RESUMO
Purpose: The research is intended for clarification of the efficacy as well as the underlying mechanism of GSK-3β inhibitors on the advancement of acute lung injuries in acute necrotizing pancreatitis (ANP) in rats. Methods: Seventy-two rats were randomly divided into 6 groups: (1)ANP-vehicle; (2)ANP-TDZD-8;(3)ANP-SB216763;(4)Sham-vehicle;(5)Sham-TDZD-8;(6)Sham-SB216763; Blood biochemical test, histopathological examination and immunohistochemical analysis of rats pancreas and lung tissues were performed. The protein expression of GSK-3β, phospho-GSK-3β (Ser9), iNOS, ICAM-1, TNF-α, and IL-10 were detected in lung tissues by Western-blot. Results: The outcomes revealed that the intervention of GSK-3β inhibitors alleviated the pathological damage of pancreas and lung (P<0.01), reduced serum amylase, lipase, hydrothorax and lung Wet-to-Dry Ratio, attenuated serum concentrations of IL-1β and IL-6 (P<0.01), inhibited the activation of NF-κB, and abated expression of iNOS, ICAM-1 and TNF-α protein, but up-regulated IL-10 expression in lung of ANP rats (P<0.01). The inflammatory response and various indicators in ANP-TDZD-8 groups were lower than those in ANP-SB216763 groups. Conclusions: Inhibition of GSK-3β weakens acute lung injury related to ANP via the inhibitory function of NF-κB signaling pathway. Different kinds of GSK-3β inhibitors have different effects to ANP acute lung injury.(AU)
Assuntos
Animais , Masculino , Ratos , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/classificação , Lesão Pulmonar Aguda/prevenção & controle , Lesão Pulmonar Aguda/fisiopatologia , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/fisiopatologia , Glicogênio Sintase Quinase 3 beta/administração & dosagem , Glicogênio Sintase Quinase 3 beta/análise , China , Ratos WistarRESUMO
Acute pancreatitis (AP) has a fast onset and progression, which lead to an unfavorable prognosis. Therefore, the development of novel drugs for its treatment is critical. As a homologous derivative of resveratrol, pterostilbene exerts a variety of effects including anti-inflammatory, antioxidant, and antitumor effects. This study investigated the potential of pterostilbene for treatment of severe AP (SAP) and related mechanisms. Effects of pterostilbene were evaluated in a Wistar rat model of AP. Serum levels of amylase (AMY), creatinine (Cr), and alanine aminotransferase (ALT) were quantified. Furthermore, serum levels of tumor necrosis factor (TNF)-a and interleukin (IL)-1b were quantified using enzyme-linked immunosorbent assay. Nuclear factor (NF)-kB expression in pancreatic tissues was quantified by real-time PCR and western blotting. The production of reactive oxygen species (ROS) was determined using a spectrometer, while superoxide dismutase (SOD) activity was assayed. In the AP rat model, the expression of inflammatory markers TNF-a and IL-1b, expression of NF-kB, and serum indices (AMY, Cr, and ALT) increased compared to the corresponding levels in the control group (P < 0.05). Pterostilbene reduced serum levels of TNF-a and IL-1b; decreased NF-kB gene expression, serum indices, and ROS generation; and increased SOD activity in a dose-dependent manner. In conclusion, pterostilbene can alleviate SAP-induced tissue damage by decreasing the inflammatory response and by promoting antioxidation leading to the protection of pancreatic tissues.
Assuntos
Anti-Inflamatórios/farmacologia , Pancreatite Necrosante Aguda/tratamento farmacológico , Estilbenos/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Biomarcadores/sangue , Avaliação Pré-Clínica de Medicamentos , Interleucina-1beta/sangue , Masculino , NF-kappa B/metabolismo , Estresse Oxidativo , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pancreatite Necrosante Aguda/sangue , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Estilbenos/uso terapêutico , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
Although the exact mechanism is unknown, incidence of drug-induced pancreatitis from corticosteroids is well established in the medical literature. Commonly reported in chronic steroid-dependent individuals who require large doses for a wide array of pathologies, the incidence of damage to the pancreas from low-doses have not been well described. We report a case of a 68-year-old woman who presented with severe abdominal pain, nausea and vomiting, 3 days after the initiation of low-dose methylprednisolone for osteoarthritis. Inpatient laboratory analysis revealed an elevated lipase of 1770 U/L and CT scan showing extensive necrotising pancreatitis involving the head, body and tail. Cessation of the causative medication and conservative treatment successfully led to resolution of symptoms. We present this case to inform clinicians of the precipitance of pancreatitis from modest strength corticosteroid management, so that more accurate and improved performance in pharmacological decisions can be made for patient care.
