CA 19-9 levels in patients with acute pancreatitis due to gallstone and metabolic/toxic reasons

SUMMARY OBJECTIVE Acute pancreatitis (AP) is an important clinical event with an increased frequency due to increased life expectancy, obesity, and alcohol use. There are some data about the elevation of carbohydrate antigen (CA) 19-9 levels in benign and malignant pancreaticobiliary events in the literature, but in AP they are limited. The aim of this study was to evaluate the CA 19-9 level in patients with AP and determine its relationship according to the cause. METHODS Between 2010-2018, 173 patients evaluated with CA 19-9 levels as well as by standard laboratory tests were included in the study. CA 1 9-9 levels and laboratory findings were compared in patients with pancreatitis due to gallstone (group 1) and metabolic/toxic reasons such as hyperlipidemia, alcohol, or drug use (group 2). RESULTS There were 114 (66%) patients in the group 1 and 59 (34%) patients in the group 2. The majority of patients with high CA 19-9 level were in group 1 (92.1% vs 6.8%). CA 19-9 level, as well as amylase, lipase, AST, ALT and bilirubin levels were found to be statistically higher in patients with AP due to gallstone compared to patients with metabolic/toxic AP. CONCLUSIONS Patients with AP due to gallstone, were found to have a high level of CA 19-9 at admission. Early stage CA 19-9 levels may contribute to standard laboratory tests in the etiology of the disease in patients diagnosed with AP.

RESUMO OBJETIVO A pancreatite aguda (PA) é um evento clínico importante e cada vez mais frequente devido ao aumento da expectativa de vida, obesidade e do consumo de álcool. Existem alguns dados na literatura sobre a elevação dos níveis do antígeno carboidrato (CA) 19-9 em eventos pancreato-biliares benignos e malignos, mas eles são limitados em relação à PA. O objetivo deste estudo foi avaliar o nível de CA 19-9 em pacientes com PA e determinar sua relação com a causa da doença. PACIENTES E MÉTODOS Entre 2010 e 2018, 173 pacientes submetidos a uma avaliação dos níveis de CA 19-9, bem como testes laboratoriais padrão, foram incluídos no estudo. Os níveis de CA 19-9 e os achados laboratoriais foram comparados em pacientes com pancreatite devido a cálculos biliares (grupo 1) e razões metabólicas/tóxicas, como hiperlipidemia, álcool, ou uso de drogas (grupo 2). RESULTADOS Um total de 114 (66%) pacientes foi incluído no grupo 1 e 59 (34%) no grupo 2. A maioria dos pacientes com alto nível de CA 19-9 estavam no grupo 1 (92,1% versus 6,8%). O CA 19-9, bem como os níveis de amilase, lipase, AST, ALT e bilirrubina foram estatisticamente mais altos em pacientes com PA devido a cálculos biliares em comparação àqueles com PA devido a alterações metabólicas/tóxicas. CONCLUSÃO Pacientes com PA devido a cálculos biliares apresentaram um alto nível de CA 19-9 no momento da internação. O nível de CA 19-9 na fase inicial pode contribuir para testes laboratoriais padrão na etiologia da doença em pacientes com diagnóstico de PA.

Effects of baicalin on inflammatory reaction, oxidative stress and PKDl and NF-kB protein expressions in rats with severe acute pancreatitis

Abstract Purpose: To investigate the effects of baicalin on inflammatory reaction, oxidative stress and protein kinase D1 (PKD1) and nuclear factor-kappa B (NF-κB) protein expressions in severe acute pancreatitis (SAP) rats. Methods: Sixty rats were divided into sham operation, model, and low-, medium- and high-dose baicalin group. SAP model was established in later 4 groups. The later 3 groups were injected with 0.1, 0.2 and 0.4 ml/100 g 5% baicalin injection, respectively. At 12 h, the serum SAP related indexes and inflammatory factors, peripheral blood CD3 and γδT cell percentages, wet/dry ratio and pancreas ascites volume, oxidative stress indexes and PKD1 and NF-κB protein expressions in pancreatic tissue were determined. Results: Compared with model group, in high-dose baicalin group the wet/dry ratio and ascites volume, serum amylase level, phospholipase A2 activity, TNF-α, IL-1 and IL-6 levels, and pancreatic malondialdehyde level and PKD1 and NF-κB protein expression were significantly decreased (P < 0.05), and peripheral blood CD3 and γδT cell percentages and pancreatic superoxide dismutase and glutathione peroxidase levels were significantly increased (P < 0.05). Conclusion: Baicalin can resist the inflammatory reaction and oxidative stress, and down-regulate protein kinase D1 and nuclear factor-kappa B protein expressions, thus exerting the protective effects on severe acute pancreatitis in rats.

