ceruletide and Liver-Diseases

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 microg/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.

Topics: Acute Disease; Animals; Arginine; Ceruletide; Female; Free Radical Scavengers; Lipid Peroxidation; Liver Diseases; NG-Nitroarginine Methyl Ester; Pancreatitis; Pentoxifylline; Rats; Rats, Wistar; Reactive Oxygen Species

The prognosis of acute pancreatitis (AP) depends upon the degree of pancreatic necrosis and the intensity of multisystem organ failure. The liver contributes to the systemic manifestations of AP by releasing some cytokines. This study was undertaken to examine comparative effects of melatonin, antioxidant mixture containing L(+)-ascorbic acid and N-acetyl cysteine, pentoxifylline and L-arginine on hepatic damage induced by caerulein-pancreatitis.. The liver specimens of all groups showed histopathological alterations such as hepatocyte necrosis, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration. TEM studies revealed vacuole formation, mitochondrial degeneration, lysosome accumulation and necrosis. The mean histopathological score of the caerulein group was significantly different from that of each treatment group.. L-Arginine and antioxidant administration be important for reducing hepatic damage induced by AP. Improvement of hepatic damage, in turn, might be beneficial for the prognosis of AP.

Topics: Acetylcysteine; Acute Disease; Animals; Antioxidants; Arginine; Ascorbic Acid; Ceruletide; Female; Liver Diseases; Melatonin; Pancreatitis; Pentoxifylline; Rats; Rats, Wistar; Statistics, Nonparametric

Here we compare the degree of pancreatitis caused by cerulein in mice lacking 5-lipoxygenase (5-LO) and in the corresponding wild-type mice. Intraperitoneal injection of cerulein in mice resulted in severe, acute pancreatitis characterized by oedema, neutrophil infiltration and necrosis and elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for intracellular adhesion molecule-1 (ICAM-1), P-selectin and E-selectin in the pancreas and lung of cerulein-treated mice. In contrast, the degree of (1) pancreatic inflammation and tissue injury (histological score), (2) up-regulation/expression of P-selectin, E-selectin and ICAM-1, and (3) neutrophil infiltration was markedly reduced in pancreatic and lung tissue obtained from cerulein-treated 5-LO-deficient mice. These findings support the view that 5-LO plays an important, pro-inflammatory role in the acute pancreatitis caused by cerulein in mice.

Topics: Acute Disease; Animals; Arachidonate 5-Lipoxygenase; Ceruletide; E-Selectin; Intercellular Adhesion Molecule-1; Lipid Peroxidation; Liver Diseases; Mice; Mice, Knockout; Neutrophil Infiltration; P-Selectin; Pancreatitis; Respiratory Distress Syndrome

The aim of this study was to evaluate the controversial specificity of the plasma amino acid (AA)-consumption test in detecting pancreatic diseases by using two different quantitative methods. A total of 55 subjects: 13 healthy subjects, 13 patients with chronic pancreatitis (three mild/moderate, eight severe), 13 patients with pancreatectomy and complete suppression of the exocrine pancreatic secretion, eight patients with chronic liver disease (five with impaired synthetic function), and eight patients with chronic renal failure. Total plasma AAs were quantified by a colorimetric method (p-benzoquinone) in all subjects, at 0, 30, 45, and 60 min during and 30 min after minute 60 of i.v. cerulein infusion (50 ng/kg/h). Either total and individual AAs were quantified by chromatography (high-performance liquid chromatography; HPLC) in 10 healthy subjects, 10 patients with pancreatectomy, and 10 with chronic pancreatitis at 0 and 60 min after the start of the cerulein infusion. For the colorimetric method, healthy subjects had maximal percentage decreases of total AA concentrations not significantly different from those of patients with pancreatectomy and significantly higher than those of patients with chronic pancreatitis (p < 0.0001) or chronic liver disease (p < 0.001). Pancreatic function, as assessed by fecal elastase-1 test, was not significantly correlated to the maximal percentage decrease in total plasma AAs. For the chromatographic method, total AA concentrations were not significantly correlated to those determined by colorimetry. The concentration of each of the individual plasma AAs varied considerably in each group. Fecal elastase-1 values were normal (> or = 200 microg/g) in all patients without pancreatic disease and in only one of 11 patients with chronic pancreatitis and exocrine insufficiency. The type of method used can explain the different results of the AA-consumption test. This test is not very specific for the pancreas.

