Plasma Amylase Research Articles

Berberine Attenuates Cerulein-Induced Acute Pancreatitis by Modulating Nrf2/NOX2 Signaling Pathway via AMPK Activation.

AMP-activated protein kinase (AMPK) is the master regulator of cellular energy which gets activated during energy stress and restores tissue homeostasis. AMPK is widely expressed in the pancreas and is involved in protein synthesis. In cerulein-induced acute pancreatitis (AP), diminished AMPK activity in the pancreatic tissue may be associated with pancreatic inflammation and oxidative stress. Our results demonstrated that berberine (BR) treatment produced significant decrease in plasma amylase and lipase levels and improved histopathological features in AP mice model. Myeloperoxidase (MPO) activity indicated that BR suppressed the infiltration of neutrophils in pancreas. BR treatment markedly decreased the levels of proinflammatory cytokines including interleukins (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) via inhibition of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression. In addition, BR activates the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and inhibits cerulein-induced oxidative-nitrosative stress. Mechanistically, we found inhibition of AMPK activity in cerulein-induced AP, while BR-treated animals showed marked increase in the AMPK expression. Together, our study indicated that BR-mediated AMPK activation in pancreatic tissues demonstrated attenuation of cerulein-induced oxidative stress and inflammation. Based on our observations, further exploration of this promising natural product against AP and associated complications may lead to promising therapeutic options.

Ca2+ signaling of pancreatic acinar cells in malignant hyperthermia susceptibility

BackgroundMalignant hyperthermia susceptibility (MHS) and acute pancreatitis (AP) share a common cellular pathomechanism that is Ca2+-overload of the muscle fiber and the pancreatic acinar cell (PAC). In the muscle, gain-of-function mutations of the ryanodine receptor (RyR1) make the Ca2+-release mechanism hypersensitive to certain ligands, including Ca2+, volatile anaesthetics and succinylcholine, creating a medical emergency when the patient is exposed to these drugs. As RyR1 was shown to contribute to Ca2+-overload in PAC, we presumed that pancreata of MHS individuals are more prone to AP. Accordingly, a recent case study reported coincidence of MHS with recurrent AP, indicating a pathological link between the two diseases. MethodsWe tested if MHS poses a risk for AP in mice carrying the Y522S MHS mutation.Fluorescent Ca2+ imaging was performed in PACs. Conventional histopathological analysis and plazma amylase measurement was performed using a cerulein-induced pancreatitis mouse model. ResultsThe intracellular Ca2+-signals of PACs from MHS mice were slightly bigger then in wild type when stimulated with 0.2 and 2 μM carbachol (cch) or with 1 and 5 mM bile acid (taurocholic acid). Store-operated-Ca2+-entry was also higher in PACs from MHS mice. Nevertheless, histopathological analysis and plasma amylase levels did not indicate more severe AP in MHS. ConclusionsThese results suggest that the Y522S RyR1 mutation alter the Ca2+-homeostasis in PACs, but not as much as to cause or aggravate AP.

Risk factors of pancreatic fistula after distal pancreas resections: an observational retrospective study

BACKGROUND: The main complication of surgical pancreas interventions is the pancreatic fistula (PF) — abnormal secretion of pancreatic secretions into the abdominal cavity, which can lead to more severe complications. At the same time, some predictors of PF remain poorly understood. AIM: To investigate the risk factors for the development of PF after distal pancreatic resection. MATERIALS AND METHODS: The study included 40 patients who underwent distal resection. The influence of various clinical parameters on the development of PF after surgery was evaluated. Methods of mathematical modeling and correlation analysis were used. Mathematical modeling was carried out using the Random forest machine learning algorithm, and the indicator of the relative importance of the “importance” parameters was evaluated. RESULTS: According to the Random forest model, on day 1 after surgery, the most significant predictors of the development of PF were: the volume of neoplasm, age and stage of the oncological process, for which “importance” was 53.2, 13.7 and 12.5 (AUC ROC=62%); on day 3–5, “importance” was 61.7, 11.5 and 5.2 (AUC ROC=79%). An increase in the concentration of pancreatic amylase in blood plasma for 2–3 and 3–5 days correlated with its increase in the drainage discharge for 5-7 days after the intervention (r=0.48 and 0.76; p 0.05). A correlation was found between the level of amylase in the drainage discharge on 3–5 days after the intervention and the level of leukocytes according to the general blood test (r=0.62, p 0.05). CONCLUSION: An increase in plasma amylase levels is the main risk factor for the development of PF. An increase in the concentration of amylase in the drainage discharge can be considered as a potential risk factor for the development of pancreatic fistulas with clinical manifestations in the following days. The stage of the oncological process, the size of the neoplasm and the age of the patient are also risk factors.

