Effect of pancreatin on acute pancreatitis resulting from L-arginine administration in mice, a morpho-histopathological and biochemical study

Abstract Acute pancreatitis (AP) is a life-unpleasant situation with contradictory and inadequate treatments. In this regard, the present study evaluated the effect of the possible pretreatment of lipase-pancreatin on L-arginine-induced AP. Forty adult mice were selected and divided into five groups: I) control group, II and III) AP groups (i.p.) receiving L-arginine of 2×300 and 2×400 mg/100 g body weight (b.w.), IV) AP (2×300 L-arginine) group + pancreatin (mice were i.p. injected by 350 U-lipase), and V) AP (2×400 L-arginine) group + pancreatin (mice were i.p. injected by 350 U-lipase). All AP groups displayed a significant increase in serum levels of ALT, AST, TBARS, and TNF-alpha compared to the control group. Moreover, pancreatic tissue edema, inflammation, and vacuolization of acinar cells were significantly higher in the untreated L-arginine group compared to the control and pancreatin groups. Conversely, the diameter of pancreatic islets significantly declined after induction of pancreatitis compared with control and pancreatin groups. Pancreatin treatment can be used in pancreatic dysfunction, however, this medicine showed no protective effect against L-arginine-induced AP in the mouse model.

Corticosteroid associated lupus pancreatitis

SUMMARY The relationship between acute pancreatitis and the administration of glucocorticoids is unclear because most reported cases have been diagnosed with systemic vascular diseases, such as systemic lupus erythematosus, which may be responsible for pancreatitis. A 22-year-old woman with eye involvement of a newly diagnosed systemic lupus erythematosus was admitted to our hospital. Pulse intravenous methylprednisolone therapy was given at 1mg/kg day for 3 days, and oral prednisolone at 40 mg/day thereafter. During pulse steroid therapy, she had abdominal pain, back pain, distention, nausea, and vomiting. Her physical examination was compatible with acute abdomen and peritonitis. Abdomen Computerized Tomography scan revealed diffuse liquid perihepatic and perisplenic area with heterogeneity around the mesentery. Due to the symptoms of acute abdomen, explorative laparotomy was performed. There was diffuse free fluid in the abdomen and edematous changes were observed around the pancreas. Amylase and lipase from intraabdominal fluid were studied and found to be high. The postoperative prednol dose was reduced carefully. On the sixth postoperative day, the drain was removed, and the patient was discharged without any problem. Physicians should keep in mind that acute pancreatitis may also be a cause of differential diagnosis of newly developed abdominal pain in patients receiving pulse steroid therapy with a normal level of serum amylase and lipase.

RESUMO A relação entre pancreatite aguda e a administração de glicocorticoides é incerta pois a maioria dos casos relatados foram diagnosticados com doenças vasculares sistêmicas, como lúpus eritematoso sistêmico, que pode causar pancreatite. Uma paciente de 22 anos com envolvimento ocular e lúpus eritematoso sistêmico recém-diagnosticado foi admitida em nosso hospital. Pulsoterapia intravenosa com metilprednisolona 1mg/kg foi administrada por 3 dias. Depois disso, a paciente foi tratada com prednisolona oral 40 mg/dia. Durante a pulsoterapia com corticoides, a paciente apresentava dor abdominal, dor nas costas, distensão, náusea e vômitos. O exame físico era compatível com quadro de abdome agudo e peritonite. Tomografia computadorizada do abdome revelou líquido difuso na região perihepática e periesplênica, com heterogeneidade ao redor do mesentério. Devido aos sintomas de abdome agudo, foi realizada laparotomia exploradora. Havia líquido livre difuso no abdome e alterações edematosas foram observadas em torno do pâncreas. A amilase e lipase do líquido intra-abdominal foram analisadas e consideradas elevadas. A dose pós-operatória de prednol foi reduzida com cuidado. No sexto dia de pós-operatório, o dreno foi retirado, e a paciente recebeu alta sem qualquer problema. Médicos devem lembrar que a pancreatite aguda também pode ser uma causa de diagnóstico diferencial para dor abdominal recém-desenvolvida em pacientes recebendo pulsoterapia com corticoides e com níveis normais de amilase e lipase séricas.

