scholarly journals The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Maximilian Weniger ◽  
Leonard Reinelt ◽  
Jens Neumann ◽  
Lesca Holdt ◽  
Matthias Ilmer ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Chronic Pancreatitis ◽  
Analgesic Effect ◽  
Tissue Injury ◽  
Behavioral Observation ◽  
Pancreatic Tissue ◽  
Mechanical Sensitivity ◽  
Risks And Benefits ◽  
Reduction Of Pain ◽  
Acute And Chronic Pancreatitis

Background. Chronic pancreatitis is one of the main risk factors for pancreatic cancer. In acute and chronic pancreatitis, oxidative stress is thought to play a key role. In this respect, the recently described mitochondria-targeted antioxidant SkQ1 effectively scavenges reactive oxygen species at nanomolar concentrations. Therefore, we aimed to characterize the influence of SkQ1 on tissue injury and pain in acute and chronic pancreatitis.Methods. Both acute and chronic pancreatitis were induced in C57BL/6 mice by intraperitoneal cerulein injections and treatment with SkQ1 was carried out by peroral applications. Hyperalgesia was assessed by behavioral observation and measurement of abdominal mechanical sensitivity. Blood serum and pancreatic tissue were harvested for analysis of lipase and histology.Results. SkQ1 did not influence pain, serological, or histological parameters of tissue injury in acute pancreatitis. In chronic pancreatitis, a highly significant reduction of pain-related behavior (p<0.0001) was evident, but histological grading revealed increased tissue injury in SkQ1-treated animals (p=0.03).Conclusion. After SkQ1 treatment, tissue injury is not ameliorated in acute pancreatitis and increased in chronic pancreatitis. However, we show an analgesic effect in chronic pancreatitis. Further studies will need to elucidate the risks and benefits of mitochondria-targeted antioxidants as an analgesic.

scholarly journals Validation of a commercial 1,2-o-dilauryl-rac-glycero glutaric acid-(6’-methylresorufin) ester lipase assay for diagnosis of canine pancreatitis

2018 ◽  
Vol 5 (1) ◽  
pp. e000270 ◽  
Author(s):  
Emily L Goodband ◽  
Gonçalo Serrano ◽  
Fernando Constantino-Casas ◽  
Joy Archer ◽  
Penny J Watson ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Chronic Pancreatitis ◽  
Sensitivity And Specificity ◽  
Glutaric Acid ◽  
Reference Interval ◽  
Pancreatic Tissue ◽  
Serum Samples ◽  
Technical Validation ◽  
Two Parameters ◽  
Acute And Chronic Pancreatitis

The objectives of this study were fourfold: technical validation of a commercial canine 1,2-o-dilauryl-rac-glycero glutaric acid-(6’-methylresorufin) ester (DGGR) lipase assay, to calculate a reference interval for DGGR lipase by the indirect a posteriori method, to establish biological validity of the assay, and to assess agreement between DGGR lipase and specific canine pancreatic lipase (Spec cPL) assays. Dogs with histologically confirmed acute pancreatitis (n=3), chronic pancreatitis (n=8) and normal pancreatic tissue (n=7) with stored (−80°C) serum samples were identified. Relevant controls were selected. Precision, reproducibility and linearity of DGGR lipase, and the effect of sample haemolysis and freezing, were assessed. Sensitivity and specificity of DGGR lipase and Spec cPL were determined. Agreement between these two parameters was calculated using Cohen’s kappa coefficient (κ). The DGGR lipase assay demonstrated excellent precision, reproducibility and linearity. Sample haemolysis and storage at −80°C for 12 months did not influence the assay. DGGR lipase (>245IU/l) and Spec cPL (>400µg/l) both showed poor sensitivity but excellent specificity for acute pancreatitis, and poor to moderate sensitivity but excellent specificity for chronic pancreatitis. Substantial agreement (κ=0.679) was found between DGGR lipase and Spec cPL. The validated DGGR lipase assay had similar sensitivity and specificity for the diagnosis of acute and chronic pancreatitis to Spec cPL. DGGR lipase is a reliable alternative to Spec cPL for the diagnosis of pancreatitis.

scholarly journals Positive predictive value of acute and chronic pancreatitis diagnoses in the Danish National Patient Registry: A validation study

2018 ◽  
Vol 48 (1) ◽  
pp. 14-19 ◽  
Author(s):  
Jakob Kirkegård ◽  
Marie R. Mortensen ◽  
Ida R. Johannsen ◽  
Frank V. Mortensen ◽  
Deirdre Cronin-Fenton
Keyword(s):  
Acute Pancreatitis ◽  
Chronic Pancreatitis ◽  
Positive Predictive Value ◽  
Predictive Value ◽  
Medical Records ◽  
Patient Registry ◽  
National Patient Registry ◽  
Danish National Patient Registry ◽  
National Patient ◽  
Acute And Chronic Pancreatitis

Aims: To examine the validity of the diagnoses of acute and chronic pancreatitis registered in the Danish National Patient Registry. Methods: We identified all patients in the Danish National Patient Registry admitted to two Danish hospitals with acute or chronic pancreatitis from 1996 to 2013. From this population, we randomly sampled 100 patients with acute pancreatitis and 100 patients with chronic pancreatitis. For each cohort, we computed the positive predictive values and associated 95% confidence intervals (CIs) for the discharge diagnosis of acute or chronic pancreatitis using medical records as the gold standard. Results: We identified 2617 patients with acute pancreatitis and 1284 patients with chronic pancreatitis discharged from either of the two hospitals during the study period. Of these, 776 (19.9%) had a diagnosis of both acute and chronic pancreatitis and are thus present in both cohorts. From the 200 sampled patients, a total of 138 (69.0%) medical records were available for review. The positive predictive value for a diagnosis of acute pancreatitis in the Danish National Patient Registry was 97.3% (95% CI 90.5–99.2%) and for chronic pancreatitis 83.1% (95% CI 72.2–90.3%). Conclusions: The validity of diagnoses of acute and chronic pancreatitis registered in the Danish National Patient Registry since 1996 is generally high.

Determination of Plasma Glycoprotein 2 Levels in Patients With Pancreatic Disease

2004 ◽  
Vol 128 (6) ◽  
pp. 668-674 ◽  
Author(s):  
Ying Hao ◽  
Jing Wang ◽  
Ningguo Feng ◽  
Anson W. Lowe
Keyword(s):  
Pancreatic Cancer ◽  
Acute Pancreatitis ◽  
Chronic Pancreatitis ◽  
Tertiary Care ◽  
Pancreatic Disease ◽  
Pancreatic Acinar Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Assay Sensitivity ◽  
Acute And Chronic Pancreatitis

Abstract Context.—Blood tests possessing higher diagnostic accuracy are needed for all the major pancreatic diseases. Glycoprotein 2 (GP2) is a protein that is specifically expressed by the pancreatic acinar cell and that has previously shown promise as a diagnostic marker in animal models of acute pancreatitis. Objective.—This study describes the development of an assay for GP2, followed by the determination of plasma GP2 levels in patients with acute pancreatitis, chronic pancreatitis, and pancreatic cancer. Design.—Rabbit polyclonal antisera and mouse monoclonal antibodies were generated against human GP2 and used to develop an enzyme-linked immunosorbent assay. The assay was tested in patients with an admitting diagnosis of pancreatic disease at 2 tertiary care facilities. The diagnosis of acute or chronic pancreatitis and pancreatic cancer was determined using previously established criteria that incorporated symptoms, radiology, pathology, and serology. Plasma GP2 levels were determined in 31 patients with acute pancreatitis, 16 patients with chronic pancreatitis, 36 patients with pancreatic cancer, and 143 control subjects without pancreatic disease. Amylase and lipase levels were also determined in patients with acute pancreatitis. Results.—The GP2 assay's sensitivity values were 0.94 for acute pancreatitis, 0.81 for chronic pancreatitis, and 0.58 for pancreatic cancer, which were greater than the 0.71 for acute pancreatitis and 0.43 for chronic pancreatitis (P = .02) observed for amylase. The lipase assay sensitivity for acute pancreatitis was 0.66. The accuracy of the GP2 assay was greater than that of the amylase or lipase assays for acute pancreatitis (GP2 vs lipase, P = .004; GP2 vs amylase, P = .003) when analyzed using receiver operator characteristic curves. When daily serial blood samples were obtained for 13 patients with acute pancreatitis, GP2 levels remained abnormally elevated for at least 1 day longer than the amylase or lipase levels. Conclusion.—The GP2 assay is a useful new marker for acute and chronic pancreatitis.