Hesperidin Alleviates Acute Necrotizing Pancreatitis by Activating SIRT1 - Molecular Docking, Molecular Dynamics Simulation, and Experimental Validation.

Acute necrotizing pancreatitis is a serious pancreatic injury with limited effective treatments. This study aims to investigate the therapeutic effects of hesperidin on Larginine- induced acute pancreatitis and its potential targets. The authors induced acute pancreatitis in mice by administering two hourly intraperitoneal injections of L-arginine-HCl, and evaluated the impact of hesperidin on pancreatic and lung tissues, plasma amylase activity, and myeloperoxidase content. Additionally, necrosis and mitochondrial function was tested in primary pancreatic acinar cells. The interactions between hesperidin and proteins involved in necrosis and mitochondrial dysfunction were further invested using in silico molecular docking and molecular dynamic simulations. Hesperidin effectively ameliorated the severity of acute necrotizing pancreatitis by reducing plasma amylase, pancreatic MPO, serum IL-6 levels, pancreatic edema, inflammation, and pancreatic necrosis. Hesperidin also protected against acute pancreatitis-associated lung injury and prevented acinar cell necrosis, mitochondrial membrane potential loss, and ATP depletion. In addition, hesperidin exhibited a high binding affinity with SIRT1 and increased the protein levels of SIRT1. The SIRT1 inhibitor EX527 abolished the protective effect of hesperidin against necrosis in acinar cells. These findings indicate that hesperidin alleviates the severity of acute necrotizing pancreatitis by activating SIRT1, which may provide insight into the mechanisms of natural compounds in treating AP. Hesperidin has potential as a therapeutic agent for acute necrotizing pancreatitis and provides a new approach for novel therapeutic strategies.

Renalase peptides reduce pancreatitis severity in mice.

Acute pancreatitis, an acute inflammatory injury of the pancreas, lacks a specific treatment. The circulatory protein renalase is produced by the kidney and other tissues and has potent anti-inflammatory and prosurvival properties. Recombinant renalase can reduce the severity of mild cerulein pancreatitis; the activity is contained in a conserved 20 aa renalase site (RP220). Here, we investigated the therapeutic effects of renalase on pancreatitis using two clinically relevant models of acute pancreatitis. The ability of peptides containing the RP220 site to reduce injury in a 1-day post-endoscopic retrograde cholangiopancreatography (ERCP) and a 2-day severe cerulein induced in mice was examined. The initial dose of renalase peptides was given either prophylactically (before) or therapeutically (after) the initiation of the disease. Samples were collected to determine early pancreatitis responses (tissue edema, plasma amylase, active zymogens) and later histologic tissue injury and inflammatory changes. In both preclinical models, renalase peptides significantly reduced histologic damage associated with pancreatitis, especially inflammation, necrosis, and overall injury. Quantifying inflammation using specific immunohistochemical markers demonstrated that renalase peptides significantly reduced overall bone marrow-derived inflammation and neutrophils and macrophage populations in both models. In the severe cerulein model, administering a renalase peptide with or without pretreatment significantly reduced injury. Pancreatitis and renalase peptide effects appeared to be the same in female and male mice. These studies suggest renalase peptides that retain the anti-inflammatory and prosurvival properties of recombinant renalase can reduce the severity of acute pancreatitis and might be attractive candidates for therapeutic development.NEW & NOTEWORTHY Renalase is a secretory protein. The prosurvival and anti-inflammatory effects of the whole molecule are contained in a 20 aa renalase site (RP220). Systemic treatment with peptides containing this renalase site reduced the severity of post-endoscopic retrograde cholangiopancreatography (ERCP) and severe cerulein pancreatitis in mouse models.

