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Biomedical subjects

J Devière

Publications and source records attributed to J Devière.

At least 109 records · Page 6Linked to original sources

Role of reactive oxygen intermediates in interleukin 10 release after cold liver ischemia and reperfusion in mice.

BACKGROUND & AIMS: Reactive oxygen intermediates and cytokines are key effectors in reperfusion injury after liver ischemia. We hypothesized that reactive oxygen intermediates act as a signal for the release of tumor necrosis factor (TNF) and interleukin 10 (IL-10) after reperfusion of cold-preserved livers. METHODS: An endotoxin-free isolated perfused mouse liver system was designed. Harvested mouse livers were stored at 4 degrees C for 0-28 hours and reperfused for 90 minutes with a warm oxygenated Hank's balanced salt solution (alone or with additives). Cytokine messenger RNA (mRNA) from whole liver was measured by reverse-transcription polymerase chain reaction. Cytokine protein levels and liver injury assessed by alanine aminotransferase levels were evaluated in liver effluent during reperfusion. RESULTS: TNF and IL-10 mRNA and protein concentrations were increased after reperfusion of ischemic livers. N-Acetylcysteine and allopurinol dramatically decreased TNF (-64% and -62%) and IL-10 (-49% and -57%) levels in the effluents, as did an inhibitor of the transcription factor NF-kappaB mobilization (-73% and -76% for TNF and IL-10, respectively). Liver injury was decreased by -40%, -43%, and -54% for the three inhibitors, respectively. CONCLUSIONS: Reactive oxygen intermediates are involved in TNF and IL-10 release after reperfusion of cold-preserved livers.

Animals↗

Endoscopic treatment of gastric outlet obstruction caused by a gallstone (Bouveret's syndrome) after extracorporeal shock-wave lithotripsy.

Two patients with gastric outlet obstruction caused by a gallstone were treated by endoscopic lithotripsy. All fragments of significant size were removed orally, except for one that was left in the stomach in the first patient. This fragment caused a recurrent ileus after initial clinical improvement. The other patient remained clinically well after hospital discharge.

Aged↗

Different expression of transforming growth factor beta 1 in pancreatic ductal adenocarcinoma and cystic neoplasms.

Pancreatic neoplasms harbor different prognoses according to their histological type: a benign course for serous cystadenoma, a low malignant potential for intraductal papillary mucinous neoplasms (IPMN), and high aggressiveness for ductal adenocarcinoma (ADC). Transforming growth factor beta 1 (TGF beta 1) may regulate tumor growth. The present study analyzes and compares the expression of its precursor beta 1-latency-associated peptide (beta 1-LAP), its latent binding protein (LTBP), and its mRNA in ductal adenocarcinoma (n = 10), in IPMN (n = 8), in serous cystadenoma (n = 2), and in normal tissues (n = 5). LTBP is thought to play a strategic role in the processing and active secretion of latent TGF beta 1 and its stockage in the extracellular matrix. Localization of beta 1-LAP and LTBP was assessed by immunohistochemistry using specific antibodies and expression of TGF beta 1 mRNA by reverse-transcriptase polymerase chain reaction analysis. beta 1-LAP was only slightly expressed in normal specimens, while LTBP was not detected. beta 1-LAP was detected in the cytoplasm of neoplastic cells in 9 of 10 patients with ADC. An intense staining was present in stromal cells surrounding the neoplastic glands in all cases except in one carcinoma in situ. LTBP was detected only in stromal cells and in the surrounding extracellular matrix. In IPMN with mild-grade dysplasia and in cystadenoma, beta 1-LAP was strongly expressed in the epithelial cells, while it was poorly detected in invasive IPMN; stromal cells were poorly or not all stained by beta 1-LAP, except in invasive IPMN (n = 2). LTBP was detected in neoplastic cells of three cases with benign IPMN and two of two cases with cystadenoma, while stroma was not immunostained. TGF beta 1 mRNA was strongly expressed in most of the tumors and no difference in expression was observed between the different types of neoplasms. There is no quantitative difference in expression of TGF beta 1 in ADC and in IPMN or cystadenoma. However, the latter are able to secrete TGF beta 1 efficiently, in contrast to ductal ADC as shown by the ability of the neoplastic cells to express both beta 1-LAP and LTBP. Invasive stroma reaction was associated with enhanced beta 1-LAP and LTBP expression in stromal cells and could be mediated by TGF beta 1 via LTBP

Adenocarcinoma, Mucinous↗

Pancreatic duct: morphologic and functional evaluation with dynamic MR pancreatography after secretin stimulation.

