Gallbladder Stem/progenitor cells are able to repopulate and rescue the damaged liver in a experimental mouse model of liver cirrhosis

The human biliary tree contains stem cells within peribiliary glands (Cardinale et al., 2011). Human Gallbladder contains stem/progenitors (hGSCs) located in mucosal crypts (Carpino et al., 2012). Our aim was to evaluate the capability of hGSCs to repopulate and rescue the damaged liver in a model of liver cirrhosis. hGSCs were selected for Epithelial Cell Adhesion Molecule. Cirrhosis was induced by intraperitoneal injection, twice a week, of carbon tetrachloride for 7 weeks. hGSCs were injected into the liver via the spleen of normal or cirrhotic SCID mice. As controls, cirrhotic SCID mice were injected only with the medium or with mature human hepatocytes. 2 months after the injection, the necrotic areas were lower in mice treated with hGSCs in comparison with controls. In hGSCs-injected cirrhotic mice, the expression of the human antigens indicated that ≈10% of the host hepatocyte mass was represented by in vivo differentiated human hepatocytes derived from injected hGSCs. This value was significantly higher with respect to mice injected with human adult hepatocytes. The presence of human cells in murine livers was confirmed by in situ hybridization for human chromosomes. hGSCs injection dictated an improvement of serum liver biochemistry with a significant reduction of transaminases and an improvement of synthetic functions. In this model, hGSC engraftment and differentiation determinate the improvement of histological liver damage and serum liver biochemistry. These data could open future perspectives for a role of gallbladder as a source of stem cells for liver regenerative medicine

A Geological Itinerary Through the Southern Apennine Thrust-Belt (Basilicata—Southern Italy)

Open access via Springer Compact AgreementPeer reviewedPublisher PD

Sudden Unexpected Deaths and Vaccinations during the First Two Years of Life in Italy: A Case Series Study

Background The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy. Methodology/Principal Findings The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0–14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined. Conclusions The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age

Antibiotic Prescriptions and Prophylaxis in Italian Children. Is It Time to Change? Data from the ARPEC Project.

BACKGROUND: Antimicrobials are the most commonly prescribed drugs. Many studies have evaluated antibiotic prescriptions in the paediatric outpatient but few studies describing the real antibiotic consumption in Italian children's hospitals have been published. Point-prevalence survey (PPS) has been shown to be a simple, feasible and reliable standardized method for antimicrobials surveillance in children and neonates admitted to the hospital. In this paper, we presented data from a PPS on antimicrobial prescriptions carried out in 7 large Italian paediatric institutions. METHODS: A 1-day PPS on antibiotic use in hospitalized neonates and children was performed in Italy between October and December 2012 as part of the Antibiotic Resistance and Prescribing in European Children project (ARPEC). Seven institutions in seven Italian cities were involved. The survey included all admitted patients less than 18 years of age present in the ward at 8:00 am on the day of the survey, who had at least one on-going antibiotic prescription. For all patients data about age, weight, underlying disease, antimicrobial agent, dose and indication for treatment were collected. RESULTS: The PPS was performed in 61 wards within 7 Italian institutions. A total of 899 patients were eligible and 349 (38.9%) had an on-going prescription for one or more antibiotics, with variable rates among the hospitals (25.7% - 53.8%). We describe antibiotic prescriptions separately in neonates ( = 30 days to <18 years old). In the neonatal cohort, 62.8% received antibiotics for prophylaxis and only 37.2% on those on antibiotics were treated for infection. Penicillins and aminoglycosides were the most prescribed antibiotic classes. In the paediatric cohort, 64.4% of patients were receiving antibiotics for treatment of infections and 35.5% for prophylaxis. Third generation cephalosporins and penicillin plus inhibitors were the top two antibiotic classes. The main reason for prescribing antibiotic therapy in children was lower respiratory tract infections (LRTI), followed by febrile neutropenia/fever in oncologic patients, while, in neonates, sepsis was the most common indication for treatment. Focusing on prescriptions for LRTI, 43.3% of patients were treated with 3rd generation cephalosporins, followed by macrolides (26.9%), quinolones (16.4%) and carbapenems (14.9%) and 50.1% of LRTI cases were receiving more than one antibiotic. For neutropenic fever/fever in oncologic patients, the preferred antibiotics were penicillins with inhibitors (47.8%), followed by carbapenems (34.8%), aminoglycosides (26.1%) and glycopeptides (26.1%). Overall, the 60.9% of patients were treated with a combination therapy. CONCLUSIONS: Our study provides insight on the Italian situation in terms of antibiotic prescriptions in hospitalized neonates and children. An over-use of third generation cephalosporins both for prophylaxis and treatment was the most worrisome finding. A misuse and abuse of carbapenems and quinolones was also noted. Antibiotic stewardship programs should immediately identify feasible targets to monitor and modify the prescription patterns in children's hospital, also considering the continuous and alarming emergence of MDR bacteria