Effects of prolonged hydroxychloroquine use on the pancreatic tissue and expected ameliorative effect of lactoferrin in rats (biochemical, histological, and morphometric study)

Hydroxychloroquine (HCQ), an antimalarial drug widely used in treating rheumatoid disorders. Many side effects have been reported with HCQ administration indicating its hazardous effects on various organs. No previous studies reported the effect of long-term administration of oral HCQ on pancreatic tissue. Our study assessed pancreatic tissues functional and histopathological alterations following prolonged oral administration of HCQ. We also investigated the possible ameliorative effects of the lactoferrin (LF) coadministration with HCQ in adult male albino rats. Forty adult male Wister albino rats were divided into: negative control, LF positive control (2 g/kg), HCQ-treated (200 mg/kg), and HCQ+LF treated. Biochemical, histological, immunohistochemical, and morphometric analyses of the pancreatic tissues were conducted. Our findings revealed that prolonged oral administration of HCQ induced significant disruption of the pancreatic acinar architecture, enlarged congested islets of Langerhans, and elevated plasma insulin, amylase, and lipase levels. Interestingly, LF administration ameliorated the deleterious effects of prolonged HCQ administration on pancreatic tissue of adult male albino rats. In conclusion, prolonged oral administration of HCQ induced pancreatic tissue damage in rats, while LF attenuates HCQ-induced pancreatic injury. Our results emphasized the necessity of prescribing HCQ with caution, considering both dosage and treatment duration.

Western diet-induced ultrastructural changes in mouse pancreatic acinar cells.

Mouse models of diet-induced type 2 diabetes mellitus provide powerful tools for studying the structural and physiological changes that are related to the disease progression. In this study, diabetic-like glucose dysregulation was induced in mice by feeding them a western diet, and light and transmission electron microscopy were used to study the ultrastructural changes in the pancreatic acinar cells. Acinar necrosis and vacuolization of the cytoplasm were the most prominent features. Furthermore, we observed intracellular and extracellular accumulation of lipid compounds in the form of lipid droplets, structural enlargement of the cisternae of the rough endoplasmic reticulum (RER), and altered mitochondrial morphology, with mitochondria lacking the typical organization of the inner membrane. Last, autophagic structures, i.e., autophagosomes, autolysosomes, and residual bodies, were abundant within the acinar cells of western diet-fed mice, and the autolysosomes contained lipids and material of varying electron density. While diets inducing obesity and type 2 diabetes are clearly associated with structural changes and dysfunction of the endocrine pancreas, we here demonstrate the strong effect of dietary intervention on the structure of acinar cells in the exocrine part of the organ before detectable changes in plasma amylase activity, which may help us better understand the development of non-alcoholic fatty pancreas disease and its association with endo- and exocrine dysfunction.

High-Dose Vitamin C Alleviates Pancreatic Necrosis by Inhibiting Platelet Activation Through the CXCL12/CXCR4 Pathway in Severe Acute Pancreatitis.

Platelet activation in the early stage of pancreatitis is the key step developing into pancreatic necrosis. Studies suggested that vitamin C (Vit C) can inhibit platelet activity by targeting CXCL12/CXCR4 pathway. High-dose Vit C were showed to reduce pancreatic necrosis in severe acute pancreatitis (SAP) but the mechanism remains unclear. Here we speculate high-dose Vit C reduce pancreatic necrosis by inhibiting platelet activation through downregulating CXCL12/CXCR4 pathway. The pancreatic microcirculation of rats was observed by intravital microscopy. The platelet activity of SAP rats treated with or without high-dose Vit C was analyzed by platelet function test. Besides, the activity of platelets preincubated with high-dose Vit C or vehicle from SAP patients was also evaluated. Then, the TFA (CXCR4 agonist) and rCXCL12 were used to neutralize the effect of high-dose Vit C in SAP rats treated with high-dose Vit C. Meanwhile, the levels of enzymes and inflammatory cytokines in rat plasma, and rats' pancreatic histopathology and mortality were assessed. Platelets from animals and patients with SAP are more sensitive to agonists and are more easily activated. Administration of high-dose Vit C significantly ameliorated excessive activation of platelets in SAP rats, ultimately increasing the microvessel density and inducing microthrombus and blood stasis; these results were consistent with clinical sample analysis. Moreover, high-dose Vit C significantly inhibited the release of amylase, lipase, TNF-α, and IL-6 in SAP rat plasma, reducing pancreatic damage and the mortality of SAP rats. However, using TFA and rCXCL12 significantly reversed the effect of high-dose Vit C on excessive activation of platelets, aggravating microcirculation impairment and pancreatic damage. The present study suggests that high-dose Vit C can ameliorate pancreatic necrosis by improving microcirculation disorders of SAP. For the first time, the underlying mechanism is related with inhibiting platelet activation through the CXCL12/CXCR4 pathway.

