Search

Background/Aims: Pirfenidone has been recently shown to reduce dimethynitrosamine-induced liver fibrosis in the rat, but no information are available on the effect of this drug on cultured hepatic stellate cells (HSC).Methods: HSC proliferation was evaluated by measuring bromodeoxyuridine incorporation; PDGF-receptor autophosphorylation, extracellular signal-regulated kinase (ERK1/2) and pp70S6K activation were evaluated by western blot; protein kinase C activation was evaluated by western blot and by ELISA; type I collagen accumulation and α1(I) procollagen mRNA expression were evaluated by ELISA and northern blot, respectively.Results: Pirfenidone significantly inhibited PDGF-induced HSC proliferation, starting at a concentration of 1 μM, with a maximal effect at 1000 μM, without affecting HSC viability and without inducing apoptosis. The inhibition of PDGF-induced HSC proliferation was associated neither with variations in PDGF-receptor autophosphorylation, or with ERK1/2 and pp70S6K activation. On the other hand, pirfenidone was able to inhibit PDGF-induced activation of the Na+/H+ exchanger, which is involved in PDGF-induced HSC proliferation in HSC, with a maximal effect at 1000 μM and inhibited PDGF-induced protein kinase C activation. Pirfenidone 100 and 1000 μM inhibited type I collagen accumulation in the culture medium induced by transforming growth factorβ1 by 54% and 92%, respectively, as well as TGFβ1-induced α1(I) procollagen mRNA expression.Results: Pirfenidone could be a new candidate for antifibrotic therapy in chronic liver diseases. [Copyright &y& Elsevier]

Background/Aims: Cytoskeletal reorganization plays an important role in the regulation of different cell functions, such as proliferation and migration. Since platelet-derived growth factor (PDGF) stimulates both proliferation and chemotaxis of hepatic stellate cells (HSC), we investigated the effects of this cytokine on cytoskeletal components of cultured rat HSC.Methods/Results: Exposure of HSC to PDGF induced the formation of stress fibres and of a ruffled configuration of the plasma membrane, evaluated by both fluorescence and electron microscopy. These modifications were also induced by exposure to the protein kinase C (PKC) activator phorbol-12-myristate-13-acetate (PMA) and abolished by pretreatment with the PKC inhibitor calphostin C, with the Rho inhibitor C3 exoenzyme and with the intracellular calcium chelator MAPTAM, but not with the PI-3 kinase inhibitor wortmannin or with the mitogen-activated protein kinase kinase inhibitor PD 98059. PDGF induced a translocation of Rho from the cytosol to the membrane which was inhibited by C3 exoenzyme and by calpostin C, and which was also induced by PMA. Moreover, PDGF induced a rearrangement of vinculin which was prevented by C3 exoenzyme and calphostin C.Conclusions: PDGF-induced cytoskeletal reorganization in HSC is dependent on PKC and Rho, thus suggesting that these two pathways may play an important role in the response of liver to injury. [Copyright &y& Elsevier]

Presents a study which evaluated intracellular potential of hydrogen ions (pH) regulation in nonactivated and activated rat hepatic stellate cells (HSC). Examination of HSC proliferation; Details on HSC regulation of pH; Description of HSC cells.

Examines intracellular pH (pHi) regulation in nonactivated and activated rat hepatic stellate cells (HSC). pHi regulation in the absence and presence of bicarbonate (HCO3-); Recovery of pHi from an acute acid load; Effects of platelet-derived growth factor on baseline activity, sodium/hydrogen pump activity and HSC proliferation.