Antifibrotic Effect of Marine Ovothiol in an In Vivo Model of Liver Fibrosis

Liver fibrosis is a complex process caused by chronic hepatic injury, which leads to an excessive increase in extracellular matrix protein accumulation and fibrogenesis. Several natural products, including sulfur-containing compounds, have been investigated for their antifibrotic effects; however, the molecular mechanisms underpinning their action are partially still obscure. In this study, we have investigated for the first time the effect of ovothiol A, π-methyl-5-thiohistidine, isolated from sea urchin eggs on an in vivo murine model of liver fibrosis. Mice were intraperitoneally injected with carbon tetrachloride (CCl4) to induce liver fibrosis and treated with ovothiol A at the dose of 50 mg/kg 3 times a week for 2 months. Treatment with ovothiol A caused a significant reduction of collagen fibers as observed by histopathological changes and serum parameters compared to mice treated with control solution. This antifibrotic effect was associated to the decrease of fibrogenic markers involved in liver fibrosis progression, such as the transforming growth factor (TGF-β), the α-smooth muscle actin (α-SMA), and the tissue metalloproteinases inhibitor (TIMP-1). Finally, we provided evidence that the attenuation of liver fibrosis by ovothiol A treatment can be regulated by the expression and activity of the membrane-bound γ-glutamyl-transpeptidase (GGT), which is a key player in maintaining intracellular redox homoeostasis. Overall, these findings indicate that ovothiol A has significant antifibrotic properties and can be considered as a new marine drug or dietary supplement in potential therapeutic strategies for the treatment of liver fibrosis

Expression of apoptosis-related proteins in rat with induced colitis

Inflammatory bowel diseases (IBD) evoke a damage-repair process accompanied by the activation of apoptotic genes. Data on transglutaminase (TG) expression in apoptotic cells in inflamed colonic epithelium has not been reported, although TG cross-links proteins within typical apoptotic bodies in various cell lines. In an experimental model of colitis we investigated the expression of different markers of apoptosis related to the degree and development of colonic inflammation

Electronic cigarette effectiveness to quit smoking in the representative Italian population PASSI survey, 2014 - 2016

Background This study explored electronic cigarette (e-cigarette) use as an aid to quit smoking and compared abstinence rates for different quitting methods in a representative sample of the Italian population, 2014-2016. Methods In the 2014-2015 PASSI survey, the ongoing Italian behavioural risk factor surveillance system, 6,112 adults who smoked and made at least one quit attempt in the previous 12 months, were categorised into three groups according to the method used in their most recent quit attempt: ecigarette only, no aid, other quitting methods (medications; programmes delivered in smoking cessation services; other unspecified methods). The primary outcome was self-reported abstinence for a period ≥6 months, adjusted for potential confounders. We will perform the same analysis for 2016 Passi survey. Results Eleven percent used e-cigarettes only, 86% no aid, 3% other quitting methods. Smoking abstinence was reported among 9% of those using no aid; 8% of e-cigarette users; 15% of those using other methods. Compared with those reporting no aid to quit smoking, no statistically significant differences in abstinence were observed for e-cigarette users compared with those reporting no aid (adjusted Prevalence Ratio [aPR]=0.81;95% Confidence Interval (CI)=0.58-1.14), neither for those using other quitting methods (aPR=1.42;95%CI=0.95-2.13). Changing the reference group to e-cigarette users, users of other quitting methods were significantly more likely to report abstinence than e-cigarette users e-cigarette users (aPR=1.76; 95%CI=1.07-2.88). We will add results for the 2016 Passi survey. Conclusions One out of ten smokers who attempted to quit in 2014-2015 in Italy used e-cigarettes, a proportion three times higher than that recorded for other quitting methods. E-cigarettes users were no more as likely to report abstinence than as those using no aid, but were less likely to report abstinence than users of established quitting methods. Further studies are needed to understand the relationship between e-cigarette types used to quit and abstinence rates