Overt Vitamin B-6 Deficiency Affects Rat Pancreatic Digestive Enzyme and Glutathione Reductase Activities

Previous reports suggest that vitamin B-6 deficiency contributes to pancreatic insufficiency. However, the susceptibility of pancreatic function to marginal vitamin B-6 intake has not been defined. The present study examines digestive enzyme activity and steady-state mRNA levels, as well as antioxidant enzyme status from rats fed different vitamin B-6 diets. Groups (n = 12) of adult female Long-Evans rats were assigned to five dietary groups and fed their respective diets for 6 wk. Control and food-restricted rats were fed the control diet (7 mg pyridoxine/kg diet) freely, or food intake was restricted to the lowest intake of the experimental groups. The experimental groups were fed purified diets containing 0 (deficient), 0.25 or 1 (marginal) mg pyridoxine/kg diet. Plasma amylase and pancreatic amylase, trypsin and chymotrypsin activities were significantly lower in deficient rats compared with rats fed the control diet. Lower enzyme activities were accompanied by 83 and 55% lower amylase and trypsinogen mRNA levels compared with levels in rats fed the control diet. Other than low glutathione reductase in deficient rats, pancreatic antioxidant enzyme activity was similar in all dietary groups. These data suggest that the exocrine pancreas is impaired by vitamin B-6 deficiency, but marginal pyridoxine intake maintains function.

Antidiabetic actions of GPR55 agonist Abn-CBD and sitagliptin in obese-diabetic high fat fed mice

GPR55 has been recognized as a novel anti-diabetic target exerting positive effects on beta cell function and mass. This study evaluated the metabolic actions and therapeutic efficacy of GPR55 agonist abnormal cannabidiol (Abn-CBD) administered alone and in combination with sitagliptin in diet-induced obese-diabetic mice.Chronic effects of 21-day oral administration of Abn-CBD (0.1 µmol/kg BW) monotherapy and in combination with sitagliptin (50 mg/kg BW) were assessed in obese-diabetic HFF mice (n = 8). Assessments of plasma glucose, circulating insulin, DPP-IV activity, CRP, amylase, lipids, body weight and food intake were undertaken. Glucose tolerance, insulin sensitivity, DEXA scanning and islet morphology analysis were performed at 21-days.Sitagliptin, Abn-CBD alone and in combination with sitagliptin attenuated plasma glucose by 37–53 % (p < 0.01 – p < 0.001) and enhanced circulating insulin concentrations by 23–31 % (p < 0.001). Abn-CBD alone and with sitagliptin reduced bodyweight by 9–10 % (p < 0.05). After 21-days, Abn-CBD in combination with sitagliptin (44 %; p < 0.01) improved glucose tolerance, whilst enhancing insulin sensitivity by 79 % (p < 0.01). Abn-CBD increased islet area (86 %; p < 0.05), beta cell mass (p < 0.05) and beta cell proliferation (164 %; p < 0.001), whilst in combination with sitagliptin islet area was decreased (50 %; p < 0.01). Abn-CBD alone, in combination with sitagliptin or sitagliptin alone decreased triglycerides by 34–65 % (p < 0.001) and total cholesterol concentrations by 15–25 % (p < 0.001). In addition, Abn-CBD in combination with sitagliptin reduced fat mass by 19 % (p < 0.05) and reduced CRP concentrations (39 %; p < 0.05).These findings advocate Abn-CBD monotherapy and in combination with sitagliptin as a novel and effective approach for bodyweight control and the treatment of glucose intolerance and dyslipidaemia in type-2-diabetes.

