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Introduction and Aim: Refractory ulcerative proctitis is defined as the failure of topical and oral 5-aminosalicylate and corticosteroids treatment. Management of refractory proctitis is often challenging. Curcumin was reported to be efficacious in inducing and maintaining remission in patients with ulcerative colitis (UC). We investigated curcumin in patients with refractory ulcerative proctitis, non responder to conventional therapies (rectal 5 aminosalycilate or steroid in combination with oral 5 aminosalycilate, steroid or azathioprine). Methods: In a randomized, placebo controlled trial, 10 patients were randomly assigned to assume curcumin capsules (3g/die), in a slow release oral formulation and curcumin enema (3g/die) for one month. Ten patients assumed an identical placebo for 1 month. Primary outcome was clinical remission at week 4. Endoscopic and biochemical data were also recorded. Results: After one month the number of patients achieving clinical remission was significantly higher in the curcumin treated group (p

Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stromal cells (MSC) are currently under evaluation in phase III clinical trials for inflammatory bowel disease and other intestinal disease manifestations. The therapeutic efficacy of these treatments may derive from a combination of the differentiation, trophic and immunomodulatory abilities of the transplanted cells. We investigated intestinal tissues as sources of MSC: such cells may support tissue-specific functions and hold advantages for engraftment and contribution in the gastrointestinal environment.Intestinal specimens were collected, and the mucosa and submucosa mechanically separated and enzymatically digested. Mesenchymal stromal populations were isolated, expanded and characterized under conditions commonly used for MSC. The differentiation potential, trophic effect and immunomodulatory ability were investigated. Results We successfully isolated and extensively expanded populations showing the typical MSC profile: CD29+, CD44+, CD73+, CD105+ and CD166+, and CD14(-), CD34(-) and CD45(-). Intestinal mucosal (IM) MSC were also CD117+, while submucosal cultures (ISM MSC) showed CD34+ subsets. The cells differentiated toward osteogenic, adipogenic and angiogenic commitments. Intestinal-derived MSC were able to induce differentiation and organization of intestinal epithelial cells (Caco-2) in three-dimensional collagen cultures. Immunomodulatory activity was evidenced in co-cultures with normal heterologous phytohemagglutinin-stimulated peripheral blood mononuclear cells. Conclusions Multipotent MSC can be isolated from intestinal mucosal and submucosal tissues. IM MSC and ISM MSC are able to perform trophic and immunomodulatory functions. These findings could open a pathway for novel approaches to intestinal disease treatment.

Low-dose aspirin is standard treatment for prevention of cardiovascular events in at-risk patients. However, long-term administration of low-dose aspirin is associated with a greater risk of adverse events, including gastroduodenal ulcers. This study determined the efficacy of esomeprazole for reducing the risk of gastric and/or duodenal ulcers and dyspeptic symptoms in patients receiving continuous, low-dose aspirin therapy.Patients agedor =60 yr, without baseline gastroduodenal ulcer at endoscopy, who were receiving aspirin 75-325 mg once daily, were randomized to esomeprazole 20 mg once daily or placebo for 26 wk. The presence of endoscopic gastric and/or duodenal ulcers and esophageal lesions was assessed at weeks 8 and 26. Upper gastrointestinal symptoms were assessed at weeks 8, 16, and 26.The intention-to-treat population comprised 991 patients (esomeprazole, N = 493; placebo, N = 498). Twenty-seven patients (5.4%) in the placebo group developed a gastric or duodenal ulcer during 26 weeks' treatment compared with eight patients (1.6%) in the esomeprazole group (life-table estimates: 6.2%vs 1.8%; P= 0.0007). At 26 wk, the cumulative proportion of patients with erosive esophagitis was significantly lower for esomeprazole versus placebo (4.4% and 18.3%, respectively; P0.0001). At 26 wk, esomeprazole-treated patients were more likely to experience resolution of heartburn, acid regurgitation, and epigastric pain (P0.05).Esomeprazole 20 mg once daily reduces the risk of developing gastric and/or duodenal ulcers and symptoms associated with the continuous use of low-dose aspirin in patients agedor =60 yr without preexisting gastroduodenal ulcers.

Summary Background The effects of ursodeoxycholic acid on human placental bile acids and bilirubin transporters in intrahepatic cholestasis of pregnancy are still undefined. Aim To evaluate whether ursodeoxycholic acid affects MRP2, MRP3 and MRP4 expression in the placenta. Materials and methods Forty-three pregnant women were enrolled; fourteen subjects had physiological pregnancies. Intrahepatic cholestasis of pregnancy patients were divided into two groups: (i) 13 received ursodeoxycholic acid (20 mg/kg/day) and (ii) 16 untreated. Total bile acid and bilirubin in serum and cord blood were determined in each subject. Multidrug resistance proteins expression (immunoblot, quantitative real-time PCR) was evaluated in placentas collected at delivery. anova test was used for statistical analysis of data. Results Ursodeoxycholic acid administration significantly improved maternal serum bile acid and cord blood bilirubin and bile acid levels. MRP2 protein and RNA expression was significantly increased in placentas from treated patients compared to controls (P

Background and aims Omega-3 fatty acids in fish oil exert a protective effect on the development of colorectal cancer in animal models. Patients with colorectal adenomas have been shown to have increased crypt cell proliferation and decreased apoptosis in macroscopically normal appearing colonic mucosa. We investigated whether dietary supplementation with eicosapentaenoic acid (EPA) could alter crypt cell proliferation and apoptosis in such patients. Patients/methods Thirty subjects were randomised to either 3 months of highly purified EPA in free fatty acid form (2 g/day) or to no treatment. Colonic biopsies were taken at the initial colonoscopy and repeated 3 months later, and analysed for cell proliferation and apoptosis (immunohistochemistry) and mucosal fatty acid content. Results/findings Crypt cell proliferation was significantly reduced whilst apoptosis was significantly increased after EPA supplementation. Neither crypt cell proliferation nor apoptosis were altered in the control group. EPA in the mucosa increased significantly after EPA supplementation, whereas there was no significant change in controls. Conclusions Dietary supplementation with EPA significantly increases levels of this fatty acid in colonic mucosa, associated with significantly reduced proliferation and increased mucosal apoptosis. Further studies are needed to assess the potential efficacy of EPA supplementation in preventing polyps in the chemoprevention of colorectal cancer.

