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.

Activation of neural cholecystokinin-1 receptors induces relaxation of the isolated rat duodenum which is reduced by nitric oxide synthase inhibitors

Cholecystokinin (CCK) influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal muscle in the presence of atropine and guanethidine. CCK-8S (EC50: 39; 95 percent CI: 4.1-152 nM) and cerulein (EC50: 58; 95 percent CI: 18-281 nM) induced a concentration-dependent and tetrodotoxin-sensitive relaxation. Nomeganitro-L-arginine (L-NOARG) reduced CCK-8S- and cerulein-induced relaxation (IC50: 5.2; 95 percent CI: 2.5-18 æM) in a concentration-dependent manner. The magnitude of 300 nM CCK-8S-induced relaxation was reduced by 100 æM L-NOARG from 73 ± 5.1 to 19 ± 3.5 percent in an L-arginine but not D-arginine preventable manner. The CCK-1 receptor antagonists proglumide, lorglumide and devazepide, but not the CCK-2 receptor antagonist L-365,260, antagonized CCK-8S-induced relaxation in a concentration-dependent manner. These findings suggest that CCK-8S and cerulein activate intrinsic nitrergic nerves acting on CCK-1 receptors in order to cause relaxation of the rat duodenum longitudinal muscle.

The Role of Nitric Oxide in Experimental Cerulein Induced Pancreatitis

An enhanced formation of nitric oxide(NO), due to the induction of inducible nitric oxide synthase(iNOS), has been implicated in the pathogenesis of shock and inflammation, but its role in acute pancreatitis still remains controversial. To clarify the role of NO in acute pancreatitis, the present experiment investigated the expression of iNOS and the effect of NOS inhibition on cerulein-induced pancreatitis in rats. Group I received intraperitoneal (ip) injection of normal saline. Group II received two ip injections of cerulein (20 microgram/kg). Group III received injections of N(G)-nitro-L-arginine methyl este(L-NAME) (30 mg/kg) with cerulein. Group IV received L-arginine(250 mg/kg) with cerulein and L-NAME. The expression of iNOS in the pancreas was examined by western blot analysis. The plasma concentration of NO metabolites was measured. The severity of pancreatitis was assessed by measuring serum amylase, pancreas water content and histopathological examination. Compared with controls, the cerulein group displayed significantly increased expression of iNOS and raised plasma NO metabolites. Treatment with L-NAME significantly decreased hyperamylasemia, plasma NO level, and the extent of pancreatic injury. Treatment with L-arginine reversed the effects of L-NAME. These findings suggest that an enhanced formation of NO by iNOS plays an important role in the development of acute pancreatitis, and inhibition of NO production has the beneficial effects in reducing pancreas injury.

Estudo cintilográfico do esvaziamento da vesícula biliar na doença de Chagas crônica / Scintigraphic study of gallbladder emptying in chronic Chagas' disease

Estudos anteriores sobre a motilidade da vesícula biliar na doença de Chagas têm apresentado resultados conflitantes. Este estudo reavalia esta questäo, determinando o esvaziamento da vesícula de pacientes chagásicos crônicos, em respostaà ceruleína, pelo emprego de um método cintilográfico quantitativo. Pacientes chagásicos (n = 18) e controles (n = 12) foram submetidos a estudo cintilográfico do esvaziamento da vesícula biliar em resposta à injeçäo intra-venosa de ceruleína (60 ng/Kg) feita 90 minutos após a administraçäo de 99mTc-HIDA. Cinco minutos antes e logo antes da injeçäo de ceruleína foram obtidas imagens da vesícula biliar em gamacâmera acoplada a computador, o que foi repetido a cada 5 minutos, até 45 minutos após a aplicaçäo do estímulo. As contagens obtidas em regiöes de interesse correspondentes à vesícula biliar, permitiram calcular a fraçäo de ejeçäo do orgäo, bem como compor curvas individuais do esvaziamento da vesícula biliar. Os valores da fraçäo de ejeçäo obtidos na amostra global de pacientes chagásicos (mediana 67,8%, variaçäo de 4,0 a 99,0%) foram maiores que os verificados no grupo controle (mediana: 34,2%; variaçäo de 13,1 a 88,0%), mas a diferença näo atingiu significância estatística (p > 0,05). Entretanto a análise qualitativa das curvas individuais dos pacientes chagásicos sugeriu a existência de dois subgrupos. Em um deles (n = 9), as curvas foram muito semelhantes as dos controles. No outro subgrupo (n = 9) as curvas indicaram um esvaziamento muito rápido e intenso. Estes resultados sugerem que o comprometimento da vesícula biliar na doença de Chagas pode levar a heterogeneidade dos padröes de alteraçäo da motilidade do órgäo, ressaltando-se um conjunto de pacientes em que há hipersensibilidade a um agente colecistocinético exógeno