Deoxyarbutin attenuates severe acute pancreatitis via the HtrA2/PGC-1α pathway

Severe acute pancreatitis (SAP) is an inflammatory disorder of the exocrine pancreas associated with high morbidity and mortality. SAP has been proven to trigger mitochondria dysfunction in the pancreas. We found that Deoxyarbutin (dA) recovered impaired mitochondrial function. High-temperature requirement protein A2 (HtrA2), a mitochondrial serine protease upstream of PGC-1α, is charge of quality control in mitochondrial homeostasis. The molecular docking study indicated that there was a potential interaction between dA and HtrA2. However, whether the protective effect of dA against SAP is regulated by HtrA2/PGC-1α remains unknown. Our study in vitro showed that dA significantly reduced the necrosis of primary acinar cells and reactive oxygen species (ROS) accumulation, recovered mitochondrial membrane potential (ΔΨm) and ATP exhaustion, while UCF-101 (HtrA2 inhibitor), and SR-18292 (PGC-1α inhibitor) eliminated the protective effect of dA. Moreover, HtrA2 siRNA transfection efficiently blocked the protective of dA on HtrA2/PGC-1α pathway in 266-6 acinar cells. Meanwhile, dA also decreased LC3II/I ration, as well as p62, and increased Parkin expression, while UCF-101 and Bafilomycin A1 (autophagy inhibitor) reversed the protective effect of dA. Our study in vivo confirmed that dA effectively alleviated severity of SAP by reducing pancreatic edema, plasma amylase, and lipase levels and improved the HtrA2/PGC-1α pathway. Therefore, this is the first study to identify that dA inhibits pancreatic injury caused by oxidative stress, mitochondrial dysfunction, and impaired autophagy in a HtrA2/PGC-1α dependent manner.

Plasma Polyamines Decrease in Patients with Obstructive Cholecystitis

Polyamines (PAs), endogenous metabolites with a wide range of biological activities, are synthesized at a high rate in liver supporting hepatocyte proliferation and survival. The liver appears as an important regulator of plasma PAs; however, the perspective to exploit plasma PA measurements as indicators for liver function was not explored. This study aimed to evaluate the value of the plasma levels of PAs as a biomarker of pathological changes in the liver in patients with obstructive cholecystitis. The levels of polyamines and their acetylated forms were measured using HPLC/UV in the plasma of patients with obstructive cholecystitis and in healthy subjects. PA turnover was assessed by the ratio between an acetylated form of PA and PA. An effect of diet preference of cheese or meat, the major exogenous sources of PAs, smoking, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in anamnesis was also evaluated in healthy subjects. We found that the plasma levels of spermine and acetylated spermidine decreased in patients with obstructive cholecystitis without a concurring increase in the total plasma bilirubin and amylase levels. The turnover of spermine and spermidine was also changed, suggesting a decrease in the rate of PA degradation in the liver. In healthy subjects, the PA levels tended to mirror chronic smoking and recent SARS-CoV-2 infection but were not relevant to diet factors. A number of observations indicated the role of physical exercise in the regulation of the plasma pool of PA. The decrease in plasma PA levels and index of PA turnover in the cholestasis syndrome indicate the liver’s metabolic function reduction. A conceivable effect of lung-related conditions on plasma PA, while indicating low specificity, nonetheless, speaks favorably about the high sensitivity of plasma PA measurement as an early diagnostic test in the clinic.

Dietary Arginine Modulates Growth Performance, Hemato-Biochemical Indices, Intestinal Enzymes, Antioxidant Ability and Gene Expression of TOR and 4E-BP1 in Rainbow Trout, Oncorhynchus mykiss Fingerlings

We evaluated the effect of arginine on growth, hemato-biochemical variables, intestinal enzymes, antioxidant ability, and expression of target of rapamycin (TOR) signaling pathway related genes in fingerling Oncorhynchus mykiss. A series of six uniform diets consisting of 450 g kg-1 of protein and 20.9 g-1 of energy with graduated levels (10.0, 12.5, 15.0, 17.5, 20.0, and 22.5 g kg-1) of arginine were formulated. Significant (p &amp;lt; 0.05) variations were observed in various analyzed parameters. Growth parameters showed a positive linear trend with increasing arginine levels up to 17.5 g kg-1. Fish offered 17.5 g kg-1 of dietary arginine exhibited highest body protein, lowest moisture, and intermediate fat contents, whereas, body ash content did not significantly (p &amp;gt; 0.05) change with respect to each dietary arginine offered diet, except for the lowest levels. Each group also produced significant (p &amp;lt; 0.05) changes in their hematological variables with maximum hemoglobin (Hb), hematocrit (Hct) content, and red blood cell (RBC) count noted at 17.5 g kg-1 arginine diet. Although the majority of blood plasma parameters were insignificantly (p &amp;gt; 0.05) different with respect to varied arginine fed diets, plasma aspartate transaminase (AST) showed significant (p &amp;lt; 0.05) variations across the treatments. Moreover, total protein, alkaline phosphatase (ALP) and albumin contents increased significantly (p &amp;lt; 0.05) with increasing arginine concentrations up to 17.5 g kg-1 and, thereafter, a declined trend in these parameters were noted. Intestinal enzymes and antioxidant properties showed significant (p &amp;lt; 0.05) variations, except plasma amylase, which showed insignificant variation. The maximum up-regulation of TOR and 4E-BP1 gene expression levels were found for fish fed 17.5 g kg-1 of dietary arginine compared to the lower (10.0 and 12.5 g kg-1) and higher (20.0 and 22.5 g kg-1) arginine levels, which indicates that fish utilize arginine more efficiently at this point. Quadratic regression analysis of live weight gain (LWG), feed conversion ratio (FCR), protein efficiency ratio (PER) and body protein deposition (BPD) indicated the optimal arginine requirement of rainbow trout to be 17.61 g kg-1 of dry diet, corresponding to 39.13 g kg-1 of dietary protein, which enhances growth, immunity, antioxidant ability, and also promote TOR signaling pathway in rainbow trout.