CD64 Expression Is Increased in Patients with Severe Acute Pancreatitis: Clinical Significance

BACKGROUND/AIMS: Upregulated CD64 expression on neutrophils is the most useful marker for acute bacterial infections and systemic inflammation. However, it is unknown whether CD64 is involved in the pathogenesis of acute pancreatitis (AP). This study was designed to determine whether CD64 is implicated in severe acute pancreatitis (SAP), and thus, is a suitable marker for SAP. METHODS: SAP was induced in rats with an intraperitoneal injection of L-arginine. CD64 expression in the rat pancreas was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. Additionally, the CD64 mRNA expression in peripheral blood leukocytes from 21 patients with mild acute pancreatitis (MAP) and 10 patients with SAP was investigated at the time of admission and during remission by qRT-PCR. RESULTS: CD64 mRNA and protein expression in the pancreas was significantly higher in rats with SAP, compared to the controls. The CD64 expression was higher in the patients with SAP than in the patients with MAP. During remission, CD64 mRNA decreased in both the MAP and SAP patients. The area under the curve of CD64 expression for the detection of SAP was superior to both the Ranson and the Acute Physiology and Chronic Health Evaluation II scores. CONCLUSIONS: The CD64 level was significantly increased in correlation with the disease severity in SAP and may act as a useful marker for predicting the development of SAP.

Do opioid receptors play a role in the pathogenesis of the inflammatory response in acute pancreatitis? / Os receptores opioides desempenham papel na patogênese da resposta inflamatória na pancreatite aguda?

PURPOSE: To investigate the effect of the opioid blocker naltrexone in the inflammatory response in acute pancreatitis (AP). METHODS: Acute pancreatitis was induced in anesthetized male Wistar rats by retrograde injection of 2.5% sodium taurocholate diluted in 0.5ml saline into the main pancreatic duct. Animals were randomized to the following experimental groups: Control Group (n=9): animals received an intraperitoneal injection of saline solution (0.5ml), 15 minutes before the induction of AP. Naltrexone Group (n=9): animals received an intraperitoneal injection of naltrexone 0.5ml (15 mg/kg), 15 minutes before induction of AP. Peritoneal levels of TNF-α and serum levels of IL-6 and amylase were determined The volume of the ascitic fluid was also evaluated. Myeloperoxidase (MPO) activities were analyzed in homogenates of pulmonary tissue. RESULTS: There were no significant differences in the ascitic fluid volume, nor in TNF-a and IL-6 levels in the naltrexone group compared to controls. Treatment with naltrexone did not affect the lung MPO activity compared to control group. CONCLUSIONS: The opioid receptors don't play an important role in the pathogenesis of the inflammatory response in acute pancreatitis. If opioids affect leukocytes inflammatory signaling, there are no major implications in the pathogenesis of acute pancreatitis.

OBJETIVO: Investigar o efeito do bloqueador opióide naltrexone na resposta inflamatória da pancreatite aguda. METODOS: Pancreatite aguda foi induzida em ratos machos Wistar, através de injeção retrógada de solução de taurocolato de sódio a 2,5% nos ductos pancreáticos. Os animais foram alocados em dois grupos: Grupo controle (n=9) animais receberam 0,5 ml de solução salina intra-peritonial 15 minutos antes da indução da pancreatite aguda e Grupo naltrexone (n=9) animais receberam naltrexone (15mg/kg de peso), em 0,5 ml de volume final por via intraperitoneal, 15 minutos antes da indução da pancreatite aguda. Foram avaliados o volume de ascite, os níveis séricos de amilase e IL-6, assim como TNF-α peritoneal e a atividade da mieloperoxidase (MPO) no tecido pulmonar. RESULTADOS: Não foram encontradas diferenças significantes nos parâmetros analisados entre o grupo que recebeu solução salina e o que recebeu naltrexone . CONCLUSÕES: Os receptores opióides não desempenham papel importante na resposta inflamatória sistêmica associada à pancreatite aguda. Se os opioides alteram a sinalização inflamatória nos leucócitos está ação não se reflete na patogênese da pancreatite aguda.

