Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microvascular permeability was studied in the isolated perfused rat pancreas using a rapid multiple indicator-dilution technique. Capillary extractions, permeability-surface area products (PS), and extravascular volumes of distribution (EVV) were determined for 22Na+, 51Cr-labeled EDTA, [57Co]-cyanocobalamin (B12), and 125I-labeled insulin at various perfusion flows. Permeability to albumin was negligible. PS for Na+ and EDTA increased with increasing flow, whereas PS for cyanocobalamin and insulin approached diffusion-limited exchange at flows greater than 3 ml.min-1.g-1. Permeability coefficients for Na+, EDTA, B12, and insulin were 36, 22, 11, and 3.48 x 10(-5) cm/s, respectively, and the permeability ratio for B12/insulin (3.16) indicated restricted diffusion to insulin. In the presence of unlabeled B12 and insulin EVV (0.15-0.19 ml/g) for EDTA, B12 and insulin approximated the interstitial volume. Caerulein-induced pancreatitis or treatment with the synthetic protease inhibitor camostate had no significant effects on permeability. In caerulein-treated rats, EVV for B12 was elevated (0.17 +/- 0.01 vs. 0.28 +/- 0.06; P less than 0.01), reflecting the interstitial edema associated with this model of pancreatitis. Permeability of the rat pancreatic microvasculature is similar to that of other fenestrated tissues, but it is 10- to 20-fold greater than that of continuous capillaries. Contrary to previous assumptions, permeability does not appear to be increased after induction of acute interstitial pancreatitis.
 ...
PMID:Pancreatic microvascular permeability in caerulein-induced acute pancreatitis. 192 54

We have examined the possibility that the 33- and 39-amino acid forms of cholecystokinin (CCK) are cleaved to produce CCK-octapeptide (CCK-8) during circulation in humans. When a mixture of the 33- and 39-amino acid forms of porcine CCK was infused at 0.1-2.5 pmol/kg.min into normal subjects, material indistinguishable from CCK-8 by gel filtration and in region-specific radioimmunoassays appeared in plasma, together with an intermediate form that eluted between the 33- and 8-amino acid peptides. During infusions, plasma concentrations of CCK-33/39, CCK-8, and the intermediate CCK rose to 63 +/- 26 (mean +/- SE), 57 +/- 12, and 18 +/- 10 pmol/L, respectively. Cholecystokinin-octapeptide appeared rapidly and constituted approximately 40% of total CCK-like immunoreactivity after 5 min of infusion. Octapeptide-like material also appeared, but at a slower rate, when CCK-33 was incubated at 37 degrees C with human plasma. Thus after 5 min, and throughout the incubation, CCK-8 comprised approximately 20% and CCK-33 approximately 75% of total immunoreactivity. Cholecystokinin-33 disappeared more rapidly and small forms appeared in higher concentrations in plasma from patients with acute pancreatitis. Thus, after incubation for 120 min, CCK-33 and CCK-8 comprised 45% +/- 7% and 13% +/- 3% of initial immunoreactivity in normal plasma, but 18% +/- 6% and 33% +/- 9%, respectively, in plasma from patients with pancreatitis. Ethylenediaminetetraacetic acid, but not aprotinin, inhibited the cleavage of CCK-33 to produce CCK-8, and the degradation of CCK-8 in normal plasma in vitro.
 ...
PMID:Cholecystokinin cleavage to cholecystokinin-octapeptide in vivo and in vitro: accelerated cleavage in acute pancreatitis. 245 90

Four hours after hemorrhagic necrotizing pancreatitis was induced in experimental animals the concentration of lysolecithin in pancreatic tissue rose (p = 0.0025). Parenteral administration of unspecific inhibitors of phospholipase A2, such as chlorpromazine, gabexat mesilat and CaNa2 EDTA, can neither inhibit elevation of the enzyme nor influence the course of the disease.
 ...
PMID:Lysolecithin concentration in pancreatic tissue during therapy with phospholipase A2-inhibitors in acute necrotizing pancreatitis. 249 78