Kinetics of Changes in the Blood Digestive Enzyme Amylase in Partridges (Alectoris Chukar) In Ontogenesis

This article presents experimental data on the detection of age-related changes in the blood digestive enzyme blood amylase in partridges (Alectoris chukar). The purpose of the work is to determine the kinetics of changes in the blood digestive enzyme amylase in partridges in ontogenesis with the complex use of vitamins and an anti-stress drug. Experimental studies revealed the dynamics of changes in the digestive enzyme amylase in the blood plasma of partridge chicks from the moment of hatching and up to 2 months of age, with the complex use of vitamins (A-20000 IU, D3 -1250 IU, E-50 mg), as well as the anti-stress preparation of succinic acid) at the rate of 0.03 g per 1 kg of mass. Determination of the activity of the blood digestive enzyme amylase in partridges was carried out spectrophotometrically according to the method of Karavea, on a Specol 1500 spectrophotometer (Analitik Jena), at a wavelength of 690 nm. It was revealed that the activity of the blood digestive enzyme amylase in 1-day-old control partridges significantly exceeds the activity of this enzyme in 7, 13, 22, 31 and 60-day partridges by 1.6, 1.9, 2.2,1.9, 1.8 times, respectively. The activity of the blood digestive enzyme amylase in 1-day experimental groups of partridges significantly exceeds the activity of this enzyme in 7, 13, 22, 31 and 60-day experimental groups of partridges by 1.4, 2.3, 2.6, 1.8, 1.9 times, respectively.

Loss of LAT1 sex-dependently delays recovery after caerulein-induced acute pancreatitis.

BACKGROUNDThe expression of amino acid transporters is known to vary during acute pancreatitis (AP) except for LAT1 (slc7a5), the expression of which remains stable. LAT1 supports cell growth by importing leucine and thereby stimulates mammalian target of rapamycin (mTOR) activity, a phenomenon often observed in cancer cells. The mechanisms by which LAT1 influences physiological and pathophysiological processes and affects disease progression in the pancreas are not yet known.AIMTo evaluate the role of LAT1 in the development of and recovery from AP.METHODSAP was induced with caerulein (cae) injections in female and male mice expressing LAT1 or after its knockout (LAT1 Cre/LoxP). The development of the initial AP injury and its recovery were followed for seven days after cae injections by daily measuring body weight, assessing microscopical tissue architecture, mRNA and protein expression, protein synthesis, and enzyme activity levels, as well as by testing the recruitment of immune cells by FACS and ELISA.RESULTSThe initial injury, evaluated by measurements of plasma amylase, lipase, and trypsin activity, as well as the gene expression of dedifferentiation markers, did not differ between the groups. However, early metabolic adaptations that support regeneration at later stages were blunted in LAT1 knockout mice. Especially in females, we observed less mTOR reactivation and dysfunctional autophagy. The later regeneration phase was clearly delayed in female LAT1 knockout mice, which did not regain normal expression of the pancreas-specific differentiation markers recombining binding protein suppressor of hairless-like protein (rbpjl) and basic helix-loop-helix family member A15 (mist1). Amylase mRNA and protein levels remained lower, and, strikingly, female LAT1 knockout mice presented signs of fibrosis lasting until day seven. In contrast, pancreas morphology had returned to normal in wild-type littermates.CONCLUSIONLAT1 supports the regeneration of acinar cells after AP. Female mice lacking LAT1 exhibited more pronounced alterations than male mice, indicating a sexual dimorphism of amino acid metabolism.