PURPOSE: To assess the utility of dynamic MR pancreatography in the evaluation of the behavior of the pancreatic duct after secretin stimulation and to estimate pancreatic exocrine reserve in patients suspected of having acute recurrent or chronic pancreatitis. MATERIALS AND METHODS: Ten healthy volunteers and 13 patients suspected of having pancreatic disease and no obvious markers of chronic pancreatitis were studied. Single-shot turbo spin-echo T2-weighted dynamic MR pancreatograms were obtained before and every 30 seconds during the 10 minutes after secretin administration. Morphologic features and diameter of the pancreatic duct were monitored before and during secretin stimulation. Duodenal filling volume was graded. Results were compared with those of endoscopic retrograde cholangiopancreatography and secretin stimulation testing with collection of pancreatic fluid. RESULTS: Secretin improved the delineation of ductal morphologic features in both groups. Persistent dilatation of the pancreatic duct after stimulation (five patients) was a significant finding (P = .0015) in the diagnosis of papillary stenosis. The mean duodenal filling score was significantly lower in patients with reduced exocrine function (six patients) than that in the volunteers (P < .0001). CONCLUSION: The use of dynamic MR pancreatography with secretin stimulation may be useful for diagnosing pancreatic papillary stenosis or dysfunction and for detecting reduced pancreatic exocrine reserve.

Adult↗

Adenosine enhances IL-10 secretion by human monocytes.

Adenosine is a potent endogenous antiinflammatory agent released by cells under metabolically unfavorable conditions. Its effects on the production of IL-10 by human monocytes were presently investigated. Pre-incubation with adenosine dose-dependently enhanced IL-10 release by TNF stimulated human monocytes (+29, +58, and +116% at 1, 10, and 100 muM, respectively.) Adenosine also significantly enhanced IL-10 production after hydrogen peroxide and LPS stimulation and dose-dependently inhibited TNF secretion. Pre-incubation was not mandatory to achieve these effects, since addition of adenosine at the time of or 30 min after the stimulus led to the same results. Blocking IL-10 with anti-IL-10 mAbs partially restored adenosine-induced TNF inhibition. The enhanced IL-10 production was not observed when cells were preincubated with adenosine A1 or A2 receptor agonists (R-phenylisopropyladenosine, 5'-N-ethylcarboxamido-adenosine, and 2-chloroadenosine) and was not affected by pretreatment with theophyllin, an antagonist of both A1 and A2 receptors, or with dipyridamole, an inhibitor of adenosine cellular uptake. In conclusion, adenosine, in the submillimolar concentration range, increases IL-10 secretion by stimulated monocytes. This phenomenon participates in TNF inhibition, a known property of adenosine, but is not mediated through the occupancy of A1 or A2 receptors. This may represent a novel antiinflammatory property of adenosine by which it could modulate inflammation and limit ischemia-reperfusion injury.

Adenosine↗

Endoscopic pancreatic drainage in chronic pancreatitis associated with ductal stones: long-term results.

BACKGROUND: In severe chronic pancreatitis associated with intraductal stones, therapeutic endoscopy aims to reduce increased intraductal pressure by pancreatic sphincterotomy and stone clearance. METHODS: Results of treatment were evaluated in 70 new patients who underwent pancreatic sphincterotomy and attempted stone removal. Technical results and frequency of pain relief and recurrence are compared. RESULTS: Complete ductal clearance of calculi was obtained in 50% of cases. Immediate clinical improvement occurred in 95% of patients with painful attacks. No severe complications or mortality occurred. Fifty-four percent of all patients with painful chronic pancreatitis did not experience any pain recurrence within 2 years. Associations found to be statistically significant by multivariate analysis were ductal clearance and extracorporeal shock wave lithotripsy, pain disappearance and ductal clearance, pain recurrence and long evolution, and severe disease before treatment and presence of a ductal substenosis. CONCLUSIONS: In this subset of patients our results indicate that the pain of chronic pancreatitis is mainly related to increased intraductal pressure. Endoscopic management appears to be a safe, conservative, alternative to surgery. The best results are obtained when it is performed early in the course of calcifying chronic pancreatitis.

Adolescent↗

Transforming growth factor beta promotes development of fibrosis after repeated courses of acute pancreatitis in mice.

