Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1389183 (autodigestion)
 317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The level of adenosine 3':5'-cyclic monophosphate (cAMP) and the activity of adenyl cyclase were studied in the pancreas under normal conditions and during acute hemorrhagic pancreatitis induced by intraductal injection of fresh trypsin-bile-blood mixture. In addition, the adenyl cyclase was localized histochemically in the pancreas. Basal cAMP concentration and adenyl cyclase activity were 0.88 +/- 0.11 pmoles/mg wet tissue and 3.39 +/- 0.21 pmoles/mg protein/min, respectively. The acute pancreatitis drastically reduced the adenyl cyclase activity at 15 minutes to 1.66 +/- 0.54 pmoles/mg protein/min, and totally suppressed adenyl cyclase activity at 30 minutes after the onset of pancreatitis without affecting cAMP levels. The presence of sodium fluoride in the incubation medium prolonged the enzyme activity up to 45 minutes. The progressive disappearance of adenyl cyclase activity presumably resulted from the destruction of cellular integrity caused by autodigestion by the active proteolytic enzymes released during pancreatitis.
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PMID:Adenyl cyclase and cyclic AMP (cAMP) in acute experimental pancreatitis. 18 29

Bovine pancreatic trypsin was coupled to dextran after activation of the polysaccharide by cyanogen bromide. The soluble dextran-trypsin conjugated was purified by molecular sieve chromatography. After coupling, 53% of the esterase activity of trypsin remained, but the conjugate had only 7% of the caseinolytic activity of the native enzyme. The modified trypsin showed greater resistance than the native enzyme to inactivation by heat treatment, autodigestion, or denaturing agents, and was also more resistant to inhibition by trypsin inhibitors, particularly ovomucoid. Treatment with dextranase partly removed the improved stability properties and resistance to inhibition of the trypsin-dextran conjugate. The conjugated enzyme preparation consists of a heterogenous mixture of macromolecular aggregates, each containing many trypsin and many dextran molecules linked together. Intramolecular cross-linking of enzyme molecules by polysaccharide chains is considered to be responsible for stabilization of the tertiary structure of the enzyme molecules in the conjugate.
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PMID:Preparation and characterization of a dextran-trypsin conjugate. 94 52

In the pathogenesis of acute pancreatitis, the events and mechanisms increasing the digestibility of the pancreatic acinar cells are widely unknown. Therefore, the possible contribution of a disturbed energy supply (provoked by anoxia or partial uncoupling) to the induction of autodigestion was studied in experiments on acinar cells isolated from the pancreas. During incubation viability, respiration under normal and maximally stimulated conditions, and trypsin-inhibiting capacity (TIC) of these cells were determined. With increasing duration of anoxia, the portion of surviving cells was strongly diminished, and the number of cells with blebs and vesicularly transformed endoplasmic reticulum was increased. Although the endogenous respiration was not influenced up to 1.5 h of anoxia, 30 min of anoxia substantially decreased the capacity of oxidative energy production. The survival curves were characterized by a self-accelerating course of cell destruction. The alteration of the cellular energy metabolism found its reflection in the decreased TIC of the cells.
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PMID:Influence of anoxia, reoxygenation, and uncoupling on survival, respiration, and trypsin-inhibiting capacity of isolated pancreatic acinar cells. 175 30

Skin lesions associated with alpha 1-antitrypsin deficiency are becoming better defined and understood. Deficiency in this major antiproteinase, which neutralizes multiple proteolytic enzymes ranging from collagenases and elastases to trypsin and chymotrypsin, thus results in significant tissue autodigestion. This anti-proteinase is secreted by activated lymphocytes and macrophages, suggesting the existence of homeostasis which titrates the release of proteolytic enzymes by these cells, and the adequate neutralization of these proteases in order to prevent excessive tissue autodigestion each time these inflammatory cells are activated. We report a patient with alpha 1-antitrypsin deficiency who, following insect bites and cellulitis developed widespread itching and scratching, leading to widespread lesions of prurigo nodularis. The colonization of his multiple skin lesions with Staphylococcus aureus and the release of potent T cell mitogens, such as Protein A and enterotoxin A from the bacterial cell membrane may have resulted in the release of additional proteolytic enzymes by the activated lymphocytes and macrophages, without the concomitant secretion of alpha 1-antitrypsin with subsequent aggravation of his pruritus. These concepts are supported by electron microscopic evidence of excessive tissue autodigestion, and by immunocytochemical data identifying the presence of T helper and T cytotoxic/suppressor lymphocytes as well as macrophages within the upper dermis.
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PMID:Alpha-1 antitrypsin deficiency in a patient with widespread prurigo nodularis. 182 11