Hypertonic saline and reduced peroxynitrite formation in experimental pancreatitis

OBJECTIVES: In this study, we tested the hypothesis that hypertonic saline exerts anti-inflammatory effects by modulating hepatic oxidative stress in pancreatitis. INTRODUCTION: The incidence of hepatic injury is related to severe pancreatitis, and hypertonic saline reduces pancreatic injury and mortality in pancreatitis. METHODS: Wistar rats were divided into four groups: control (not subjected to treatment), untreated pancreatitis (NT, pancreatitis induced by a retrograde transduodenal infusion of 2.5 percent sodium taurocholate into the pancreatic duct with no further treatment administered), pancreatitis with normal saline (NS, pancreatitis induced as described above and followed by resuscitation with 0.9 percent NaCl), and pancreatitis with hypertonic saline (HS, pancreatitis induced as described above and followed by resuscitation with 7.5 percent NaCl). At 4, 12, and 24 h after pancreatitis induction, liver levels of inducible nitric oxide synthase (iNOS), heat-shock protein 70, nitrotyrosine (formation of peroxynitrite), nitrite/nitrate production, lipid peroxidation, and alanine aminotransferase (ALT) release were determined. RESULTS: Twelve hours after pancreatitis induction, animals in the HS group presented significantly lower iNOS expression (P<0.01 vs. NS), nitrite/nitrate levels (P<0.01 vs. NS), lipid peroxidation (P<0.05 vs. NT), and ALT release (P<0.01 vs. NS). Twenty-four hours after pancreatitis induction, nitrotyrosine expression was significantly lower in the HS group than in the NS group (P<0.05). DISCUSSION: The protective effect of hypertonic saline was related to the establishment of a superoxide-NO balance that was unfavorable to nitrotyrosine formation. CONCLUSIONS: Hypertonic saline decreases hepatic oxidative stress and thereby minimizes liver damage in pancreatitis.

The effect of anti-hypertensive drugs on the obstructive pancreatitis in rats / Efeitos de fármacos anti-hipertensivos sobre pancreatite obstrutiva em ratos

PURPOSE: To investigate the effect of ACE inhibitor, lisinopril and AT1 blocker, losartan, on the obstructive pancreatitis in rat. METHODS: Acute pancreatitis in rats (n=21) was induced for a common hepatic duct were ligated proximal to its entry into the pancreas and the common bile - pancreatic duct were also ligated near its junction with the duodenum, under ether anesthesia, after which the abdomen were closed. The animals was divided in tree groups, being two treated and control group. The animals was treated with Losartan and Lisinopril at the dose of 10µg/Kg body weight per day, i.p., in a proportional volume, for five days, before and after treatement. RESULTS: The inflammation, collagen deposition in the pancreas of treated animals were smaller, suggesting that the use of antihypertensive agents interfered positively in the depletion of the injury of the pancreas. Scythe showed a correlation between activity of pancreatic stellate cells (PSCs) lower in treated animals when compared to control. CONCLUSION: The pancreatic stellate cells strength are involved in collagen production during acute pancreatitis and why antihypertensive drugs such as lisinopril and losartan may possibly have beneficial effects in reducing pancreatic fibrosis in models of experimental obstructive pancreatitis.

OBJETIVO: Investigar o efeito de um inibidor da ECA, lisinopril e bloqueador AT1, losartan, a pancreatite obstrutiva em ratos. MÉTODOS: Pancreatite aguda em ratos (n = 21) foi induzida por um ducto hepático comum foram ligados proximal à sua entrada no pâncreas e da bílis comum - ducto pancreático também foram ligados perto de sua junção com o duodeno, sob anestesia com éter, após o que abdome foram fechadas. Os animais foram divididos em três grupos, sendo dois tratados eo grupo controle. Os animais foram tratados com lisinopril e losartan na dose de 10µg/Kg de peso corporal por dia, IP, em um volume proporcional, por cinco dias, antes e depois do tratamento com. RESULTADOS: A inflamação, deposição de colágeno no pâncreas de animais tratados foram menores, sugerindo que o uso de agentes anti-hipertensivos interferiram positivamente na diminuição da lesão do pâncreas. Este estudo mostrou uma correlação entre a atividade das células pancreáticas estreladas (CSP) menor nos animais tratados quando comparados ao control. CONCLUSÃO: A força das células pancreáticas estreladas está envolvida na produção de colágeno durante a pancreatite aguda e por medicamentos anti-hipertensivos, tais como lisinopril e losartan pode eventualmente ter efeitos benéficos na redução da fibrose do pâncreas em modelos experimentais de pancreatite obstrutiva.