Prediction and consequences of postoperative pancreatitis after pancreaticoduodenectomy.

BackgroundRecent studies have suggested postoperative acute pancreatitis (POAP) as a serious complication after pancreaticoduodenectomy (PD) and have speculated on its possible role in the pathogenesis of postoperative pancreatic fistula (POPF). This study aimed to assess the impact of POAP on post-PD outcomes and fistula risk score (FRS) performance in predicting POAP.MethodsAll PDs at Helsinki University Hospital between 2013 and 2020 were analysed. POAP was defined as a plasma amylase activity greater than the normal upper limit on postoperative day (POD) 1 and stratified as clinically relevant (CR)-POAP once C-reactive protein (CRP) reached or exceeded 180 mg/l, and non-CR-POAP once CRP was less than 180 mg/l on POD 2. The Comprehensive Complication Index (CCI) was used to assess total postoperative morbidity. Different FRSs were assessed using receiver operating characteristic curves.ResultsOf the 508 patients included, POAP occurred in 202 (39.8 per cent) patients, of whom 91 (17.9 per cent) had CR-POAP. The incidence of CR-POPF was 12.6 per cent (64 patients). Patients with non-CR-POAP had a similar morbidity to patients with no POAP (median CCI score 24.2 versus 22.6; P = 0.142), while CCI score was significantly higher (37.2) in patients with CR-POAP (P < 0.001). CR-POAP was associated with increased rates of CR-POPF, delayed gastric emptying, haemorrhage, and bile leak, while non-CR-POAP was associated only with CR-POPF. Ninety-day mortality was 1.6 per cent, 0.9 per cent, and 3.3 per cent in patients with no-POAP, non-CR-POAP, and CR-POAP, respectively. Updated alternative FRS showed the best performance in predicting CR-POAP (area under the curve 0.834).ConclusionCR-POAP was associated with a higher CCI score, suggesting CR-POAP as a distinct entity from non-CR-POAP. FRSs can be used to assess the risk of CR-POAP.

Favorable efficacy of adalimumab treatment in experimental acute pancreatitis model.

Acute pancreatitis is a clinical picture with a wide range of symptoms from mild inflammation to multiorgan failure and death. The aim of this study is to investigate the effects of Adalimumab (ADA) on inflammation and apoptosis in a cerulein-induced acute pancreatitis model in rats. Experimental cerulein-induced acute pancreatitis model was created by applying 4 intraperitoneal cerulein injections at 1-h intervals. A total of 40 rats, 8 in each group, were randomly distributed into five groups. In the groups that ADA treatment was given, two different doses of ADA were administered 5 mg/kg and 20 mg/kg as low and high doses, respectively. The rats were sacrificed 12 h after the last intraperitoneal administration of ADA. Blood samples were obtained from each rat for amylase, IL-6, and IL-1β measurements. Hematoxylin and Eosin (H&E) stains were used to undertake the histopathological analysis of the pancreas. The terminal deoxynucleotidyl transferase-mediated nick-end-labeling (TUNEL) method was used to evaluate apoptosis. : Plasma amylase, IL-6, and IL-1β levels were significantly elevated in acute pancreatitis groups (p < 0.05). It was determined that both low (5 mg/kg) and high doses (20 mg/kg) of ADA ameliorated the parameters (plasma amylase, IL-6, and IL-1β) (p < 0.05). Although significant improvements were detected in the Schoenberg scoring system and the apoptotic index from the TUNEL method after highdose ADA treatment, no significant amelioration was observed in the histopathological examinations in the low-dose ADA group. : It has been determined that the administration of high-dose ADA effectively alleviated the symptoms of acute pancreatitis and reduced the level of apoptosis. In line with the findings of our study, we have predicted that high-dose (20 mg/kg) ADA can be used as an effective and safe drug in the treatment of patients with acute pancreatitis.

