement in pediatric acute pancreatitis

Imaging studies have shown enlargement of pancreatic parts in children diagnosed with acute pancreatitis. The purpose here is to develop imaging based diagnostic evaluation criterion for acute pancreatitis in children. This study included 62 children of acute pancreatitis in the age range of 0.33 to 13 years, as reported in a single hospital center (1994-2019). A study was planned including 1116 normal healthy children in the age range of 0.16 to 18 years for pancreatic evaluation during 2016-17. Ultrasonography based measurement of three pancreatic parts were obtained for each individual in disease and normal groups. Age-adjusted receiver operating characteristics curve analysis was performed on each pancreatic part independently to derive respective cut-offs using a training set. These cut-offs were further referred to dichotomize the measurement data for each individual and was subjected to multiple logistic regression with presence/absence of acute pancreatitis as dependent variable. A probability score and accordingly the cut-off were obtained indicating a collective impression of enlargement of pancreas in disease condition independently for males and females. On test data, the accuracy of age-adjusted cut-offs for three parts was near 80% for males, while it ranged between 81-85% for females. ROC analysis of probability score resulted into threshold value of 0.024 for males and 0.044 for females, with sensitivity of 94.11% and 90.91% respectively. The classification accuracy of score derived for males and females was nearly same (83%). The extent of enlargement of pancreas in acute pancreatitis in children can be determined using the MLR method along with hypoechogenicity.

Inhibition of hypoxia-inducible factor-1α alleviates acinar cell necrosis in a mouse model of acute pancreatitis

Hypoxia-inducible factor-1α (Hif1α) is activated in hypoxia and is closely related to oxidative stress, immunity and cell metabolism. Recently, it is reported that Hif1α is involved in atherosclerosis, ischemia-reperfusion (I/R) injury, alcoholic liver disease and pancreatic tumors. In this study, we found that Hif1 signal pathway is significantly changed in pancreas of acute pancreatitis (AP) mice. Meanwhile, we verified that the high expression of Hif1α injured pancreatic tissues of cerulean-induced AP mice, which prompting that Hif1α participated in the progress of histopathology on AP. We applied a Hif1α inhibitor PX478 and observed that it could alleviate histological injury of pancreas as well as the levels of serum amylase, lipase and proinflammatory cytokine in the murine model of AP induced by caerulein. In addition, PX478 could reduce the formation of necrosome (RIP3 and p-MLKL) and the generation of reactive oxygen species (ROS) in AP mice. Correspondingly, we further confirmed the effectiveness of PX478 in vitro and found that inhibiting Hif1α could mitigated the necrosis of pancreatic acinar cells via reducing the RIP3 and p-MLKL expression and the ROS production. In conclusion, inhibiting Hif1α could protect against acinar cells necrosis in AP, which may provide a new target for the prevention and treatment of AP clinically.

PSD-95 protects the pancreas against pathological damage through p38 MAPK signaling pathway in acute pancreatitis.

Acute pancreatitis is one of the leading causes of gastrointestinal disorder-related hospitalizations, yet its pathogenesis remains to be fully elucidated. Postsynaptic density protein-95 (PSD-95) is closely associated with tissue inflammation and injury. We aimed to investigate the expression of PSD-95 in pancreatic acinar cells, and its function in regulating the inflammatory response and pancreatic pathological damage in acute pancreatitis. A mouse model of edematous acute pancreatitis was induced with caerulein and lipopolysaccharide in C57BL/6 mice. Tat-N-dimer was injected to inhibit the PSD-95 activity separately, or simultaneously with SB203580, inhibitor of p38 MAPK phosphorylation. Rat pancreatic acinar cells AR42J were cultured with 1 μM caerulein to build a cell model of acute pancreatitis. PSD-95-knockdown and negative control cell lines were constructed by lentiviral transfection of AR42J cells. Paraffin-embedded pancreatic tissue samples were processed for routine HE staining to evaluate the pathological changes of human and mouse pancreatic tissues. Serum amylase and inflammatory cytokine levels were detected with specific ELISA kits. Immunofluorescence, immunohistochemical, Western-blot, and qRT-PCR were used to detect the expression levels of PSD-95, p38, and phosphorylated p38. Our findings showed that PSD-95 is expressed in the pancreatic tissues of humans, C57BL/6 mice, and AR42J cells, primarily in the cytoplasm. PSD-95 expression increased at 2 h, reaching the peak at 6 h in mice and 12 h in AR42J cells. IL-6, IL-8, and TNF-α increased within 2 h of disease induction. The pancreatic histopathologic score was greater in the PSD-95 inhibition group compared with the control (P < 0.05), while it was lesser when phosphorylation of p38 MAPK was inhibited compared with the PSD-95 inhibition group (P < 0.05). Moreover, phosphorylation of p38 MAPK increased statistically after PSD-95 knocked-down. In conclusion, PSD-95 effectively influences the pathological damage of the pancreas in acute pancreatitis by affecting the phosphorylation of p38 MAPK.

