Hepatitis C Virus Infection and Human Pancreatic β-Cell Dysfunction

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Ecology and technological capability of lactic acid bacteria isolated during Grillo grape vinification in the Marsala production area.

Grapes of “Grillo” variety, used to produce Marsala wine, were harvested from five vineyards different for climatic and agronomic parameters, in order to obtain a first mapping of lactic acid bacteria (LAB) inhabiting the production area. Marsala base wine production was followed at large-scale and two experimental vinifications, different for lysozyme and SO2 concentration and combination, were carried out at pilot-plant scale. LAB communities and conventional chemical parameters were periodically analysed. LAB were found on grapes at an average concentration of about 102 CFU g-1 which decreased during the transformation process. A total of 146 colonies were collected, but only 35 were recognized as presumptive LAB. On the basis of phenotypic differences and isolation source, 16 isolates were then subjected to genotypic identification and gathered into the following species: Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris, Enterococcus faecium, Leuconostoc fallax and Sporalactobacillus nakayamae subsp. nakayamae. Lactococcus lactis subsp. lactis strains was the species most frequently isolated during winemaking showing the highest resistance to SO2 and lysozyme

Beta-cell hyperplasia and direct acinar-beta-cell trans-differentiation in insulin-resistant partially eNOS-deficient mice.

eNOS-defi cient mice were shown to develop hypertension and insulin resistance either in basal conditions (eNOS null) or upon high fat diet, HFD (eNOS +/- heterozygotes). In the model of HFD-fed eNOS +/- mice, we investigated putative pancreatic morphological changes to fi nd out clues of the cellular mechanisms responsible for their compensatory hyperinsulinemic response. C57BL6 wild type (WT) and eNOS +/- mice were fed with either chow or HFD for 16 weeks. A group of chow-fed eNOS null mice was also studied. Basal blood glucose and insulin were monitored and glucose and insulin tolerance tests performed. Then mice were sacrifi ced and fragments of pancreas were routinely processed for histological, immunohistochemical and ultrastructural observation (with suitable image analysis). Both WT and eNOS +/- mice fed with HFD developed insulin resistance, as assessed by fasting hyperglycemia with hyperinsulinemia, glucose intolerance and reduced response to exogenous insulin. In HFDfed groups, evidence of compensatory adaptation of -cells was provided by increased total pancreatic insulin content, larger -cell fractional area and enhanced number of extra-islet -cell clusters (2-5 cells) as compared to chow-fed groups. At ultrastructural level, in the HFD-fed eNOS +/- group only, besides single -cells surrounded by exocrine cells, a number of cells simultaneously containing zymogen and insulin granules were surprisingly observed in most pancreases examined. Such cells, usually retaining the extended and thick endoplasmic reticulum typical of acinar cells, represent an interesting example of direct exocrine/-cell trans-differentiation, likely triggered by strong insulin-demanding metabolic stress, yet independent on damaging stimuli, such as duct ligation as reported in literature. The reason why such trans-differentiation process was only detected in the eNOS +/- mice fed with HFD remains an interesting matter of future investigation

Loss of PTEN expression in colorectal cancer (CRC) metastases (mets) but not in primary tumors predicts lack of activity of cetuximab plus irinotecan treatment

ntroduction: PTEN is a key tumor suppressor that inactivates PI3K, a downstream effector of the EGFR cascade. Mutations resulting in PTEN loss lead to uncontrolled activation of PI3K/AKT signalling pathway that may result in resistance to EGFR-blockade. Methods: We retrospectively investigated the role of PTEN immunoreactivity loss (anti-PTEN antibody clone 17.A, Immunomarkers) both on primary CRC and related mets in predicting the activity of cetuximab plus irinotecan combination treatment in EGFR-positive irinotecan-refractory metastatic CRC patients (pts). Results: As of today 102 pts have been included. M/F=60/42, median age=62 (38- 78), median number of previous lines of chemotherapy=2 (1-5). Among the 100 pts evaluable for response we observed a partial (PR) or a complete response (CR) in 13 and 1 cases respectively for an overall response rate of 14%. PTEN immunostaining resulted positive (+), negative (-) or unconclusive (NE) in respectively 48, 36, 11 out 98 primary tumors. On 57 mets PTEN analysis was +, - or NE in 31, 22, 4 cases respectively. PTEN positivity or negativity on primaries was confirmed on 45 related mts in 27 cases (60%) while 7 (16%) + and 11 (24%) - primaries resulted respectively - and + on mets. PTEN status tested on primary tumor was not significantly predictive of response nor PFS. Defining as responders those pts obtaining a PR or CR (RECIST) or SD lasting >6 mos and clearly progressed on previous irinotecan-based regimen with a TTP<3 mos (5 pts), analysis of PTEN on mets showed: 1- vs 12+ responders and 21- vs 19+ non responders (p=0.008). Median PFS in pts with PTEN+ mets was 4.8 vs 3.3 mos in PTEN- (p= 0.009, HR=0.50, 95% CI 0.23-0.81). Conclusions: Loss of PTEN immunoreactivity tested on mets may predict the activity of cetuximab plus irinotecan combination treatment. Further analysis on KRAS mutational status and p-AKT immunostaining are ongoing. Final data will be presented at the meeting. Supported by A.R.C.O. Foundatio

Spoilage potential of Brettanomyces bruxellensis strains isolated from Italian wines

Brettanomyces bruxellensis is an important wine spoilage agent. In this study a population of Brettanomyces strains isolated from Italian wines was thoroughly investigated to evaluate adaptability to wine conditions and spoilage potential. The presumptive isolates of Brettanomyces were identified at species level with 26S rRNA gene sequencing and species-specific PCR, and subsequently subjected to analysis of intra-species variability through the study of intron splice sites (ISS-PCR). Although, some strains were tracked in wines from different regions, extensive genetic biodiversity was observed within the B. bruxellensis population investigated. All strains were evaluated for their growth ability in the presence of ethanol, high sugar content, low pH, different temperatures and sulphur dioxide, using optical density and flow cytometry measurement. The ability of yeasts to produce ethyl phenols in red wines with different chemical compositions was evaluated by means of high performance liquid chromatography with electrochemical detection (HPLC-ECD). The results highlighted wide variability in B. bruxellensis in response to wine limiting factors and in terms of the accumulation of ethyl phenols. As regards this last aspect, the differences found among strains were closely related to chemical composition of wine and strain resistance to environmental stress factors, making a priori evaluation of risk of wine alteration quite difficult. These results suggest that strategies for the control of Brettanomyces should be tailored on the basis of strain distribution and wine characteristics

Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms

This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms. (C) 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms

This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms. (C) 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved