TY - JOUR. T1 - Induction of apoptosis reduces the severity of caerulein-induced pancreatitis in mice. AU - Saluja, Ashok. AU - Hofbauer, Bernd. AU - Yamaguchi, Yoshikazu. AU - Yamanaka, Kenji. AU - Steer, Michael. PY - 1996/3/27. Y1 - 1996/3/27. N2 - The recent observation that the severity of pancreatitis is inversely related to the extent of apoptosis in five experimental models of the disease has suggested the possibility that apoptosis might protect against pancreatic injury in pancreatitis. This hypothesis was tested by inducing pancreatitis in mice during a phase of extensive apoptosis. Mice were fed a raw soya diet for five weeks to stimulate pancreatic growth and then switched to a regular chow diet for 27 hrs to permit involution of the hypertrophied gland. That involution is characterized by extensive apoptosis of acinar cells. Pancreatitis was induced, in either control mice or mice undergoing pancreatic involution, by repeated intraperitoneal administration of a supramaximally ...
TY - JOUR. T1 - Effect of cerulein hyperstimulation on the paracellular barrier of rat exocrine pancreas. AU - Fallon, Michael B.. AU - Gorelick, Fred S.. AU - Anderson, James M.. AU - Mennone, Albert. AU - Saluja, Ashok. AU - Steer, Michael L.. PY - 1995/6. Y1 - 1995/6. N2 - Background/Aims: Cerulein-induced pancreatitis causes a rapid increase in pancreatic enzyme levels in serum and decreases in pancreatic duct secretion and interstitial edema. One mechanism to explain these early events is disruption of the actin tight junction paracellular seal of acinar and intralobular pancreatic duct cells. Methods: To examine the paracellular barrier of the proximal exocrine pancreas, rats were hyperstimulated with 5.0 μg · kg-1 · h-1 of cerulein. Actin was visualized with rhodamine phalloidin and by electron microscopy and tight junctions were visualized with antibodies to the tight-junction protein ZO-1. Paracellular permeability was measured by movement of horseradish peroxidase from interstitium ...
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Injury to pancreatic acinar cells is thought to be the initiating point for the progression of acute pancreatitis, and, therefore, they represent an ideal experimental system to study the mechanisms of experimental acute pancreatitis (Bhatia et al., 2005). In experimental acute pancreatitis models, SP has been shown to be up-regulated and plays a proinflammatory role (Lau and Bhatia, 2006). The use of PPT-A gene knockout models and pharmacological antagonism of NK1R reduced the severity of AP and its associated lung injury, showing the importance of SP-NK1R interaction in AP (Bhatia et al., 1998; Lau et al., 2005). SP and NK1R are expressed in the pancreatic acinar cells, and this expression could contribute to the overall outcome of caerulein-induced AP.. Our results showed that treatment of pancreatic acinar cells with caerulein up-regulated gene expression of PPT-A and NK1R and also peptide levels of SP. At a physiological concentration of caerulein (10−10 M), the expression of PPT-A, NK1R, ...
The protective role of hemeoxygenase-1 (HO-1) in various inflammatory conditions is mediated in part by its products, carbon monoxide (CO) and biliverdin. Here we investigated a therapeutic role for CO and CO-primed cells in acute pancreatitis (AP). In a mouse model of AP, treatment with CO-releasing molecule-2 (CORM-2) decreased mortality, pancreatic damage, and lung injury. CORM-2 decreased systemic inflammatory cytokines, suppressed systemic and pancreatic macrophage TNF-α secretion, and inhibited macrophage TLR4 receptor complex expression. In both human and mouse cells, CORM-2 inhibited endogenous and exogenous ligand-dependent TLR4 activation, which indicates that CORM-2 could be therapeutic for both early and late stages of AP, which involve sterile- and endotoxin-mediated inflammation, respectively. Mice engrafted with TLR4-deficient hematopoietic cells were protected against caerulein-induced AP. In the absence of leukocyte TLR4 expression, CORM-2 did not confer additional protection, ...