Hydrogen sulfide formation in experimental model of acute pancreatitis.

Acute pancreatitis (AP) is a disease defined as acute or chronic inflammatory process of the pancreas characterized by premature activation of digestive enzymes within the pancreatic acinar cells and causing pancreatic auto-digestion. In mammalian tissues, H2S is synthesized endogenously from L-cysteine in regulated enzymatic pathways catalyzed by pyridoxal phosphate-dependent enzymes: cystathionine beta - synthase (CBS), gamma - cystathionase (CTH) and cysteine aminotransferase (CAT) coupled with 3-mercaptopyruvate sulfurtransferase (MPST). In the mitochondria, hydrogen sulfide is oxidized to sulfite, which is then converted to thiosulfate (sulfane sulfur-containing compound) by thiosulfate sulfurtransferase (rhodanese; TST). The activity and the expression of CBS, CTH, MPST, and TST have been determined in vivo in pancreas of control rats, rats with acute pancreatitis and sham group. Levels of low-molecular sulfur compounds such as reduced and oxidized glutathione, cysteine, cystine and cystathionine were also determined. The study showed the significant role of MPST in H2S metabolism in pancreas. Stress caused by the surgery (sham group) and AP cause a decrease in H2S production associated with a decrease of MPST activity and expression. Markedly higher level of cysteine in the AP pancreas may be caused by a reduced rate of cysteine consumption in reaction catalyzed by MPST but it can also be a sign of the processes of proteolysis occurring in the changed tissue.

CT modern potential in acute pancreatitis visualization (part 3)

Currently, magnetic resonance imaging (MRI) acquires a special popularity in visualization of the pancreas in acute pancreatitis. The article deals with the effectiveness of MRI in the diagnostics and treatment of severe acute pancreatitis. Advantages of MRI can be listed as following: better zoom of soft tissue structures and minimal pathological changes, absence of ionizing radiation, informative value of unenhanced investigation (including vessels), possibility of MRCP with all its advantages. For patients with severe acute pancreatitis the MRI importance is seen in a more precise diagnostics of necrotic changes in the pancreas and peripancreatic tissues, especially at the beginning of the disease.

ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction.Aim of the research was to study the endocrine function of pancreas in acute pancreatitis. To define the role of endocrine pancreatic function in the etiology and pathogenesis of the acute pancreatitis. To assess the prospects of the use of pancreatic hormones in the treatment and predicting the outcomes of acute pancreatitis.Materials and methods of the research Survey of publications in specialized periodical medical journals, PubMed sources developed by the National Center for Biotechnology Information. Search in PubMed was carried out in the following databases: MEDLINE, Pre MEDLINE.Results of the research. In a significant proportion of patients who recovered from acute pancreatitis, exocrine and endocrine functional impairments were found. This finding was not detected only in patients after severe acute pancreatitis. Routine evaluation of pancreatic function after acute pancreatitis should be considered. The comparative analysis of the synthetic analogues (somatostatin, calcitonin, leu-enkefalin-dalargin) influence on the glucose metabolism of rats in acute pancreatitis of was made. Physiological reaction of beta-cells is preserved in infusion of somatostatin. However, infusion of calcitonin results in the distortion of counterregulatory action of insulin and glucagon. It was detected that pancreatic renin-angiotensin system is markedly activated in the experimental rat models of chronic hypoxia and acute pancreatitis. The activation of the pancreatic renin-angiotensin system by chronic hypoxia and experimental pancreatitis could play role in the physiology and pathophysiology of the pancreas. The significant changes of pancreatic renin-angiotensin system may have clinical relevance in acute pancreatitis and hypoxia-induced injury in the pancreas. Detection of the pancreatic polypeptide level, oral glucose tolerance test assesses the state of the pancreas after acute pancreatitis in the long term.Conclusions:The biggest impact in the hormonal secretion of pancreatic islet has pancreatic renin-angiotensin system. Permissive factor for pancreatic endocrine dysfunction is chronic hypoxia due to violation of organ perfusion.Endocrine function of the pancreas are more affected after resection treatment of acute pancreatitis.Serological tests of pancreatic polypeptide promising for early diagnosis and prediction of the outcome of acute pancreatitis.

