Acid-induced Acute Pancreatitis Research Articles

¿Pero esto qué es? ¿El ácido valproico es el culpable?

Acute pancreatitis in children can result from a wide variety of etiologies, one of them being drug toxicity. Although the list of medications associated with acute pancreatitis is extensive, the literature provides stronger evidence for drugs such as 6-mercaptopurine, azathioprine, angiotensin-converting enzyme (ACE) inhibitors, metronidazole, asparaginase, acetaminophen and valproic acid. Valproic acid is a drug frequently used in pediatrics. Although most side effects associated with its use are benign, it may also be linked to severe adverse reactions. The most commonly reported include hepatotoxicity, teratogenicity, and acute pancreatitis. Valproic acid-induced acute pancreatitis is thought to occur due to an idiosyncratic reaction, which is independent of drug levels in the blood and can happen at any time during treatment.

Valproic acid-induced acute pancreatitis: First case report in Morocco and literature review

Acute pancreatitis is an inflammation of the pancreas following self-destruction by its own enzymes responsible for local lesions and systemic response. In rarely cases, several drugs are described as having adverse effects causing acute pancreatitis outside of a context of drug intoxication. Classically, drug-induced acute pancreatitis tends to be edematous and has a relatively limited course over time. Several cases of pancreatitis due to sodium valproate are described in the literature. We describe a first clinical case in Morocco of an epileptic adolescent treated with sodium valproate who developed severe acute pancreatitis. Making a diagnosis of drug-induced acute pancreatitis is based to evaluate intrinsec and extrinsec imputability of this drug. The mortality of valproate acid-related pancreatitis is estimated at 15%. Neurologists, pediatricians and emergency physicians must be informed of this complication.

Valproic acid-induced acute pancreatitis.

Valproic acid-induced acute pancreatitis.

A case report of valproate-induced acute pancreatitis

Valproic acid is a branched chain aliphatic carboxylic acid which is widely used as antiepileptic drug. Valproic acid-induced acute pancreatitis is an uncommon cause of acute pancreatitis. Hereby we describe a 23-year-old unmarried female, who developed acute pancreatitis following the 12 th day of valproate monotherapy prescribed for seizure disorder. Valproate was immediately stopped and replaced with levetiracetam. She improved on conservative management.

Valproic acid-induced acute pancreatitis in pediatric age: case series and review of literature.

Valproic acid (VPA) is commonly prescribed medication for epilepsy, migraine and bipolar disorder. Although the common adverse effect associated with VPA are typically benign, less common adverse effect can occur; these include hepatotixicity, teratogenicity and acute pancreatitis (AP). VPA-induced pancreatitis does not depend on valproic acid serum level and may occur anytime after onset of therapy. Re-challenge with VPA is dangerous and should be avoided. The diagnosis of VPA-induced pancreatitis seems to be underestimated because of difficulties in determining the causative agent and the need for a retrospective re-evaluation of the causative factor. More of idiopathic pancreatitis should be a drug-induced pancreatitis. We report four cases of VPA-induced AP found in a group of 52 cases of AP in children come to our attention from January 2008 to December 2012. The aim of these reports is to point out our experience about clinical presentation, diagnosis, management, outcome in children with VPA-induced AP and review of literature.

Sa1793 Bile Acid-Induced Acute Pancreatitis in Mice Is Caused by Acinar Cell Leukotriene B4 Secretion Through a Calcium-Independent Pathway