Liver lipid peroxidation and antioxidant capacity in cerulein-induced acute pancreatitis

The aim of this study was to evaluate the role of oxidative damage in pancreatitis-induced hepatic injury. Thirty-five rats were divided into five groups (each of 7 rats): control, cerulein (100 µg/kg body weight), cerulein and pentoxifylline (12 mg/kg body weight), cerulein plus L-NAME (10 mg/kg body weight) and cerulein plus L-arginine (160 mg/kg body weight). The degree of hepatic cell degeneration differed significantly between groups. Mean malondialdehyde levels were 7.00 ± 2.29, 20.89 ± 10.13, 11.52 ± 4.60, 18.69 ± 8.56, and 8.58 ± 3.68 nmol/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Mean catalase activity was 3.20 ± 0.83, 1.09 ± 0.35, 2.05 ± 0.91, 1.70 ± 0.60, and 2.85 ± 0.47 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively, and mean glutathione peroxidase activity was 0.72 ± 0.25, 0.33 ± 0.09, 0.37 ± 0.04, 0.34 ± 0.07 and 0.42 ± 0.1 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Cerulein-induced liver damage was accompanied by a significant increase in tissue malondialdehyde levels (P < 0.05) and a significant decrease in catalase (P < 0.05) and GPx activities (P < 0.05). L-arginine and pentoxifylline, but not L-NAME, protected against this damage. Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage.

Analysis of human pancreatic juice in tests of pancreatic function

No abstract available.

NF-kB and cytokines in pancreatic acinar cells

Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and deveolpment of pancreatitis. A hallmark of the inflammatory response is the induction of cytokine gene expression, which may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-KB). Present study aims to investigate whether neutrophils primed by 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) affect the productions of H2O2 and lipid peroxide (LPO), NF-kappaB activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by N-acetylcysteine (NAC) and superoxide dismutase (SOD). ROS generation in neutrophils increased by PMA, which was inhibited by NAC and SOD. The productions of H2O2, LPO and TNF-alpha were increased with the amounts of PMA-primed neutrophils added to acinar cells while the productions of H2O2, LPO and cytokines increased with time. PMA-primed neutrophils resulted in the activation of two species of NF-kappaB dimers (a p50/p65 heterodimer and a p50 homodimer). Both NAC and SOD inhibited neutrophil-induced alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates NF-kappaB, resulting in upregulation of inflammatory cytokines in acinar cells. Antioxidants such as NAC might be clinically useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-KB and decreasing cytokine production.

Evidence for oxidant stress in chronic pancreatitis.

BACKGROUND: Oxidant stress leading to lipid peroxidation is reported to be the common link in the pathogenesis of chronic pancreatitis irrespective of etiology. AIM: To look for evidence of lipid peroxidation in duodenal juice in patients with chronic pancreatitis. METHODS: 19 patients with chronic pancreatitis (14 tropical, 5 alcoholic) and 19 age- and sex-matched subjects with abdominal pain without any cause were studied. Contents were aspirated from the second part of the duodenum during gastroduodenoscopy. Malonyl dialdehyde (MDA) levels were measured in duodenal juice by the thiobarbituric acid method. RESULTS: MDA levels were higher in patients than in the control group (mean [SD] 42.6 [17.0] vs 29.2 [11.7] nmol/mL; p < 0.05). On linear and multiple regression analysis, none of the disease factors correlated with duodenal juice MDA levels. CONCLUSIONS: Lipid peroxidation products are increased in patients with chronic tropical and alcoholic pancreatitis.

Gasto energético y estado metabólico en pancreatitis aguda grave con y sin sepsis / Energy expenditure and metabolic status in patients with acute severe pancreatitis with or without sepsis

