Leptin attenuates ischemia-reperfusion injury in the rat liver.

Leptin is an adipocytokine that reduces ischemic damage in several organs including brain and heart. STAT3 activation is a key step for the attainment of leptin effects in various tissues. We evaluated the possible effect of leptin on liver viability and STAT3 activation, in a rat model of ischemia-reperfusion injury. Rat livers, flushed and stored with Belzer solution (4° C for 24 h), were warmly reperfused (3.5 ml/min/g liver for 1 h at 37° C with O(2) ) with Krebs-Ringer bicarbonate. Treatment group underwent an identical protocol with the adjunct of Leptin (10 ng/ml). Liver effluent was harvested to assess LDH and AST output. Liver tissue was used for pSTAT3 expression (western blot and immunostaining), optical microscopy, TUNEL, and Cell Death Detection assays. The pSTAT3 expression was enhanced by administration of leptin. In parallel, LDH and AST output were reduced (P = 0.04 and P = 0.02 for LDH and AST, respectively). Optical microscopy, TUNEL, and Cell Death Detection assay results demonstrated increased viability in livers treated with leptin in comparison with others (Optical microscopy P = 0.02; TUNEL P = 0.01; Cell death Detection assay P = 0.003). In conclusion, cold storage and reperfusion with leptin reduce liver ischemia-reperfusion injury. This effect is associated with an increased expression of pSTAT-3.

Patterns of chronic hepatitis B in Central Italy: a cross-sectional study.

We investigated the patterns of chronic hepatitis B virus (HBV)-related disease in a large cohort of HBsAg-positive patients, in Central Italy, by collecting a screening form with demographic, clinical and laboratory data. Overall, 737 HBsAg-positive cases were included (70% male; median age 52 years): 30% were inactive HBsAg carriers, 51% had chronic hepatitis B (CHB) and 19% had HBV-related cirrhosis. Patients from non-European Union (EU) countries (n = 65) were significantly younger, had a higher prevalence of HBeAg-positive infection and hepatitis delta virus (HDV) co-infection than patients of Italian origin. Therefore, as immigration from non-EU countries continues to grow, we can expect a change in the landscape of HBV-related disease in our area.

Components for Material Master Data Management in Swiss Hospitals.

The material master data catalogue in large hospitals may well exceed 50'000 articles required at one or another location for patient diagnosis and treatment. Most hospitals use a commercial material management IT system to deal with orders, eProcurement, incoming goods, warehouse management, internal commissioning and distribution. An analysis in three Swiss hospitals (including a hospital chain) demonstrated however, that despite existing standards maintenance of the material master data catalogue is often done manually based on different incoming formats such as csv, mail etc. We present components, which may enable seamless master data update using standardized formats and discuss in detail current barriers within hospital supply to give finally recommendations how to overcome them.

Assembly of biliary lipids in native hepatic bile after orthotopic liver transplantation: A biochemical and ultra-structural study in humans.

BACKGROUND: In gallbladder bile, lipids aggregate as micelles and vesicles, yet the presence of lamellae remains controversial. Little is known on lipid assembly in dilute hepatic bile. Liver transplantation represents a condition in which bile is diluted immediately after transplant and tends to normalize thereafter. AIM: To study biliary lipidic carriers after liver transplantation in relation to the increasing bile lipid concentration. METHODS: Three bile samples were harvested from six patients (3M/3F) with normal post-transplant outcome: sample 1 at days 2-3, sample 2 at 1 week, and sample 3 at 2 weeks after transplant. Samples were analyzed by biochemical, morphological and quasi-elastic light scattering methodology. RESULTS: Lipid concentration increased from 0.6g/dl at day 2-3 to 3.6g/dl at week 2. Electron microscopy showed the presence of unilamellar vesicles in all samples. Large amorphous particles interpreted as proteic aggregates were also present at day 2-3, while lamellae coexisted with vesicles later. Quasi-elastic light scattering data were consistent with electron microscopic findings. Liquid crystals were observed at polarizing microscopy with increasing bile lipid concentration. CONCLUSIONS: Normalization of biliary lipid secretion after liver transplantation is associated with: (i) increased proportion of vesicles and reduction of their size; (ii) presence of lamellae.