Background. Some authors have reported, using different protocols, that 13C-urea breath test (13C-UBT) is capable of assessing the intragastric Helicobacter pylori bacterial load, whereas others have not confirmed these data. Our aim is to evaluate the correlation between 13C-UBT values and H. pylori bacterial load. Materials and Methods. One hundred ninety-two patients diagnosed H. pylori-positive by rapid urease test, histology, and 13C-UBT were enrolled. H. pylori bacterial load (H. pylori score) and gastritis activity (activity score) were evaluated according to the Updated Sydney System. 13C-UBT was performed according to the European Standard Protocol. Breath samples were obtained every 10 minutes for 60 minutes in 52 patients and at 30 minutes (T30) in 140 patients and analyzed by mass spectrometry. Results. At T30, mean ± SD excess delta 13CO2 excretion was 17.4 ± 1.1, 29.9 ± 2.2, and 48.7 ± 4.8 in patients with H. pylori scores 1, 2, and 3, respectively. This difference was statistically significant: H. pylori score 1 versus 2, p

Evaluation of protein expression in tissues and cells by electrophoretic and blotting techniques or by the quantification of the mRNA coding for the target protein is a common procedure in biochemistry research and clinical diagnoses. In this article, an alternative approach, based on an immunohistochemical procedure with chemiluminescent imaging detection, is described. The assay exploited the peculiar characteristics of the chemiluminescent detection of enzyme labels (high sensitivity and specificity, low background, easy quantification of the signal) for performing the direct, simple, and rapid quantitative evaluation of protein expression in tissues. When applied to the study of the levels of MRP2, a member of the human multidrug resistance-associated protein family, in samples obtained from formalin-fixed, paraffin-embedded liver biopsies, it allowed the reliable evaluation of the protein content of the tissue. Moreover, the analysis of clinical samples from patients with primary biliary cirrhosis under therapy with ursodeoxycholic acid gave results in line with those, previously reported in the literature, obtained with conventional protein expression analysis techniques.

Colon cancers displaying microsatellite instability (MSI) are clinically less aggressive. Based on in vitro studies and recent clinical data, cancers displaying MSI do not respond to 5-fluorouracil (5-FU). The reasons why MSI tumors are clinically less aggressive and do not respond to 5-FU–based therapies have not been fully elucidated. Purpose: We investigated biomolecular markers in an attempt to explain the different clinical behavior and chemotherapeutic responses of MSI and non-MSI colon cancers. Experimental Design: One hundred ninety-two sporadic colon cancers were tested for MSI with five mononucleotide markers and methylation of the hMLH1 promoter. Slides were stained for thymidylate synthase (TS), p53, MDM2, p21WAF1/CIP1, β-catenin, vascular endothelial growth factor, hMLH1, hMSH2, and hMSH6. Tumors were regarded as having wild-type, functional p53 (Fp53) if reduced expression of p53 and positive MDM2 and p21WAF1/CIP1 expressions were found. Results: Of the cases, 12.5% were MSI-H (at least two markers mutated). Of MSI-H cases, 83.3% were characterized by a complete loss of at least one of the mismatch repair proteins, in particular loss of hMLH1 by promoter hypermethylation. MSI-H colon cancers showed higher expression of TS compared with MSS (no mutated markers)/MSI-L (one mutated marker) colon cancers (66.6% for MSI-H versus 14.8% MSS/MSI-L; P < 0.0001); 20.8% of MSI-H cases showed high expression of the vascular endothelial growth factor, compared with 45.8% MSS/MSI-L colon cancers (P = 0.0005); 45.8% MSI-H cases had Fp53 compared 11.9% MSS/MSI-L cases (P < 0.0001). Conclusions: About 12% of colon cancers display MSI mostly due to lack of hMLH1 resulting from promoter hypermethylation. These tumors have high expression of TS and retain fully functional p53 system. Thus, these data suggest why sporadic hMLH1-defective colon cancers often do not respond to 5-FU.

Background. Measurement of the severity of dyspepsia symptoms before and after treatment and determining what is a significant change is a major problem in designing dyspepsia treatment studies. Objectives. To assess the reproducibility, validity and responsiveness to treatment of a dyspepsia questionnaire to be used in clinical and population-based studies. Methods. Seventy-three dyspeptic patients (35 male, 38 female; mean age 52 years) and 75 healthy volunteers (32 male, 43 female; mean age 52 years) were included. Subjects were interviewed for the presence/absence and severity/frequency of 19 gastrointestinal symptoms. Severity was measured on a 5-point scale. Frequency was also recorded on a 5-point scale. A global symptom index (severity × frequency) was calculated for the eight most severe symptoms; a mean global symptom index (8-MGSI) was considered for the evaluation of the instrument. To evaluate intra-observer variation, one author interviewed subjects (T0) and then repeated the interview 1 week later (T1). For inter-observer variation, two authors interviewed patients. Validity was measured by comparing 8-MGSI of the dyspepsia patients to those of healthy volunteers. Responsiveness was assessed by comparing mean global symptom index before and 1 month after appropriate therapy. Results. Reproducibility: The mean 8-MGSI was 4.5 at T0 and 3.7 at T1 with a correlation coefficient of 0.62. As for inter-observer variation, the average 8-MGSI was 4.8 by the first author and 3.9 by the second with a correlation coefficient of 0.60. Validity: The mean 8-MGSI was, respectively, 1.4 in healthy volunteers and 4.8 in dyspeptic patients (p = 0.001). Responsiveness: After treatment, a significant improvement in 8-MGSI was detected (p = 0.001). Conclusions. This questionnaire is a reliable, valid and responsive instrument for measuring the presence, severity and frequency of dyspepsia.

BACKGROUND/AIMS Apolipoprotein (apo)A-I(M) (ilano), is a molecular variant of apoA-I(wild-type), associated with dramatically low HDL-cholesterol levels, but no increased risk for cardiovascular disease. In view of the present uncertainties on the role of apoA-I in liver cholesterol removal by way of bile acids and neutral sterols, and of the greater capacity of apoA-I(M) (ilano) to remove arterial cholesterol, biliary sterol metabolism was evaluated in transgenic mice expressing apoA-I(M) (ilano). METHODS ApoA-I(M) (ilano) mice were fed a high-cholesterol/high-fat diet, and compared with human apoA-I(wild-type) mice. Plasma lipid levels, hepatic bile flow and composition, hepatic and intestinal cholesterol and bile acid content, and faecal sterol content were measured. Moreover, the expression of hepatic ABCA1, SR-B1 and that of hepatic and intestinal genes involved in bile acid metabolism were evaluated. RESULTS The dietary treatment led to a strong elevation in HDL-cholesterol levels in A-I(M) (ilano) mice, associated with an increased expression of hepatic ABCA1. ApoA-I(M) (ilano) mice showed lower cholesterol output from the liver compared with apoA-I(wild-type) mice, in the absence of liver sterol accumulation. Faecal excretion of neutral sterols and bile acids was similar in the two mouse lines. CONCLUSIONS In spite of a different response to the dietary challenge, with an increased ABCA1 expression and a lower hepatic cholesterol output in apoA-I(M) (ilano) mice, the net sterol excretion is comparable in the two transgenic lines.