Trimethylamine N-oxide promotes hyperlipidemia acute pancreatitis via inflammatory response

2021 ◽  
pp. 1-7
Author(s):  
Guodong Yang ◽  
Xiaoying Zhang
Keyword(s):  
Acute Pancreatitis ◽  
Inflammatory Response ◽  
Tissue Injury ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pancreatic Injury ◽  
Pancreatic Tissue ◽  
Lipoprotein Cholesterol ◽  
Model Group ◽  
New Ideas

Trimethylamine N-oxide (TMAO), a metabolite of gut microbiota, is involved in the regulation of lipid metabolism and inflammatory response; however, the role of TMAO in hyperlipidemia acute pancreatitis (HAP) is not clear. In this study, HAP mice were used as an animal model to explore the effects and possible mechanism of TMAO on HAP, which may provide new ideas for the treatment of HAP. Results found that the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, nonestesterified fatty acid, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, α-amylase, TMAO, and flavin-containing monooxygenase 3 were significantly increased, the levels of high-density lipoprotein cholesterol and insulin were significantly decreased, and there was an obvious pancreatic injury and inflammatory response in the model group. The choline analogue 3,3-dimethyl-1-butanol (DMB) treatment reversed the changes of serum biochemical parameters, alleviated the pancreatic tissue injury, and reduced the levels of inflammatory cytokines. Further studies of toll-like receptor (TLR)/p-glycoprotein 65 (p65) pathway found that the expressions of TLR2, TLR4, and p-p65/p65 in the model group were significantly increased, which was more obvious after Escherichia coli (Migula) Castellani & Chalmers treatment, while activation of the TLR/p65 pathway was inhibited by DMB. The results indicated that TMAO promotes HAP by promoting inflammatory response through TLR/p65 signaling pathway, suggesting that TMAO may be a potential target of HAP.

scholarly journals Isoliquiritigenin Ameliorates Acute Pancreatitis in Mice via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Xinnong Liu ◽  
Qingtian Zhu ◽  
Min Zhang ◽  
Tao Yin ◽  
Rong Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Tissue Injury ◽  
Pancreatic Tissue ◽  
Zinc Protoporphyrin ◽  
Dependent Manner ◽  
Protective Effects ◽  
Stress Injury ◽  
Oxidative Stress Injury ◽  
Flavonoid Monomer

Oxidative stress plays a crucial role in the pathogenesis of acute pancreatitis (AP). Isoliquiritigenin (ISL) is a flavonoid monomer with confirmed antioxidant activity. However, the specific effects of ISL on AP have not been determined. In this study, we aimed to investigate the protective effect of ISL on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, dynamic changes in oxidative stress injury of the pancreatic tissue were observed after AP onset. We found that ISL administration reduced serum amylase and lipase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Meanwhile, ISL decreased the oxidative stress injury and increased the protein expression of the Nrf2/HO-1 pathway. In addition, after administering a Nrf2 inhibitor (ML385) or HO-1 inhibitor (zinc protoporphyrin) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of ISL on AP in mice. Furthermore, we found that ISL mitigated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by L-arginine. Taken together, our data for the first time confirmed the protective effects of ISL on AP in mice via inhibition of oxidative stress and modulation of the Nrf2/HO-1 pathway.

Mechanisms of polyamine catabolism-induced acute pancreatitis

2007 ◽  
Vol 35 (2) ◽  
pp. 326-330 ◽  
Author(s):  
M.T. Hyvönen ◽  
M. Merentie ◽  
A. Uimari ◽  
T.A. Keinänen ◽  
J. Jänne ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Cathepsin B ◽  
Tissue Injury ◽  
Necrotizing Pancreatitis ◽  
Acinar Cells ◽  
Pancreatic Tissue ◽  
Early Event ◽  
Zymogen Activation ◽  
Polyamine Catabolism ◽  
Trypsinogen Activation