Abstract: Melatonin, an antioxidant, protects the pancreas against acute inflammation but, although this indole is released mainly at night, no study has been undertaken to determine circadian changes of plasma melatonin levels and the severity of acute pancreatitis. The aims of this study were: (a) to compare the severity of caerulein-induced pancreatitis (CIP) produced in the rat during the day and at the night, and (b) to assess the changes of plasma melatonin level and the activity of an antioxidative enzyme; superoxide dismutase (SOD), in the pancreas subjected to CIP during the day time and at night without or with administration of exogenous melatonin or its precursor; l-tryptophan. Rats were kept in 12 hr light/dark cycle. CIP was induced by subcutaneous infusion of caerulein (5 μg/kg/hr for 5 hr). Melatonin (5 or 25 mg/kg) or l-tryptophan (50 or 250 mg/kg) was given intraperitoneally 30 min prior to the start of CIP. CIP induced during the day time was confirmed by histological ...
Background and Aims: Acute pancreatitis is an inflammatory disease involving acinar cell injury, and the rapid production and release of inflammatory cytokines, which play a dominant role in local pancreatic inflammation and systemic complications. Toll-like receptor 4 (TLR4) initiates a complex signalling pathway when it interacts with lipopolysaccharide (LPS), which ultimately results in a proinflammatory response. We hypothesised that TLR4 is important in the pathophysiology of acute pancreatitis, independently of LPS. Using two different models of acute pancreatitis, we investigated how genetic deletion of TLR4 or its co-receptor CD14 effects its progression and severity.. Methods: We induced acute pancreatitis by administering either caerulein or l-arginine to wild-type, TLR4−/−, and CD14−/− mice. Control mice received normal saline injections. The severity of acute pancreatitis was determined by measuring serum amylase activity, quantifying myeloperoxidase (MPO) activity in the ...
Caerulein caused a marked decrease in levels of guanosine 3,5-cyclic monophosphate (cGMP) in the cerebellum in rats. This effect was observed to be dose-dependent after the intraperitoneal administration of caerulein for doses over 20 micrograms/kg and lasted for about 4 hr in doses of 100 micrograms/kg. However, in vagotomized rats, caerulein failed to alter the level of cGMP in the cerebellum. Caerulein suppressed harmaline-induced increases in cGMP in the cerebellum for more than 30 hr. In contrast, the increases in levels of cGMP in the cerebellum, induced by treatment with methamphetamine, apomorphine and picrotoxin, were not inhibited by pretreatment with caerulein. These results suggest that the peripheral administration of caerulein can inhibit the activity of climbing fibers for a long period of time in the cerebellum of the rat through the stimulation of the abdominal vagus nerves.
Effect of endothelin-1 receptor antagonists on histological and ultrastructural changes in the pancreas and trypsinogen activation in the early course of caerulein-induced acute pancreatitis in rats
Context Oxidative stress is understood to have a critical role in the development of acinar injury in experimental acute pancreatitis. We have previ..
Cytosolic free calcium concentrations ([Ca2+]i) and amylase secretion were measured in isolated rat pancreatic acini loaded with the intracellularly trapped fluorescent indicator quin2. Both caerulein and carbamoylcholine caused a rapid increase in [Ca2+]i, with a maximal 3-fold increase at 10(-9) M-caerulein and 10(-4) M-carbamoylcholine. However, caerulein (10(-12) M and 10(-11) M) as well as carbamoylcholine (10(-7) M) caused a significant stimulation of amylase release, while not inducing any detectable rise in [Ca2+]i. Changes in [Ca2+]i after addition of either secretagogue were transient and did not last more than 2-3 min. By contrast, when amylase secretion was monitored as a function of time, two distinct secretory phases could be observed upon addition of either carbamoylcholine (10(-5) M) or caerulein (10(-10) M). An initial, rapid phase (0-5 min) which caused a 6-7-fold increase above basal, followed by a sustained (5-30 min), but less marked, secretory rate (2-3-fold above basal). ...
