Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury.

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.

Phytobezoar: a rare cause of intestinal obstruction.

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.

The effect of trifluoperazine, a calmodulin antagonist, on the growth of normal and malignant epidermal keratinocytes in culture.

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.