Objetivo: medir el estado metabólico, el gasto energético en reposo (GER) y el cociente respiratorio (CR) de pacientes con pancreatitis aguda grave (PAG) con y sin sepsis asociada. Material y métodos; Se evaluaron 10 pacientes con PAG; todos estaban con ventilación mecánica controlada y sedados. Para medir el GER y El CR se realizó calorimetría indirecta (CI). El estado metabólico de los pacientes se obtuvo comparando el gasto energético en reposo medido (GERm) con el gasto energético calculado (GERc), obtenido por la fórmula de harris-Benedict basal de acuerdo con la calsificación de Feurer y Foster. Se midió la excreción de nitrógeno ureico urinario (NUU) en orina de 24 horas. Resultados; siete pacientes estaban hipermetabólicos (Germ > 10 por ciento GERc). Al realizar el promedio del GERm éste fue 25 por ciento mayor que el GERc en cinco pacientes con PAG y sepsis (1958 ñ 170 versus 1568 ñ 138 Kcal/día) y 15 por ciento en dos de tres pacientes con PAG sin sepsis (1916 ñ 170 versus 1663 ñ 164 Kcal/día). El CR fue de 0.95 ñ 0.05 y de 0.85 ñ 0.04 en los pacientes con PAG con y sin sepsis respectivamente. Dos pacientes con PAG y sepsis se encontraron normometabólicos (Germ en tres 0 a 9 por ciento versus GERc), un paciente con PAG sin sepsis se encontró hipometabólico (GERm < 10 por ciento GERc). El promedio de la excreción de NUU fue de 15.5 g/día. Conclusión: la medición del GER por CI demostró que 70 por ciento de los pacientes con PAG se encontraban hipermetabólicos. En los pacientes con PAG el GERm se incrementa en promedio 15 por ciento; este incremento llega hasta 25 por ciento cuando existe sepsis asociada. Los resultados del CR sugieren una utilización de sustraro energético mixto. El catabolismo proteínico de pacientes con pancreatitis aguda grave es intenso

Nuclear magnetic resonance spectroscopy in pancreatic disorders

Nuclear magnetic resonance spectroscopy (NMRS) is a powerful technique that enables continuous monitoring of biochemical processes in tissues and organs in a non-invasive manner. A model of isolated perfused rat pancreas, suitable for NMRS studies, was developed. Acute pancreatitis was induced by injections of either 0.5 me 5 per cent sodium taurocholate (TC) into the bile ducts, or 1.0 ml 10 per cent TC injection into the pancreatic parenchyma. Phosphorus (P) NMRS of experimental pancreatitis were characterized by a transient signal at -0.18ñ0.04 ppm which was assigned as solubilized lecithin, and cana be used as an indicator of the early also found during acute pancreatitis,and paralleled the extension of the pathological damage. The role of NMRS in pancreatic cancer diagnosis and its treatment were assessed in three moeels of pancreatic neoplasms. Perfused MIA PaCa-2 human pancreatic cancer cells, subcutaneously implanted pancreatic tumors in hamster, and pancreatic tumors induced in-situ in rats by direct application of the carcinogen 7,12-dimethil benzanthracene, were studied by phosphorus (P), sodium (Na) and proton (H) NMRS. P spectra of pancreatic cancer were similar in both the normal pancreas and the pancreatic tumors (39-40 mmol/g wet weight)...

La dieta hiperlipidica cronica intensifica la pancreatitis aguda inducida por ceruleina en la rata / Cerulein-induced acute pancreatitis enhanced by chronic hyperlipidic diet in the rat

El modelo experimental de pancreatitis aguda (PA) inducido por ceruleína (CR) está caracterizado por un significativo aumento de la lipasa sérica, edema inersticial pancreático, observación poco frecuente de cariorrexis y aparición de vacuolas acinares. Ratas Wistar macho adultas fueron alimentadas por una dieta hiperlipídica (lípidos al 45 por ciento) durante 6 semanas, usando como control ratas con dieta normolipídica (lipidos 5 por ciento). Se indujo una PA mediante una dosis única de CR intraperitoneal de 50 mugr/Kg. El incremento de la lipasa sérica fue similar en ambos grupos tratados con CR (dieta control e hiperlipídica). Por otra parte se comprobó incremento del edema intersticial, de la cariorrexis y fundamentalmente del grado de vacuolización de las células acinares con respecto al grupo control. Se concluye que la dieta hiperlipídica administrada en forma crónica intensifica las lesiones histopatológicas de la PA inducida por CR.

Distribuiçäo do colágeno I e III nas pancreatites crônicas alcoólicas e näo alcoólicas pelo método picro sirius polarizaçäo / Distribution of collagen I and III in alcoholic and non-alcoholic chronic pancreatitis by the picro sirius polarizations method

Estuda-se a distribuiçäo dos colágenos I e III nas pancreatites crônicas alcoólicas e näo alcoólicas utilizando o método picro sirius polarizaçäo, notando-se em ambas o predomínio das fibras tipo I sobre as do tipo III com aspectos característicos (densas e fragmentadas) e invadindo a regiäo intralobular. Um elemento característico das pancreatites crônicas alcoólicas é o aumento relativo das fibras do tipo III intralobular