BACKGROUND & AIMS: Transforming growth factor beta (TGF-beta) is a putative mediator of fibrosis in several chronic diseases. Recently, chronic pancreatitis was suggested to be related to acute pancreatitis in the so-called necrosis-fibrosis sequence hypothesis. The present study investigated whether TGF-beta is able to promote chronic fibrosis after repeated courses of necrotizing acute pancreatitis induced by cerulein in mice. METHODS: Six episodes of acute pancreatitis were repeatedly induced at weekly intervals in mice receiving either recombinant TGF-beta (4 micrograms in 4 days) or excipient alone at each induction. One week after the last induction, pancreatic lesions and collagen deposition were histologically assessed. Expression of pancreatic fibronectin messenger RNA was also examined in both groups. RESULTS: TGF-beta had no influence on a single course of acute pancreatitis. After six courses of acute pancreatitis, only mild inflammatory changes were observed in the control group. In contrast, important areas of perilobular and intralobular fibrosis were observed adjacent to inflammatory and necrotic foci in the TGF-beta group. Fibronectin messenger RNA expression was significantly higher in this group. CONCLUSIONS: TGF-beta promotes development of pancreatic fibrosis after recurrent episodes of acute pancreatitis. This model of pancreatic fibrosis could be used as a model of chronic pancreatitis consistent with the necrosis-fibrosis sequence hypothesis.

Acute Disease↗

Relationship between hepatocyte proliferative activity and liver functional reserve in human cirrhosis.

Hepatocyte proliferative activity is elevated in cirrhotic patients who develop hepatocellular carcinoma (HCC) and decreased in alcohol-induced hepatitis patients with poor outcome. Hepatocyte proliferative activity has not been evaluated in an unselected population of cirrhotic patients regarding the severity of the disease. Forty-six cirrhotic patients (21 alcoholic, 20 viral, and 5 other) were prospectively analyzed by proliferating cell nuclear antigen (PCNA) immunostaining on methanol-fixed, paraffin-embedded liver biopsy specimens. In these conditions, the PCNA-labeling index (PCNA-LI) measures the number of cells in the S-phase and assesses tissue proliferation. The median value of the PCNA-LI for all samples was 4.3% (range, 0%-20.2%). It declined with worsening Child-Pugh score: 9.15% (range, 3.3%-20.2%), 5.3% (range, 1.2%-18%), and 2.4% (range, 0%-4.4%) in Child classes A, B, and C, respectively (P < .05). Using the best cutoff PCNA-LI value to divide cirrhosis into slowly and rapidly proliferating tissue subsets, the PCNA index was independently associated with serum albumin. The probability of survival in patients with a high PCNA-LI ( > 4.4%) was significantly higher than in those with a lower PCNA-LI (0.93 vs. 0.53, at a median follow-up of 153 days; P = .01). In all 6 patients undergoing placement of a transjugular intrahepatic portosystemic shunt (TIPS), the PCNA-LI decreased after the procedure. This early impairment of hepatocyte proliferative activity after TIPS placement might reflect the functional alterations induced by this treatment. In conclusion, hepatocyte proliferative activity assessed by PCNA-LI is increased in cirrhotic patients and decreases with worsening of the disease.

Adult↗

Pulmonary hypertension after transjugular intrahepatic portosystemic shunt: effects on right ventricular function.

The short- and mid-term hemodynamic effects of transjugular intrahepatic portosystemic shunt (TIPS) were studied in 16 sedated cirrhotic patients. Indications included relapsing variceal bleeding (n = 10) and refractory ascites (n = 6). The decrease of porto-atrial pressure gradient (from 20.4 +/- 4.2 mm Hg to 10.1 +/- 2.4 mmHg; P < .05) was associated with an increase of mean pulmonary artery pressure (MPAP) (from 12.3 +/- 3.0 mm Hg to 20.3 +/- 5.3 mm Hg; P < .05) and of right atrial pressure (RAP) from 3.4 +/- 2.6 mm Hg to 8.3 +/- 3.7 mm Hg; P < .05), whereas right ventricular end-diastolic volume (RVEDVI) remained unchanged. The significant increase of cardiac index (CI) (from 4.5 +/- 1.2 L/min/m2 to 5.0 +/- 1.1 L/min/m2; P < .05) was essentially attributable to an increase of heart rate (HR) (from 81 +/- 11 to 88 +/- 10 beats/min; P < .05). Systemic vascular resistance (SVR) decreased (from 812 +/- 281 to 666 +/- 191 dynes/sec/cm5; P < .05), whereas pulmonary vascular resistance (PVR) increased (from 60.6 +/- 29.6 to 82.0 +/- 34.6 dynes/sec/cm5; P < .05). After transient shunt occlusion with a balloon catheter, all of the hemodynamic parameters returned to baseline values, except pulmonary artery pressure, which also decreased but remained significantly increased. One month after TIPS, pulmonary pressure remained elevated, and CI further increased. It is concluded that increased PVR is the major hemodynamic alteration occurring after TIPS placement. It correlates with the decrease of porto-atrial gradient and is probably mediated by both mechanical and neurohumoral factors.

Adult↗

Interleukin 10 prevents necrosis in murine experimental acute pancreatitis.

