thiourea and Pancreatitis

Endoplasmic reticulum (ER) stress in the pancreas is closely associated with the development of acute pancreatitis. However, the role of the protein kinase RNA-like ER kinase (PERK) in this disease is not fully understood. We investigated whether an inhibitor of the dephosphorylation of eukaryotic initiation factor 2α, salubrinal, could improve murine experimental pancreatitis through the amelioration of ER stress.. Acute pancreatitis was induced by the intraperitoneal administration of cerulein (50 μg/kg) six times at 1-h intervals followed by lipopolysaccharide (10 mg/kg). Salubrinal was administered intraperitoneally immediately after lipopolysaccharide injection and 3 h later. Mice were sacrificed 24 h after the first injection of cerulein, and serum amylase and proinflammatory cytokines were measured. The severity of pancreatitis was evaluated histologically using a scoring system. The expression levels of ER stress-related proteins were evaluated by Western blotting.. The administration of salubrinal significantly attenuated the increase in serum amylase levels and improved histologically assessed pancreatitis. The serum levels of proinflammatory cytokines were significantly suppressed in salubrinal-treated mice, as was the expression of glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, and cleaved caspase-3.. The amelioration of ER stress through augmentation of the PERK-signaling pathway may be a therapeutic target for the treatment of acute pancreatitis.

Topics: Acute Disease; Amylases; Animals; Apoptosis; Ceruletide; Cinnamates; Cytokines; Endoplasmic Reticulum Stress; Eukaryotic Initiation Factor-2; Injections, Intraperitoneal; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Pancreatitis; Phosphorylation; Thiourea

The content of pancreatic enzymes in the duodenum was studied in two patients with pancreatic achylia after a standard meal supplemented with commercial pancreatic extract. Gastric transit of the enzymes, with appearance of near-normal amounts in the duodenal contents, occurred only after inhibition of gastric secretion and buffering of residual gastric acid with antacids. Gastric inhibition and neutralisation of acid are therefore necessary for the satisfactory treatment of patients with pancreatic exocrine insufficiency but normal gastric function.

Topics: Chronic Disease; Duodenum; Gastric Juice; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Metiamide; Pancreatic Diseases; Pancreatic Extracts; Pancreatic Juice; Pancreatitis; Thiourea; Time Factors

Metiamide was given to patients with peptic ulcer or oesophagitis in a pilot study to establish the therapeutic value of the drug. Administration of metiamide resulted in relief of pain within a week in the majority of patients. Healing of duodenal and gastric ulcers was observed.

Topics: Duodenal Ulcer; Esophagitis; Gastric Acidity Determination; Gastric Juice; Humans; Metiamide; Nausea; Pain; Pancreatitis; Secretory Rate; Stimulation, Chemical; Stomach Ulcer; Thiourea; Time Factors