Pancreatitis aguda como efecto adverso de L-asparginasa en el tratamiento de la leucemia linfocítica aguda / Acute pancreatitis as an adverse side effect of L-asparaginase in the treatment of acute lymphoblastic leukemia

Resumen La leucemia linfocítica aguda es la enfermedad oncológica con mayor incidencia en la población pediátrica, tanto a nivel mundial como en Costa Rica. Para su tratamiento requiere protocolos de quimioterapia complejos, lo que representa un reto constante para los médicos, ya que deben equilibrar los riesgos y beneficios del manejo. Es necesario tomar en cuenta los factores de riesgo de cada paciente, el grado de severidad de la enfermedad y los potenciales efectos adversos del tratamiento. A continuación, se reporta un caso de pancreatitis aguda edematosa no biliar, secundaria al uso de L-asparginasa, en un paciente con diagnóstico de leucemia linfocítica aguda, atendido en el Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera". El paciente, quien se encontraba cumpliendo el régimen poliquimioterapeútico AHOPCA 2008, presentó clínica sugestiva de pancreatitis aguda en el día 50 de este, por lo que se decidió no colocar la quimioterapia indicada e inmediatamente se trasladó al Servicio de Emergencias. El cuadro clínico estaba asociado a laboratorios y ultrasonido anormales, por lo que fue tratado interdisciplinariamente y su pronóstico fue favorable; actualmente continúa con tratamiendo quimioterapeútico, como fue indicado.

Abstract The acute lymphocytic leukemia is the oncological disease with the highest incidence in the pediatric population both worldwide and in Costa Rica. It requires complex chemotherapy protocols, which confers a constant challenge on physicians to balance the risks and benefits of management. Therefore, it is necessary to take into account the risk factors of each patient, the degree of severity of the disease and the potential adverse effects of the treatment. A case report is presented with an acute non-biliary edematous pancreatitis, secondary to the use of L-asparaginase in a patient diagnosed with acute lymphocytic leukemia, seen at the National Children's Hospital "Dr. Carlos Sáenz Herrera". The patient who was started on the AHOPCA 2008 polychemotherapy regimen presented symptoms suggestive of acute pancreatitis on the day 50 of the same, so it was decided not to apply the indicated chemotherapy and transfer the patient to the Emergency Room. The clinical picture was associated with abnormal laboratories and ultrasound, so it was immediately treated interdisciplinarily, which is why its prognosis was favorable and currently he continues with chemotherapy treatment as indicated.

The m-rna, expression of serca2 and ncx1 in the process of pharmacological cell protection in experimental acute pancreatitis induced by taurocholate / Expressão do rna-m, da serca2 e do ncx1 no processo de proteção celular farmacológica na pancreatite aguda experimental induzida por taurocolato

ABSTRACT Background: Intracellular calcium overload is known to be a precipitating factor of pancreatic cell injury in acute pancreatitis (AP). Intracellular calcium homeostasis depends of Plasmatic Membrane Calcium ATPase (PMCA), Sarcoplasmic Endothelial Reticulum Calcium ATPase 2 (SERCA 2) and the Sodium Calcium Exchanger (NCX1). The antioxidant melatonin (Mel) and Trisulfate Disaccharide (TD) that accelerates NCX1 action could reduce the cell damage determined by the AP. Aim: To evaluate m-RNA expressions of SERCA2 and NCX1 in acute pancreatitis induced by sodium taurocholate in Wistar rats pre-treated with melatonin and/or TD. Methods: Wistar rats were divided in groups: 1) without AP; 2) AP without pre-treatment; 3) AP and Melatonin; 4) AP and TD; 5) AP and Melatonin associated to TD. Pancreatic tissue samples were collected for detection of SERCA2 and NCX1 m-R NA levels by polymerase chain reaction (PCR). Results: Increased m-RNA expression of SERCA2 in the melatonin treated group, without increase of m-RNA expression of the NCX1. The TD did not affect levels of SERCA2 and NCX1 m-RNA expressions. The combined melatonin and TD treatment reduced the m-RNA expression of SERCA2. Conclusions: The effect of melatonin is restricted to increased m-RNA expression of SERCA2. Although TD does not affect gene expression, its action in accelerating calcium exchanger function can explain the slightest expression of SERCA2 m-RNA when associated with Melatonin, perhaps by a joint action of drugs with different and but possibly complementary mechanisms.

RESUMO Racional: A lesão celular da pancreatite aguda (PA) envolve sobrecarga de cálcio, regulada pela atividade da Cálcio ATPase de membrana (PMCA), Cálcio ATPase do Retículo (SERCA2) e pelo Trocador Sódio Cálcio (NCX1). A melatonina (antioxidante) e o Dissacarídeo Trissulfatado (acelerador do NCX1) poderiam reduzir a lesão celular na PA. Objetivo: Avaliar a expressão do RNAm da SERCA2 e NCX1 em modelo animal de pancreatite aguda tratados com melatonina e/ou dissacarídeo trissulfatado (DT). Método: Ratos Wistar foram divididos em grupos: 1) sem pancreatite aguda; 2) com pancreatite aguda por taurocolato; 3) PA e Melatonina; 4) PA e DT; 5) PA e Melatonina com DT. Amostras de tecido foram colhidas para detecção dos níveis de RNAm da SERCA2 e NCX1 por PCR. Resultados: Houve aumento da expressão do RNAm da SERCA2 no grupo com PA tratados com Melatonina, porém sem aumento de expressão do NCX1. O DT não afetou os níveis de SERCA2 e NCX1. O tratamento conjunto com Melatonina e DT diminuiu a expressão da SERCA2. Conclusões: O efeito da Melatonina é restrito ao aumento da expressão da SERCA2. O DT não tem ação na expressão gênica, porém sua ação na aceleração do trocador na retirada do cálcio pode explicar a menor expressão da SERCA2 quando associado à Melatonina, pela ação conjunta de drogas com mecanismos diferentes e possivelmente complementares.