Using immunohistochemistry, Northern blotting and a semi-quantitative PCR technique, epidermal growth factor (EGF), transforming growth factor-α (TGF-α) and epidermal growth factor receptor (EGFR) expression were studied in the pancreas of N-nitrosobis(2-oxopropyl)-amine (BOP)-treated hamsters. After initiation pancreatic carcinogenesis was modulated by a high fat diet or by injections with the cholecystokinin analogue caerulein. Autopsies were performed 6 and 12 months after the last injection with BOP. Immunohistochemistry revealed a weak expression of TGF-α innormal acinar cells and a stronger expression in ductular and centro-acinar cells. Over-expression of TGFα was observed in advanced putative preneoplastic lesions (classified as borderline lesions) and in ductular adenocarcinomas. EGFR immunoreactivity was present only in ductular adenocarcinomas. EGF peptide expression was observed both in acinar and ductular normal and tumorous cells and the level of expression did not change ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Gitta M Seleznik, Theresia Reding, Lukas Peter, Anurag Gupta, Sabrina G Steiner, Sabrina Sonda, Caroline S Verbeke, Emmanuel Dejardin, Igor Khatkov, Stephan Segerer, Mathias Heikenwalder, Rolf Graf ...
Abstract:. Pancreatitis is an inflammatory disease that starts in pancreatic acinar cells and results in significant morbidity and mortality. Currently there is no therapy for pancreatitis because of lack of complete understanding of the disease mechanism. Premature trypsinogen activation is considered to be the key event in the disease development. However recent research in the field has pointed out that besides trypsinogen activation there are many other important factors that play important role in the disease. Our recent study in Trypsinogen-7 knock out (T7-/-) mice has supported this and for the first time shown that intra-acinar trypsinogen activation contributes only partially to acinar injury and local and systemic inflammation progress independently of trypsin activation during pancreatitis. NF-κB activation that happens parallel and independent to trypsinogen activation can still drive the development of the acute or chronic pancreatitis even in absence of trypsin.. 1. ...
Background Peroxisome proliferator-activated receptors (PPARs) are ligand activated transcription factors belonging to the nuclear receptor superfamily. PPARs activation has a profound impact on the local immune response with consequences affecting the progression of chronic inflammatory diseases. Relatively little is known on the role of PPAR-β/δ in the regulation of inflammatory responses. The aim of the present study was to evaluate the influence of PPAR-β/δ receptor in a model of edematous pancreatitis induced in mice by administration of cerulein at supramaximal doses, as well as in necrohemorrhagic model induced by intraductal administration of sodium taurocholate (STC). Measurements Mice were treated with cerulein (50 μg/kg) or STC (5%). GW0742 (0.3 mg/kg) was intraperitoneally administered 1 and 6 hours after cerulein injection or was injected 2 hours before STC infusion. The pancreas and exopancreatic organs were carefully removed for microscopic examination. Pancreatic weight, ...
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Caerulein-induced acute pancreatitis accelerates the progression of pancreatic intraepithelial neoplasia (PanIN) lesions in a pancreas-specific KrasG12D mouse model. The purpose of this study was to explore whether serum microRNAs (miRNAs) can serve as sensitive biomarkers to detect occult PanIN in the setting of acute pancreatitis. Serum miRNA profiles were quantified by an array-based method and normalized by both Variance Stabilization Normalization (VSN) and invariant methods. Individual miRNAs were validated by TaqMan real-time PCR with synthetic spike-in C. elegans miRNAs as external controls. Serum miRNA profiles distinguished KrasG12D mice with pancreatitis from wild-type mice without pancreatitis, but failed to differentiate KrasG12D mice with pancreatitis from wild-type mice with pancreatitis. Most individual miRNAs that increased in KrasG12D mice with pancreatitis were not significantly different between KrasG12D mice without pancreatitis and wild-type mice without pancreatitis. ...