Acute pancreatitis is an autodigestive disease, in which the pancreatic tissue is damaged by the digestive enzymes produced by the acinar cells. Among the tissues in the mammalian body, pancreas has the highest concentration of the natural polyamine, spermidine. We have found that pancreas is very sensitive to acute decreases in the concentrations of the higher polyamines, spermidine and spermine. Activation of polyamine catabolism in transgenic rats overexpressing SSAT (spermidine/spermine-N1-acetyltransferase) in the pancreas leads to rapid depletion of these polyamines and to acute necrotizing pancreatitis. Replacement of the natural polyamines with methylated polyamine analogues before the induction of acute pancreatitis prevents the development of the disease. As premature trypsinogen activation is a common, early event leading to tissue injury in acute pancreatitis in human and in experimental animal models, we studied its role in polyamine catabolism-induced pancreatitis. Cathepsin B, a lysosomal hydrolase mediating trypsinogen activation, was activated just 2 h after induction of SSAT. Pre-treatment of the rats with bismethylspermine prevented pancreatic cathepsin B activation. Analysis of tissue ultrastructure by transmission electron microscopy revealed early dilatation of rough endoplasmic reticulum, probable disturbance of zymogen packaging, appearance of autophagosomes and later disruption of intracellular membranes and organelles. Based on these results, we suggest that rapid eradication of polyamines from cellular structures leads to premature zymogen activation and autodigestion of acinar cells.

scholarly journals The Use of Neoprene in Experimental Pancreatitis

2019 ◽  
Vol 70 (2) ◽  
pp. 676-678
Author(s):  
Alexandru Grigorovici ◽  
cristian Velicescu ◽  
Delia Hinganu ◽  
Alina Calin ◽  
Marius Valeriu Hinganu ◽  
...  
Keyword(s):  
Experimental Study ◽  
Acute Pancreatitis ◽  
Chronic Pancreatitis ◽  
Pancreatic Duct ◽  
Genetically Modified ◽  
Pancreatic Tissue ◽  
Experimental Pancreatitis ◽  
Pancreatic Ducts ◽  
Genetically Modified Animals

The concept of chronic pancreatitis has been stated in our country much later than acute pancreatitis. This manuscript proposes a synthesis of the etiopathogenic, diagnostic and therapeutic data in chronic pancreatitis based on actual information correlated with the results of our experimental study. The experiment was conducted on 18 animals, in which was performed the intraduodenal ligation of the pancreatic duct apertures and the obstruction of the pancreatic ducts with intraparenchymatous, intraoperative neoprene injections. We investigated the lesions by using intraoperative pancreatic tissue collected after injections. The results encourage us to continue the research and to choose genetically modified animals because are closer to the human one.

Acute and Chronic Pancreatitis

2020 ◽  
Author(s):  
Thomas J. Howard
Keyword(s):  
Acute Pancreatitis ◽  
Chronic Pancreatitis ◽  
Physical Examination ◽  
Clinical Evaluation ◽  
Gallbladder Disease ◽  
Scoring Systems ◽  
Whipple Procedure ◽  
General Surgeon ◽  
Enhanced Computed Tomography ◽  
Acute And Chronic Pancreatitis

Clinical evaluation and surgical decision making in patients with acute pancreatitis (AP) and chronic pancreatitis (CP) are two of the most complex conditions that a general surgeon faces. Each entity has unique laboratory and radiographic investigations, operations, and postoperative care. The clinical evaluation, history, and physical examination of AP is described. The clinical features necessary for diagnosis are listed, and contrast-enhanced computed tomography is described as the gold standard for diagnosis. This review uses definitions and terminology developed at the Atlanta symposium in 1992. The severity of an episode of AP is described in terms of established scoring systems (APACHE II [Acute Physiology and Chronic Health Evaluation II], Glasgow Coma Scale score, Ranson criteria). AP can range from mild to severe necrotizing, with each described. The clinical course is described in detail. For CP, the history, physical examination, and diagnosis via investigative and imaging studies are described. The anatomic and morphologic subtypes of chronic pancreatitis are listed and the operations directed at patients with CP are detailed, and can involve drainage or combined resection and drainage.  This review contains 12 figures, 14 tables, and 48 references. Keywords: Acute pancreatitis, chronic pancreatitis, gallbladder disease, alcoholism, amylase, Whipple procedure