The effect of quercetin on cerulein-induced acute pancreatitis / Efeito da quercetina sobre a pancreatite induzida por ceruleína

OBJECTIVE: The aim of this study was to evaluate the protective and therapeutic effects of quercetin on pancreatic injury in cerulein-induced acute pancreatitis. METHOD: Thirty-two rats were randomly divided into four groups, eight per group: (CT): untreated controls, (CER) treated with cerulein, 50 µg/kg body weight; (Q+CER) pre-treatment with quercetin, 100 mg/kg body weight, followed by cerulein, 50 µg/kg; (CER+Q) post-treatment, cerulein followed by quercetin, same doses. Cerulein was divided into four doses, given at 1-hour intervals by intraperitoneal injection. Quercetin was given either 1-hour before (in pre-treatment group) or 1-hour after (in post-treatment group) cerulein. Pancreatic malondialdehyde (MDA), carbonyl, myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), reduced and oxidized glutathione (GSH and GSSG, respectively) were measured. Histology of the pancreas was studied. RESULTS: (1) MDA, carbonyl, MPO, TNF-a and IL-6 levels were significantly higher in CER vs CT rats. (2) MDA, carbonyl, MPO and TNF-α decreased significantly in pre-treated rats vs. CER. (3) MDA, MPO, TNF-α, IL-6 were significantly lower in post-treated rats vs. CER. (4) The reduced vs. oxidized glutathione ratio (GSH/GSSG) of was significantly lower CER vs. CT rats. (5) Pre- and post-treatment with quercetin significantly increased this ratio. (6) Pancreatic histology showed that quercetin had no significant effect on the histological image of the pâncreas CONCLUSION: These results suggest that quercetin can attenuate the severity of cerulein-induced acute pancreatitis by acting as an antioxidant and anti-inflammatory agent and combating oxidative stress. Further studies are needed to clearly explain its utility on acute pancreatitis.

OBJETIVO: O objetivo deste estudo foi avaliar os efeitos protetores e terapêuticos da quercetina na lesão pancreática da pancreatite aguda induzida por ceruleína. MÉTODO: Trinta e dois ratos foram divididos aleatoriamente em quatro grupos, oito por grupo: (CT): controles não tratados (CER) tratados com ceruleína, 50 µg/kg de peso corporal; (Q+CER) pré-tratamento com quercetina, 100 mg / kg de peso corporal, seguido de ceruleína, 50 µg/kg; (CER+Q) pós-tratamento, ceruleína seguida de quercetina, mesmas doses. A ceruleína foi dividida em quatro doses, administradas a intervalos de 1 hora por injeção intraperitoneal. A quercetina foi administrada 1 hora antes (no grupo de pré-tratamento) ou 1 hora após (no pós-tratamento) a administração de ceruleína. Foram medidos o malondialdeído pancreático (MDA), carbonilo, mieloperoxidase (MPO), fator de necrose tumoral alfa (TNF-a), interleucina-6 (IL-6), glutationa reduzida e oxidada (GSH e GSSG, respetivamente). Foi estudada a histologia do pâncreas. RESULTADOS: Os níveis de MDA, carbonila, MPO, TNF-a e IL-6 foram significativamente maiores nos ratos CER vs. CT. MDA, carbonila, MPO e TNF-α diminuíram significativamente em ratos pré-tratados versus CER. MDA, MPO, TNF-α, IL-6 também foram significativamente menores em ratos pós-tratados versus CER. A proporção reduzida de glutationa oxidada (GSH/GSSG) foi significativamente menor ratos CER vs. CT; pré e pós-tratamento com quercetina aumentaram significativamente esta proporção. A histologia pancreática mostrou que a quercetina não teve efeito morfológico significativo. CONCLUSÃO: Estes resultados sugerem que a quercetina pode atenuar a gravidade da pancreatite aguda induzida por ceruleína, atuando como agente antioxidante e anti-inflamatório e combater o estresse oxidativo. Mais estudos são necessários para explicar claramente suas utilidades na pancreatite aguda.

