gastrins and Wounds-and-Injuries

A number of growth factors affect the regeneration of intestinal epithelia following injury, but the effects of amidated gastrin have not previously been assessed. We therefore investigated the effects of gastrin on intestinal regeneration following a range of stimuli.. Intestinal crypt regeneration was assessed in transgenic mice overexpressing amidated gastrin (INS-GAS) and mice in which hypergastrinemia was induced using omeprazole, following gamma-radiation, 5-fluorouracil, and dextran sulphate sodium (DSS). Abundance of the CCK-2 receptor was assessed in intestinal epithelia and IEC-6 intestinal epithelial cells following gamma-radiation.. Four days following 14 Gy gamma-radiation, or 2 injections of 400 mg/kg 5-fluorouracil, INS-GAS mice exhibited significantly increased small intestinal and colonic crypt survival compared with their wild-type counterparts (FVB/N). INS-GAS mice treated with 3% DSS for 5 days showed less weight loss and increased colonic crypt regeneration at 8 days compared with FVB/N. Increased small intestinal and colonic crypt survival was also demonstrated following gamma-radiation in FVB/N mice rendered hypergastrinemic using omeprazole. The increased crypt survival in INS-GAS mice following 14 Gy gamma-radiation was inhibited by administration of a CCK-2 receptor antagonist (YF476). Increased abundance of the CCK-2 receptor was demonstrated in intestinal epithelia following 14 Gy gamma-radiation by Western blotting and immunohistochemistry. Similarly, increased CCK-2 receptor mRNA abundance and increased 125I-gastrin binding was demonstrated in IEC-6 cells following 4 Gy gamma-radiation.. Hypergastrinemia increases regeneration of intestinal epithelia following diverse forms of injury. Induction of the CCK-2 receptor in damaged epithelium confers potential for protection against injury by administration of gastrin.

Topics: Animals; Benzodiazepinones; Cell Line; Cell Proliferation; Colitis; Dextran Sulfate; Enteritis; Enzyme Inhibitors; Fluorouracil; Gamma Rays; Gastrins; Growth Substances; Intestinal Mucosa; Mice; Mice, Inbred Strains; Mice, Transgenic; Omeprazole; Phenylurea Compounds; Proton Pump Inhibitors; Receptor, Cholecystokinin B; Regeneration; Wounds and Injuries

Patients who had cranial injuries and those who were less severely injured had a normal gastric acid output. Pepsin output decreased throughout the first 72 hours after trauma. Gastric juice protein output was slightly increased. Gastric mucosal cell renewal as estimated by gastric juice DNA was increased. Patients who were more severely injured and those with intra-abdominal trauma had markedly increased gastric acid, pepsin, and protein output after increased gastric mucosal cell exfoliation but a relatively decreased gastric mucosal cell renewal between 36 and 72 hours after trauma. It is concluded that the gastric mucosa must be protected by antacids and/or gastric aspiration before 24 hours after trauma and continued through at least 72 hours. This study supports the importance of acid-pepsin damage during gastric mucosal cell exfoliation and decreased renewal in trauma patients and indicates the timing and value of prophylactic treatment.

Topics: Adolescent; Adult; Aged; Female; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Pepsin A; Permeability; Secretory Rate; Time Factors; Wounds and Injuries

Topics: Adolescent; Adult; Animals; Brain Injuries; Cattle; Craniocerebral Trauma; Gastrins; Humans; Male; Military Medicine; Rabbits; Radioimmunoassay; Spinal Cord Injuries; Stomach Ulcer; Stress, Psychological; Vietnam; Wounds and Injuries

Topics: Adolescent; Adult; Central Nervous System; Gastrins; Humans; Male; Military Medicine; Peptic Ulcer; Vietnam; Warfare; Wounds and Injuries