Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study of the cavitary and membrane digestion of lipids, carbohydrates, proteins and data of the histological structure of the bioptate of the duodenal mucosa in 34 patients with chronic pancreatitis revealed the morphological picture of chronic duodenitis. This resulted in a reduction of the sorption properties of the intestinal epithelium that was manifested in a reduction of the rate of membranous digestion, mainly of lipids and lactose. Lesser degrees of protein, starch and saccharose hydrolysis were observed. Biopsy specimens of the duodenal mucosa showed a reduced activity of enterokinase and alkaline phosphatase. Antacids (almagel, phosphalugel), mineral waters ("Borzhomi", "Poliana Kvasova"), regeneration stimulators (Metacyl, retalil), agents stimulating the motor function (cerukal, reglan and oth.) are recommended for the complex treatment of concomitant duodenitis.
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PMID:[The functional-morphological changes in the duodenum in chronic pancreatitis]. 147 21

Oedematous pancreatitis is pancreatic acinar cell damage with leakage into the peritoneal cavity and circulation of the inactive zymogens of digestive enzymes and active amylase and lipase. Pancreatic oedema and intra-abdominal fat necrosis occur. Necrotising pancreatitis is pancreatic acinar cell damage accompanied by the specific conversion of trypsinogens to trypsins, at a rate, and on a scale, sufficient to overwhelm local defences. Rapid release of the whole spectrum of activated pancreatic enzymes leads to necrosis of parts of the pancreas and blood vessels, and the disseminated enzyme-mediated damage which characterises the molecular pathology of the established severe disease. Chronic pancreatitis, although less well understood, is also associated with trypsinogen activation within the gland. Two mechanisms have emerged as initiators of trypsinogen activation, lysosomal cathepsins and bile-borne enterokinase. Chemotherapeutic strategies against disease initiation include preparation of synthetic enterokinase and Cathepsin B inhibitors. Chemotherapeutic strategies against second-stage mediation of multi-organ damage in the disease, include oligopeptide or organic functionalities with novel catalytic site-directed moieties (such as fluoromethyl ketones) suitable for in vivo use and the specific inhibition of the relevant range of enzymes in complex with alpha 2-macroglobulin. Interference with pancreatic enzyme biosynthesis using proteolysis-resistant constructs mimicking receptor-binding domains of inhibitor peptide hormones as well as inhibitors of pancreatic signal peptidase are promising additional chemotherapeutic approaches worthy of active investigation.
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PMID:A rational approach to the specific chemotherapy of pancreatitis. 391 64

Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.
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PMID:A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis. 1669 18