Pancreatitis inducida por drogas / DRUG-INDUCED ACUTE PANCREATITIS

Introducción. Las Reacciones Adversas Medicamentosas (RAM) son una de las principales causas de hospitalización y mortalidad en el sistema de salud (en países desarrollados y en vías de desarrollo), y la relevancia va creciendo año tras año. El objetivo de este estudio fue determinar la incidencia de pancreatitis aguda inducida por drogas y los grupos de drogas que más frecuentemente se ven involucrados. Material y Métodos: Se realizó un estudio retrospectivo tomando como fuente una base de datos de farmacovigilancia del Hospital General de Agudos ¨Dr. Cosme Argerich¨ con información de los últimos cinco años. Resultados: Se detectaron siete casos de pancreatitis inducida por drogas de los cuales fueron dos por quimioterápicos (lapatinib e imatinib), tres por antirretrovirales, uno por inmunosupresores y uno por antihipertensivos (enalapril). En cinco casos fue necesaria la hospitalización y un evento fue mortal. Conclusión: De acuerdo a la bibliografía internacional, a pesar de que los fármacos son solo responsables del 1-2% de casos de pancreatitis aguda inducida por drogas, es importante destacar que es difícil encontrar la causalidad entre el fármaco y el cuadro del paciente, lo que lleva muchas veces a un subdiagnóstico como una pancreatitis idiopática. En el presente estudio, estos casos deben considerarse por su impacto, no solo a nivel de la salud del paciente

Adverse Drug Reactions (ADR) are nowadays an increasing problem in health systems and represents between the 4th and the 6th cause of death in developing countries. Drug induced pancreatitis in a rare ADR but reports are increasing with antiretroviral drugs and new antiviral and anticancer drugs. The aim of this study was to determine the incidence of drug ­ induced pancreatitis in a tertiary care hospital. We used a pharmacovigilance database applying de Naranjo Score for drug causality in adverse medical events. From a total of 2990 ADR we detected 7 cases of pancreatitis. Antiretroviral and anticancer drugs were the drugs most frequently involved.

Therapeutic effects of ellagic acid on L-arginin induced acute pancreatitis

ABSTRACT PURPOSE: To investigate the therapeutic effects of ellagic acid on L-arginin ınduced acute pancreatitis in rats. METHODS: Thirty-two were split into four groups. Group 1 (control) rats were performed only laparotomy, no drugs were administered. Group 2 (control+EA) rats were administered 85mg/kg EA orally. Rats were sacrificed by cardiac puncture 24 hours after the administration. Group3 (AP) 24 hours after intraperitoneal L-arginine administration, rats were sacrificed by cardiac puncture. Group 4 (EA)-(AP): 85mg/kg EA was administered orally after the L-arginine administration. 24 hours later, rats were sacrificed by cardiac puncture. Serum TNF-α, IL-1β, IL-6, total oxidative status (TOS), total antioxidant capacity (TAC), amylase levels were determined in all groups. RESULTS: Group 3 (AP) rats showed significantly raised TOS level as compared to Group1 (control) rats (p<0.001). Following the EA therapy, a decrease in TOS was observed in Group 4 (AP+EA). TAC levels were significantly raised in the Group 4 (AP+EA) compared to the Group 3 (AP) (p=0.003). Group 3 (AP) showed significantly increased TNF-α, IL-1β and IL-6 serum levels as compared to Group 4 (AP+EA). Histopathological changes were supported our result. CONCLUSION: The healing effects of ellagic acid on inflammatory and oxidative stress were confirmed by histopathological and biochemical evaluations of the pancreatic tissue.

Acute pancreatitis associated with boceprevir: a case report

Approximately 170 million people are infected with hepatitis C, and the sustained virological response rate to treatment with pegylated interferon and ribavirin is 30-50%. In an attempt to improve the chances of cure, boceprevir is being added to therapy, but it is associated with an increased incidence of adverse events. We herein report a case of acute pancreatitis developed during treatment with pegylated interferon, ribavirin and boceprevir. Boceprevir was the most likely cause of drug-associated pancreatitis after the most common causes were ruled out, since this adverse event had not occurred when the patient had previously been exposed to pegylated interferon and ribavirin and there was no recurrence of the episode of pancreatitis when these two drugs were reintroduced. Acute pancreatitis is a rare adverse event associated with boceprevir therapy, but a potentially fatal event. Sequential determination of pancreatic enzymes should be considered during hepatitis C treatment with boceprevir.