Topics: Adult; Aged; Amino Acids; Ceruletide; Chromatography, Ion Exchange; Colorimetry; Evaluation Studies as Topic; Feces; Female; Humans; Kidney Failure, Chronic; Liver Diseases; Male; Middle Aged; Pancreatectomy; Pancreatic Diseases; Pancreatic Elastase; Pancreatic Function Tests; Pancreatitis; Time Factors

The diagnostic usefulness of fasting total serum bile acids (SBA/F) in the detection of liver diseases and assessment of different aspects of hepatic function alteration was evaluated in 61 healthy subjects and 186 patients with liver disease. The value of SBA/F was compared with other routine tests. In 49 healthy subjects and 92 patients, serum bile acids were also measured after the im administration of Ceruletide as a cholecystokinetic agent (SBA/C). The diagnostic efficacy for the detection of disease states was better with aspartate-aminotransferase (EC 2.6.1.1) and alanine-aminotransferase (EC 2.6.1.2) than with SBA/F. When SBA/C was also determined the diagnostic efficacy was not substantially better than the SBA/F test. In the assessment of hepatocellular necrosis SBA/F showed a higher rate of misclassification errors compared to alanine-aminotransferase (mean error 45% vs 17%), whereas SBA/F gave similar results with direct bilirubin and pseudocholinesterase (EC 3.1.1.8) in the evaluation of cholestasis (mean error 40% vs 41%) and impaired biosynthesis (mean error 39% vs 40%), respectively. Serum bile acid determination did not show any significant diagnostic advantage with respect to the other routine liver tests.

Topics: Adolescent; Adult; Aged; Alanine Transaminase; Aspartate Aminotransferases; Bile Acids and Salts; Bilirubin; Butyrylcholinesterase; Ceruletide; Cholestasis; Fasting; Female; gamma-Glutamyltransferase; Humans; Liver; Liver Diseases; Liver Function Tests; Male; Middle Aged; Necrosis

Series of total bile acid levels in blood plasma of definite time intervals before and after administration of three different stimulants, i.e. caerulein, egg yolk and fatty meal, were investigated in 10 normal subjects as a control group, in three patients in the florid stage of acute viral hepatitis, in 15 patients in the convalescent stage of acute viral hepatitis, in 10 patients with chronic persistent hepatitis, in 15 patients with chronic aggressive hepatitis, in 20 patients with cirrhosis of the liver and in 15 patients with fatty liver. This procedure can be regarded as an endogenous bile acid tolerance test and can be utilized as a differential diagnostic tool for chronic liver diseases.

Topics: Adult; Aged; Bile Acids and Salts; Ceruletide; Chronic Disease; Dietary Fats; Egg Yolk; Enterohepatic Circulation; Fatty Liver; Female; Gallbladder; Hepatitis; Humans; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Muscle Contraction

Twenty-four liver patients and seven healthy subjects underwent the enzymatic-fluorimetric assay of total serum bile acids during fasting and after a hyperlipidic meal, both alone and with the intramuscular administration of 0.3 microgram/kg of cerulein. A third test with cerulein alone was carried out on the control group and on 12 liver patients. The liver patients were divided into two groups; those with moderate and severe liver disease, according to the degree of liver function impairment and the clinical data. The best discriminant efficiency was observed in the test with the meal alone, even if, in the liver patients, the meal with cerulein caused a greater percentual increase of serum bile acids. After taking into account the most significant correlations between serum bile acids and liver function tests, the addition of cerulein to the meal may be recommended for liver patients with previous cholecystectomy or gallbladder pathology.

Topics: Adult; Aged; Bile Acids and Salts; Ceruletide; Dietary Fats; Drug Evaluation; Fasting; Female; Humans; Liver Diseases; Liver Function Tests; Male; Middle Aged

Plasma cyclic AMP levels were determined during a 40 minute secretin infusion (1 Cl.U kg-1h-1) followed by a 40 minute combined secretin (1 Cl.U kg-1h-1) caerulein (75 ng kg-1h-1) infusion. In nine healthy subjects, both secretin alone and secretin in combination with caerulein did not affect plasma cyclic AMP levels. The same was observed in six patients with chronic pancreatitis. By contrast, in patients suffering from liver disease (nine cases) or extrahepatic cholestasis (six cases), secretin elicited large increases in plasma cyclic AMP concentration; the mean values attained being, respectively, seven and four times higher than before the infusion. On the other hand, increases in plasma cyclic AMP 10 minutes after a bolus injection of glucagon (1 mg) were four times lower in the liver disease group as compared to the controls. The results reported here suggest that the liver plays a major role in the degradation of plasma cyclic AMP produced by target tissues responding to secretin, and in the release of cyclic AMP under glucagon. Liver disease reduce the capacity of the liver to clear cyclic AMP from the blood. The pancreas does not contribute significantly to the cyclic AMP in the blood.

Topics: Ceruletide; Cholestasis; Cyclic AMP; Female; Glucagon; Humans; Liver Diseases; Male; Pancreatic Diseases; Secretin