Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial.

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E.

Nuclear expression of S100A4 calcium-binding protein increases cholangiocarcinoma invasiveness and metastasization.

Unlabelled: Cholangiocarcinoma (CCA) carries a severe prognosis because of its strong invasiveness and early metastasization. In several patients, otherwise eligible for surgical resection, micrometastasis are already present at the time of surgery. The mechanisms responsible for CCA invasiveness are unclear.

Therapy of inflammatory bowel diseases in pregnancy and lactation.

Inflammatory bowel diseases (IBDs) are a group of disorders characterised by chronic or relapsing inflammation within the gastrointestinal tract of variable severity. A chronic medication is often needed and management of fertile women is a crucial point because of the possible adverse effects associated with the administered drugs and the disease itself. The risk of pregnancy-related complications and the disease behaviour during pregnancy depends mainly on disease activity at time of conception.

Combined versus sequential diuretic treatment of ascites in non-azotaemic patients with cirrhosis: results of an open randomised clinical trial.

Objective: The aim of the study was to compare sequential versus combined diuretic therapy in patients with cirrhosis, moderate ascites and without renal failure.

Design: One hundred patients were randomly assigned to the two diuretic treatments. The sequential treatment provided potassium canrenoate at the initial dose of 200 mg/day, then increased to 400 mg/day.

Changing trends in acute upper-GI bleeding: a population-based study.

Background: Advances in medical practice in recent decades have influenced the etiology and management of acute upper-GI bleeding (UGIB), but their impact on the incidence and mortality is unclear.

Objective: To analyze the time trends of UGIB in 2 different management eras.

Design: Prospective observational study.

The patient presenting with isolated hyperbilirubinemia.

Hyperbilirubinemia is a common laboratory finding in clinical practice, being found in several haematological and liver diseases as well as in familial conditions (5-10% in Western countries). Although most of the familial forms of hyperbilirubinemia are classically viewed as benign conditions, they have gained an increased interest in the last few years since recent data have indicated that subjects with an impaired bilirubin metabolism may have an increased susceptibility to drug toxicity. The authors briefly review the main steps of bilirubin metabolism, with a special emphasis on the emerging concepts on the molecular mechanisms of regulation by nuclear receptors (NRs) and genetic factors.

Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development.

Unlabelled: Intrahepatic bile ducts maintain a close anatomical relationship with hepatic arteries. During liver ontogenesis, the development of the hepatic artery appears to be modulated by unknown signals originating from the bile duct. Given the capability of cholangiocytes to produce angiogenic growth factors and influence peribiliary vascularization, we studied the immunohistochemical expression of vascular endothelial growth factor (VEGF), angiopoietin-1, angiopoietin-2, and their cognate receptors (VEGFR-1, VEGFR-2, Tie-2) in fetal human livers at different gestational ages and in mice characterized by defective biliary morphogenesis (Hnf6(-/-)).

Ursodeoxycholic acid stimulates cholangiocyte fluid secretion in mice via CFTR-dependent ATP secretion.

Background & Aims: Cholangiopathies are characterized by impaired cholangiocyte secretion. Ursodeoxycholic acid (UDCA) is widely used for cholangiopathy treatment, but its effects on cholangiocyte secretory functions remain unclear and are the subject of this study.

Methods: Polarized mouse cholangiocytes in tubular (isolated bile-duct units [IBDU]) or monolayer configuration were obtained from wild-type (WT) and B6-129-Cftr(tm1Kth) and Cftr(tm1Unc) mice that are defective in CFTR, an adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated Cl(-) channel expressed in cholangiocytes.

Analysis of liver repair mechanisms in Alagille syndrome and biliary atresia reveals a role for notch signaling.

Patients with Alagille syndrome (AGS), a genetic disorder of Notch signaling, suffer from severe ductopenia and cholestasis, but progression to biliary cirrhosis is rare. Instead, in biliary atresia (BA) severe cholestasis is associated with a pronounced "ductular reaction" and rapid progression to biliary cirrhosis. Given the role of Notch in biliary development, we hypothesized that defective Notch signaling would influence the reparative mechanisms in cholestatic cholangiopathies.

