The cytotoxic effects of a novel IH636 grape seed proanthocyanidin extract on cultured human cancer cells.

Grape seed proanthocyanidins are natural antioxidants which possess a broad spectrum of chemoprotective properties against free radicals and oxidative stress. In this study, we have assessed the cytotoxicity of a novel IH636 grape seed proanthocyanidin extract (GSPE) against MCF-7 human breast cancer cells, A-427 human lung cancer cells, CRL-1739 human gastric adenocarcinoma cells and K562 chronic myelogenous leukemic cells at 25 and 50 mg/lit concentrations for 0-72 h using cytomorphology and MTT cytotoxicity assay. In addition, we compared the effects on normal human gastric mucosal cells and normal J774A.1 murine macrophage cells with the effects on the cancer cell lines. Concentration- and time-dependent cytotoxic effects of GSPE were observed on the MCF-7 breast cancer, A-427 lung cancer and gastric adenocarcinoma cells. Following incubation of the MCF-7 cells with 25 mg/lit of the GSPE approximately 6.5, 30 and 43% inhibitions in cell growth were observed at 24, 48 and 72 h of incubation, respectively, while incubation of the MCF-7 cells with 50 mg/lit of the GSPE resulted in 11, 35 and 47% inhibition in cell growth at these same points, respectively. Similar results were observed in the A-427 and gastric adenocarcinoma cells. GSPE exhibited no cytotoxicity toward the neoplastic K562 myelogenous leukemic cells. However, GSPE enhanced the growth and viability of the normal human gastric mucosal cells and J774A.1 murine macrophage cells. These data demonstrate that GSPE exhibited cytotoxicity towards some cancer cells, while enhancing the growth and viability of the normal cells which were examined.

Mechanism of gastroprotection by bismuth subsalicylate against chemically induced oxidative stress in cultured human gastric mucosal cells.

Reactive oxygen species (ROS) are implicated in the pathogenesis of chemically induced gastric mucosal injury. We have investigated the effects of ethanol, hydrochloric acid (HCl), and sodium hydroxide (NaOH) on: (1) enhanced production of ROS including superoxide anion and hydroxyl radicals, (2) modulation of intracellular oxidized states by laser scanning confocal microscopy, and (3) DNA fragmentation, indices of oxidative tissue, and DNA damage in a primary culture of normal human gastric mucosal cells (GC), which were isolated and cultured from Helicobacter pylori-negative endoscopic biopsies from human subjects. The induction of ROS and DNA damage in these cells following exposure to ethanol (15%), HCl (150 mM) and NaOH (150 mM) were assessed by cytochrome c reduction (superoxide anion production), HPLC detection for enhanced production of hydroxyl radicals, changes in intracellular oxidized states by laser scanning confocal microscopy, and DNA damage by quantitating DNA fragmentation. Furthermore, the protective ability of bismuth subsalicylate (BSS) was assessed at concentrations of 25, 50, and 100 mg/liter. Incubation of GC with ethanol, HCI, and NaOH increased superoxide anion production by approximately 8.0-, 6.1-and 7.1-fold and increased hydroxyl radical production by 13.3-, 9.6-, and 8.9-fold, respectively, compared to the untreated gastric cells. Incubation of GC with ethanol, HCl, and NaOH increased DNA fragmentation by approximately 6.7-, 4.3-, and 4.8-fold, respectively. Approximately 20.3-, 17.5-, and 13.1-fold increases in fluorescence intensities were observed following incubation of gastric cells with ethanol, HCl, and NaOH, respectively, demonstrating dramatic changes in the intracellular oxidized states of GC following exposure to these necrotizing agents. Preincubation of GC with 25, 50, and 100 mg/liter of BSS decreased ethanol-induced increases in intracellular oxidized states in these cells by 36%, 56%, and 66%, respectively, demonstrating a concentration-dependent protective ability by BSS. Similar results were observed with respect to BSS in terms of superoxide anion and hydroxyl radical production, and DNA damage. The present study demonstrates that ethanol, HCl, and NaOH induce oxidative stress and DNA damage in GC and that BSS can significantly attenuate gastric injury by scavenging these ROS.