Background: Understanding the mechanism of chronic pancreatitis (CP) is limited by the lack of mouse models that mimic progression of the disease. The current mouse model of CP involves causing 20 episodes of acute pancreatitis by administering cerulein (50μg/kg x7, hourly x twice weekly X 10 weeks) making it an expensive and time consuming model. Resulting chronic pancreatitis in this model tends to resolve. Here, we present a novel model for induction of CP based on an L-Arginine induced acute pancreatitis model previously developed by our group. Methods: Animals in the CP group underwent four L-arginine induced episodes of acute pancreatitis over a four week period. For each episode, animals were given two injections (one hour apart) of either saline or L-arginine (4.5 g/kg) followed by a saline injection 1 hour later. Animals were sacrificed at 7, 14 and 21 days after the last cycle of injections. The entire pancreas was dissected and weighed. Pancreatic tissue was processed for RNA, protein, histology and immunohistochemistry. Feces were collected and analyzed for fat content. Results: There was significant pancreatic atrophy on day 7 after completion of L-arginine induced episodes (70.5+12.6 mg in L-arginine injected vs. 243.8+2.9mg in saline injected animals, p <0.05). This atrophy persisted in animals sacrificed on day 14 and 21 after the last dose of L-arginine (88.0+25.3 mg at day 14 and 54.6+22.5 at day 21) in L-arginine treated animals. Histologically, in comparison to saline injected, Larginine treated animals showed destruction of acini, formation of tubular complexes, abnormal architecture, and fibro fatty replacement. In addition, Sirius red staining showed a significant increase in fibrosis in the L-arginine treated chronic pancreatitis group (day 7: 14.8+2.6%; day 14:15.9+3.9%; and day 21: 15.4+2.7%) compared to pancreas from control animals (1.4 + 0.1%).Furthermore, there was a significant increase in α-smooth muscle actin, desmin and, vimentin expression representing an increase in stellate cell activation and proliferation respectively. There was increase in inflammation as indicated by increase in expression of Cox-2 and nuclear localization of p65 in L-arginine treated animals as compared to control. We also observed an increase in fecal fat content in L-Arginine treated animals compared to control, although the animals were not on a high fat diet. Importantly, all the differences observed in the CP vs. normal groups persisted until at least three weeks after the last L-arginine injections. Conclusions: The L-arginine induced model of chronic pancreatitis is a relatively easy and inexpensive model which mimics all features of human chronic pancreatitis including pancreatic atrophy, fibrosis, inflammation, exocrine insufficiency and loss of architecture and the observed changes were stable.

Valproic Acid-Induced Pancreatitis in a 15-Year-Old Boy With Juvenile Myoclonic Epilepsy

Drug-induced acute pancreatitis is a rare condition in childhood, and information about the incidence of valproic acid-induced acute pancreatitis in the pediatric population is scarce. In this clinical case, we report a first documented pediatric case of valproic acid-induced pancreatitis in Estonia. A 15-year-old boy with juvenile myoclonic epilepsy developed acute pancreatitis after 2-month therapy with valproic acid. The symptoms of pancreatitis subsided within 1 week after the discontinuation of treatment with valproic acid. Acute pancreatitis should be suspected in any pediatric patient with gastrointestinal symptoms during valproate treatment.

Valproic Acid-Induced Acute Pancreatitis and Multiorgan Failure in a Child

Valproic acid (VPA) is still an important antiepileptic drug, with the broadest spectrum used in all types of seizures and syndromes. It has serious adverse effects such as hepatotoxicity, hyperammonemic encephalopathy, coagulation disorders, and pancreatitis. The incidence of VPA-associated pancreatitis has been estimated to be 1:40,000. We present a 6-year-old boy who developed acute pancreatitis (AP) and multiple-organ failure after 3 months of VPA therapy. The patient's laboratory values showed that his kidney and hepatic function had impaired and thrombocytopenia, and coagulopathy had developed. The patient's abdominal tomography showed a suspected appearance, which was consistent with pancreatitis. Because amylase and lipase levels were found to be high, AP was considered. The patient improved after cessation of VPA treatment. Ten days later, the patient recovered both clinically and laboratorial. Consequently, the patient was discharged with cure. In conclusion, AP is a rare, severe adverse reaction to VPA treatment. If a child, who is receiving VPA, develops abdominal pain and vomits, VPA-associated pancreatitis must be considered.