Antiretroviral drugs and acute pancreatitis in HIV/AIDS patients: is there any association? A literature review / Drogas antirretrovirais e pancreatite aguda em pacientes com HIV/AIDS: existe alguma associação? Revisão da literatura

In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when combined antiretroviral therapy, known as HAART (highly active antiretroviral therapy), was introduced, a broad spectrum of harmful factors to the pancreas, such as opportunistic infections and drugs used for chemoprophylaxis, dropped considerably. Nucleotide analogues and metabolic abnormalities, hepatic steatosis and lactic acidosis have emerged as new conditions that can affect the pancreas. To evaluate the role of antiretroviral drugs to treat HIV/AIDS in a scenario of high incidence of acute pancreatitis in this population, a systematic review was performed, including original articles, case reports and case series studies, whose targets were HIV-seropositive patients that developed acute pancreatitis after exposure to any antiretroviral drugs. This association was confirmed after exclusion of other possible etiologies and/or a recurrent episode of acute pancreatitis after re-exposure to the suspected drug. Zidovudine, efavirenz, and protease inhibitors are thought to lead to acute pancreatitis secondary to hyperlipidemia. Nucleotide reverse transcriptase inhibitors, despite being powerful inhibitors of viral replication, induce a wide spectrum of side effects, including myelotoxicity and acute pancreatitis. Didanosine, zalcitabine and stavudine have been reported as causes of acute and chronic pancreatitis. They pose a high risk with cumulative doses. Didanosine with hydroxyurea, alcohol or pentamidine are additional risk factors, leading to lethal pancreatitis, which is not a frequent event. In addition, other drugs used for prophylaxis of AIDS-related opportunistic diseases, such as sulfamethoxazole-trimethoprim and pentamidine, can produce necrotizing pancreatitis. Despite comorbidities that can lead to pancreatic involvement in the HIV/AIDS population, antiretroviral drug-induced pancreatitis should always be considered in the diagnosis of patients with abdominal pain and elevated pancreatic enzymes.

Em HIV-soropositivos, a incidência de pancreatite aguda pode chegar até 40% ao ano, o que é consideravelmente maior que na população geral, cuja incidência é de 2%. A partir de 1996, com a introdução da terapia antirretroviral combinada, conhecida pela sigla HAART (highly active antiretroviral therapy), o espectro de fatores nocivos ao pâncreas, como infecções oportunistas e uso de drogas para sua quimioprofilaxia, diminuiu consideravelmente. Análogos nucleotídeos e anormalidades metabólicas, esteatose hepática e acidose láctica despontaram como novas condições que podem acometer o pâncreas. A fim de avaliar o papel das drogas antirretrovirais para tratamento do HIV/AIDS na incidência elevada de pancreatite aguda nessa população, foi realizada revisão sistemática, com inclusão de artigos originais, relatos e séries de caso, cujos alvos de estudo eram pacientes HIV-soropositivos que evoluíram com pancreatite aguda após exposição a alguma das drogas que compõem o esquema antirretroviral. Essa associação foi confirmada após exclusão de outras possíveis etiologias e/ou recorrência do episódio de pancreatite aguda após reexposição ao fármaco suspeito. Zidovudina, efavirenz e os inibidores de protease são suspeitos de levar a uma pancreatite secundária à hiperlipidemia. Já os análogos nucleotídeos da transcriptase reversa, apesar de serem potentes inibidores da replicação viral, possuem grande espectro de efeitos colaterais, entre eles a mielotoxicidade e a pancreatite aguda. Didanosina, zalcitabina e estavudina já foram reportados como produtores de pancreatite crônica e aguda, tendo risco elevado com dose cumulativa. Didanosina com hidroxiureia, álcool ou pentamidina são fatores de risco adicionais, podendo induzir a uma pancreatite fatal, embora pouco frequente. Além disso, outras drogas usadas para profilaxia de doenças oportunistas relacionadas à AIDS, como sulfametoxazol-trimetoprima e pentamidina, podem produzir pancreatite necrotizante. Apesar das comorbidades que podem levar ao acometimento pancreático na população com HIV/AIDS, pancreatite medicamentosa desencadeada por drogas antirretrovirais sempre deve ser considerada no diagnóstico diferencial desses pacientes que se apresentam com dor abdominal e elevação das enzimas pancreáticas.

Acute Pancreatitis Secondary to Ciprofloxacin Therapy in Patients with Infectious Colitis

BACKGROUND/AIMS: Ciprofloxacin is considered to be a safe and effective treatment for acute infectious colitis. However, this drug may cause drug-induced pancreatitis, albeit rarely. METHODS: From March 2007 to February 2012, we studied 227 patients who were hospitalized for infectious colitis at St. Mary's Hospital. All of the patients received ciprofloxacin therapy for the treatment of infectious colitis. We observed a few cases of rare adverse events, including ciprofloxacin-induced acute pancreatitis diagnosed based on the Naranjo algorithm. RESULTS: During ciprofloxacin therapy, seven of 227 patients (3.1%) developed rare pancreatitis as defined by the Naranjo algorithm; pancreatic enzyme activity was sporadically elevated with ciprofloxacin use. After ciprofloxacin administration, the average interval until the development of pancreatitis was 5.5 days (range, 4 to 7 days). On abdominal computed tomography, pancreatic swelling and homogenous enhancement was noted in three of seven patients. Complicating acute pancreatitis was gradually but completely resolved after cessation of ciprofloxacin administration. The mean recovery time was 11.3 days (range, 8 to 15 days). CONCLUSIONS: We observed that ciprofloxacin-induced pancreatitis may occur with an incidence of approximately 3%. Ciprofloxacin-induced pancreatitis presents a short latency, suggesting an idiosyncratic hypersensitivity reaction. Practitioners should be aware that drug-induced pancreatitis can occur during ciprofloxacin therapy.