Acute pancreatitis is a common clinical inflammatory disease with variable severity from mild, self-limiting attacks to a severe lethal attack with a high mortality. In most of the cases, acute pancreatitis is either caused by gallstone obstruction or excessive alcohol consumption. Clinical symptoms include elevated levels (minimum 3 times than normal) of pancreatic enzymes such as amylase or lipase in serum. It is generally believed that earliest event in acute pancreatitis occur in acinar cells which includes premature protease activation and cytoplasmic vacuole formation. Premature trypsinogen activation has been considered as chief culprit as it can activate other proteases in a cascade like manner in acinar cells. Trypsin activity takes place in a biphasic curve with elevated levels at 1 h and 8 h in the initial stages up to 24 h in caerulein induced pancreatitis in mice. It has been shown that cytoplasmic vacuoles observed in pancreatitis are of autophagic nature. The role of autophagy for ...
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Sreelatha S, Vedavathy Nayak*, Gayathri C , Renuka Ramaiah. ABSTRACT. Objective: The purpose of this study was to assess whether hyoscine butyl bromide is effective in improving cervical effacement and dilatation, thus reducing the duration of first stage of labour without causing any maternal and neonatal complications. Materials and Methods: It was a prospective, comparative, observational study. 80 women with term pregnancies in active labour were recruited for the study. They were allocated into 2 groups, study and control group each with 40 patients. The duration of active labour was taken from 3 cm dilatation to full dilatation of the cervix. The study group received 40 mg HBB as slow I V injection (over 1 - 2 min) given at hourly intervals up to a maximum of 3 doses starting at 3 cm dilatation. Results: The mean duration of active phase of labour was 109.28 ± 58. 42 minutes in the study group and 317.48 ± 108.9 in the control group. The difference between the 2 groups was statistically ...
n. the most common congenital disease; the childs lungs and intestines and pancreas become clogged with thick mucus; caused by defect in a single gene; no cure is ...
Exposure of peripheral blood mononuclear cells to unsaturated fatty acids at concentrations lower than those in the serum during SAP, results in their necro-apoptotic cell death (71). In Vivo Models of Obesity Associated Severe Acute Pancreatitis. Role of Intra Pancreatic Fat (IPF) in Pancreatic Necrosis. Histologically, several studies show pancreatic acinar necrosis to border fat necrosis (48, 62, 65, 75, 86). Those studies analyzing intrapancreatic fat in human autopsy samples (4, 48, 62, 68, 85, 86), surgically resected samples (82) and radiological appearance of pancreas (58, 85) show intrapancreatic fat to be increased with BMI. Intrapancreatic fat amounts in obese individuals are on an average, two fold higher than non-obese individuals (85). Analysis of pancreatic adipocyte triglyceride composition in humans showed increasing amounts of unsaturated triglycerides with higher amounts of fat. (79) Pancreatic necrosis fluid collected from obese patients with necrotizing pancreatitis had ...
References. 1. Day HL, Taylor RM. The liver. Part 5: acute liver failure. Nurs Times 2006; 102: 26-27. [ Links ] 2. Kawasaki T, Ishihara K, Ago Y, Nakamura S, Itoh S, Baba A, et al. Protective effect of the radical scavenger edaravone against methamphetamine-induced dopaminergic neurotoxicity in mouse striatum. Eur J Pharmacol 2006; 542: 92-99, doi: 10.1016/j.ejphar.2006.05.012. [ Links ] 3. Yang T, Mao YF, Liu SQ, Hou J, Cai ZY, Hu JY, et al. Protective effects of the free radical scavenger edaravone on acute pancreatitis-associated lung injury. Eur J Pharmacol 2010; 630: 152-157, doi: 10.1016/j.ejphar.2009.12.025. [ Links ] 4. Okatani Y, Wakatsuki A, Enzan H, Miyahara Y. Edaravone protects against ischemia/reperfusion-induced oxidative damage to mitochondria in rat liver. Eur J Pharmacol 2003; 465: 163-170, doi: 10.1016/S0014-2999(03)01463-8. [ Links ] 5. Ito K, Ozasa H, Noda Y, Arii S, Horikawa S. Effects of free radical scavenger on acute liver injury induced by d-galactosamine and ...
