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Ischemia/reperfusion (I/R) injury is the main cause of primary graft dysfunction of liver allografts. Cobalt-protoporphyrin (CoPP)–dependent induction of heme oxygenase (HO)-1 has been shown to protect the liver from I/R injury. This study analyzes the apoptotic mechanisms of HO-1-mediated cytoprotection in mouse liver exposed to I/R injury. HO-1 induction was achieved by the administration of CoPP (1.5 mg/kg body weight i.p.). Mice were studied in in vivo model of hepatic segmental (70 %) ischemia for 60 min and reperfusion injury. Mice were randomly allocated to four main experimental groups (n = 10 each): (1) A control group undergoing sham operation. (2) Similar to group 1 but with the administration of CoPP 72 h before the operation. (3) Mice undergoing in vivo hepatic I/R. (4) Similar to group 3 but with the administration of CoPP 72 h before ischemia induction. When compared with the I/R mice group, in the I/R+CoPP mice group, the increased hepatic expression of HO-1 was associated with a significant reduction in liver enzyme levels, fewer apoptotic hepatocytes cells were identified by morphological criteria and by immunohistochemistry for caspase-3, there was a decreased mean number of proliferating cells (positively stained for Ki67), and a reduced hepatic expression of: C/EBP homologous protein (an index of endoplasmic reticulum stress), the NF-κB’s regulated genes (CIAP2, MCP-1 and IL-6), and increased hepatic expression of IκBa (the inhibitory protein of NF-κB). HO-1 over-expression plays a pivotal role in reducing the hepatic apoptotic IR injury. HO-1 may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation.

Spontaneous hepatic rupture is a rare clinical event associated with various pathologies of the liver. Most series to date reported the incidence and characteristics of a single etiology.Data were collected for all patients admitted with spontaneous hepatic rupture from 1995 to 2007.Ten patients met the study criteria. Hepatocellular adenoma was the cause of the rupture in six female patients, in their second to fourth decade. In the remaining patients, the ruptures were because of hepatocellular carcinoma in two, metastatic gastrointestinal stromal tumor in one, and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) in one. Nine out of 10 patients were treated surgically.Spontaneous hepatic rupture requires a high index of suspicion for a correct and timely diagnosis. Outcome is potentially grave and greatly depends on the underlying condition.

p73 is the first identified homolog of p53, but its function has not been established. Our study investigated the expression of p73 in liver tissue of patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC). RT-PCR was performed on RNA extracted from tumorous and nontumorous liver tissue of HCV-associated HCC, and control tissue and the cDNA were sequenced. Anti-p73 polyclonal antibodies were used for protein analysis and immunohistochemistry, and patients' sera were analyzed for anti-p73 antibodies by radioimmunoassay. Analysis of the p53 gene was performed by SSCP and RFLP-PCR. The p73 mRNA and protein were highly expressed and accumulated in HCC tissues. Immunohistochemical studies revealed significant immunoreactivity in the nuclei of HCC cells. No mutations were detected in the p73 gene or in p53, and no loss of heterozygosity of the p53 gene was found. Anti-p73 antibodies were detected in sera of HCC patients, but were not significantly different from that occurring in non-HCV or non-HCC patients. In conclusion, p73 protein is overexpressed and accumulates in the nuclei of HCV-associated HCCs and may play a role in HCC development.

Liver transplantation is the only therapy of proven benefit in fulminant hepatic failure (FHF). Lipopolysaccharide (LPS), D-galactosamine (GalN)-induced FHF is a well established model of liver injury in mice. Toll-Like Receptor 4 (TLR4) has been identified as a receptor for LPS. The aim of this study was to investigate the role of TLR4 in FHF induced by D-GalN/LPS administration in mice. Wild type (WT) and TLR4 deficient (TLR4ko) mice were studied in vivo in a fulminant model induced by GalN/LPS. Hepatic TLR4 expression, serum liver enzymes, hepatic and serum TNF-α and interleukin-1β levels were determined. Apoptotic cells were identified by immunohistochemistry for caspase-3. Nuclear factor-kappaβ (NF-κ β) and phosphorylated c-Jun hepatic expression were studied using Western blot analysis. All WT mice died within 24 hours after administration of GalN/LPS while all TLR4ko mice survived. Serum liver enzymes, interleukin-1β, TNF-α level, TLR4 mRNA expression, hepatic injury and hepatocyte apoptosis all significantly decreased in TLR4ko mice compared with WT mice. A significant decrease in hepatic c-Jun and IκB signaling pathway was noted in TLR4ko mice compared with WT mice. In conclusion, following induction of FHF, the inflammatory response and the liver injury in TLR4ko mice was significantly attenuated through decreased hepatic c-Jun and NF-κB expression and thus decreased TNF-α level. Down-regulation of TLR4 expression plays a pivotal role in GalN/LPS induced FHF. These findings might have important implications for the use of the anti TLR4 protein signaling as a potential target for therapeutic intervention in FHF.