Background and Study Aim: The traditional endoscopic therapy of anastomotic strictures (AS) after orthotopic liver transplantation (OLT) is multiple ERCPs with the insertion of an increasing number of plastic stents side‐by‐side. Fully covered self‐expanding metal stents (cSEMS) could be a valuable option to decrease the number of procedures needed or non‐responders to plastic stents. This study aims to retrospectively analyse the results of AS endoscopic treatment by cSEMS and to identify any factors associated with its success. Patients and Methods: Ninety‐one patients (mean age 55.9 ± 7.6 SD; 73 males) from nine Italian transplantation centres, had a cSEMS positioned for post‐OLT‐AS between 2007 and 2017. Forty‐nine (54%) patients were treated with cSEMS as a second‐line treatment. Results: All the procedures were successfully performed without immediate complications. After ERCP, adverse events occurred in 11% of cases (2 moderate pancreatitis and 8 cholangitis). In 49 patients (54%), cSEMSs migrated. After cSEMS removal, 46 patients (51%) needed further endoscopic (45 patients) or radiological (1 patient) treatments to solve the AS. Lastly, seven patients underwent surgery. Multivariable stepwise logistic regression showed that cSEMS migration was the only factor associated with further treatments (OR 2.6, 95% CI 1.0–6.6; p value 0.03); cSEMS implantation before 12 months from OLT was associated with stent migration (OR 5.2, 95% CI 1.7–16.0; p value 0.004). Conclusions: cSEMS appears to be a safe tool to treat AS. cSEMS migration is the main limitation to its routinary implantation and needs to be prevented, probably with the use of new generation anti‐migration stents. [ABSTRACT FROM AUTHOR]

Background: The most appropriate endo‐therapeutic approach to biliary anastomotic strictures is yet to be defined. Aim: To retrospectively report on the endo‐therapy of duct‐to‐duct anastomotic strictures during 2013 in Italy. Methods: Data were collected from 16 Endoscopy Units at the Italian Liver Transplantation Centers (BASALT study group). Results: Complete endo‐therapy and follow‐up data are available for 181 patients: 101 treated with plastic multistenting, 26 with fully covered self‐expandable metal stenting and 54 with single stenting. Radiological success was achieved for 145 patients (80%), that is, 88% of plastic multistenting, 88% of self‐expandable metal stenting and 61% of single stenting (P < 0.001 vs plastic multistenting; P < 0.05 vs self‐expandable metal stenting). After first‐line endo‐therapy failure, the patients underwent a second‐line endo‐therapy with plastic multistenting for 25%, fully covered self‐expandable metal stenting for 53% and single stenting for 22% of cases, and radiological success was achieved for 84%, that is, 100%, 85% and 63% with plastic multistenting, self‐expandable metal stenting and single stenting (P < 0.05 vs plastic multistenting or self‐expandable metal stenting) respectively. Procedure‐related complications occurred in 7.8% of endoscopic retrograde cholangiopancreatographies. Overall, clinical success was achieved in 87% of patients after a median follow‐up of 25 months. Conclusion: Plastic multistenting is confirmed as the preferred first‐line treatment, while fully covered self‐expandable metal stenting as rescue option for biliary anastomotic strictures. Single stenting has sub‐optimal results and should be abandoned. See Editorial on Page 1197 [ABSTRACT FROM AUTHOR]

Arthritis is the most frequent extra-intestinal manifestation in patients with inflammatory bowel diseases (IBD). The coexistence of intestinal and articular inflammation advocates the need for a multidisciplinary management of patients with IBD-associated spondyloarthritis. Consecutive IBD patients were evaluated jointly by the gastroenterologist and the rheumatologist in a combined clinic. All the patients were assessed and screened for articular involvement, disease activity and health related quality of life. After the prescription of a shared treatment, patients with spondyloarthritis were followed up for 24 months. Two hundred sixty-two IBD patients, including 80 who were classified as affected by spondyloarthritis according to the ASAS criteria, were included in the study. At baseline, patients with both IBD and spondyloarthritis showed worse quality of life in both the physical and mental domains. The multidisciplinary management provided a significant improvement of gastrointestinal and articular manifestations, as well as the health-related quality of life. Moreover, global and gastrointestinal-specific quality of life significantly correlated with articular disease activity. The multidisciplinary management significantly improves both articular and gastrointestinal disease activities and the quality of life of patients with IBD-associated spondyloarthritis. An appropriate screening strategy and the integrated management of these patients should be encouraged and employed in clinical practice. • The presence of a SpA is often overlooked in IBD, with consequent diagnostic delay • The early diagnosis may be achieved by a combined gastro-rheumatological clinic • The combined clinic improved disease activity and quality of life in SpA/IBD • The improvement of disease activity and quality of life lasted up to 2 years • The multidisciplinary management of SpA/IBD is effective and feasible in clinical practice [ABSTRACT FROM AUTHOR]