Radiocontrast agent and intraductal pressure promote the progression of post-ERCP pancreatitis by regulating inflammatory response, cellular apoptosis, and tight junction integrity

ObjectivePost-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication following ERCP and the mechanism is not fully understood. This study evaluated the changes in the inflammatory response, cellular apoptosis, and tight junction integrity in a rat model of pancreatitis to explore the underlying mechanism. MethodsPEP was induced in rats by retrograde biliopancreatic ductal infusion of contrast agents or saline. Pancreatic tissues were harvested and evaluated by histopathologic, immunohistochemical, immunofluorescence, and Western blot analyses. In addition, amylase and proinflammatory cytokines in plasma were quantified by ELISA assay. ResultsPEP rats developed more severe acute pancreatitis than the sham group after injection of the contrast agent or isotonic saline. PEP rats exhibited increased tissue damage, plasma amylase, proinflammatory cytokines, necrosis, inflammatory infiltrates, apoptosis, and tight junction disruption. At the molecular level, contrast agent and isotonic saline-injected PEP rats demonstrated elevated NF-κB p65 and STAT3 pathways activation, altered expression and activation of apoptosis-related proteins, and suppressed expression of tight junction molecules. However, the contrast agent concentration had no effect on these changes. ConclusionsIn models of acute pancreatitis induced using contrast agent and hydrostatic pressure, the contrast agent and high hydrostatic pressure easily induced the inflammatory response, apoptosis, and tight junction disruption. It is noteworthy that no significant difference in damaged pancreatic acinar cells was observed with different concentrations of the contrast agent.

Zeolite Improves High-Fat Diet-Induced Hyperglycemia, Hyperlipidemia and Obesity in Mice.

Zeolite, an abundant mineral in the Earth's crust, is utilized in a wide range of fields because of its well-known adsorption properties. Its application as a functional food ingredient resembling dietary fiber is expected, but it has not yet been investigated in the context of prevention of lifestyle-related diseases. The present study was designed to evaluate the availability and safety of a natural zeolite preparation for this purpose. Acute oral toxicity testing showed that the lowest lethal dose of zeolite was more than 2,000 mg/kg body weight for both male and female mice. In a prolonged feeding test for 18 wk using model mice with high-fat-induced obesity and type 2 diabetes mellitus, intake of a 10% zeolite-containing diet suppressed body weight gain, as well as liver and visceral fat weights, without any changes in food and energy intake. Moreover, plasma lipid (triacylglycerol, total cholesterol and high-density-lipoprotein cholesterol) levels and fasting blood glucose levels decreased in parallel with zeolite intake. No changes in the glycated hemoglobin level were found. However, in an oral glucose tolerance test at week 12, increased postprandial blood glucose levels were suppressed in accordance with zeolite intake, and then insulin secretion was also decreased. On the other hand, a decrease of plasma amylase activity and increases in total bilirubin and urea nitrogen suggested the need for further investigation of safety.

Acute pancreatitis in a COVID-19 patient in Brazil: a case report

BackgroundThe consequences of the coronavirus disease 2019 pandemic have already exceeded 10 million infected and more than 560,000 deaths worldwide since its inception. Currently, it is known that the disease affects mainly the respiratory system; however, recent studies have shown an increase in the number of patients with manifestations in other systems, including gastrointestinal manifestations. There is a lack of literature regarding the development of acute pancreatitis as a complication of coronavirus disease 2019.Case reportWe report a case of acute pancreatitis in a white male patient with coronavirus disease 2019. A 35-year-old man (body mass index 31.5) had acute epigastric pain radiating to his back, dyspnea, nausea, and vomiting for 2 days. The patient was diagnosed with severe acute pancreatitis (AP)-APACHE II: 5, SOFA: 3, Marshall: 0; then he was transferred from ED to the semi-intensive care unit. He tested positive for severe acute respiratory syndrome coronavirus 2 on reverse transcription-polymerase chain reaction, and his chest computed tomography findings were compatible with coronavirus disease 2019. Treatment was based on bowel rest, fluid resuscitation, analgesia, and empiric antibiotic therapy. At day 12, with resolution of abdominal pain and improvement of the respiratory condition, the patient was discharged.ConclusionSince there is still limited evidence of pancreatic involvement in severe acute respiratory syndrome coronavirus 2 infection, no definite conclusion can be made. Given the lack of other etiology, we consider the possibility that the patient’s acute pancreatitis could be secondary to coronavirus disease 2019 infection, and we suggest investigation of pancreas-specific plasma amylase in patients with coronavirus disease 2019 and abdominal pain.