The SDF-1/CXCR4 axis regulates migration of transplanted bone marrow mesenchymal stem cells towards the pancreas in rats with acute pancreatitis

Stromal cell-derived factor-1 (SDF-1) and its receptor, CXC chemokine receptor-4 (CXCR4), are important regulators in the migration of bone marrow mesenchymal stem cells (BMSCs). However, the mechanisms underlying this effect in acute pancreatitis (AP) have not been investigated. In this study, BMSCs were identified by specific cell surface markers and differentiation potentials, and labeled with chloromethylbenzamido-1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (CM-Dil) for in vivo cell tracking. AP was induced by retrograde infusion of sodium taurocholate into the common bile duct in rats. The expression of SDF-1 in the injured pancreas was determined by immunohistochemistry and western blot analysis. BMSCs were incubated with or without anti-CXCR4 antibody and the contribution of SDF-1 to the migration of BMSCs was investigated. Our results demonstrated that the expression of SDF-1 was significantly increased in the injured pancreas, and that these levels peaked on days 5–7 and began to decrease on day 10. SDF-1 induced a dose-dependent migration of BMSCs in an in vitro transwell migration assay, which was almost completely blocked by AMD3100 (CXCR4-specific antagonist) or anti-CXCR4 antibody. In addition, by encouraging the migration of CM-Dil-labeled BMSCs, the SDF-1/CXCR4 axis facilitated the repair of the injured pancreas. This effect was inhibited by the anti-CXCR4 antibody. Taken together, these results indicate that the interaction of locally produced SDF-1 with CXCR4 on BMSCs, has an important regulatory role in the migration of BMSCs towards the injured pancreas in AP.

Disulfide stress: a novel type of oxidative stress in acute pancreatitis

Glutathione oxidation and protein glutathionylation are considered hallmarks of oxidative stress in cells because they reflect thiol redox status in proteins. Our aims were to analyze the redox status of thiols and to identify mixed disulfides and targets of redox signaling in pancreas in experimental acute pancreatitis as a model of acute inflammation associated with glutathione depletion. Glutathione depletion in pancreas in acute pancreatitis is not associated with any increase in oxidized glutathione levels or protein glutathionylation. Cystine and homocystine levels as well as protein cysteinylation and γ-glutamyl cysteinylation markedly rose in pancreas after induction of pancreatitis. Protein cysteinylation was undetectable in pancreas under basal conditions. Targets of disulfide stress were identified by Western blotting, diagonal electrophoresis, and proteomic methods. Cysteinylated albumin was detected. Redox-sensitive PP2A and tyrosine protein phosphatase activities diminished in pancreatitis and this loss was abrogated by N-acetylcysteine. According to our findings, disulfide stress may be considered a specific type of oxidative stress in acute inflammation associated with protein cysteinylation and γ-glutamylcysteinylation and oxidation of the pair cysteine/cystine, but without glutathione oxidation or changes in protein glutathionylation. Two types of targets of disulfide stress were identified: redox buffers, such as ribonuclease inhibitor or albumin, and redox-signaling thiols, which include thioredoxin 1, APE1/Ref1, Keap1, tyrosine and serine/threonine phosphatases, and protein disulfide isomerase. These targets exhibit great relevance in DNA repair, cell proliferation, apoptosis, endoplasmic reticulum stress, and inflammatory response. Disulfide stress would be a specific mechanism of redox signaling independent of glutathione redox status involved in inflammation.

Construction of Network for Protein Kinases That Play a Role in Acute Pancreatitis

This study aimed to search for protein kinases that play a role in acute pancreatitis and analyze their potential connection with each other. Information of human protein kinases were collected in protein kinase database, and then a systematic search was performed using PubMed for studies addressing the association between these kinases and acute pancreatitis. Gene Ontology Annotations were used to build interactions network for acute pancreatitis-associated protein kinases. A total of 570 human protein kinases were found, in which 28 kinases play a role in acute pancreatitis. Among the 28 kinases, RIPK1, JAK2, SRC, EGFR, FYN, MET, JAK1, TYK2, and MTOR were annotated in Gene Ontology database. A gene ontology interactions network was built to visualize the common biological process these kinases participated in. This study provides observations that protein kinases participate in all the sequential events in the exocrine pancreas in acute pancreatitis and that protein kinases are potential therapeutical target for acute pancreatitis.