Acute Pancreatitis Induced by Methimazole Treatment in a 51-Year-Old Korean Man: A Case Report

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.

Acute Pancreatitis Induced by Methimazole Treatment in a 51-Year-Old Korean Man: A Case Report

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.

Protective effect of lawsone on L-Arginine induced acute pancreatitis in rats.

The efficacy of lawsone against L-arginine induced acute pancreatitis was determined at 24 h by determination of serum levels of amylase, lipase and proinflammatory cytokines [tumor necrosis factor (TNF)-α, C-reactive proteins and interleukin (IL)], pancreatic myeloperoxidase (MPO) activity, lipid peroxidation (thiobarbituric acid reactive substances (TBARS)], nitrate/nitrite levels, and the wet weight/body weight ratio. Lawsone and methylprednisolone treatments significantly attenuated the L-arginine- induced increases in pancreatic wet weight/body weight ratio, and decreased the serum levels of amylase and lipase, and TNF-α and IL-6 and significantly lowered pancreatic levels of MPO, TBARS, and nitrate/nitrite. The histoimmunological findings further proved the amelioration of pancreatic injury by lawsone and further proved anti-inflammatory and antioxidant agent property of lawsone.

A Case of Acute Pancreatitis and Acute Hepatitis Caused by Ingestion of Ceramium kondoi / 대한소화기학회지

In Korea, the use of herbal remedies is a common cause of drug-induced liver injury. However, the occurrence of both acute pancreatitis and acute hepatitis after taking herbal remedies has rarely been reported. Herein, we report a case of concurrent acute pancreatitis and acute hepatitis associated with Ceramium kondoi ingestion. A 58-year-old woman was diagnosed with advanced gastric cancer 7 months ago. Total gastrectomy and adjuvant chemotherapy was performed without complications. The patient had been well until recently, when she presented with severe abdominal pain after ingestion of Ceramium kondoi for 4 weeks. The laboratory findings demonstrated elevated liver enzymes and lipase, and abdominal computed tomography revealed pancreas swelling with fat infiltration. The diagnosis was made based on the diagnostic criteria for drug induced pancreatitis and the Russel Uclaf Causality Assessment Method scale for drug-induced liver injury. After cessation of Ceramium kondoi, she showed clinical and biochemical improvement.

Preventive effect of cichorium intybus l. two extracts on cerulein-induced acute pancreatitis in mice

Acute pancreatitis is an inflammatory condition of pancreas with sudden onset, high mortality rate and multiple organ failure characteristics. It has been shown that oxygen free radicals have an important role in development of pancreatitis and its complications. Antioxidant, anti-inflammatory, anti-hepatotoxicity and gastroprotective properties of Cichorium intybus L. suggest that this plant may have beneficial effects in the management of acute pancreatitis. Five intraperitoneal [i.p.] injection of cerulean [50 microg/ kg at 1 h intervals] in mice resulted in acute pancreatitis, which was characterized by edema, neutrophil infiltration, as well as increases in the serum levels of amylase and lipase in comparison to normal mice. Different doses of C. intybus root [CRE] and aerial parts hydroalcoholic extract [CAPE] orally [50, 100, 200 mg/kg] and intraperitoneally [50, 100, 200 mg/kg] were administrated 1.0 and 0.5 h respectively before pancreatitis induction on separate groups of male mice [n=6]. Control groups treated with normal saline [5 ml/ kg] similarly. Both extracts in greater test doses [100 mg/kg and 200 m/kg, i.p.] were effective to decrease amylase [23-36%] and lipase [27-35%] levels. In oral route, the dose of 200 mg/ kg showed a significant decrease in levels of amylase [16%] and lipase [24%] activity while the greatest dose [200 mg/kg, i.p.] was only effective to diminish inflammatory features like edema and leukocyte infiltration in pancreatitis tissue [P<0.01]. Vacuolization was not significantly reduced in extracts treated groups. These data suggest that C. intybus hydroalcoholic extracts were effective to protect against experimental acute pancreatitis and the efficacy was partly dependent to the dose and was more significant after parenteral administration

Preventive action of curcumin in experimental acute pancreatitis in mouse.