Esophageal manometry and 24-hour pH testing in the management of gastroesophageal reflux patients.

BACKGROUND: With rising interest in gastroesophageal reflux disease, an evaluation of the importance of manometry (M) and 24-hour pH testing (pH) for decisions regarding these patients is appropriate. METHODS: Two gastroenterologists and two surgeons were presented with history and physical examination, endoscopy, histology, and esophagram data ("DATA") from 100 patients and asked to make a treatment decision. After some time, either pH or M was added to DATA, and a further decision requested. Finally, DATA plus pH plus M was presented, and a decision was requested. Decisions were evaluated for changes in medical therapy, changes between medical and surgical therapy, and changes in type of surgery offered. RESULTS: Overall, 43% (173 of 400) of decisions were altered by the addition of both M and pH to DATA, with 28.5% (114 of 400) of decisions changed from medical therapy to surgery or vice versa by the addition of both tests to DATA. The addition of M alone changed decisions more often than pH alone especially with regard to the type of surgery offered (P <0.05). CONCLUSIONS: Together, M and pH alter clinical decisions and often alter the decision regarding surgery. Both tests appear important, but M more frequently alters overall management decisions and the type of surgery offered. Despite the need for cost containment, these clinical tools are essential to important decisions regarding the care of patients with gastroesophageal reflux disease.

The hypertensive lower esophageal sphincter.

BACKGROUND: This study defines the entity of the hypertensive lower esophageal sphincter (HLES) and its treatment, including surgical implications. METHODS: Esophageal manometry was performed on 1,300 patients. Of these, 53 (4%) had HLES with resting pressure > 26.5 mm Hg, defined as the upper limit of normal resting LES pressure. Thirty-two of these patients had 24-hour esophageal pH studies. The response to treatment was assessed. RESULTS: Fourteen patients (26%) with HLES had achalasia. Of the remaining 39 (74%), 25 had an isolated HLES with normal esophageal body motility, 5 had a nonspecific esophageal motility disorders (NEMD), 4 were post-Nissen fundoplication, 3 had a nutcracker esophagus, and 2 had diffuse esophageal spasm (DES). Nineteen percent of HLES patients had gastroesophageal reflux on pH studies. Eighty-two percent of HLES patients responded well to symptom-directed medical therapy. Two patients with esophageal body dysmotility responded well to an esophageal myotomy with a partial fundoplication. CONCLUSIONS: Patients with the HLES form a heterogeneous group. Gastroesophageal reflux in HLES patients is not uncommon. Patients with HLES respond well to medical therapy. Carefully selected patients require surgery.

An alternative technique for treatment of choledocholithiasis found at laparoscopic cholecystectomy.

OBJECTIVE: To introduce a new strategy for dealing with abnormal cholangiograms at laparoscopic cholecystectomy that makes postoperative cholangiograms possible and facilitates stone extraction by assuring access to the duct for a guide-wire-assisted endoscopic retrograde sphincterotomy. DESIGN: Retrospective review of a prospectively maintained database. PATIENTS: Twenty-four patients with abnormal cholangiograms had a percutaneously placed double-lumen catheter threaded through the cystic duct and advanced into the duodenum. RESULTS: Ten successful guide-wire-assisted endoscopic retrograde sphincterotomies were performed without complications. Eleven normal postoperative cholangiograms suggested spontaneous stone passage or false-positive intraoperative cholangiograms. There were three technical failures in the early part of the series. CONCLUSIONS: This strategy is a reasonable alternative to laparoscopic common bile duct exploration (1) when the cholangiogram is questionably positive, (2) when prolonged anesthesia (poor-risk patient) should be avoided, (3) when the equipment for laparoscopic common bile duct exploration is not available, and (4) when spontaneous stone passage seems likely. Postoperative endoscopic retrograde sphincterotomy with stone extraction is facilitated when it becomes necessary because a guide wire can be introduced through the catheter.