Different expression of VEGF and EGFL7 in human hepatocellular carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is one of several angiogenic factors expressed in cirrhosis and during progression to malignancy, that seem to play a major role in hepatocellular carcinoma development. Lately, another angiogenic factor, epidermal growth factor-like domain multiple 7 (EGFL7), has attracted interest due to its possible relationship with hepatocellular carcinoma metastasis. AIMS: To evaluate expression of VEGF and EGFL7 in human hepatocellular carcinoma, compared to corresponding cirrhotic surrounding tissue. METHODS: Tumoural and cirrhotic tissue was harvested from 12 consecutive patients undergoing surgical resection. VEGF and EGFL7 were assessed by immunofluorescence and quantitative reverse transcriptase-polymerase chain reaction, compared with normal controls. RESULTS: Both angiogenic factors were over-expressed in cirrhotic livers compared to normal controls. VEGF and EGFL7 expressions did not differ according to disease aetiology, nodule size or other clinical variables. While VEGF expression was constant, regardless of tumour differentiation stage and unchanged compared to surrounding cirrhotic tissue, EGFL7 expression increased in less differentiated hepatocellular carcinoma. CONCLUSIONS: The preferential expression of EGFL7 in less differentiated hepatocellular carcinoma compared to VEGF, suggests a possible important role of this angiogenic factor in a later oncogenic and infiltrative/metastatic phase.

TUDCA prevents cholestasis and canalicular damage induced by ischemia-reperfusion injury in the rat, modulating PKCalpha-ezrin pathway.

Cholestasis, induced by liver ischemia-reperfusion injury (IRI), is characterized by dilatation of bile canaliculi and loss of microvilli. Tauroursodeoxycholic acid (TUDCA) is an anti-cholestatic agent, modulating protein kinase C (PKC) alpha pathway. PKC reduces ischemic damage in several organs, its isoform alpha modulates ezrin, a key protein in the maintenance of cell lamellipoidal extensions. We evaluated the effects of TUDCA on cholestasis, canalicular changes and PKCalpha-ezrin expression in a rat model of liver IRI. Livers flushed and stored with Belzer solution or Belzer + 10 mm TUDCA (4 degrees C for 6 h) were reperfused (37 degrees C with O(2)) with Krebs-Ringer bicarbonate + 2.5 micromol/min of Taurocholate or TUDCA. Bile was harvested for bile flow assessment. Liver tissue was employed for Electron Microscopy (EM) and for PKCalpha and ezrin immunoblot and immunofluorescence. The same experiments were conducted with the PKCalpha inhibitor Go-6976. TUDCA-treated livers showed increased bile flow (0.25+/-0.17 vs. 0.042+/-0.02 microl/min/g liver, P<0.05) and better preservation of microvilli and bile canalicular area at EM. These effects were associated with increased PKCalpha and ezrin expression (P=0.03 and P=0.04 vs. control respectively), as also confirmed by immunofluorescence data. PKCalpha inhibition abolished these TUDCA effects. TUDCA administration during IRI reduces cholestasis and canalicular damage in the liver modulating PKCalpha-ezrin pathway.

Interferon-alpha treatment of hepatitis D induces tuberculosis exacerbation in an immigrant.

This report describes the case of a young Romanian patient who developed a severe exacerbation of pulmonary tuberculosis during interferon-alpha treatment for chronic hepatitis D. While this occurrence underscores that clinical guidelines should be applied with caution in immigrants from underdeveloped countries, due to the possible presence of unrecognized or unreported comorbidity, the mechanisms for an interferon-related exacerbation of pulmonary tuberculosis are also examined. We propose that IFN-induced weight loss and anorexia may have played an important role in promoting clinical manifestations of tuberculosis in our patient.

Cyclosporine A versus tacrolimus monotherapy. Comparison on bile lipids in the first 3 months after liver transplant in humans.

Biliary lipids output is reduced after liver transplantation and tends to normalize thereafter. Cyclosporine A (CyA) is reported to interfere with the normal bile-restoring process after liver grafting, but data are inconclusive, in particular regarding the comparison with the other widely used calcineurin inhibitor tacrolimus (TCR). Furthermore, previous researches were conducted in patients taking multiple immunosuppressive therapies and with a short follow up. In this study we readdressed this issue by comparing biliary lipids in the first 3 months after liver transplant, in 20 patients randomized to receive immunosuppression with CyA or TCR monotherapy. Bile samples, harvested through a T-tube at days 1, 3, 7, 15, 30, 60 and 90 were assessed for cholesterol, phospholipids, and total and individual concentrations of bile acids (BA). Liver and kidney function tests were evaluated as well. We found no differences between CyA and TCR in biochemical findings or in total biliary BAs, cholesterol, and phospholipids. However, CyA-treated patients showed lower levels of glycochenodeoxycholic acid at day 15, compared to those treated with TCR (P < 0.04). This difference normalized thereafter, without any biochemical or clinical effect at 3-month follow up.