Background & objectives: Curcuma longa (turmeric) has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. The purpose of the present study was to investigate the preventive effects of curcumin against acute pancreatitis (AP) induced by caerulein in mouse and to elucidate possible mechanism of curcumin action. Methods: Curcumin (50 mg/kg/day) was intraperitoneally injected to Kun Ming male mice for 6 days, followed by injection of caerulein to induce AP. GW9662 (0.3 mg/kg), a specific peroxisome proliferator-activated receptor gamma (PPARγ) antagonist, was intravenously injected along with curcumin. Murine macrophage RAW264.7 cells were treated with 100 μmol/l curcumin for 2 h, and then stimulated with 0.1 μ g/ml lipopolysaccharide (LPS). Serum amylase and transaminase levels were measured at 10 h after AP. TNF-α level in mouse serum and cell culture medium were detected by ELISA. Expression of PPARγ and NF-κB were analyzed by RT-PCR and Western blot. Results: Curcumin significantly decreased the pancreas injury and reversed the elevation of serum amylase, ALT and AST activities and TNF-α level in mice with AP. Curcumin treatment inhibited the elevation of NF-κB-p65 in the nucleus of mouse pancreas AP group and RAW264.7 cells, but significantly increased the expression of PPARγ. GW9662 could abolish the effects of curcumin on serum levels of amylase, ALT, AST, TNF-α, and NF-κB level. Interpretation & conclusions: Our results suggest that curcumin could attenuate pancreas tissue and other organ injury by inhibiting the release of inflammatory cytokine TNF-α. These effects may involve upregulation of PPARγ and subsequent downregulation of NF-κB.

Ação do tacrolimus na pancreatite aguda experimental induzida pela arginina / Action of tacrolimus in arginine induced experimental acute pancreatitis

OBJETIVO: verificar se o tacrolimus administrado em ratos, em vigência de pancreatite induzida pela L-Arginina, interfere nos níveis séricos da amilase e glicose e no padrão histológico do parênquima pancreático. MÉTODOS: quarenta ratos Wistar foram distribuídos em quatro grupos com 10 ratos cada. Grupo controle (C), grupo tacrolimus (T), grupo pancreatite (P) e grupo pancreatite-tacrolimus (PT). Foram avaliados os níveis séricos de amilase, glicose e tacrolimus e feitas avaliações histológicas do pâncreas, A indução de pancreatite foi feita pela inoculação de L-Arginina na dose de 500mg/100g de peso corporal por via intraperitoneal e o tratamento com tacrolimus na dose de 1ìg/kg por via subcutânea durante quatro dias. RESULTADOS: a amilasemia estava mais elevada (p=0,0000) nos grupos PT, T e P do que no grupo controle. A média do grupo PT foi maior (p=0,0009) que a do grupo T, mas não diferiu (p=0,6802) da média do grupo P. Entre os grupos P e T não houve diferença (p=0,2568). Não houve diferença nas médias de glicemia entre os grupos (p=0,4920) e os níveis séricos de tacrolimus foram similares nos grupos PT e T (p=0,7112). Não ocorreram alterações histológicas nos grupos T e C e não ocorreu hemorragia no pâncreas dos ratos dos grupos P e PT. No grupo P, em 30 por cento não se observou edema, em 20 por cento observou-se a forma leve e em 50 por cento, a moderada; quanto à infiltração inflamatória, em 80 por cento moderada e em 20 por cento não ocorreu, e a atrofia do parênquima foi de 60 por cento moderada e 40 por cento acentuada. No grupo PT, houve ocorrência de edema, infiltração inflamatória e atrofia do pâncreas em todos os ratos. CONCLUSÃO: o tratamento pelo tacrolimus induziu aumento nos níveis séricos de amilase em ratos normais, não alterou a glicemia nem o padrão histológico do parênquima pancreático. Na vigência de pancreatite induzida pela L-Arginina o tacrolimus induziu edema, infiltração inflamatória e atrofia com maior gravidade no parênquima pancreático.

OBJECTIVE: To determine whether tacrolimus administered to rats, in the presence of pancreatitis induced by L-Arginine, interferes with the serum levels of amylase and glucose and the histological pattern of the pancreatic parenchyma. METHODS: Forty Wistar rats were divided into four groups with 10 rats each: control group (C), tacrolimus group (T), pancreatitis group (P) and pancreatitis-tacrolimus group (PT). We evaluated serum levels of amylase, glucose, and tacrolimus and made histological assessments of the pancreas. Induction of pancreatitis was made by inoculation of L-Arginine at a dose of 500mg/100g body weight intraperitoneally, and tacrolimus treatment at a dose of 1ìg/kg subcutaneously for four days. RESULTS: Serum amylase was higher (p = 0.0000) in groups PT, P and T than in the control group. The PT group mean was higher (p = 0.0009) than in the T group, but did not differ (p = 0.6802) from the average of the P group. There was no difference between groups P and T (p = 0.2568). Neither in mean blood glucose between the groups (p = 0.4920); serum levels of tacrolimus were similar in PT and T groups (p = 0.7112). There were no histological changes in groups T and C and no hemorrhage in the pancreas of rats in groups P and PT. In group P, there was no edema in 30 percent, mild edema in 20 percent and in 50 percent, moderate; as for inflammatory infiltration, it was moderate in 80 percent and absent in 20 percent, and atrophy of the parenchyma was moderate in 60 percent and severe in 40 percent. In the PT group, there was edema, inflammatory infiltration or atrophy in the pancreas in all rats. CONCLUSION: Treatment with Tacrolimus induced an increase in serum amylase in normal mice, but did not affect blood glucose or the histological pattern of the pancreatic parenchyma. In the presence of pancreatitis induced by L-Arginine tacrolimus induced edema, inflammatory infiltration and more severe atrophy in the pancreatic parenchyma.