A new sustained-release formulation (sustained release Ibifen) that gradually releases ketoprofen within 24 h and ensures therapeutic plasma concentration for the entire period has been developed. It consists of tableted pH-dependent barrier film-coated ketoprofen granules and was administered at a single dose of 200 mg to 12 volunteers. Ketoprofen plasma profiles were compared with: (1) administration of Orudis retard 200 capsule (200 mg); (2) two 12-h doses of prompt release Ibifen capsules (100 mg). In vitro dissolution kinetics and ketoprofen plasma levels were measured by HPLC. Sustained release Ibifen dissolution rate was constant for 10 h, whereas Orudis retard 200 dissolution profile presented one higher slope (0-6 h) and a lower one (6-12 h). Both formulations showed a delayed kinetics with respect to prompt release Ibifen. After sustained release Ibifen administration, ketoprofen plasma peak, reached within 2 h, remained practically constant for at least 12 h (average 4 microg/ml), which is higher than therapeutic levels. Differently, Orudis retard 200 produced a delayed, higher C(max) (5.91+/-0.66 vs. 4.51+/-0.65 microg/ml; P

Objectives: As part of a cross-sectional study on cholelithiasis, 1533 out of 1840 residents in Loiano/Monghidoro, a rural area in Northern Italy (792 men, 741 women, age range 28–80 years), agreed to be further evaluated in relation to their Helicobacter pylori status. Methods: Each participant performed a 13C-urea breath test (13C-UBT) and provided information on sociodemographic, lifestyle and clinical characteristics. Results: The 13C-UBT was positive in 1041 subjects (67.9%; men: 69%; women: 67%) and was positively associated with increasing age (P

In the evaluation of patients suffering from portal hypertension, a knowledge of morphofunctional characteristics of the portal tree and of the shunts with the systemic circulation is fundamental. To the methods traditionally used for this purpose such as endoscopy, transabdominal sonography, angiography, magnetic resonance, and computed tomography, endosonography has been recently added as a minimally invasive and sensitive technique. By endosonography, it is possible to visualize portal branches, esophageal-gastric and rectal varices, collateral extraparietal veins, and small ascitic effusions that other diagnostic methods may miss.

To establish a correct preoperative differential diagnosis between gastric lymphoma and cancer is essential but can be difficult as endoscopic biopsies can sometimes provide a low diagnostic yield. By EUS, infiltrative carcinoma tends to show a vertical growth in the gastric wall, while lymphoma tends to show mainly a horizontal extension. EUS provides an accurate staging of gastric lymphoma, showing the exact level of infiltration and the presence of perigastric lymph nodes, thus the physician can obtain an accurate prognosis for each patient and select the best form of treatment accordingly. The response to chemoradiotherapy can also be investigated very accurately by EUS. Large gastric folds are seen in a great number of benign and malignant conditions. Diagnosis represents a clinical challenge because etiology may be extremely varied and standard biopsies are often inconclusive. Different diseases show different levels of infiltration of the gastric wall, thus a characteristic echo-pattern helps for the differential diagnosis. Endosonography, used always in combination with biopsy, allows to rule out malignancies and to select the most appropriate treatment for each patient (medical or surgical).

We describe the case of a young female referred to our unit because of acute upper abdominal symptoms. Upper gastrointestinal endoscopy showed a gastric picture resembling lymphoma or acute non-steroidal anti-inflammatory drug gastropathy (deep, large and irregular ulcers), but the clinical history and the histological examination of gastric biopsies were consistent only with acute gastritis Helicobacter pylori-correlated. The patient was treated with omeprazole and antibiotics with complete recovery. As the patient's cat had suffered from an acute gastrointestinal distress two weeks earlier, a case of zoonosis was hypothesized and an upper gastrointestinal endoscopy was performed also on the cat. Unfortunately, we were not able to detect Helicobacter pylori in the cat gastric mucosa, but only urease-producing spiral microorganisms. Possible sources of infection and pathogenetic mechanisms of the severe gastritis are discussed.

The fact that about 50% of the world's population is infected with Helicobacter (H.) pylori and the important role that this bacterium plays in public health have been important incentives in the search for accurate diagnostic methods. A large number of invasive and non-invasive methods have been used to diagnose H. pylori infection. Each method has its advantages and disadvantages and each practitioner should choose the best diagnostic method according to the facilities available. Non-invasive tests for the diagnosis of H. pylori infection are largely used in clinical practice and in management of patients with gastroduodenal disease. Serology is the most widespread test but its use is not advised in the post-treatment follow-up. The Urea Breath Test is a simple, safe and highly accurate method ideal for evaluating the short-term follow-up of H. pylori eradication after therapy.

As immunosuppressive agents, corticosteroids maybe considered an appropriate treatment for primarybiliary cirrhosis, even if bone loss and other sideeffects may occur. We studied biliary lipid metabolism in 10 nonicteric patients, with histologicallyproven primary biliary cirrhosis (stage I-IV). Weadministered methylprednisolone (24 mg daily) for 30days to ascertain its effects on biliary lipidmetabolism, which are largely still unknown. All patientsunderwent a 30-day drug-washout period before enteringthe trial. The following parameters were studied beforeand after methylprednisolone treatment: serum biochemistry; cholic acid pool size, kineticsand synthesis; biliary lipid secretion; biliary bileacid pattern; biliary lipid molar percentage; andcholesterol saturation index. Methylprednisolone induced a statistically significant (Wilcoxon ranktest) increase in cholic acid turnover (from 0.26± 0.04 to 0.50 ± 0.05 K/day, P = 0.005)and synthesis (from 0.42 ± 0.12 to 0.78 ±0.11 mmol/day, P = 0.04), and in bile deoxycholic acid molarpercentage (from 19.4 ± 2.7 to 30.6 ± 4.4%molar, P = 0.01). On the other hand, a significantdecrease in biliary cholesterol molar percentage (from7.9 ± 0.7 to 6.4 ± 0.5 % molar, P =0.005), cholesterol saturation index (from 1.11 ±0.11 to 0.95 ± 0.07, P = 0.05), and biliarycholesterol secretion (from 64.7 ± 5.4 to 53.0± 4.5 μmol/hr, P = 0.005) was observed. These findings show thatshort-term administration of methylprednisolone inpatients with primary biliary cirrhosis does not induceexpansion of the cholic acid pool but increases cholicacid synthesis and turnover, as well as intestinalproduction of deoxycholic acid. If long-term treatmentis considered, the beneficial immunosuppressive effectsof corticosteroids have to be weighed against the hepatotoxic properties of deoxycholicacid.

A chemiluminescent urease activity assay has been developed and optimized using the chemiluminescent pH indicator phthalhydrazidylazoacetylacetone. This compound is stable at pH

Background: This multicentre, randomized study was designed to assess the clinical efficacy, safety and tolerability of three novel 7-day triple therapies containing ranitidine bismuth citrate (RBC) and two antibiotics. Methods: We studied patients with non-ulcer dyspepsia and gastritis who were randomly assigned to one of three treatment regimens given for 7 days in a b.d. dosing schedule: RBC 400 mg plus clarithromycin 250 mg and tinidazole 500 mg (RBCCT); RBC 400 mg plus clarithromycin 500 mg and amoxycillin 1 g (RBCCA); RBC 400 mg plus tinidazole 500 mg and amoxycillin 1 g (RBCTA). H. pylori status was determined by CLO-test, histology and 13C-urea breath test. A repeat breath test was performed at least 28 days after completion of therapy to assess eradication. Results: One hundred and fifty-seven patients were eligible for intention-to-treat analysis (ITT) and 140 patients completed the study and returned for assessment of eradication. Intention-to-treat cure rates were 78% with RBCCT, 71% with RBCCA and 61% with RBCTA. An all-patients-treated analysis (APT), performed on evaluable patients, demonstrated eradication rates of 85% with RBCCT, 81% with RBCCA and 70% with RBCTA. No statistically significant difference was found between treatment groups. Twenty-four patients experienced side-effects, but in only seven cases was treatment discontinued due to adverse events. Conclusions: A 7-day course of RBC, clarithromycin and either tinidazole or amoxycillin provides a good rate of H. pylori eradication. Three novel RBC-based triple therapies proved to be safe and well tolerated, with discontinuations due to side-effects occurring in less than 5% of cases.

Background: No clinical study has been performed to-date to evaluate the efficacy of the dual therapy of ranitidine bismuth citrate (RBC) plus clarithromycin (C) 500 mg b.d. given for 7 days for the eradication of H. pylori. Aim: To assess the eradication rates achieved by treatment with RBC 400 mg b.d. for 28 days combined with clarithromycin 500 mg b.d. for 7 days in H. pylori-positive duodenal ulcer patients. Methods: One hundred and twelve H. pylori-positive patients with endoscopically proven active duodenal ulcer were included in a multicentre, open, randomized trial. H. pylori infection was initially detected by CLO-test and histology on antral and corpus biopsies, and by 13C-urea breath test (UBT). Patients were included if at least two of the tests were positive for H. pylori infection. Patients were randomized to receive RBC 400 mg b.d. for 4 weeks combined with clarithromycin 500 mg b.d. for the first 7 days (Group A) or 14 days (Group B). A second endoscopy was performed at least 28 days after the end of therapy for the assessment of ulcer healing and H. pylori infection. Eradication was assumed if all the tests (CLO-test, histology and UBT) were negative for H. pylori. Results: Fifty patients in Group A and 55 in Group B were assessed for H. pylori eradication and ulcer healing. The eradication rates according to intention-to-treat analysis were 75% in Group A and 80% in Group B. Considering only those patients with evaluable data at least 28 days after the end of therapy, H. pylori eradication was achieved in 84% and 82% in Group A and B, respectively. No statistically significant difference in eradication was found between the two groups by Mantel–Haenszel test. Only one patient, in Group A, was withdrawn because of adverse events (epigastric pain and pruritus). Conclusions: Dual therapy with RBC plus clarithromycin for 7 days could be an effective regimen for H. pylori eradication.

Near infrared reflectance analysis (NIRA) is a useful test for diagnosing fat malabsorption. Three-day stool collection and determination of fecal fat output are recommended. The measurement of fat concentration on spot samples may be of some use only in screening malabsorption of pancreatic origin; moreover, it does not discriminate between steatorrhea resulting from pancreatic insufficiency and that caused by gastrointestinal disorders.NIRA has been proposed as an accurate method for the determination of fecal fat excretion. The aim of this study was to ascertain whether utilization of this technique to measure fat concentration in spot samples of feces is useful in screening for malabsorption.Twenty-five patients with chronic pancreatic disease and 95 with other digestive disorders were studied. In all patients, fecal fat assay with NIRA was performed on three different samples from each daily stool collection for 3 d. In 14 patients with pancreatic disease and 21 with gastrointestinal disorders, a colorimetric assay for fecal fat was performed for comparison.When mean 3-d or daily fat fecal output were considered, a strict linear relationship was found between NIRA and the colorimetric method (r = 0.97 and 0.94, respectively). Using fat concentration, the two tests correlated less well (r= 0.74). Fat concentration was significantly higher in pancreatic than in nonpancreatic steatorrhea, even though values overlapped widely, and thus discrimination was not possible. The diagnostic efficiency of fat concentration for pancreatic and nonpancreatic steatorrhea was 72 and 61%, respectively.

Since there are now several ways to treat symptomatic gallstone disease, one is able to select treatment on the basis of the patient's comfort, the practicability, effectiveness, and side effects of the technique, and the relative costs. In order to assess the present status of contact dissolution with methyl tert-butyl ether with regard to these aspects, the present enquiry reports the data of 21 European hospitals. Eight hundred three patients were selected for contact litholysis of cholesterol gallbladder stones using methyl tert-butyl ether. Percutaneous transhepatic puncture of the gallbladder was performed under x-ray or ultrasound guidance. Dissolution rate, side effects, and treatment times of 268 patients from one single center were compared to those of 535 patients from the other 20 centers. Two hundred sixty-four patients were followed for five years to assess stone recurrence. Physicians were asked how they assessed the expenditure of the method, the discomfort to the patients, and the staffing situation. Patients were asked to indicate their acceptance on an analog scale. Puncture was successful in 761 (94.8%) patients. Prophylactic administration of antibiotics was not necessary. Stones were dissolved in 724 (95.1%) patients. In 315 (43.5%) sludge remained in the gallbladder. The most severe complication was bile leakage, which led 12 (1.6%) patients to have elective cholecystectomy. Toxic injuries due to the ether were not reported. Method-related lethality amounted to 0%, 30-day-lethality to 0.4%. Stone recurrence rate was about 40% in solitary stones and about 70% in multiple stones over five years. Patients with multiple stones developed recurrent stones almost twice as often as those with solitary stones. The probability of stone recurrence in patients with sludge in the gallbladder after catheter removal was not statistically significantly different from those without sludge. Seventy to 90% of the centers found the puncture to be simple and not distressing for patients and the relation between expenditure and therapeutic success to be acceptable. The acceptance of contact litholysis by the patients was excellent. Contact litholysis when applied by an experienced team provides real advantages in the treatment of gallstone disease. The method is technically simple, well accepted by the patients, and can be easily applied in community hospitals. Contact litholysis may be of particular value in patients who are not suitable for anesthesia or surgery.

Oxygen free radicals generation is a major cause of liver injury during reperfusion. Luminescence analysis has been recently proposed to measure free radical generation by isolated cells or organs, but it allows only global tissue luminescence. Using a special Saticon videocamera with image intensifier we aimed to visualize and localize oxygen free radical generation in isolated perfused livers exposed to an oxydative stress. Livers isolated from rats aged 4 and 30 months were exposed to ischemia/reperfusion; photons emission by the organs was continuously recorded. Lucigenin was utilized as a chemiluminigenic probe to assess superoxide anion generation. In both groups, chemiluminescence was not detectable during ischemia, while it was observed after reperfusion. Photons emission started after few minutes of reperfusion, was maximal after 15-20 min and disappeared within 50-60 min. Chemiluminescence emitted by livers from younger rats however, was significantly higher when compared to chemiluminescence emitted by organs isolated from old rats (0.8 +/- 0.1 vs 0.44 +/- 0.08 photons x 10(5)/s, respectively, after 15 min; p.01). The superimposition of chemiluminescent and live image permitted to determine the regional production rate and distribution of photons. In conclusion, the age of the rats influences significantly the amount of oxyradicals produced in the liver during post-ischemic reperfusion. The method described, allowing the visualization in real time of oxygen free radicals generation on the surface of isolated intact organs, represents a novel and potent tool for the study of oxidative stress.

Background—A non-invasive test for assessment of fat digestion has been developed based on the intraluminal hydrolysis of cholesteryl-[1-13C]octanoate by pancreatic esterase.Aims—To determine the diagnostic performance of this breath test in the assessment of exocrine pancreatic function.Methods—The test was performed in 20 healthy controls, 22 patients with chronic pancreatic disease (CPD), four with biliopancreatic diversion (BPD), and 32 with non-pancreatic digestive diseases (NPD); results were compared with those of other tubeless tests (faecal chymotrypsin and fluorescein dilaurate test).Results—Hourly recoveries of13CO2 were significantly lower in CPD when compared with healthy controls or NPD. In patients with CPD with mild to moderate insufficiency, the curve of 13CO2recovery was similar to that of healthy controls, while in those with severe insufficiency it was flat. In three patients with CPD with severe steatorrhoea, a repeat test after pancreatic enzyme supplementation showed a significant rise in13CO2 recovery. The four BPD patients had low and delayed 13CO2 recovery. Only eight of the 32 patients with NPD had abnormal breath test results. There was a significant correlation between the results of the breath test and those of faecal chymotrypsin, the fluorescein dilaurate test, and faecal fat measurements. For the diagnosis of pancreatic disease using the three hour cumulative 13CO2 recovery test, the sensitivity was 68.2% and specificity 75.0%; values were similar to those of the other two tubeless pancreatic function tests. In seven healthy controls, nine patients with CPD, and nine with NPD a second breath test was performed using Na-[1-13C]octanoate and a pancreatic function index was calculated as the ratio of13C recovery obtained in the two tests: at three hours this index was abnormal in eight patients with CPD and in three with NPD.Conclusion—The cholesteryl-[1-13C]octanoate breath test can be useful for the diagnosis of fat malabsorption and exocrine pancreatic insufficiency.

The epidemiological associations of gallstone disease were evaluated in a general population sample of 29,584 individuals (15,910 men and 13,674 women; age range, 30-39 years) belonging to 14 cohorts examined between December 1984 and April 1987. Subjects were screened for the presence of gallstones by gallbladder ultrasonography, completed a questionnaire, and underwent a physical examination and blood chemistry tests. Participants were considered to have gallstone disease if they had already had cholecystectomy or gallstones. Statistical associations were established by univariate analysis of the age-standardized data and by stepwise multiple logistic regression. Increasing age and body mass index and a maternal family history of gallstone disease were the most consistent associations (both at univariate and multivariate analysis and in both sexes) found in this study. Personal history of dieting was associated with gallstone disease in men, and at univariate analysis, in women. Decreasing serum total cholesterol levels and increasing serum triglycerides were associated with gallstone disease in both sexes in the multivariate analysis. In women, associations were also found with a number of pregnancies and paternal family history of gallstone disease. A slight but negative association with contraceptive pill use was identified only at multivariate analysis. Associations (investigated at univariate analysis) were also found with diabetes, cirrhosis, angina or myocardial infarction, and peptic ulcer. There was no association with smoking habits and use of aspirin or antirheumatic drugs.

Dose-response curves for taurocholate and tauroursodeoxycholate were performed in rat and rabbit livers to get more insight into species differences in the hepatic bile acid uptake. The bile acids showed saturation kinetics in both animals, the Vmax in rat being higher than in rabbit and the Km being lower in the rat than in the rabbit for both the bile acids, with no significant difference in the hepatic cells morphometric parameters. Therefore, it is possible that differences in the kinetic parameters are related to the number and, to a lesser extent, to the affinity of the transporters on the sinusoidal plasma membranes.

Background & Aims: Increasing evidence indicates that inherited susceptibility is important in the pathogenesis of colorectai neoplasia. The aim of this study was to clarify whether having only one first-degree relative with colorectal cancer increases the risk of developing adenomatous polyps and whether total colonoscopy is an appropriate screening measure in these patients. Methods: The frequency of such a history was evaluated in 397 asymptomatic patients who underwent total colonoscopy. Of these patients, 155 had colorectal polyps and the remaining 242 did not have polyps. Results: Among polyp cases, 27 of 155 (17.4%) had a positive history; among those without polyps, 12 of 242 (5.0%) had a positive history. Alternatively expressed, 27 of 39 patients (69%) with family history and 128 of 358 patients (36%) without family history had adenomas. The estimated risk for polyps associated with family history was 1.9. Among polyp cases, 14 of 27 patients (51.9%) with family history and 32 of 128 patients (25.0%) without family history had only proximal polyps ( χ 2 test; P = 0.006; odds ratio, 3.2). In the same groups, frequency of high-grade dysplasia was 8 of 27 patients (29.6%) and 16 of 128 patients (12.5%), respectively ( χ 2 test; P = 0.04; odds ratio, 2.9). Conclusions: Relative to subjects with no family history, asymptomatic patients with one first-degree relative with colorectal cancer had nearly double the risk of developing adenomatous polyps, greater frequency of severely dyspiastic lesions, and significantly higher frequency of proximal polyp location. This suggests that total colonoscopy screening is indicated in these subjects.

A new enteric-coated formulation of sodium ursodeoxycholate was prepared and administered to man. The barrier film disintegrates and releases the drug only at pH > or = 5.5. The sodium salt of glycoursodeoxycholate was also prepared and encapsulated like ursodeoxycholate. Serum levels of ursodeoxycholate and glycoursodeoxycholate were measured by specific enzyme immunoassay after oral administration of their sodium salts in an enteric-coated formulation at equimolar doses of 475 and 540 mg. The same subjects also received in separate experiments ursodeoxycholic acid, sodium ursodeoxycholate, and glycoursodeoxycholic acid in gelatin capsules. The mean area under the curve (mumol/L.hr) following administration of enteric-coated sodium ursodeoxycholate (45 +/- 8) was significantly higher than that of either ursodeoxycholic acid (26 +/- 5; P < 0.01) or sodium ursodeoxycholate (25 +/- 6; P < 0.001) administered in a conventional gelatin capsule. No differences were found when glycoursodeoxycholic acid was administered as an enteric-coated sodium salt or in acid form in gelatin capsules. Ursodeoxycholic was administered at a dose of 10 mumol/min/kg over 1 hr to bile fistula rats both intraduodenally (i.d.) and intravenously (i.v.). The experiment included administration of the sodium salt in solution and the acid as a suspension. A similar experiment was performed with glycoursodeoxycholic acid. The ratio of the amount recovered from bile in the i.d. to that in the i.v. experiment is almost 1 for the sodium salt of ursodeoxycholate in solution, while it drops to 0.55 for ursodeoxycholic acid. No differences were found between i.v. and i.d. administration when glycoursodeoxycholic acid was administered in acid form and as a soluble sodium salt.(ABSTRACT TRUNCATED AT 250 WORDS)

Many studies have attempted to prove a link between Helicobacter pylori infection and functional dyspepsia but the results have been conflicting. Several mechanisms have been postulated for how H pylori associated inflammation disturbs antral and duodenal function but no pathophysiological explanation of how H pylori may cause dyspeptic symptoms is presently available.