PANCREATOGENIC MORPHOSTRUCTURAL CHANGES IN THE HEART, LUNGS AND OTHER TARGET ORGANS IN DESTRUCTIVE PANCREATITIS

2021 ◽  
Vol 5 (1) ◽  
pp. 1217-1222
Author(s):  
P. Koshevsky ◽  
◽  
S. Alekseyev ◽  
O. Popkov ◽  
V. Ginyuk ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Retrospective Analysis ◽  
Kidney Tissue ◽  
Pancreatic Tissue ◽  
Leukocyte Infiltration ◽  
Target Organs ◽  
Pancreas Necrosis ◽  
Acute And Chronic Pancreatitis ◽  
Inflammatory Changes ◽  
Cardiopulmonary System

Introduction. Pathomorphological changes in destructive pancreatitis develop both in the pancreas and in various organs and tissues, it determining the clinical course and outcome of the disease. Most often in destructive pancreatitis, the cardiopulmonary system is affected, as well as the liver, kidneys, and brain. Damage to these target organs is one of the main elements of pathogenesis and thanatogenesis in destructive pancreatitis and is of interest not only for surgeons, but also for other clinical specialists, including cardiologists. Aim. To conduct a retrospective analysis of the most common morphostructural changes in the cardiopulmonary system and other target organs based on the results of autopsy reports of the deceased from destructive forms of acute and chronic pancreatitis and to identify the most characteristic morphostructural changes in the target organs. Materials and methods. A retrospective analysis of the findings of histological examination of target organs of 203 patients who died from acute pancreatitis (K.85) and chronic pancreatitis with an outcome of pancreonecrosis (K. 86) in the in-patient surgical departments and intensive care and resuscitation units of Minsk over the period of 2015-2019 was performed. Results. In the course of study, we investigated the nature and structure of morphostructural changes in the pancreas and target organs (heart, lungs, liver, kidneys, spleen, and stomach) in destructive pancreatitis. Conclusions. In destructive pancreatitis, deep dystrophic, necrotic, circulatory and inflammatory changes are observed not only in the pancreatic tissue, but also in the target organs, which are primarily the heart, lungs, liver, kidneys and brain. In the myocardium, edema, circulatory and dystrophic changes are detected, in the lungs - edema, circulatory changes and alveocyte damage. In the pancreas, necrosis, leukocyte infiltration and hemorrhages are noted, i.e. both necrotic and inflammatory changes are observed at the same time. In the liver, the most typical changes are leukocyte infiltration of the portal tracts, fatty dystrophy of hepatocytes, vascular fullness and dilation of capillaries, central veins and sinusoids. The kidney tissue is dominated by circulatory changes, necrosis and dystrophy of the epithelium of the convoluted tubules, which are the morphological substrate of acute renal failure. Edema, circulatory and dystrophic changes are detected in the brain.

scholarly journals Mesenchymal Stromal Cell Therapy for Pancreatitis: A Systematic Review

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Sara M. Ahmed ◽  
Mahmoud Morsi ◽  
Nehal I. Ghoneim ◽  
Mohamed M. Abdel-Daim ◽  
Nagwa El-Badri
Keyword(s):  
Clinical Trials ◽  
Acute Pancreatitis ◽  
Chronic Pancreatitis ◽  
Cell Therapy ◽  
Animal Studies ◽  
Meta Analysis ◽  
Cell Types ◽  
Inclusion Criteria ◽  
Acute And Chronic Pancreatitis ◽  
Substantial Heterogeneity

Background. Based on animal studies, adult mesenchymal stromal cells (MSCs) are promising for the treatment of pancreatitis. However, the best type of this form of cell therapy and its mechanism of action remain unclear. Methods. We searched the PubMed, Web of Science, Scopus, Google Scholar, and Clinical Trials.gov websites for studies using MSCs as a therapy for both acute and chronic pancreatitis published until September 2017. Results. We identified 276 publications; of these publications, 18 met our inclusion criteria. In animal studies, stem cell therapy was applied more frequently for acute pancreatitis than for chronic pancreatitis. No clinical trials were identified. MSC therapy ameliorated pancreatic inflammation in acute pancreatitis and pancreatic fibrosis in chronic pancreatitis. Bone marrow and umbilical cord MSCs were the most frequently administered cell types. Due to the substantial heterogeneity among the studies regarding the type, source, and dose of MSCs used, conducting a meta-analysis was not feasible to determine the best type of MSCs. Conclusion. The available data were insufficient for determining the best type of MSCs for the treatment of acute or chronic pancreatitis; therefore, clinical trials investigating the use of MSCs as therapy for pancreatitis are not warranted.

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