Sa1851 Bile Acid-Induced Acute Pancreatitis Is Mediated by Acinar Cell Leukotriene B4 Secretion

Sa1851 Bile Acid-Induced Acute Pancreatitis Is Mediated by Acinar Cell Leukotriene B4 Secretion

Su1247 The Role of TRPV1 in Ethanol Plus Fatty Acid-Induced Acute Pancreatitis in Mice

Su1247 The Role of TRPV1 in Ethanol Plus Fatty Acid-Induced Acute Pancreatitis in Mice

A case of valproic acid–induced acute pancre­atitis in tuberous sclerosis coexisting with end-stage renal disease

Tuberous sclerosis complex (TCS) is a genetic disorder with a variable clinical presentation. It is commonly characterized by seizures, mental retardation and cutaneous angiofibromas. Renal manifestations frequently include angiomyolipomas and cysts which lead to chronic kidney disease. We report a case of valproic acid-induced acute pancreatitis in a dialysis patient affected by TCS. The case demonstrates the importance of assessing antiepileptic drug treatment in dialysis patients.

Effects of octreotide on acute necrotizing pancreatitis in rabbits.

To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis, and to evaluate the preventive effects of octreotide towards the development of acute pancreatitis. Acute pancreatitis was induced in male New Zealand white rabbits by retrograde injection of 0.8 mL/kg.b.m. of 50 g/L sodium taurocholate (NaTC) in the pancreatic duct. Sham-operated animals served as control. Octreotide 1 mg/kg.b.m. was administered subcutaneously before the induction of pancreatitis. Blood was taken from the jugular vein before and at 1, 3, 6, 12 and 24 h after pancreatitis induction. Serum activities of amylase, IL-6 and TNF-alpha and levels of malonyl dialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn-, Cu-, and Zn-SOD) in pancreatic tissue were measured. Serum TNF-alpha and IL-6 levels increased significantly 3 h after the onset of pancreatitis, and then returned to control level. The tissue concentration of MDA was significantly elevated at 24 h, while the GSH level and GP-x, catalase, Mn-SOD, Cu-, Zn-SOD activities were all significantly decreased in animals with pancreatitis as compared to the control. Octreotide pretreatment significantly reversed the changes in cytokines and reactive oxygen metabolites. Octreotide treatment did not alter the serum amylase activity and did not have any beneficial effects on the development of histopathological changes. Oxygen-derived free radicals and proinflammatory cytokines are generated at an early stage of NaTc-induced acute pancreatitis in rabbits. Prophylactic octreotide treatment can prevent release of cytokines and generation of reactive oxygen metabolites, but does not have any beneficial effects on the development of necrotizing pancreatitis.

Experimental acute pancreatitis results in increased blood–brain barrier permeability in the rat: a potential role for tumor necrosis factor and interleukin 6

Pancreatic encephalopathy is a severe complication of acute pancreatitis. Proinflammatory cytokines may play a role in the development of multi-organ failure during pancreatitis. In the present study, we measured the changes in the blood–brain barrier (BBB) permeability concomitantly with the determination of serum tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels in rats before, as well as 6, 24 and 48 h after the beginning of intraductal taurocholic acid-induced acute pancreatitis. Cytokine concentrations were measured in bioassays with specific cell lines (WEHI-164 for TNF and B-9 for IL-6), while the BBB permeability was determined for a small (sodium fluorescein, molecular weight (MW) 376 Da), and a large (Evans' blue-albumin, MW 67 000 Da) tracer by spectrophotometry in the parietal cortex, hippocampus, striatum, cerebellum and medulla of rats. The serum TNF level was significantly ( P<0.05) increased 6 and 24 h after the induction of pancreatitis, while the IL-6 level increased after 24 and 48 h. A significant ( P<0.05) increase in BBB permeability for both tracers developed at 6 and 24 h in different brain regions of animals with acute pancreatitis. We conclude that cytokines, such as TNF and IL-6, may contribute to the vasogenic brain edema formation during acute pancreatitis.