The survival of isolated pancreatic acinar cells and of hepatocytes from rats was compared to mimic cell injury and death during the pathogenesis of acute pancreatitis in the presence of varying concentrations of trypsin, chymotrypsin and of the uncoupler 2.4-dinitrophenol (DNP). While hepatocytes were quickly damaged by trypsin they still excluded trypan blue though an excess amount of DNP was added. Pancreocytes revealed a reversed susceptibility to both noxae. The reduced sensitivity of pancreocytes to extracellular trypsin action could represent a special protectiveness against autodigestion and their increased susceptibility to an alteration of the cellular energy state stresses the importance of this factor to the survival of pancreatic tissue under normal and noxious conditions.
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PMID:Differences in time course of hepatocyte and pancreocyte damage after incubation with trypsin, chymotrypsin and 2.4-dinitrophenol. 207 4

Incubation of alpha-chymotrypsin and alpha-lytic protease with chloro(2,2':6',2''-terpyridine)platinum(II), [Pt(trpy)Cl]+, results in attachment of Pt(trpy)2+ tags at both His 57 and His 40 in the former and His 57 in the latter. The [Pt(trpy)His]2+ chromophores are readily detected and quantitated owing to their characteristic, strong UV absorption. Although the tagging of His 57 modifies the catalytic triad (Ser 195, His 57, and Asp 102) and disrupts the charge relay, the platinated enzymes retain significant esterase and amidase activity for both specific and nonspecific substrates. Unlike suicide inhibitors, which inactivate the enzymes by filling the active site and imitating the tetrahedral intermediate, [Pt(trpy)Cl]+ reacts with a particular amino acid and permits binding of substrates. The kinetic constants for the following are reported: two esters and two amides with alpha-chymotrypsin and an amide with alpha-lytic protease. The kcat values are between 1 and 25% of, and the Km values are a little higher than, the corresponding values for the native enzymes. The catalytic activity is not due to the native enzymes, trypsin, or some zinc-containing protease. Activities of the native and of the platinated alpha-chymotrypsin depend similarly on pH although the pKa of His 57 is raised to 9.7 upon platination. The platinated enzymes undergo autodigestion slower than do the native enzymes. Because the Pt(trpy)2+ tags are noninvasive, stable, and yet easily removable by thiourea, [Pt(trpy)Cl]+ may be used to retard autodigestion of stored proteolytic enzymes.
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PMID:Catalytic activity of the serine proteases alpha-chymotrypsin and alpha-lytic protease tagged at the active site with a (terpyridine)platinum(II) chromophore. 222 78

Acute pancreatitis (AP) is believed to result from intraparenchymal activation of trypsin and other digestive enzymes within the pancreas followed by autodigestion of the gland. Gabexate mesilate (FOY), a synthetic guanidino acid ester exhibiting potent and versatile inhibitory actions on a number of proteinases (e.g., trypsin, kallikrein, C1-r, C1 esterase, plasmin, thrombin, phospholipase A2), was examined for its ability to protect the rat pancreas against development of AP induced by pharmacological doses of ceruletide (CRT). Rats were i.v. infused for 6 h with either CRT (5 micrograms/kg/h) or CRT + FOY (50 mg/kg/h). In FOY-treated rats the serum amylase and trypsinogen concentrations were reduced by 60 and 80%, respectively, compared to rats infused with CRT alone. Histologically, the extent of acinar cell vacuolization in the pancreas was significantly reduced and interstitial edema, although not assessed by quantitative morphometric techniques, appeared to be qualitatively lessened in the FOY-treated rats. The ability of FOY to inhibit significantly AP produced by supramaximal doses of CRT, coupled with its inhibitory properties on components of the coagulation and complement cascades, stress the importance of continued research on this compound as a potential therapeutic agent for treatment of AP and its systemic sequelae.
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PMID:Gabexate mesilate (FOY) protects against ceruletide-induced acute pancreatitis in the rat. 244 41

