1,720,986 research outputs found
Altered lipid peroxidation/glutathione ratio in experimental extrahepatic cholestasis.
No full text1. Lipid peroxidation can occur in the presence of a cellular antioxidant-oxidant imbalance, but the role of lipid peroxides in cholestasis is not well understood.
2. This study was undertaken in order to: (i) evaluate the behaviour of a product of lipid peroxidation (thiobarbituric acid-reactive species), and of an important antioxidant tripeptide, reduced glutathione, in the course of experimental extrahepatic cholestasis; and (ii) ascertain whether there was a link between this aspect and the alterations in liver morphology.
3. Forty-five male Sprague-Dawley rats (250-300 g) were double bile duct ligated and followed from 1 to 28 days. At the end of each experimental period, blood and liver samples were collected for thiobarbituric acid-reactive species and glutathione determinations.
4. Bile duct ligated rats showed a marked increase in liver weight which was related to cholestasis duration and to some anatomical alterations such as bile duct proliferation and dilation and liver fibrosis (periportal, perivenular, perineoductular and parenchymal).
5. An increase in serum lipid peroxidation was also observed but this was not linked to hepatic thiobarbituric acid-reactive species. Erythrocyte and hepatic glutathione decreased in relation to cholestasis duration. Serum lipid peroxides and erythrocyte glutathione were correlated with liver cell necrosis.
6. In conclusion, experimental extrahepatic cholestasis determines bile duct proliferation and fibrosis, the degree of which is directly related to the duration of cholestasis itself and to liver cell necrotic phenomena. Furthermore, extrahepatic cholestasis is associated with increased lipid peroxide formation and with a depletion of reduced glutathione both in the liver and in the erythrocytes. The alteration in the oxidative balance may be a contributory factor in necrotic liver cell phenomena
Increased serum phospholipase A2 activity in advanced chronic liver disease as an expression in the acute phase response
No full textRenal functional alterations in extrahepatic cholestasis: Can oxidative stress be involved?
No full textRenal function may be compromised by extrahepatic cholestasis. In this context, the nephrotoxic role of bile salts is well known. Recently, however, it has been claimed that other factors, such as lipid peroxides, are involved. We therefore created bile duct ligation in 40 Sprague-Dawley rats. During the follow-up (from 1 to 28 days), significant variations were found in liver histological parameters, but not in renal morphology. Fourteen days after ligation, significant increases were found in serum and urinary thiobarbituric-acid-reactive species and phospholipase A2 (indirect indices of lipid peroxidation), whereas 8-10 days after ligation, a significant decrease was observed in erythrocytic and hepatic GSH levels. The variations in urinary thiobarbituric-acid-reactive species and in phospholipase A2 were not correlated with concomitant variations in the sera. Urinary lipid peroxides were directly correlated with the degree of liver morphological alterations and inversely with circulating GSH. Urinary outputs of lipid peroxides, phospholipase A2 and N-acetyl-glucosaminidase were correlated with each other. These results suggest that there is an imbalance in the oxidative-antioxidant hepatic system in experimental extrahepatic cholestasis. The reduced bioavailability of blood GSH may alter the oxidative equilibrium in other organs, such as the kidney, triggering and favoring the lipoperoxidative cascade
The pancreatic cancer cell line MIA PaCa2 produces one or more factors able to induce hyperglycemia in SCID mice
No full textA reduced glucose tolerance or frank diabetes mellitus is a frequent finding in patients with pancreatic cancer. The aim of this study was to verify whether the pancreatic cancer cell line MIA PaCa2 was able to produce any factor which could induce hyperglycemia in SCID (severe complete immunodeficient) mice. MIA PaCa2 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) for 7 days. Twenty-five female SCID mice were used. They were daily i.p. injected with 300 ul of cell culture supernatants (Group T, n = 13) or with 300 ul of DMEM (Group C, n = 12) and followed up for 82 days. Blood glucose levels were significantly higher in Group T than in Group C on days 10 and 25. Intravenous glucose tolerance test, success-fully performed in 9 animals (4 controls and 5 treated), demonstrated a significantly reduced glucose tolerance in Group T compared to Group C mice. At sacrifice, plasma and pancreatic insulin and glucagon levels did not vary between groups. The ratio between pancreatic and plasma insulin was significantly lower in Group T than in Group C. We conclude that: 1. The pancreatic cancer cell line MIA PaCa2 produces one or more soluble factors able to cause hyperglycemia in vivo; 2. this effect is not immunologically mediated, and 3. this/these factor/s could both interfere with the pancreatic beta cells and/or with insulin peripheral action
Cytokines and the progression of liver damage in experimental bile duct ligation
No full text1. Cytokines are soluble factors whose action has been documented in physiological and pathological conditions. Some may be involved in the pathogenesis of cholestasis, whether of acute or chronic origin. 2. The aim of the present study was to evaluate the influence of epidermal growth factor (EGF), transforming growth factor (TGF)-β1 interleukin (IL)-6 and tumour necrosis factor (TNF) on cholestasis. Findings from Sprague-Dawley rats submitted to bile duct ligation for 1-28 days were compared with those from controls, which underwent laparotomy but not bile duct ligation. 3. Biochemical and morphological findings confirmed that the experimental procedure was successful. At the end of each follow-up period, the hepatic levels of the cytokines were determined and compared with liver histology findings. 4. The four cytokines studied showed different patterns of activation: hepatic levels of EGF, higher in the experimental than the control group, were comparable with the proliferative picture. The TGF-β1 pattern was correlated with data of periportal, perivenular and perineoductular fibrosis, confirming that this cytokine has a role in mediating the synthesis of matrix proteins. A fluctuating, phasic pattern was found for TNF in the experimental group, with high values on day 0, a decrease on the first and second postoperative days and then two peaks on days 8 and 14. Finally, immediately after surgical manipulation, high levels of IL-6 were found in the experimental group, followed by a decrease in levels until zero values were obtained. 5. This suggests that the obstructive condition produces several cytokine responses, each of which contributes to determine the cholestatic condition
Extra-hepatic cholestasis determines a reversible increase of glycoproteic tumour markers in benign and malignant diseases.