Assuntos
Glucocorticoides/efeitos adversos , Metilprednisolona/efeitos adversos , Osteoartrite/tratamento farmacológico , Pâncreas/efeitos dos fármacos , Pancreatite Necrosante Aguda/etiologia , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Idoso , Gerenciamento Clínico , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Lipase/sangue , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Pâncreas/patologia , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: The aim of this study was to evaluate whether pancreatic necrosis with presence of gas is an absolute indication for surgery or if there is a possibility for the medical management of this pathology. METHODS: This study is a retrospective study including 56 patients with diagnosis of pancreatic necrosis and gas on computed tomography from April 2003 to March 2011. We recorded all the factors related to each group of treatment, including APACHE II score, C-reactive protein level, Tomographic Severity Index, organ and multiorgan failure, and infected necrosis after fine-needle puncture, to evaluate the differences between surgical and medical treatment. RESULTS: Thirty-six (64%) of these patients were submitted to surgery, whereas 20 (36%) were managed conservatively. Twenty-eight patients (78%) who underwent surgery had infected necrosis. Thirty-five percent of the patients (7 patients) in the medical group had organ failure versus 83% of the patients in the surgical group. CONCLUSIONS: Pancreatic necrosis with gas on computed tomography is a relative indication for surgery. Medical management is a feasible and safe possibility for this pathology in selected cases. The presence of organ failure and infected necrosis often precludes a surgical treatment.
Assuntos
Enfisema/terapia , Pancreatectomia , Pancreatite Necrosante Aguda/terapia , APACHE , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biópsia por Agulha Fina , Proteína C-Reativa/análise , Enfisema/sangue , Enfisema/diagnóstico , Enfisema/microbiologia , Enfisema/cirurgia , Feminino , Gases , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/microbiologia , Insuficiência de Múltiplos Órgãos/terapia , Pancreatectomia/efeitos adversos , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/diagnóstico , Pancreatite Necrosante Aguda/microbiologia , Pancreatite Necrosante Aguda/cirurgia , Seleção de Pacientes , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The most common etiology of acute pancreatitis results from the impaction of gallstones or sludge in the distal common bile duct (CBD). The result is pancreatic duct obstruction, diversion of bile into the pancreas, or cholestasis. In the current study, we examined whether combining both aspects, that is, infusion of the bile acid taurocholate (TC) followed by bile duct ligation (BDL), could yield a more severe form of pancreatitis that mimics biliary pancreatitis. METHODS: In mice, after laparotomy, the CBD was infused with either normal saline (NS) or TC. Subsequently, the CBD was ligated at the ampulla. RESULTS: Mice receiving TC infusion followed by BDL (TC + BDL) had higher mortality compared with animals receiving intraductal NS with BDL (NS + BDL). The TC + BDL arm developed more severe and diffuse pancreatic necrosis. In addition, serum amylase, IL-6, and bilirubin were significantly higher. However, pancreatic edema as well as lung and liver injury were unchanged between TC + BDL and NS + BDL. CONCLUSIONS: In summary, the combination of bile infusion into the pancreas followed by BDL causes a more severe, necrotizing pancreatitis. We believe that this novel model of pancreatitis is useful because it can be used in transgenic mice and recapitulates several aspects of biliary pancreatitis.
Assuntos
Colestase/complicações , Ducto Colédoco/cirurgia , Cálculos Biliares/induzido quimicamente , Pancreatite Necrosante Aguda/induzido quimicamente , Ácido Taurocólico , Amilases/sangue , Animais , Bilirrubina/sangue , Biomarcadores/sangue , Modelos Animais de Doenças , Interleucina-6/sangue , Ligadura , Masculino , Camundongos , Pâncreas/enzimologia , Pâncreas/patologia , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/patologia , Índice de Gravidade de Doença , Fatores de TempoRESUMO
OBJECTIVES: Acute pancreatitis is a severe and frequently life-threatening disease, which can lead to pancreatic necrosis, acute lung injury, systemic inflammatory response syndrome, and other complications. In this study, we hypothesized that the expression of heme oxygenase-1 determined by the number of guanidinium thiocyanate (GT) repeats can influence the occurrence of acute pancreatitis. METHODS: Patients with acute pancreatitis (n = 131) and age- and sex-matched healthy controls (n = 108) were studied. The polymerase chain reaction products were analyzed by ABI 3130 genetic analyzer and the exact size of the polymerase chain reaction products was determined by GeneMapper software. A short allele was defined as containing 27 GT repeats or fewer, whereas a long allele was more than 27 repeats. RESULTS: The subjects were categorized into 3 groups on the basis of the genotype results: 1 short and 1 long, 2 short, and 2 long alleles (L/L). Patients with necrotizing disease more frequently were carriers of LL genotype compared with those who had edematous acute pancreatitis. Furthermore, logistic regression analysis revealed that the presence of L/L allele type doubles the risk for developing pancreatic necrosis in patients with acute pancreatitis. CONCLUSIONS: The polymorphism of the GT repeats in the heme oxygenase-1 promoter region may be a risk factor for developing severe and necrotizing acute pancreatitis.
