Assessment of the involvement of oxidative stress and Mitogen-Activated Protein Kinase signaling pathways in the cytotoxic effects of arsenic trioxide and its combination with sulindac or its metabolites: sulindac sulfide and sulindac sulfone on human leukemic cell lines.

The purpose of the study was to characterize the involvement of reactive oxygen species (ROS) in mediating the cytotoxic effects of arsenic trioxide (ATO) in combination with sulindac or its metabolites: sulfide (SS) and sulfone (SF) on human leukemic cell lines. Jurkat, HL-60, K562, and HPB-ALL cells were exposed to the drugs alone or in combinations. Cell viability was measured using WST-1 or XTT reduction tests and ROS production by dichlorodihydrofluorescein diacetate staining (flow cytometry). Modulation of (a) intracellular glutathione (GSH) level was done by using L: -buthionine sulfoximine (BSO) or diethylmaleate (DEM), (b) NADPH oxidase by using diphenyleneiodonium (DPI), and (c) MAP kinases by using SB202190 (p38), SP600125 (JNK), and U0126 (ERK) inhibitors. ATO cytotoxicity (0.5 or 1 µM) was enhanced by sulindacs, with higher activity showed by the metabolites. Strong cytotoxic effects appeared at SS and SF concentrations starting from 50 µM. The induction of ROS production seemed not to be the major mechanism responsible for the cytotoxicity of the combinations. A strong potentiating effect of BSO on ATO cytotoxicity was demonstrated; DEM (10-300 µM) and DPI (0.0025-0.1 µM; 72 h) did not influence the effects of ATO. Some significant decreases in the viability of the cells exposed to ATO in the presence of MAPK inhibitors comparing with the cells exposed to ATO alone were observed; however, the effects likely resulted from a simple additive cytotoxicity of the drugs. The combinations of ATO with sulindacs offer potential therapeutic usefulness.

Band erosion: incidence, etiology, management and outcome after banded vertical gastric bypass.

BACKGROUND: Prosthetic devices have been used in bariatric operations to control the outlet of the gastric pouch and thus maintain weight loss. A complication of these prostheses is erosion or migration into the gastric lumen. The transected banded vertical gastric bypass (TBVGBP) is one of the modifications of gastric bypass. This modification has a silastic ring placed around the pouch to form the stoma. METHOD: The records of patients with band erosion (BE) after this operation were reviewed, to determine the incidence, etiology, management and outcome during a 9-year period. RESULTS: From May 1992 through May 2001, 2,949 primary and secondary TBVGBP were performed through the Center for Surgical Treatment of Obesity, utilizing 3 hospitals. 48 patients (1.63%) were documented to have BE: 40 documented by us and 8 by subsequent treating surgeons or at other facilities. Presenting symptoms were weight regain (18), stenosis or obstruction (17), pain (9), bleeding (7), and 5 were incidental findings. Some patients presented with more than one symptom. 8 were treated expectantly with spontaneous extrusion of the band. 16 bands have been removed endoscopically in 14 patients. 26 patients had open surgical revision, with 12 having band removal only and 14 band removal and revision of either the gastroenterostomy with or without band replacement or conversion to a distal Roux-en-Y gastric bypass (DRYGBP). Two patients who had revision to DRYGBP were re-revised to a longer common limb because of protein malnutrition. Three patients who had revision of the gastroenterostomy with band removal and replacement developed leaks that were managed non-surgically. Two of these re-eroded and the band was removed endoscopically with a subsequent revision to a DRYGBP. There was no death due to BE. CONCLUSION: BE is an uncommon complication of TBVGBP. Infection, previous bariatric operations and surgical technique play a role in BE. BE is best managed by endoscopic removal but can be treated expectantly or by open surgical intervention. Band removal without replacement or revision to DRYGBP may result in weight regain.