Objectives. SSc is a clinically heterogeneous and generalized disease, characterized by thickness of the connective tissue of the skin and internal organs, such as the digestive tract, impairing gastrointestinal (GI) motility. Our aim is to evaluate retrospectively abnormalities of oesophageal motility, gastric emptying, oro-cecal transit time (OCTT) and small intestine bacterial overgrowth (SIBO) in a large cohort of SSc patients.Methods. Ninety-nine SSc patients were included in the study. Forty-two patients underwent oesophageal conventional manometry, 45 performed a [13C]octanoic acid breath test to measure gastric emptying time and all 99 patients performed a lactulose breath test in order to evaluate OCTT and SIBO. Data were compared with healthy controls.Results. In SSc patients, median lower oesophageal sphincter (LOS) pressure [14 mmHg (25th–75th; 8–19) vs 24 mmHg (19–28); P < 0.01] and median wave amplitude [30 mmHg (16–70) vs 72 mmHg (48–96); P < 0.01] were lower than in controls. Oesophageal involvement, defined as reduced LOS pressure and ineffective oesophageal motility pattern, was encountered in 70% of SSc patients. A delayed gastric emptying time was present in 38% of SSc patients: mean t½ was 141 ± 79 min vs 90 ± 40 min of controls (P < 0.01). Also, OCTT was significantly delayed in SSc: median OCTT was 160 min (25th–75th; 135–180) vs 105 min (25th–75th; 90–135) of controls (P < 0.01). SIBO was observed in 46% of SSc compared with 5% of controls (P < 0.01).Conclusion. GI involvement is very frequent in SSc patients. Oesophagus and small bowel are more frequently impaired, whereas delayed gastric emptying is less common. [ABSTRACT FROM PUBLISHER]

The aim of this study is to assess the associations between chronic spontaneous urticaria (CSU), Helicobacterpylori infection and small intestinal bacterial overgrowth. Forty- eight patients with CSU were studied by scoring the urticaria activity and assesing the quality of life. Patients with H. pylori infection (n=11) or small intestinal bacterial overgrowth (n=13) were specifically treated for one week and clinically evaluated both before and 4 weeks after the eradication therapy. Eradication of H. pylori infection led to a significant improvement in CSU (p<0.002). In contrast, eradication of small intestinal bacterial overgrowth was not associated with any clinical improvement in CSU, despite the fact that these patients had statistically significant more urticaria activity at baseline. Thus there is no evidence to support the eradication of small intestinal bacterial overgrowth in CSU, but eradication of H. pyiori infection may result in an improvement of the disease. [ABSTRACT FROM AUTHOR]

Paraoxonase-1 (PON1) plays an antioxidant and anti-inflammatory role. Aim of the study was to investigate the alteration of paraoxonase-1 activity in celiac disease (CD), an intestinal disorder characterized by toxic injury exerted by gluten peptides. Activities of PON1, levels of biochemical markers of lipid peroxidation and total antioxidant capacity were evaluated in serum obtained from 27 celiac patients (11 at diagnosis, 16 treated with gluten free diet) and 25 healthy subjects. Moreover, the serum susceptibility of Cu2+-induced lipid peroxidation was investigated in controls and patients. The results showed a lower PON1 activity in serum of both groups of celiac patients with respect to control subjects. PON1 activity in CD was related with markers of disease severity and was negatively correlated with the levels of lipid hydroperoxide and with the susceptibility of serum to lipid peroxidation induced in vitro by metal ions. The alteration of PON1 activity and markers of lipid peroxidation realized at lower extent in patients who were on a gluten-free diet. [ABSTRACT FROM AUTHOR]