Assuntos
Repetições de Dinucleotídeos , Heme Oxigenase-1/genética , Pancreatite Necrosante Aguda/genética , Polimorfismo Genético , Regiões Promotoras Genéticas/genética , Doença Aguda , Adulto , Idoso , Colelitíase/complicações , Gorduras na Dieta/efeitos adversos , Progressão da Doença , Edema/sangue , Edema/epidemiologia , Edema/genética , Feminino , Predisposição Genética para Doença , Genótipo , Heme Oxigenase-1/sangue , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pancreatite/sangue , Pancreatite/epidemiologia , Pancreatite/etiologia , Pancreatite/genética , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/epidemiologia , Pancreatite Necrosante Aguda/etiologia , Pancreatite Alcoólica/complicações , Estudos Prospectivos , Fatores de RiscoRESUMO
PURPOSE: To investigate the effects of pentoxifylline (PTX) in experimental acute pancreatitis (AP) starting drug administration after the induction of the disease. METHODS: One hundred male Wistar rats were submitted to taurocholate-induced AP and divided into three groups: Group Sham: sham-operated rats, Group Saline: AP plus saline solution, and Group PTX: AP plus PTX. Saline solution and PTX were administered 1 hour after induction of AP. At 3 hours after AP induction, peritoneal levels of tumor necrosis factor (TNF)-α, and serum levels of interleukin (IL)-6 and IL-10 levels were assayed by Enzyme-Linked Immunosorbent Assay (ELISA). Determinations of lung myeloperoxidase activity (MPO), histological analysis of lung and pancreas, and mortality study were performed. RESULTS: PTX administration 1 hour after induction of AP caused a significant decrease in peritoneal levels of TNF-α and in serum levels of IL-6 and IL-10 when compared to the saline group. There were no differences in lung MPO activity between the two groups with AP. A decrease in mortality was observed in the PTX treatment compared to the saline group. CONCLUSIONS: Administration of PTX after the onset of AP decreased the systemic levels of proinflammatory cytokines, raising the possibility that there is an early therapeutic window for PTX after the initiation of AP.
Assuntos
Pancreatite Necrosante Aguda/tratamento farmacológico , Pentoxifilina/administração & dosagem , Animais , Ensaio de Imunoadsorção Enzimática , Interleucina-10/sangue , Interleucina-6/sangue , Pulmão/química , Pulmão/efeitos dos fármacos , Masculino , Pâncreas/efeitos dos fármacos , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Cloreto de Sódio/administração & dosagem , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
PURPOSE: To investigate the effects of pentoxifylline (PTX) in experimental acute pancreatitis (AP) starting drug administration after the induction of the disease. METHODS: One hundred male Wistar rats were submitted to taurocholate-induced AP and divided into three groups: Group Sham: sham-operated rats, Group Saline: AP plus saline solution, and Group PTX: AP plus PTX. Saline solution and PTX were administered 1 hour after induction of AP. At 3 hours after AP induction, peritoneal levels of tumor necrosis factor (TNF)-α, and serum levels of interleukin (IL)-6 and IL-10 levels were assayed by Enzyme-Linked Immunosorbent Assay (ELISA). Determinations of lung myeloperoxidase activity (MPO), histological analysis of lung and pancreas, and mortality study were performed. RESULTS: PTX administration 1 hour after induction of AP caused a significant decrease in peritoneal levels of TNF-α and in serum levels of IL-6 and IL-10 when compared to the saline group. There were no differences in lung MPO activity between the two groups with AP. A decrease in mortality was observed in the PTX treatment compared to the saline group. CONCLUSIONS: Administration of PTX after the onset of AP decreased the systemic levels of proinflammatory cytokines, raising the possibility that there is an early therapeutic window for PTX after the initiation of AP.