Effect of bone mesenchymal stem cells on p38 mitogen-activated protein kinase expression in pancreas of rats with acute pancreatitis

Objective To investigate the effect of bone mesenchymal stem cells (MSCs) on p38 mitogen-activated protein kinase (p38MAPK) expression in pancreas of rats with acute pancreatitis (AP),and the conceivable mechanism was then deduced.Methods AP was induced in SD rats by 2 intraperitoneal injection of 20％ L-arginine hydrochloride three times at a l-h interval.Rats were randomly divided into AP untreated group (n =24 ),MSCs transplanted group ( n =24 ),p38MAPK inhibited group ( n =24) and control group (n =6).MSCs with surface markers were measured by flow cytometry.p38MAPK mRNA expression in the pancreas was detected by reverse transcription-polymerase chain reaction ( RTPCR),and histological changs of the pancreas were observed.Results p38MAPK mRNA could be detected in the pancreas with low values in control group,markedly increased and peaked in 1 h in AP untreated group (P ＜0.01 ).Transplantation of MSCs could effectively inhibit p38MAPK mRNA expression.The serum inflammatory factors were highly expressed [tumor necrosis factor (TNF)-α (614.8 ± 54.6)ng/L,interleukin (IL)-1 (3040.5 ±506.4) ng/L,IL-17 (4.5±0.4) U/L],and pancreatic chemotactic factors ( MCP-1,CINC ) were markedly increased ( P ＜ 0.05 ) in AP untreated group.After MSCs transplantation,the levels of serum inflammatory factors were reduced [TNF-α(277.5± 60.8) ng/L,IL-1 (1.56.2±563.1 ) ng/L,IL-17 ( 1.2 ±0.4) U/L],and pancreatic chemotactic factors were decreased (P＜0.05).Conclusion The expression of p38MAPK mRNA is increased in the pancreas of AP and the pancreas injuries are aggravated. MSCs could markedly inhibit p38MAPK mRNA expression in the pancreas of AP,which would lead to relief of pancreas injury. Key words: p38 mitogen-activated protein kinase; Bone-marrow mesenchymal stem cells; Acute pancreatitis; Transplantation

Fluid Collections in and Around the Pancreas in Acute Pancreatitis

The advent of computed tomographic scan with its wide use in the evaluation of acute pancreatitis has opened up a new topic in pancreatology i.e. fluid collections. Fluid collections in and around the pancreas occur often in acute pancreatitis and were defined by the Atlanta Symposium on Acute Pancreatitis in 1992. Two decades since the Atlanta Conference additional experience has brought to light the inadequacy and poor understanding of the terms used by different specialists involved in the care of patients with acute pancreatitis when interpreting imaging modalities and the need for a uniformly used classification system. The deficiencies of the Atlanta definitions and advances in medicine have led to a proposed revision of the Atlanta classification promulgated by the Acute Pancreatitis Classification Working Group. The newly used terms "acute peripancreatic fluid collections," "pancreatic pseudocyst," "postnecrotic pancreatic/peripancreatic fluid collections," and "walled-off pancreatic necrosis" are to be clearly understood in the interpretation of imaging studies. The current treatment methods for fluid collections are diverse and depend on accurate interpretations of radiologic tests. Management options include conservative treatment, percutaneous catheter drainage, open and laparoscopic surgery, and endoscopic drainage. The choice of treatment depends on a correct diagnosis of the type of fluid collection. In this study we have attempted to clarify the management and clinical features of different types of fluid collections as they have been initially defined under the 1992 Atlanta Classification and revised by the Working Group's proposed categorization.