Inheritance of hyperbilirubinemia: evidence for a major autosomal recessive gene.

Background And Aim: To clarify the precise mode of inheritance of Gilbert syndrome, an unconjugated familial hyperbilirubinemia, where impaired bilirubin conjugation is caused by reduced UGT1A1 activity determined by a defective function of the A(TA)6TAA promoter region of the UGT1A1 gene.

Subjects And Methods: Serum bilirubin levels were measured in a large, homogeneous resident population from North-Eastern Italy, consisting of 1.639 males (age 44.

Effects of angiogenic factor overexpression by human and rodent cholangiocytes in polycystic liver diseases.

Liver involvement in autosomal dominant polycystic kidney disease (ADPKD) is characterized by altered remodeling of the embryonic ductal plate (DP) with presence of biliary cysts and aberrant portal vasculature. The genetic defect causing ADPKD has been identified, but mechanisms of liver cyst growth remain uncertain. To investigate the possible role of angiogenic mechanisms, we have studied the immunohistochemical expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and their receptors (VEGFR-1, VEGFR-2, Tie-2) in ADPKD, Caroli's disease, normal and fetal livers.

Hepatitis C virus infection in a resident elderly population: a 10-year follow-up study.

Background: The natural history of hepatitis C virus infection in the elderly is poorly known.

Objective: To assess the mortality rate, the progression of liver disease, the hepatitis C virus carrier state and the co-morbidity in a cohort of 35 out of 1,063 anti-hepatitis C virus positive elderly people prospectively followed-up from 1992 to 2002.

Methods: Liver function tests, hepatitis C virus-RNA analysis, hepatitis C virus genotyping and abdominal ultrasonography were assessed at the beginning of the study, and then, liver function tests and ultrasonography were performed annually during the first 5 years of the follow-up.

Glibenclamide stimulates fluid secretion in rodent cholangiocytes through a cystic fibrosis transmembrane conductance regulator-independent mechanism.

Background & Aims: Progressive liver disease is a severe complication of cystic fibrosis, a genetic disease characterized by impaired epithelial adenosine 3',5'-cyclic monophosphate-dependent secretion caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). In the liver, CFTR is expressed in cholangiocytes and regulates the fluid and electrolyte content of the bile. Glibenclamide, a sulfonylurea and a known CFTR inhibitor, paradoxically stimulates cholangiocyte secretion.

Novel association of HLA-haplotypes with primary sclerosing cholangitis (PSC) in a southern European population.

Aims: In patients with with primary sclerosing cholangitis we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Methods: In 64 PSC patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies.

Results: Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs.

Association of keratin 8 gene mutation with chronic pancreatitis.

Background: Keratin 8 (K8) and 18 (K18) are the major components of the intermediate filament cytoskeleton of pancreatic acinar cells and play a relevant role in pancreatic exocrine homeostasis. Transgenic mice for K8 have shown to display progressive exocrine pancreas alterations, including dysplasia, loss of acinar architecture, redifferentiation of acinar to ductal cells, inflammation, fibrosis, and substitution of exocrine tissue by adipose tissue.

Aim: To investigate whether mutations in the keratin 8 gene are associated with chronic pancreatitis.

Treatment of primary sclerosing cholangitis with low-dose ursodeoxycholic acid: results of a retrospective Italian multicentre survey.

Background: Data concerning the usefulness and type of drugs employed to treat patients with primary sclerosing cholangitis are controversial. Ursodeoxycholic acid has been shown to be a useful agent, however the drug dosage and its effect on the clinical course are still under debate.

Aim: To evaluate the efficacy of low-dose ursodeoxycholic acid in the treatment of primary sclerosing cholangitis.

Association of HLA-DRB1*0401 allele with chronic pancreatitis.

Introduction: Chronic pancreatitis (CP) is characterized by irreversible morphologic and functional alterations of the pancreas, clinically presenting with upper abdominal pain as well as exocrine and endocrine insufficiencies. According to a more recent hypothesis, the pathogenesis may involve genetic and immunologic factors.