Radionuclide evaluation of enterogastric reflux using caerulein to stimulate biliary excretion

O refluxo biliar desempenha um importante papel na patogenia da esofagite, gastrite e úlcera gástrica. Recentemente, um método utilizando radioisótopos tem sido empregado como o mais fisiológico na avaliaçäo desta condiçäo. No presente artigo, estudou-se o refluxo enterogástrico, empregando o Tc-99m DISIDA em 37 pacientes em várias situaçöes, a saber: esofagite de refluxo, úlcera péptica, ressecçöes gástricas, vagotomia gástrica proximal e colecistite crônica calculosa. Em 19 pacientes, o esvaziamento vesicular foi estimulado com uma dieta hipercalórica altamente concentrada e nos restantes com a injeçäo endovenosa de 5 ng/kg (14 casos) ou 50 ng/kg de ceruleína. Os resultados obtidos sugerem que a injeçäo endovenosa de ceruleína nas doses de 5 ou 50 ng/kg está associada com refluxo enterogástrico significativo

Secreción de amilasa y quimotripsinógeno en la rata diabética por estreptozotocina / Secretion of amylase and chymotrypsinogen in streptozotocin induced diabetic rats

Se ha estudiado el contenido de amilasa y quimotripsinógeno en la secreción pancreática basal y post-estimulación de la rata anestesiada, y en su respectivo homogenado pancreático. Estos valores se han comparado con los provenientes de un grupo de ratas con diabetes por estreptozotocina. La secreción basal de la rata anestesiada tiene una relación amilasa/quimotripsinógeno de 70,3 ñ 1,1, después de la estimulación con ceruleína (600ng/kg) este valor cae a 17,9 ñ 1,9, siendo de 20,3 ñ 1,2 las cifras halladas en el homogenado pancreático. Se confirma de esta manera que la secreción pancreática basal en la rata anestesiada proviene de un compartimiento minoritario, e inversamente la obtenida post-estimulación provendría de un reservorio mayoritario (proporciones enzimáticas similares a las del páncreas total). En los animales diabéticos se ha observado una relación amilasa/quimotripsinógeno de 40,6 ñ 0,6 durante la secreción basal, después de la estimulación con ceruleína esta cifra en el jugo pancreático desciende a 8,7 ñ 0,9, siendo el valor en sus respectivos homogenados pancreáticos de 9,7 ñ 0,9. La diabetes ha provocado una reducción proporcionalmente mayor para la amilasa que para el quimotripsinógeno, en la secreción basal, en la secreción post-estimulación y en el homogenado pancreático. En conclusión, la diabetes modifica el contenido de las enzimas estudiadas con similar intensidad en ambos compartimientos; la insulina no sería probablemente responsable directa de las diferentes proporciones enzimáticas presente en ambos compartimientos secretorios

Colecistograma ultra-sonográfico com ceruletide intramuscular / Ultrasonographic cholecystogran with intramuscular ceruletide

Foram estudados 13 pacientes, com idades de 19 a 30 anos (média 24,4), sete do sexo feminino e seis do masculino, sem afecçäo orgânica digestiva alta demonstrável, submetidos a exame ultra-sonográfico da vesícula biliar em jejum e 20 minutos após 300 ng/kg de ceruletide IM, sem administraçäo prévia de contraste iodado. Os cálculos volumétricos demonstraram resposta motora vesícular com esvaziamento de 67,27% + ou - 18,65, aos 20 minutos, em relaçäo aos volumes vesiculares de jejum de 18,00 ml + ou - 4,99. Näo foram detectados sinais de lesöes orgânicas e de esforço anormal de contraçäo vesicular à ultra-sonografia ou efeitos colaterais decorrentes da aplicaçäo intramuscular de ceruletide

Effects of Pancreatic Polypeptide on the Secretion of Enzymes and Electrolytes by in Vitro Preparations of Rat and Cat Pancreas

Pancreatic polypeptie (PP) is released from the pancreas in response to vagal stimulation. Amongst other effects, PP has been reported to inhibit pancreatic exocrine function. Apart from any potential physiological role, such inhibition could have important consequences for in vitro studies of pancreatic function employing acetylcholine as a stimulus. We have therefore tested the effect of bovine PP on two in vitro pancreatic preparations: the incubated, uncinate pancreas of young rats and the perfused cat pancreas. In the former, PP (10(-10)-10(-8)M) had little or no effect on enzyme discharge or45Ca efflux under basal conditions or during stimulation with caerulein, CCK-PZ or acetylcholine. In the perfused cat pancreas, similar concentrations of PP were also without effect on fluid secretion evoked by secretin infusion, or enzyme discharge evoked by CCK-PZ injection or infusion. We conclude that bovine PP has no direct effects on the cellular mechanisms responsible for pancreatic electrolyte secretion or enzyme discharge in the species studied.