Efeitos do cloreto de gadolínio na pancreatite induzida por tauracolato de sódio em ratos / Effects of gadolinium chloride on sodium taurocholate-induced pancreatitis in rats

OBJETIVO: Avaliar os efeitos do uso de cloreto de gadolínio como pré-tratamento e tratamento em um modelo experimental de pancreatite em ratos induzida por tauracolato de sódio a 3 por cento. MÉTODOS: Ratos Wistar foram divididos em cinco grupos: grupo SF - controle com solução fisiológica intra-ductal e IV; grupo TS - controle com PA induzida por tauracolato de sódio a 3 por cento e solução fisiológica a 0,9 por cento IV; grupo GD - controle com SF intra-ductal e cloreto de gadolínio IV; grupo GDTS - pré-tratamento com GD (24h antes da indução da PA) e grupo TSGD - tratamento com GD (1h após a indução da PA). Foi realizado dosagem sérica de amilase, transaminases e TNF-á; determinação da atividade da MPO no tecido pulmonar; histologia pancreática e pulmonar. RESULTADOS: O número de animais mortos antes do término previsto do experimento foi significativamente maior no grupo TSGD (p=0,046). Os escores de pancreatite e de dano pulmonar foram mais elevados nos grupos que utilizaram tauracolato em comparação aos grupos com infusão intra-ductal de solução salina. Não houve diferenças nas demais variáveis estudadas na comparação entre os grupos TS; GDTS e TSGD. CONCLUSÃO: Não foram demonstrados benefícios com o uso de cloreto de gadolínio de forma profilática e terapêutica.

OBJECTIVE: To evaluate the effects of the use of gadolinium chloride before and after induction of acute pancreatitis with sodium taurocholate 3 percent in rats. METHODS: Wistar rats were divided into five groups: SF - control with saline intra-ductal and IV; GD control with saline intra-ductal and gadolinium chloride IV; TS - with AP control induced by sodium taurocholate 3 percent and saline IV; GDTS - pre-treatment with GD (24 hours before the induction of AP) and TSGD - treatment with GD (1 hour after the induction of AP). Analysis was made in serum amylase, transaminases and TNF-á; determination of the MPO activity in lung tissue, lung and pancreatic histology. RESULTS: The number of dead animals before the end of the experiment was significantly higher in TSGD (P = 0.046). The scores of pancreatitis and lung damage were higher in the groups that used sodium taurocholate compared to groups with intra-ductal infusion of saline solution. There were no differences in other variables studied when comparing TS, GDTS and TSGD groups. CONCLUSION: The benefits with the use of gadolinium chloride as a prophylactic and therapeutic drug were not demonstrated.

A Case of Inferior Vena Cava Thrombosis and Acute Pancreatitis in a Patient with Ulcerative Colitis / 대한소화기학회지

A 21-year-old man admitted complaining of sudden severe epigastric pain for 1 day. He had been diagnosed as ulcerative colitis (UC) and taking mesalazine for two months. UC was in nearly complete remission at admission. He never drank an alcohol, and serum amylase was 377 IU/L. CT scan showed inferior vena cava (IVC) thrombosis in addition to mild acute pancreatitis. To evaluate the cause of acute pancreatitis and IVC thrombosis, magnetic resonance cholangiopancreatogram (MRCP), endoscopic ultrasonogram (EUS), lower extremity Doppler ultrasonogram (US) and blood test of hypercoagulability including factor V, cardiolipin Ab, protein C, protein S1, antithrombin III, and anti phospholipids antibody were performed. There was no abnormality except mild acute pancreatitis and IVC thrombosis in all the tests. He was recommended to stop taking mesalazine and start having anticoagulation therapy. After all symptoms disappeared and amylase returned normal, rechallenge test with mesalazine was done. Flare-up of abdominal pain occurred and the elevation of serum amylase was observed. Ulcerative colitis came to complete remission with short-term steroid monotherapy. Acute pancreatitis and IVC thrombosis were completely resolved after 3-month anticoagulation therapy with no more mesalazine. We postulated that IVC thrombosis occurred due to hypercoagulable status of UC and intra-abdominal inflammation caused by mesalazine-induced pancreatitis.