DIAGNOSIS OF ACUTE NECROTIZING PANCREATITIS BY PERFUSION CT IN THE ERALY PHASE OF ACUTE PANCREATITIS

Perfusion imaging by MDCT (perfusion CT) is a new modality to measure tissue perfusion of the pancreas in acute pancreatitis.1 We examined whether perfusion CT in the early phase of acute pancreatitis can detect ischemic area in the pancreas leading to pancreatic necrosis. We investigated pancreatic perfusion measurement using MDCT in 12 patients with acute pancreatitis within the first 72 hr after the onset and two weeks after the admission. Perfusion, peak enhancement intensity and blood volume was significantly lower in poorly perfused area of the pancreas in acute necrotizing pancreatitis (ANP) than those in acute edematous pancreatitis (AEP) and those in perfused area of the pancreas in ANP on admission (Table 1). Two weeks later, perfusion in AEP and perfused area of ANP was recovered to almost normal range, whereas perfusion in poorly perfused area (ischemic area) of the pancreas in ANP was decreased (Fig. 1). Pancreatic necrosis was confirmed by operation or follow-up CT examination in accordance with the ischemic region of the pancreas detected by perfusion CT. Perfusion CT in the early phase of acute pancreatitis is useful for detection of ischemic change in the pancreas leading to pancreatic necrosis.TABLE 1: Parameters of Perfusion CT in Cases with Acute PancreatitisFIGURE 1: Changes in perfusion parameters of the pancreas: A, perfusion; B, blood volume. AEP: acute edematous pancreatitis ANP: acute necrotizing pancreatitis.

Nitric oxide protects against pancreatic subcellular damage in acute pancreatitis.

Oxidative stress involvement in damage to the pancreas in acute pancreatitis (AP) is well documented. However, little is known about oxidative damage occurring in the different subcellular fractions of pancreatic cells. The aim of this study was to ascertain the main targets of oxidative damage inside cells after AP and the role of endogenous nitric oxide (NO) in it. A model of cerulein-induced AP in rats was used and N-nitro-l-arginine methyl ester (l-NAME) was administered as an NO production inhibitor. After pancreatitis induction, indicative parameters of lipid peroxidation and protein oxidation together with some enzymatic and nonenzymatic endogenous free radical scavengers were assessed in serum and pancreatic subcellular fractions. In pancreatitic rats, malondialdehyde and protein carbonyl group concentrations were significantly increased (P < 0.05) in serum and some fractions. The increases were higher in l-NAME-treated rats (P < 0.05). Superoxide dismutase and catalase activities were also increased (P < 0.05) but were decreased (P < 0.05) with l-NAME. The alpha-tocopherol concentration diminished (P < 0.05) in serum and all the studied subcellular fractions and the decrease was stronger in l-NAME-treated rats. Our data suggest that microsomes followed by lysosomal + mitochondrial are the fractions most susceptible to oxidative damage in AP. Endogenous NO plays a protective role against oxidative damage to subcellular fractions.

The endothelin-1 receptor antagonists ameliorate histology and ultrastructural alterations in the pancreas and decrease trypsinogen activation in severe taurocholate pancreatitis in rats.

The role of potent vasoconstrictor endothelin-1 (ET-1) in acute pancreatitis (AP) remains controversial. The aim was to compare the effect of nonselective ET RA/B (LU-302872) and selective ET RA (LU-302146) antagonists on pancreatic histology, ultrastructure and trypsinogen activation in severe taurocholate AP in rats. Male Wistar rats with AP were treated with an intraperitoneous injection of 1, 5 and 10 mg/kg of body weight of each antagonist at 0, 6, 12 and 18 h after taurocholate administration. After 24 h, the samples of pancreases were taken for histological and ultrastructural examinations and for assessment of trypsinogen activation. Both antagonists, at all investigated doses, decreased the damage to the acinar cells detected in the light microscope and ultrastructurally. Trypsinogen activation increased to 29.7 +/- 3.9% in the AP untreated in comparison to the control group [12.7 +/- 1.4% (P<0.001)]. This increase was attenuated to 13.8 +/- 2.2% in AP treated with a high dose of the nonselective antagonist and to 8.4 +/- 1.7% with low dose of selective antagonist. The obtained results indicate that ET-1 could participate in the damage to the pancreas during AP. Both antagonists of ET-1 receptors exerted a similar beneficial effect on the morphological changes of the pancreas in AP. One of the probable mechanism could be the attenuation of trypsinogen activation.

Routes of spread of pathogens into the pancreas in a feline model of acute pancreatitis.