Twenty years ago, ribavirin was first used in the treatment for chronic hepatitis C. After few years, ribavirin, in combination with interferon-alpha, showed a dramatic synergistic efficacy against hepatitis C virus infection, leading to viral clearance in about 50% of patients. Recent discovery of potent inhibitors of hepatitis C virus proteases did not replace ribavirin as the mainstay of combination therapy for chronic hepatitis C. Despite this fundamental role of ribavirin, many aspects of the mechanism of action and of the optimal dose and duration of therapy remain to be discovered or settled. In the present review, the authors recall the milestones in the history of ribavirin and try to shed light on the more relevant features of ribavirin action and utilization, and on the clinical problems encountered in managing and optimizing treatment for chronic hepatitis C. Finally, some potential off-label use of this drug in most difficult-to-treat subjects is pointed out. In conclusion, even if a sort of mystery surrounds ribavirin, its efficacy against hepatitis C virus infection fortunately remains lasting and stable.

Due to the importance of intestinal transport in pharmacological studies and the emerging role of intestinal signalling activity in the gut-liver axis, we have developed a new method to investigate intestinal transport and liver signalling using cell and serum free mesenteric perfusion system in the rat. The method regarding bile acid active absorption was validated, then, the portal venous content was examined for fibroblast growth factor 15(FGF15), a putative signalling protein produced by the ileal enterocytes following bile acid absorption. After isolation and cannulation of the relevant vessels (abdominal aorta and portal vein), the abdominal aorta and the terminal ileum were infused with respectively Krebs-Ringer solution and tauroursodeoxycholate (TUDCA) and the absorption was assessed by its recovery in the portal vein. After immunoblot, liquid chromatography and mass spectrometry analysis were performed both on gel bands digestion products and on portal outflow samples in order to evaluate if negligible amounts of FGF15 were present in the portal circulation. TUDCA absorption was efficient, intestinal morphology and oxygen consumption were normal. Despite accurate analysis, we could not find FGF15. Our method proved to be reliable for studying the active bile acid absorption. It is also suitable to identify molecules produced by enterocytes and transferred to the portal circulation in response to absorption of different substances such as nutrients or drugs. Since FGF15 was not recovered we suggest the possibilities that this protein is produced in very little amounts, poorly transferred outside the cell, or that it is extremely unstable and rapidly degraded.

Hepatic encephalopathy (HE) is a metabolic-neurophysiologic syndrome that occurs in patients with liver disease. One of the main pathogenic mechanisms is represented by circulating toxins produced from the intestinal metabolism of nitrogenous compounds. The therapeutic approach to HE includes drugs that eliminate ammoniaproducing bacteria. The aim of this study was to evaluate the efficacy and safety of rifaximin, a nonabsorbable antibacterial agent, in the treatment of chronic HE in a large population of cirrhotic patients. One hundred thirty-six cirrhotic patients (100 men, 36 women; mean age, 59.5 years) with clinical and biochemical signs of mild HE were studied under three different treatment protocols: one open study in which rifaximin (1200 mg/day) was administered for 21 days to 80 patients; and two randomized controlled studies, one in which rifaximin (1200 mg/day, 20 patients) and neomycin (3000 mg/day, 15 patients) were administered for 21 days and one in which rifaximin (1200 mg/day, 9 patients) and lactulose (40 gm/day, 12 patients) were administered for 21 days. In the open study, after 5 days of treatment, ammonia reached normal values in each patient; after 7 days, electroencephalographic abnormalities were present only in a few cases; and after 15 days, no patients showed neurologic signs of HE. In the rifaximin versus neomycin study, blood ammonia levels and neurologic signs significantly decreased during both treatments, but rifaximin induced an earlier disappearance of clinical and biochemical signs of HE. In the rifaximin versus lactulose study, both drugs were efficacious in reducing the neurologic signs of HE, but some patients treated with lactulose presented mild side effects at the beginning of the therapy, which disappeared in the course of treatment. This study confirms the usefulness of rifaximin in the management of cirrhotic patients with mild HE; the absence of significant side effects suggests its use even in more severe cases of HE, either alone or in association with other drugs.

Ursodeoxycholic acid has been proposed for the treatment of primary biliary cirrhosis. The aim of this study was to evaluate the effect of ursodeoxycholic acid administration on bile acid metabolism in patients with early-stage primary biliary cirrhosis. Biliary bile acid composition, primary bile acid pool sizes, synthesis, and fractional turnover rate were measured before and after four weeks of ursodeoxycholic acid administration (600 mg/day) in nine patients with biopsy-proven primary biliary cirrhosis (stages I-III). Molar percentages of chenodeoxycholic, cholic, and deoxycholic acids in bile were significantly decreased by ursodeoxycholic acid administration, while its biliary concentration increased to 34.2% at the end of the same four-week period. The cholic and chenodeoxycholic acid pools decreased, although not significantly, while the deoxycholic acid pool was reduced by 60% (from 0.7 +/- 0.12 to 0.29 +/- 0.07 mmol, P < 0.002). Primary bile acid synthesis was slightly increased, and fractional turnover rate was significantly increased. The conversion rate of cholic to deoxycholic acid was measured and found to be significantly increased (P < 0.05) after ursodeoxycholic acid administration; however, serum levels of both free and conjugated deoxycholic acid were significantly decreased (from 23.2 +/- 9.7 to 3.8 +/- 1.9 mumol/liter, P < 0.001). We conclude that in patients with primary biliary cirrhosis, ursodeoxycholic acid administration replaces endogenous bile acids in the enterohepatic circulation by increasing bile acid fractional turnover rate without significant increments of their hepatic synthesis.

The pathogenesis of inflammatory bowel diseases (IBDs) seems to involve a primary defect in one or more of the elements responsible for the maintenance of intestinal homeostasis and oral tolerance. The most important element is represented by the intestinal barrier, a complex system formed mostly by intestinal epithelial cells (IECs). IECs have an active role in producing mucus and regulating its composition; they provide a physical barrier capable of controlling antigen traffic through the intestinal mucosa. At the same time, they are able to play the role of non-professional antigen presenting cells, by processing and presenting antigens directly to the cells of the intestinal immune system. On the other hand, immune cells regulate epithelial growth and differentiation, producing a continuous bi-directional cross-talk within the barrier. Several alterations of the barrier function have been identified in IBD, starting from mucus features up to its components, from epithelial junctions up to the Toll-like receptors, and altered immune responses. It remains to be understood whether these defects are primary causes of epithelial damage or secondary effects. We review the possible role of the epithelial barrier and particularly describe the role of IECs in the pathogenesis of IBD.