Rats fed a diet containing 2.5% sodium saccharin (NaSacc) displayed a rapid (24-36 hr) increase in tryptic and chymotryptic activity in the lower half of the small intestine and the cecum compared with control animals. Cecal pH of rats fed NaSacc was lower than controls. The effect of NaSacc on enzymatic activity of intestinal contents and on indigenous bacterial microflora was studied further in vitro. Intestinal contents incubated anaerobically with or without NaSacc revealed that the presence of NaSacc led to higher tryptic and chymotryptic activity and higher final pH. Changes in pH do not appear, however, to be important for the increased proteolytic activity induced by NaSacc since autodigestion of trypsin and chymotrypsin in filter-sterilized samples was only slightly affected by pH during in vitro incubation. Amylolytic activity, on the other hand, was stabilized by higher pH values. Saccharin stabilized chymotryptic and led to almost complete loss of amylolytic activity during incubation of filter-sterilized samples maintained at adjusted pH values. The amount of reducing sugars remaining in the NaSacc-containing contents from either cecum (in vivo) or from in vitro incubation of unsterilized small intestinal samples was greater than controls not containing NaSacc. The growth of six bacterial strains isolated from small intestinal contents and incubated in laboratory media was inhibited by NaSacc. Extracellular proteolytic activity from bacterial sources was undetectable after incubation of intestinal bacteria in laboratory media. The present results suggest that the effect of NaSacc upon digestive enzyme composition in the small intestine of rats is not mediated through a direct physiological effect of NaSacc on pancreatic exocrine secretion. It is hypothesized that an inhibition of enzymatic activity by NaSacc in the small intestine and the bacteriostatic effect of NaSacc on bacteria may be responsible for the increased proteolytic activity observed in vivo in the cecum following the feeding of a NaSacc-containing diet to rats.
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PMID:Effects of sodium saccharin on the activity of trypsin, chymotrypsin, and amylase and upon bacteria in small intestinal contents of rats. 257 3

In the pathogenesis of acute pancreatitis the events and mechanisms increasing the digestibility of the acinar cells are widely unknown. To study these processes at cellular level, isolated exocrine cells from rat pancreas were utilized as experimental tool. The investigations revealed that extracellularly acting noxae seem to be of less importance to triggering autodigestion. The plasma membrane of the acinar cells was relatively resistant to extracellular trypsin, while anoxia or uncoupling of oxidative phosphorylation obviously reduced the survival of these cells. Combined action of small amounts of trypsin and partial uncoupling resulted in a potentiated cell destruction. The findings presented stress the importance of a well-functioning energy metabolism for the protective potential of acinar cells to further harmful conditions.
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PMID:Isolated acinar cells from rat pancreas in pathogenic studies on acute pancreatitis. 278 34

To study the dynamics of pathomorphologic alterations in the development of acute pancreatitis (AP) and the corresponding changes of the patterns of pancreatic enzymes in rats AP was induced by: 1) combination of a pancreatic juice edema and temporary pancreatic ischemia, ii) by intraductal instillation of trypsin, and iii) by trypsin instillation in combination with ischemia. At 4, 8 and 24 h postoperatively the histologic findings and the activities of lipase and alpha-amylase in the pancreas and the serum were analyzed. The histologic sum score of the individual rats did not correlate with their enzymic patterns in pancreas and in serum. In all three models there was a development of parenchymal necrosis independent of the existence of pancreatic fat necrosis. Therefore, it is not probable that fat necrosis represents an obligatory precondition for the initiation of autodigestion.
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PMID:Experimental acute pancreatitis--a quantification of dynamics at enzymic and histomorphologic levels. 281 89


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