BACKGROUND/AIMS: Inflammatory events are believed to play an important role in the pathogenesis of acute pancreatitis. Interleukin 10 (IL-10) recently emerged as a major anti-inflammatory cytokine, inhibiting the secretion of proinflammatory cytokines by monocytes and/or macrophages. The potential protective role of IL-10 in a model of acute necrotizing pancreatitis in mice was tested. METHODS: Animals received two intraperitoneal injections of either 1000 U recombinant IL-10 or control supernatant before and during induction of acute pancreatitis with repeated cerulein injections (seven intraperitoneal injections of 50 micrograms/kg at hourly intervals). RESULTS: Systemic amylase and lipase release peaked 9 hours after the first cerulein injection. This peak was significantly reduced by IL-10 treatment. Histologically, edema and inflammation of the pancreas were observed in both groups, whereas necrosis was dramatically reduced in IL-10-treated animals. Serum tumor necrosis factor levels were undetectable in this model; reverse-transcriptase polymerase chain reaction analysis of resected pancreatic tissues performed at the time of maximal morphological alterations showed a dramatically decreased expression of tumor necrosis factor alpha messenger RNA after IL-10 treatment compared with control pancreatitis. CONCLUSIONS: IL-10 is able to decrease the severity of experimental acute pancreatitis, mainly by inhibiting the development of acinar necrosis. Inhibition of local tumor necrosis factor alpha might explain, at least in part, the protective effect of IL-10.

Acute Disease↗

Plasma endotoxin and tumor necrosis factor-alpha in the hyperkinetic state of cirrhosis.

BACKGROUND/AIMS: The factors which trigger the hyperdynamic circulation in cirrhosis remain poorly defined. Plasma levels of the potent vasodilators endotoxin and tumor necrosis factor-alpha may be elevated in patients with cirrhosis, and therefore the potential role of these substance was assessed in the hyperkinetic circulation in cirrhosis. METHODS: Forty-nine patients in stable condition underwent systemic and hepatic hemodynamic measurements, and right atrial blood sampling for endotoxin and tumor necrosis factor-alpha assays. Patients were divided into three groups according to the severity of the disease: group 1 consisted of eight patients with normal liver or mild hepatic fibrosis, and groups 2 and 3 contained 17 and 24 patients with Child A and Child B or C cirrhosis, respectively. RESULTS: Systemic vascular resistance decreased and cardiac index increased from group 1 to 3: 1530 +/- 196 dyn.s.cm-5 to 990 +/- 72 dyn.s.cm-5 (mean +/- S.E.; p<0.05) and 3.1 +/- 0.3 l.min-1.m-2 to 4.2 +/- 0.2 l.min-2.m-2, respectively. Endotoxin was not detectable in any of the groups and tumor necrosis factor-alpha was increased in one patient from group 1, six from group 2 and six from group 3. Mean tumor necrosis factor-alpha levels were not different among the groups (10 +/- 5, 18 +/- 5 and 17 +/- 7 pg/ml in groups 1, 2 and 3, respectively). Systemic vascular resistance and cardiac index were not correlated to plasma tumor necrosis factor-alpha levels; patients with increased levels of this cytokine did not have worse hyperdynamic circulation in any of the groups. CONCLUSIONS: These results suggest that tumor necrosis factor-alpha and endotoxin do not play a role in the maintenance of the hyperkinetic state of cirrhosis.

Hemodynamics↗

Complete disruption of the main pancreatic duct: endoscopic management.

BACKGROUND: Complete disruption of the main pancreatic duct is an unusual event in the course of acute or chronic pancreatitis. Endoscopic management has already proven effective in the treatment of partial ruptures. METHODS: Thirteen patients presented over a 7-year period with acute (9 patients) or chronic (4 patients) pancreatitis complicated by complete disruption of the main pancreatic duct and cyst formation. Endoscopic treatment was attempted in 12. Treatment varied depending on the site of the rupture and accessibility of the pseudocyst and consisted either of transpapillary drainage (3), cystogastrostomy (3), cystoduodenostomy (2), or combined procedures (4) when one of these procedures did not induce significant decrease in collection size. Long-term results were obtained by observing the patients with ultrasound, CT, ERCP, and clinical evaluation. RESULTS: Short-term results were excellent with complete cyst resolution and clinical recovery in all but one patient treated by endoscopy. Two patients had pseudocyst infection successfully treated by drainage and antibiotics. Long-term follow-up was available for 11 patients (mean duration, 30.2 months; range, 12 to 72 months) without relapsing clinical symptoms or pseudocyst. CONCLUSIONS: Endoscopic management is effective and safe for treating patients with complete main pancreatic duct disruption. A double drainage combining transpapillary drainage and cystoenterostomy must be done in selected instances, especially when rupture occurs in the setting of chronic pancreatitis with stricture or stone distal to the rupture.

Acute Disease↗