AIM: To evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) for the management of refractory bile duct cholelithiasis in a third level referral centre. METHODS: The clinical records of all patients treated with a second generation electromagnetic lithotripter (Lithostar Plus, SIEMENS) from October 1990 to April 2005 were evaluated. All patients were monitored during the procedure and antibiotics were administered in case of cholangitis. The χ2 test and logistic regression analysis were performed as appropriate. RESULTS: Two hundred and fourteen patients (102 males, 112 females; mean age 74.8 ± 0.84 years - single stone 97, multiple stones 117) underwent ESWL. The mean number of sessions and shock waves were 3.5 ± 0.13 and 3477.06 ± 66.17, respectively. The maximum stone size was 5 cm. Complete stone clearance was achieved in 192 (89.7%) patients. Of the remaining patients 15 required surgery, 2 a palliative stent and in 5 patients stone fragmentation led to effective bile drainage with clinical resolution despite incomplete clearance. Age, sex and stone characteristics were not related to treatment outcome. Major complications occurred in two patients (haemobilia and rectal bleeding) and minor complications in 25 (3 vomiting, 22 arrhythmias). No procedure-related deaths occurred. CONCLUSION: ESWL is a safe and effective technique for clearance of refractory bile duct stones.

We report a case of a prompt reactivation of a quiescent Crohn's disease with pain, fever and abdominal abscess which occurred after seasonal and pandemic flu vaccinations. Based on the clinical history and the timing of the events, we could relate the relapse of CD to the double vaccinations.

Background and Aims: The knowledge of natural history is essential for disease management. We evaluated the natural history (e.g. frequency and characteristics of symptoms and clinical outcome) of gallstones (GS) in a population-based cohort study. Methods: A total of 11 229 subjects (6610 men, 4619 women, age-range: 29–69 years, mean age: 48 years) were studied. At ultrasonography, GS were present in 856 subjects (338 men, 455 women) (7.1%). GS were followed by means of a questionnaire inquiring about the characteristics of specific biliary symptoms. Results: At enrolment, 580 (73.1%) patients were asymptomatic, 94 (11.8%) had mild symptoms and 119 (15.1%) had severe symptoms. GS patients were followed up for a mean period of 8.7 years; 63 subjects (7.3%) were lost to follow up. At the end of the follow up, of the asymptomatic subjects, 453 (78.1%) remained asymptomatic; 61 (10.5%) developed mild symptoms and 66 (11.4%) developed severe symptoms. In subjects with mild symptoms, the symptoms disappeared in 55 (58.5%), became severe in 23 (24.5%), remained stable in 16 (17%); in subjects with severe symptoms, the symptoms disappeared in 62 (52.1%), became mild in 20 (16.8%) and remained stable in 37 (31.1%). A total of 189 cholecystectomies were performed: 41.3% on asymptomatic patients, 17.4% on patients with mild symptoms and 41.3% on patients with severe symptoms. Conclusions: This study indicates that: (i) asymptomatic and symptomatic GS patients have a benign natural history; (ii) the majority of GS patients with severe or mild symptoms will no longer experience biliary pain; and (iii) a significant proportion of cholecystectomies are performed in asymptomatic patients. Expectant management still represents a valid therapeutic approach in the majority of patients.

Summary Background Acute pouchitis, an idiopathic inflammatory condition of the ileal pouch anal anastomosis, is the most frequent complication after proctocolectomy for ulcerative colitis. Aim To test the hypothesis that sulfasalazine (SASP) might have a synergistic beneficial effect in acute pouchitis, by combining the anti-inflammatory activity of 5-aminosalicylic Acid and the bacteriostatic effect of sulphapyridine. Methods Twenty two patients were investigated for acute pouchitis; the Pouchitis Disease Activity Index (PDAI) was calculated and 11 patients with acute pouchitis (PDAI >7) were included in an open study, after obtaining their informed consent. Patients were treated with SASP 500 mg tablets, two tablets three times per day (3000 mg daily), for 2 months. Pouch endoscopy with biopsies was performed at the entry and at the end of the study. Results According to the PDAI score, 8/11 patients (73%) improved their clinical condition and 7/11 (63%) were in remission at the end of the treatment. At 8 weeks, the median PDAI index decreased from 11.2 ± 2.3 to 6.6 ± 4.7 P

Portal-systemic encephalopathy, a condition caused by liver failure, often complicates hepatic cirrhosis. Its pathogenesis is unknown, although hyperammonemia is thought to play an important role. Non-absorbable antibiotics have been used to treat hepatic encephalopathy because of their ability to reduce intestinal flora and thereby decrease the intestinal production of ammonia. We compared the effectiveness of rifaximin, a new non-absorbable antibiotic, with that of paromomycin. Thirty cirrhotic patients (20 men and 10 women, aged 39 to 75 years) suffering from portal-systemic encephalopathy with hyperammonemia were selected by Conn's grading. Fifteen patients were randomly assigned to treatment with paromomycin (1,500 mg/day), and the other 15 received rifaximin (1,200 mg/day) for 10 days. Before, after 5 days, and after 10 days of treatment, we evaluated blood ammonia levels and each patient's signs and symptoms according to Conn's grading. Baseline ammonia levels and the degree of hepatic encephalopathy were positively correlated ( r = .65; P P P

It has been recently shown that the newest hypocholesterolemic agent, simvastatin, lowers the biliary cholesterol saturation index and that its association with ursodeoxycholic acid renders it more effective. To determine the mechanism by which simvastatin decreases the biliary cholesterol saturation index, we evaluated hepatic secretion rates of cholesterol, bile acids and phospholipids, and cholic acid pool size, turnover and synthesis in eight hyperlipidemic patients (five women and three men, age range = 38 to 65 yr). These assessments were conducted before treatment, after 4 wk of simvastatin (40 mg/day), after 4 wk of ursodeoxycholic acid (600 mg/day) and after a further 4 wk of a combination therapy of simvastatin (40 mg/day) plus ursodeoxycholic acid (600 mg/day). The cholesterol saturation index was significantly reduced with simvastatin (from 1.51 +/- 0.10 to 0.94 +/- 0.05, mean +/- S.E.; p less than 0.02), with ursodeoxycholic acid (from 1.51 +/- 0.10 to 0.86 +/- 0.03, mean +/- S.E.; p less than 0.02) and with the combination of simvastatin plus ursodeoxycholic acid (from 1.51 +/- 0.01 to 0.70 +/- 0.05, p less than 0.02). The cholesterol saturation index during combination therapy was significantly lower (p less than 0.02) than that reached during the use of simvastatin and ursodeoxycholic acid. Both simvastatin and ursodeoxycholic acid significantly reduced the hepatic secretion rate of cholesterol (from 130 +/- 14 mumols/hr to 81 +/- 12 mumols/hr, p less than 0.01, and 70 +/- 9 mumols/hr, p less than 0.01) without affecting bile acid and phospholipid outputs.(ABSTRACT TRUNCATED AT 250 WORDS)

Several factors are involved in the development of gallstone formation: formation of supersaturated bile; nucleation; formation, retention and adhesion of cholesterol crystals and eventually stone growth. The dynamics of the gallbladder may play a key role in the overall process. The pathophysiologic theory of cholesterol gallstone formation and the knowledge of their physico-chemical properties support the modern concept of gallstone therapy. Chenodeoxycholic and ursodeoxycholic have been widely used as cholesterol gallstone dissolving agents and evaluated in terms of efficacy and safety.