In Diabetic ketoacidosis when pain abdomen is one of the major clinical finding, serum amylase levels are obtained, to rule out the diagnosis of acute pancreatitis (since the latter too can present with acute pain abdomen). If the serum amylase levels are found high in patients with Diabetic ketoacidosis, it may not be due…
Endocytic vacuoles can be up to 10 μm in diameter and appear specifically in pathological conditions as a result of aberrant retrieval of structures formed by compound endocytosis [7]. The co-localization hypothesis of trypsinogen activation suggests intracellular/intra-organellar activation of trypsinogen and the formation of active (and potentially damaging) trypsin as a result of fusion of trypsinogen containing organelles with organelles containing lysosomal proteases (reviewed in [31]). In our previous study, we have indeed detected trypsin activity in the endocytic vacuoles and observed that some of the vacuoles have lysosomal markers [7]. In the present study, we specifically addressed the question about the role of SOCE in the formation of these vacuoles. The results of our experiments revealed that the SOCE-mediated Ca2+ plateaus produced by CCK or TLC-S (two commonly used inducers of experimental pancreatitis) are effectively suppressed by the Orai1 inhibitor GSK-7975A and that this ...
Inhibition of Jak/STAT Signaling Reduces the Activation of Pancreatic Stellate Cells In Vitro and Limits Cerulein-Induced Chronic Pancreatitis In Vivo Investigators utilized primary and immortalized pancreatic stellate cells obtained from mice and patients with chronic pancreatitis (CP) or pancreatic cancer to examine the effect of Jak/STAT and MAPK pathway inhibition in vitro. The well-characterized cerulein model of CP was used to assess the therapeutic efficacy of Jak1/2 inhibition in vivo. [Sci Rep] Full Article The Neuronal K+Cl− Co-Transporter 2 (Slc12a5) Modulates Insulin Secretion Using molecular cloning, RT-PCR, Western blotting, immunolocalization and in vitro functional assays, researchers established that the "neuron-specific" K+Cl− co-transporter 2 (Slc12a5) is expressed in several endocrine cells of the pancreatic islet, including glucagon secreting α-cells, but particularly in insulin-secreting β-cells, where they provide evidence for its role in the insulin secretory ...
ABSTRACT The pancreatic islets are more richly vascularized than the exocrine pancreas, and possess a 5‐ to 10‐fold higher basal and stimulated blood flow, which is separately regulated
... is a sudden inflammation of the pancreas. The most common symptoms and signs include severe, dull epigastric pain, nausea, vomiting, diarrhea, anorexia and fever. Alcohol consumption and biliary stone disease cause most cases of acute pancreatitis.… Acute Pancreatitis: Read more about Symptoms, Diagnosis, Treatment, Complications, Causes and Prognosis.
Taking as the starting point a recently suggested reaction scheme for zymogen activation involving intra- and intermolecular routes and the enzyme-zymogen complex, we carry out a complete analysis of the relative contribution of both routes in the process. This analysis suggests the definition of new dimensionless parameters allowing the elaboration, from the values of the rate constants and initial conditions, of the time course of the contribution of the two routes. The procedure mentioned above related to a concrete reaction scheme is extrapolated to any other model of autocatalytic zymogen activation involving intra- and intermolecular routes. Finally, we discuss the contribution of both of the activating routes in pepsinogen activation into pepsin using the values of the kinetic parameters given in the literature ...
Market Scenario: Acute pancreatitis is an inflammatory state of the pancreas that is excruciatingly pain full and now and at times fatal. Regardless of the technological advances in critical care drugs in the course of recent years, the death rate of acute pancreatitis has stayed at around 10%. Diagnosis of pancreatic issues is regularly difficult…
The presented recommendations concern the current management of acute pancreatitis. The recommendations relate to the diagnostics and treatment of early and late phases of acute pancreatitis and complications of the disease taking into consideration surgical and endoscopic methods. All the...