p73 is the first identified homolog of p53, but its function has not been established. Our study investigated the expression of p73 in liver tissue of patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC). RT-PCR was performed on RNA extracted from tumorous and nontumorous liver tissue of HCV-associated HCC, and control tissue and the cDNA were sequenced. Anti-p73 polyclonal antibodies were used for protein analysis and immunohistochemistry, and patients' sera were analyzed for anti-p73 antibodies by radioimmunoassay. Analysis of the p53 gene was performed by SSCP and RFLP-PCR. The p73 mRNA and protein were highly expressed and accumulated in HCC tissues. Immunohistochemical studies revealed significant immunoreactivity in the nuclei of HCC cells. No mutations were detected in the p73 gene or in p53, and no loss of heterozygosity of the p53 gene was found. Anti-p73 antibodies were detected in sera of HCC patients, but were not significantly different from that occurring in non-HCV or non-HCC patients. In conclusion, p73 protein is overexpressed and accumulates in the nuclei of HCV-associated HCCs and may play a role in HCC development.

Phytobezoar is a well-known although uncommon cause of mechanical alimentary tract obstruction, mainly in patients who have undergone previous gastric operation. Between January 1988 and March 1995, we operated on 14 patients with gastrointestinal obstruction due to phytobezoar. Eleven patients (78.6%) had undergone previous gastric operation and in all of them the diagnosis was made at the time of surgery. All admissions were during winter: supposedly because of the seasonal increase in intake of citrus fruits and persimmons. During the 7-year study period, we observed an unexpected increase in the incidence of this disorder. During the first 4 years we treated 2 patients (14.3%), an average of 0.5 patients a year, whereas during the last 3 years we operated on 12 patients (87.7%), an average of 4 patients a year. The recent increase in small-bowel obstruction secondary to phytobezoars may at least in part be explained by a major immigration wave from the former USSR. These immigrants have become exposed to an abundance of cheap fruits such as citrus and persimmons that were not available in their home country. The large consumption and the failure of information regarding the risks of consuming these fruits in association with previous gastric surgery may have played a major role in the recent increase of the incidence. Since phytobezoars may play increasingly an important role in the future due to the ingestion of great quantities of different fruits containing great amounts of cellulose, these findings call for restriction of citrus fruit and persimmons in patients who have undergone gastric surgery.

Calmodulin, a cytoplasmic calcium binding protein, is present in concentrations two- to four-fold higher in malignant cells compared to normal cells. In an effort to learn the significance of these elevated levels, we examined the effect of calmodulin blockage on the growth of normal and malignant keratinocytes in vitro. The level of calmodulin in SCC12.B2, a line of keratinocytes derived from an epidermal squamous cell carcinoma (SCC), was about 3.5 times greater than in normal, human newborn foreskin keratinocytes. When exposed to trifluoperazine (TFP), an inhibitor of calmodulin, cell growth was reduced primarily in the cultures of normal keratinocytes. This growth inhibition resulted from two changes in the replicating population of cells, namely an increase in cell cycle length and an increase in rate of cell cycle withdrawal. Cell cycle withdrawal is the irreversible arrest of the cell cycle and is an early event in keratinocyte terminal differentiation. There was no measurable effect on the cell cycle time or withdrawal rate in SCC12.B2. The increased resistance to growth arrest in SCC cells may be a consequence of the elevated level of calmodulin in these cells.