The routes of spread of pathogens into the pancreas in acute pancreatitis were investigated. Four experiments were performed: (1) cats with and without acute pancreatitis were given 10(7) Escherichia coli (E coli) intravenously, (2) in cats with acute pancreatitis 10(8) E coli was placed in the colon. In half of them the colon was then enclosed in an impermeable bag to prevent transmural spread. (3) E coli (10(4)) was placed in the pancreatic duct in cats with and without acute pancreatitis. (4) In cats with acute pancreatitis 10(5) E coli was placed in the gall bladder. In half of them the common bile duct was ligated to prevent biliary-pancreatic reflux. After 24 hours, intravenous E coli infected the pancreas in six of nine cats with acute pancreatitis and three of 10 controls. After 72 hours E coli spread to the pancreas from the colon in six of nine cats with acute pancreatitis. This was prevented by enclosing the colon in an impermeable bag (p = 0.02). In five of six cats with acute pancreatitis and five of six controls E coli placed in the pancreatic duct colonised the pancreas within 24 hours. Pancreatic colonisation from the gall bladder occurred in five of six cats with a patent common bile duct and in three of six with an obstructed common bile duct. In conclusion, in cats E coli can spread to the pancreas by the blood stream, transmurally from the colon, and by reflux into the pancreatic duct.

Relationship between pancreatic enzymes and pathological changes in the pancreas in acute pancreatitis

To clarify the relationship between changes in serum pancreatic enzymes and pathological changes in pancreatic parenchyma, this study was performed by using rat models with acute pancreatitis. The models were rats with edematous and necrotizing pancreatitis. Amylase, lipase, ribonuclease (RNase), and deoxyribonuclease (DNase I, II) in the serum were determined for 48 h after the development of pancreatitis. Amylase and lipase levels rose directly in both pancreatitis groups. These enzymes in the necrotizing pancreatitis group were higher than those in the edematous pancreatitis group, but there was no significant difference. RNase levels also rose markedly, but there was no obvious difference between either of the pancreatitis groups. On the other hand, DNase levels were high in the necrotizing pancreatitis group but low in the edematous pancreatitis group, with significant differences between the two groups, especially in the DNase II levels over a 36-h period (p less than 0.05-0.01). Therefore, these results suggest that serum DNase levels reveal the necrotizing changes in pancreatic parenchyma.

Pathways of enzyme transfer in sodium taurocholate-induced acute hemorrhagic pancreatitis.

The pathways of enzyme transfer from the pancreas into the systemic circulation were analyzed in sodium taurocholate-induced acute hemorrhagic pancreatitis in the rat by estimating lipase concentrations in blood, lymph and ascites. During the first few hours of pancreatitis high enzyme levels were observed in thoracic duct lymph. However, cannulation of the thoracic duct did not prevent a significant increase in the lipase concentration in peripheral blood. The portal vein lipase concentration was found to exceed the peripheral values by approximately 10%. Extremely high concentrations of lipase were measured in the ascites collected during pancreatitis. When the ascites was transferred to the peritoneal space of healthy rats, a significant increase in the lipase concentration in peripheral blood was measured. This increase could not be prevented by transection of the parasternal lymphatics. It was concluded that the hematogenous rather than the lymphatic transport of lipase from the pancreas and the peritoneal surface is the most important pathway. In this respect, this study does not support thoracic duct drainage but advocates peritoneal lavage as a logical therapeutic measure to reduce the concentration of circulating toxic substances from the pancreas in acute pancreatitis.

Function of pancreatic endocrine cells in experimental acute pancreatitis.

AbstractThis experimental study was carried out to clarify changes in pancreatic endocrine function in acute pancreatitis. Male Donryu rats were divided into 2 groups, consisting of a group with acute pancreatitis induced by Block's method, and another group with simple laparotomy as control. Histological examination in the former group revealed an interstitial edematous pancreatitis, but there was no marked alteration of endocrine cells in spite of inflammatory changes in the exocrine region. Insulin and glucagon levels in the pancreatic tissue of rats with acute pancreatitis were significantly lower than those of control rats. Autoradiographic studies using3H‐leucine showed a significant decrease of grain counts for endocrine granules in rats with acute pancreatitis. The release of insulin from isolated islets of Langerhans was not reduced until 72 hours after the development of acute pancreatitis, while the release of glucagon from isolated islets was reduced 6 hours after the development of acute pancreatitis. These findings indicate that there is a reduction of synthesis and secretion function in endocrine cells of the pancreas in acute pancreatitis, and suggest that the damage to A cells occurs more rapidly than damage to B cells.