Severe acute pancreatitis (SAP) is characterized by an unregulated systemic proinflammatory response secondary to activation of trypsin within the …
I also have this to come. I believe I will be having this same day as the DMSA. The GFR is a test to assess the capability of the kidney to clear the blood of a substance. A small amount of dye is injected into a vein and blood samples are taken at hourly intervals for three/four hours, to measure the renal clearance of the dye. Finally I have to see the Consultant Nephrologist again as he gives the final decision as to whether I am medically fit enough etc to donate a kidney.. All the information is given to an independant Assessor and I have a meeting with him. He needs to make sure I understand everything etc etc. He then makes a report and presents to the Human Tissue Board and seeks their permission for the donation to go ahead. The producing of the report and seeking permission can take up to a month in total.. It was explained to me that there was no guarantee that it would be keyhole surgery. The surgeon would make that decision once both kidneys had been evaluted etc. It is not ...
I also have this to come. I believe I will be having this same day as the DMSA. The GFR is a test to assess the capability of the kidney to clear the blood of a substance. A small amount of dye is injected into a vein and blood samples are taken at hourly intervals for three/four hours, to measure the renal clearance of the dye. Finally I have to see the Consultant Nephrologist again as he gives the final decision as to whether I am medically fit enough etc to donate a kidney.. All the information is given to an independant Assessor and I have a meeting with him. He needs to make sure I understand everything etc etc. He then makes a report and presents to the Human Tissue Board and seeks their permission for the donation to go ahead. The producing of the report and seeking permission can take up to a month in total.. It was explained to me that there was no guarantee that it would be keyhole surgery. The surgeon would make that decision once both kidneys had been evaluted etc. It is not ...
Pancreatitis begins as acute pancreatitis; if not treated, it can become a permanent condition called chronic pancreatitis. Pancreatitis is a serious condition that can lead to severe complications and even death if it goes untreated.
Acute Pancreatitis & Green Stools Symptom Checker: Possible causes include Cystic Fibrosis. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search.
Hey all, Over the weekend I wound up in the ER because of acute pancreatitis. This had never happened before but MAN was it painful.
Pancreatic infection occurs most often as a complication of acute pancreatitis. The unique aspects of pancreatic inflammation predispose to secondary bacterial infection, which occurs in...
How long can a dog live with pancreatitis? Dogs can live quite normally with pancreatitis with treatment at home and early pancreatitis symptom recognition.
Pancreatitis - Pipeline Review, H1 2017, provides in depth analysis on Pancreatitis targeted pipeline therapeutics. The report provides comprehensive infor
Pancreatitis Pipeline Review H1 2017 provides an overview of Pancreatitis (Gastrointestinal) pipeline landscape and Therapeutic Development
The pathologic processes that initiate and perpetuate acute pancreatitis remain unclear. A recognized feature of this disease is the accumulation of vacuoles in...
Acute Pancreatitis, Aetiology and Clinical features of Pancreatitis, Diagnosis of Pancreatitis, Treatment and Complications of Pancreatitis
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If your dog is vomiting or has other symptoms of pancreatitis you need to have her treated right away. Find out why early treatment is so important!
A diabetic patient rushed to the hospital for vomiting and abdomen pain, resulting in a diagnosis of acute severe emphysematous pancreatitis.
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2. Martinez J, Sanchez-Paya J, Palazon JM, Suazo-Barahona J, Robles-Diaz G, Perez-Mateo M. Is obesity a risk factor in acute pancreatitis? A meta-analysis. Pancreatology. 2004;4(1):42-48.. 3. Banks PA, Freeman ML, for the Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol. 2006;101(10):2379-2400.. 4. Papachristou GI, Papachristou DJ, Avula H, Slivka A, Whitcomb DC. Obesity increases the severity of acute pancreatitis: performance of APACHE-O score and correlation with the inflammatory response. Pancreatology. 2006;6(4):279-285.. 5. De Bernardinis M, Violi V, Roncoroni L, Boselli AS, Giunta A, Peracchia A. Discriminant power and information content of Ransons prognostic signs in acute pancreatitis: a meta-analytic study. Crit Care Med. 1999;27(10):2272-2283.. 6. Johnson CD, Abu-Hilal M. Persistent organ failure during the first week as a marker of fatal outcome in acute pancreatitis. Gut. 2004;53(9):1340-1344. ...