No full textThis study was performed in order to assess the relative role of cholestasis in increasing some serum glycoproteic markers of malignancy (CA 19-9, TPA, CEA). 30 Patients with benign and 16 with malignant extra-hepatic cholestasis were studied on admission (stage A) and after the operative or spontaneous resolution of the cholestatic picture (stage B). CA 19-9 and TPA were found to be lower in stage B than in stage A benign diseases. A similar behaviour was found in malignant diseases, although findings were significant only for CA 19-9. In neither of the patient groups was CEA found to present a significant trend.
Extra-hepatic cholestasis appears able to increase per se serum glycoproteic markers in benign diseases, with variations proportional to the severity of the clinical picture. The same considerations can apply to malignancies, even if in these situations the production of tumour markers by the neoplastic growth should also be considered. We should therefore be cautious in assessing the diagnostic usefulness of new tumour markers when cholestasis is present
Insulin-like growth factor-I, interleukin-1 alpha and beta in pancreatic cancer: role in tumor invasiveness and associated diabetes.
No full textWe evaluated levels of insulin-like growth factor-I and interleukin-1 alpha and beta in patients with pancreatic cancer; the role of these substances in tumor spread and in hyperglycemia was also investigated. Thirty pancreatic cancer patients (21 with hyperglycemia) were compared with others with diseases causing hyperglycemia [liver cirrhosis (14 cases, 12 with hyperglycemia), chronic pancreatitis (20 cases, 12 with hyperglycemia), type I diabetes mellitus (13 cases, all hyperglycemic)]. Insulin-like growth factor-I was significantly reduced in patients with liver cirrhosis, probably due to a reduced hepatic capacity for synthesis. It was increased in 6 of 30 pancreatic cancer patients; in these subjects it was correlated with alanine aminotransferase and C-peptide, but not with tumor diameter or the presence of metastases. Interleukin-1 alpha and beta were both elevated in pancreatic cancer patients. The former was high, while the latter was low when liver metastases were present. Neither was related to glucose or C-peptide levels. In summary, insulin-like growth factor-I levels are increased in some pancreatic cancer patients but this does not seem to favor tumor spread; however IGF-I could be involved influencing glucose homeostasis. Interleukin-1 alpha increased, while interleukin-1 beta decreased in pancreatic cancer patients with metastases, suggesting a different involvement of these two substances in pancreatic cancer spread
Increased serum phospholipase A2 activity in advanced chronic liver disease as an expression of the acute phase response.
No full textPhospholipase A2 (PLA2) modifications were investigated in patients with acute and chronic liver diseases, PLA2 variations were related to indices of liver function as well as to parameters of the acute phase response. Serum PLA2 activity modifications were fluorimetrically measured in 105 patients affected by acute and chronic liver diseases or extra-hepatic diseases. One-way ANOVA demonstrated a significant difference among groups (F = 4.53, P < 0.001); Bonferroni's test for pairwise comparisons showed that patients with hepatocellular carcinoma had higher mean values than subjects with benign extra-hepatic diseases (P < 0.01) and mild chronic liver disease (P < 0.05). Multiple regression analysis, performed choosing PLA2 as the dependent variable and blood urea nitrogen, C-reactive protein, alkaline phosphatase and alpha 1-fetoprotein as predictor variables was significant (multiple R = 0.7056, multiple R2 = 0.4978, F = 15.36, P = < 0.0001). The standardized regression coefficients found to be significant were those of C-reactive protein, blood urea nitrogen and alpha 1-fetoprotein. In conclusion, in patients with chronic liver disease, serum PLA2 activity increases parallel to disease severity and accompanies the expression of proteins of the acute phase response that, like PLA2 activity, increase in serum while liver synthesis declines
Effects of pancreaticobiliary duct obstruction on the exocrine and endocrine rat pancreas
No full textExperimentally, biliary obstruction can produce morphological and functional changes in the pancreatic gland, whereas pancreatic obstruction may have short-term (hyperamylasemia, pancreatic edema, and lysosomal hydrolase redistribution) or long-term (acinar cell atrophy and interstitial fibrosis) effects. We created a pancreaticobiliary duct obstruction in rats to evaluate (a) exocrine and endocrine anatomobiochemical pancreatic modifications; (b) structural and functional liver alterations; and (c) the relationship, if any, between the alterations found in the two organs. Forty-five male Sprague-Dawley rats were subdivided on the basis of period of obstruction (from 1 to 28 days). In each rat serum we evaluated amylase, cholestatic and cytolytic indices, and glucose. In frozen pancreatic samples we measured insulin, glucagon, and DNA; in the liver the DNA content was determined. Histologically, ductal dilation and proliferation were evaluated for the liver, zymogen granules, and Langerhans' islets, and atrophy for the pancreas. Fibrosis was evaluated for both the liver and the pancreas. Short-term common pancreaticobiliary duct ligation caused an increase in serum amylase levels and mild pancreatic edema. Longer-term obstruction had either similar or different effects on the two organs. In the pancreas it caused fibrosis and exocrine and endocrine atrophy, but not acute pancreatitis. In the liver the main phenomena observed were fibrosis, ductal dilation, and proliferatio
- …