Cholelithiasis is the primary expression of obesity in the hepatobiliary system. In obese subjects the risk of developing gallstones is increased due to a higher cholesterol saturation of gall-bladder bile. During weight reduction with very low calorie diets (VLCD) the incidence of gallstones increases, but the mechanism for gallstone formation is not completely understood and several pathogenetic mechanisms have been suggested: increased saturation of bile, increased gall-bladder secretion of mucin and calcium, increased presence of prostaglandins and arachidonic acid. Alterations in gall-bladder motility may contribute to gallstone formation, but few studies have addressed the issue of gall-bladder motility during rapid weight loss and its possible role in gallstone formation. VLCD have been associated with a gall-bladder stasis, as a consequence of reduced gall-bladder stimulation by low fat content of the diets. A threshold quantity of fat (10 g) has been documented to obtain efficient gall-bladder emptying. Ursodeoxycholic acid administered during VLCD seems to have a protective role in developing a biliary cholesterol crystals. Gall-bladder emptying was lower in response to low fat meals with respect to relative higher fat meals, before as well as during the VLCD. This may account the possibility of an adaptative response of the gall-bladder motility to a given diet regimen. Adequate fat content of the VLCD may prevent gallstone formation, maintaining adequate gall-bladder motility and may be more economic and physiologically acceptable than administration of a pharmacological agent.

Intestinal bile acid absorption is mediated by a sodium-dependent transporter located in the brush border apical membrane of ileocytes. The transmembrane topology and the role of individual amino acid residues in the bile acid transport process have been investigated by means of various experimental approaches, leading to multiple hypotheses. We raised a monoclonal antibody against a segment of the transporter comprising vicinal cysteine residues, in order to evaluate its functional role. A 14 amino acid peptide, corresponding to amino acids 104−117 of the transporter, was synthesized, and a monoclonal anti-peptide antibody was raised. In vitro uptake−inhibition studies in the presence of the monoclonal anti-peptide antibody were performed using ileal brush border membrane vesicles. Rabbit ileum was perfused in vivo with 5 mM taurocholic acid in the presence of the monoclonal antibody, and bile acid absorption inhibition was evaluated. The anti-peptide monoclonal antibody significantly reduced the in vitro uptake and in vivo absorption of taurocholic acid. The present data demonstrate the functional relevance of the 104−117 peptide segment and report the generation of a novel antibody against the apical sodium-dependent bile acid transporter (ASBT) that may be used as a therapeutic agent in hypercholesterolemia and in cholestatic pruritus.

AIM: To evaluate the efficacy of granulocyte colony stimulating factors (G-CSF) in liver transplanted patients with hepatitis C (HCV) recurrence and Pegylated-IFN α-2b induced neutropenia, and to evaluate the impact of G-CSF administration on virological response. METHODS: Sixty-eight patients undergoing antiviral treatment for post-liver transplantation (OLT) HCV recurrence were enrolled. All patients developing neutropenia received G-CSF. RESULTS: Twenty three (34%) received G-CSF. Mean neutrophil count at the onset of neutropenia was 700/mmc (range 400-750/mmc); after 1 mo of G-CSF it increased to 1210/mmc (range 300-5590/mmc) (P < 0.0001). Three patients did not respond to G-CSF. Treatment duration was similar in neutropenic and non-neutropenic patients. No differences in the rate of discontinuation, infections or virological response were observed between the two groups. G-CSF was protective for the onset of de novo autoimmune hepatitis (P < 0.003). CONCLUSION: G-CSF administration is effective in the case of Peg-IFN induced neutropenia increasing neutrophil count, prolonging treatment and leading to sustained virological response (SVR) rates comparable to non-neutropenic patients. It prevents the occurrence of de novo autoimmune hepatitis.

Obesity is a condition associated with an increased frequency of gallstone disease. This study attempted to evaluate the comparative effects of two gallstone-dissolving agents, chenodeoxycholic acid and ursodeoxycholic acid, on bile acid metabolism and biliary lipid secretion in obese subjects in order to identify the bile acid of choice in preventing and treating gallstone disease in obesity. Twenty obese subjects (greater than 120% ideal body wt) were randomly treated with ursodeoxycholic acid (10 mg.kg-1.day-1.1 mo-1) and then with chenodeoxycholic acid (15 mg.kg-1.day-1.1 mo-1) or with chenodeoxycholic acid first and then with ursodeoxycholic acid. Patients 1-10 were studied while eating an unrestricted weight-maintenance diet, whereas patients 11-20 were eating a 1080-kcal/d hypocaloric diet. Biliary lipid composition, cholesterol saturation index, and biliary bile acid pattern were evaluated in all subjects before and after each treatment period; in subjects 6-10 and 16-20, biliary lipid secretion rates and bile acid pool size were also evaluated. Both ursodeoxycholic acid and chenodeoxycholic acid decreased cholesterol outputs and cholesterol saturation index. However, during the weight-maintenance period the decrease induced by chenodeoxycholic acid was not significant. Biliary cholesterol outputs and cholesterol saturation index were always lower during ursodeoxycholic acid administration than during chenodeoxycholic acid therapy. Ursodeoxycholic acid levels during ursodeoxycholic acid administration and chenodeoxycholic acid levels during chenodeoxycholic acid administration increased in bile to 50% and 77%, respectively, of total bile acid levels. Bile acid pool size remained unchanged during chenodeoxycholic acid administration and was significantly reduced by ursodeoxycholic acid administration during the weight-reduction period. In conclusion, ursodeoxycholic acid in obese subjects seems more effective than chenodeoxycholic acid, at least during weight maintenance, in reducing cholesterol saturation of bile. This effect is related to a significant decrease of biliary cholesterol output.

Proton pump inhibitors (PPI) are very effective in inhibiting acid secretion and are extensively used in many acid related diseases. They are also often used in patients with cirrhosis sometimes in the absence of a specific acid related disease, with the aim of preventing peptic complications in patients with variceal or hypertensive gastropathic bleeding receiving multidrug treatment. Contradicting reports support their use in cirrhosis and evidence of their efficacy in this condition is poor. Moreover there are convincing papers suggesting that acid secretion is reduced in patients with liver cirrhosis. With regard to Helicobacter pylori (H pylori) infection, its prevalence in patients with cirrhosis is largely variable among different studies, and it seems that H pylori eradication does not prevent gastro-duodenal ulcer formation and bleeding. With regard to the prevention and treatment of oesophageal complications after banding or sclerotherapy of oesophageal varices, there is little evidence for a protective role of PPI. Moreover, due to liver metabolism of PPI, the dose of most available PPIs should be reduced in cirrhotics. In conclusion, the use of this class of drugs seems more habit related than evidence-based eventually leading to an increase in health costs.