Aim: To investigate the major histocompatibility complex (MHC) genes as a genetic background of chronic pancreatitis.

Cytokine-stimulated nitric oxide production inhibits adenylyl cyclase and cAMP-dependent secretion in cholangiocytes.

Background & Aims: The biliary epithelium is involved both in bile production and in the inflammatory/reparative response to liver damage. Recent data indicate that inflammatory aggression to intrahepatic bile ducts results in chronic progressive cholestasis.

Methods: To understand the effects of nitric oxide on cholangiocyte secretion and biliary tract pathophysiology we have investigated: (1) the effects of proinflammatory cytokines on NO production and expression of the inducible nitric oxide synthase (NOS2), (2) the effects of NO on cAMP-dependent secretory mechanisms, and (3) the immunohistochemical expression of NOS2 in a number of human chronic liver diseases.

Hypercalcemia due to ectopic secretion of parathyroid related protein from pancreatic carcinoma: a case report.

This case is a report of a male, 52 year old, heavy smoker, with a history of about 10 years of alcohol abuse (he quitted in 1993), gastric resection for ulcer (Billroth II 1970), hypoparathyroidism and macroamylasemia, died for undiagnosed pancreatic carcinoma revealed at necroscopy. The only clinical evidence of carcinoma were pulmonary metastasis and paraneoplastic syndrome characterized from hyponatriemia due to inappropriate secretion of antidiuretic hormone and elevation of seric calcium caused by parathyroid hormone related protein. In patients without endocrine abnormalities, such unusual paraneoplastic syndrome could cause hypercalcemia, but in our patient, the increased calcemia did not reach abnormal levels due to the previous hypoparathyroidism.

Gastroprotective effects of amtolmetin guacyl: a new non-steroidal anti-inflammatory drug that activates inducible gastric nitric oxide synthase.

Background: The novel non-steroidal anti-inflammatory drug amtolmetin guacyl has been shown to possess markedly reduced ulcerogenic effects and nitric oxide-mediated gastroprotective activity against the damage induced by ethanol in the rat.

Aims: To investigate, in the rat, the role of nitric oxide and of inducible nitric oxide synthase isoform in the protective effect of amtolmetin guacyl against the gastric damage induced by ethanol.

Methods: The effects of amtolmetin guacyl on gastric transmucosal potential difference and on gastric mucosal blood flow were investigated in the anaesthetised rat; myeloperoxidase activity, inducible and endothelial nitric oxide synthase protein content were determined in rat gastric mucosal homogenates.

Proinflammatory cytokines inhibit secretion in rat bile duct epithelium.

Background And Aims: Cholestatic disorders often are associated with portal inflammation, but whether or how inflammation contributes to cholestasis is unknown. Thus we studied the effects of proinflammatory cytokines on bile duct epithelia secretory mechanisms.

Methods: Isolated bile duct units (IBDUs) were cultured with interleukin (IL)-6, interferon gamma, tumor necrosis factor (TNF)-alpha, and IL-1 alone or in combination.

Long-acting octreotide is effective in controlling rebleeding angiodysplasia of the gastrointestinal tract.

Background: Management of bleeding angiodysplasia of the gastrointestinal tract is often a major clinical problem. Lesions are frequently multiple, not detectable or missed during conventional endoscopy and patients are sometimes at high risk for complications because of advanced age and serious concomitant disorders.

Aims: To determine the efficacy of a new formulation of somatostatin analogue (octreotide long-acting) in management of recurrent bleeding angiodysplasia in patients resistant to endoscopic treatment and not suitable for surgery.

Gallstone disease in an elderly population: the Silea study.

Background: Little is known on gallbladder emptying and gallstone composition in the elderly. AIMS AND SUBJECTS: Cross-sectional survey on the prevalence of gallstone disease and associated factors, gallstone characteristics and gallbladder emptying in a population aged > or = 60 years.

Methods: Gallstone number and size as well as gallbladder motor function were assessed by ultrasound.