OBJETIVO: Investigar os efeitos da pentoxifilina (PTX) na pancreatite aguda (PA) experimental administrando a droga após a indução da doença. MÉTODOS: Cem ratos machos Wistar foram submetidos à indução da PA através da infusão de taurocolato de sódio e divididos em três grupos: Grupo Sham: sham-operated ratos, Grupo Salina: AP e solução salina, e Grupo PTX: AP e PTX. Solução salina e PTX foram administradas 1 hora após a indução da PA. Três horas após indução da PA os níveis de fator de necrose tumoral (TNF)-α no líquido peritoneal e os níveis séricos de interleucina (IL)-6 e IL-10 foram analisados pelo método de Enzima Imunoensaio (ELISA). A atividade da mieloperoxidase (MPO) foi analisada no pulmão e foram realizadas análises histológicas do pulmão e pâncreas, além do estudo da mortalidade. RESULTADOS: A administração de PTX 1 hora após a indução da PA reduziu significativamente os níveis de TNF-α peritoneal e os níveis séricos de IL-6 e IL-10 quando comparado ao grupo salina. Redução na mortalidade foi observado após o tratamento com PTX comparado ao grupo salina. CONCLUSÃO: A administração de PTX após a indução da PA diminuiu os níveis sistêmicos de citocinas pró-inflamatórias, sugerindo a possibilidade de que existe uma janela terapêutica para PTX após o início do PA.
Assuntos
Animais , Masculino , Ratos , Pancreatite Necrosante Aguda/tratamento farmacológico , Pentoxifilina/administração & dosagem , Ensaio de Imunoadsorção Enzimática , /sangue , /sangue , Pulmão/química , Pulmão/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/patologia , Distribuição Aleatória , Ratos Wistar , Cloreto de Sódio/administração & dosagem , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
OBJECTIVE: To determine the prognosis of patients with necrotic acute pancreatitis receiving medical and surgical treatments. SUMMARY: The severe acute pancreatitis treatment is multidisciplinary and requires a daily evaluation of the patient that will allow to observe changes and apply therapy in due time. The treatment includes: Admission in the ICU, fluids, nutrition and antibiotics, as well as other life supports for high-risk patients. Thus, patients undergo conservative treatment or, if it is necessary, surgery. METHODS: A retrospective study of patients with necrotic acute pancreatitis admitted to the ICU between January 2004 and August 2006. The patients with necrotic acute pancreatitis without signs of sepsis underwent a conservative medical treatment, while fine needle punction-aspiration was performed in all patients who were suffering from necrotic acute pancreatitis and persistent sepsis four weeks after their admission and after discarding and eradicating every non-pancreatic focus of infection. All Gram stain or culture positive patients underwent surgery immediately. RESULTS: Seventy patients with necrotic acute pancreatitis were included in the study. Thirty-six patients (51%) suffered acute pancreatitis with sterile necrosis and underwent a conservative treatment, while 34 patients (49%) developed acute pancreatic with infected necrosis and underwent surgery. The average age was 55.19 vs. 57.65 (p=0.57). The average amylase was 1421.74 vs. 1402.45. (p=0.96). The tomography severity index was 8.47 vs. 8.79 (p=0.36). The Apache II was 8.22 vs. 9 (p=0.46). The average number of failed organs was 0.39 vs. 0.68. (p=0.19). The ICU stay was 10.75 vs. 26.5 days (p<0.05) while the total hospital stay was 46.47 vs. 57.26 days (p<0.05). The mortality rate was (3/36) 8.3% vs. (9/34) 26.5% (p<0.05) for conservative medical treatment vs. surgical treatment, respectively. Between the first and the twelfth month the evaluated patients who attended consultation, after discharge, showed: pancreatic pseudocyst 9/36 (25%) vs. 8/34(23.5%); recurring abdominal pain 3/36 (8.3%) vs. 4/34 (11.8%); and relapsing acute pancreatitis 3/36 (8.3%) vs. 2/34 (5.8%); while 4/36 (11.1%) vs. 3/34 (8.8%) did not show any problem. There were not significant differences between the conservative and the surgical medical treatment, respectively. CONCLUSIONS: Patients suffering acute pancreatitis with sterile necrosis can undergo conservative medical treatment which will result in a lower mortality rate, while the hospital stay, in comparison with acute pancreatitis with infected necrosis, will not be affected.
Assuntos
Unidades de Terapia Intensiva , Pancreatite Necrosante Aguda/terapia , APACHE , Amilases/sangue , Antibacterianos/uso terapêutico , Biópsia por Agulha , Diagnóstico Diferencial , Humanos , Tempo de Internação , Pâncreas/patologia , Pseudocisto Pancreático/diagnóstico , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/tratamento farmacológico , Pancreatite Necrosante Aguda/patologia , Pancreatite Necrosante Aguda/cirurgia , Recidiva , Fatores de TempoRESUMO
The Severe Acute Pancreatic Unit of Edgardo Rebagliati Martins National Hospital was officially created in the year 2000. Up to date, we have cared for more than 195 patients with Pancreatic Necrosis. All of them have been treated under a management protocol presented by us. This has helped us to standardize treatment and also to compare results with work groups around the world. This Protocol comes from our own experience and that of our colleagues abroad with a wide knowledge in this kind of pathology abroad, with whom we maintain close ties.