In recent studies performed on pancreatic stones from patients with alcoholic pancreatitis, a novel secretory protein was identified: the pancreatic stone protein (PSP Mr 14,000). This protein suppresses CaCO3 precipitation, and could therefore stabilize normally supersaturated pancreatic juice. Crystallographic analysis of stones from patients with nutritional pancreatitis (NP), as well as alcoholic pancreatitis (AP), revealed that the main constituent was calcite (CaCO3). In the present study, we investigated the organic matrix of NP stones. In the 14 cases studied, the organic matrix was rendered soluble after mineral dissolution with EDTA + citrate. Analysis of the isolated matrix revealed the presence of one major protein (Mr 14,000), and of a minor protein (Mr 30,000), which is in fact an aggregate form of the 14,000 Mr protein. Using PSP antibodies, complete immunological identity was found between PSP, the immunoreactive form of PSP present in nonactivated pancreatic juice, and the protein matrix of NP stones. Moreover, protein matrix of NP stones also inhibited the nucleation of CaCO3 crystal, and decreased their growth rate in vitro. The presence of PSP in all AP and NP stones suggests that it plays a key role in stone formation during the course of chronic pancreatitis. These results also suggest the existence of some pathophysiological links between these two apparently different etiological forms of calcifying pancreatitis.
 ...
PMID:Organic matrix of pancreatic stones associated with nutritional pancreatitis. 338 20

Tetra-L-aspartyl-L-lysine (D4K) containing trypsinogen activation peptides were synthesised on solid-phase supports. Synthetic D4K peptides were N-terminally haptenised and used to generate specific C-terminally directed anti-D4K antibodies. Affinity purification of antisera using Sepharose-immobilised synthetic D4K segregated two highly purified populations of anti-D4K antibodies, one eluting with EDTA recognising the calcium chelate and the other eluting with propionic acid recognising an alternative epitope on the anionic oligopeptide. Both specific anti-D4K antibodies were C-terminally directed and did not bind trypsinogen. Specific antisera and calcium-independent antibodies were used to develop and characterise solution and solid-phase immunoassays specific for free trypsinogen activation peptides (TAP assay), with a detection limit of 10(-11) M and between assay CV of 10.7% for the solution-phase system. The release of D4K peptides by enteropeptidase activation of trypsinogen and dog pancreatic secretion is demonstrated. TAP assays specifically indicate trypsinogen activation and may contribute to the recognition and understanding of disease states such as pancreatitis.
 ...
PMID:Development of radioimmunoassays for free tetra-L-aspartyl-L-lysine trypsinogen activation peptides (TAP). 339 45

A simple RIA method for B beta 15-42 RPs has been evaluated in our laboratory to investigate experimental and clinical fibrinolytic states. The assay utilizes bentonite precipitation to remove cross-reacting fibrinogen. Due to the heterogeneity in molecular weights of the B beta RPs, the results are expressed as nanograms per milliliter. The linear range of the assay is 2 to 40 ng/ml, with a capability of detecting up to 200 ng/ml. A special anticoagulant mixture (heparin or EDTA/aprotinin) is required for sample collection. Certain precautions in the care and handling of specimens are also necessary. Increased levels of B beta RPs were observed in the following conditions: malignancy (associated with increased release of tissue plasminogen activators), pancreatitis, liver diseases, pregnancy, and postexercise testing (associated with increased release of tissue plasminogen activators). Increased levels of B beta RPs were also found during thrombolytic therapy, anabolic steroid treatment, prothrombin complex concentrate therapy, blood component therapy, and low molecular weight heparin subcutaneous therapy (associated with an increase in tissue plasminogen activator release). Our studies suggest that B beta RPs are sensitive molecular markers of the endogenous activation of fibrinolytic system and may provide useful diagnostic information on a pathologic process that often remains undetectable by routine laboratory methods.
 ...
PMID:Diagnostic efficacy of a simple radioimmunoassay test for fibrinogen/fibrin fragments containing the B beta 15-42 sequence. 651 20

A laboratory method was established for measurement of phospholipase A2 activity in buffer and serum. A series of different phospholipase A2 inhibitors was tested. The most effective inhibitors were Ca2+ chelating compounds like EDTA, DTPA, EGTA, and phytic acid. The calcium salt of EDTA also has some inhibitory effect. Serum phospholipase A2 activity in normal healthy control patients was measured. The activity in 27 patients with acute pancreatitis was tested. The activity was abnormally high in five patients. This activity was in vitro inhibited by EDTA and partly by CaNa2EDTA. The clinical picture of these patients did not differ from that of phospholipase-A2-negative patients. Six patients with acute pancreatitis were treated by intravenous infusion of CaNA2EDTA. Two of them had haemorrhagic pancreatitis and two were suspected of having early haemorrhagic pancreatitis. During the CaNa2EDTA infusion serum amylase and phospholipase A2 activities decreased. All patients recovered. No harmful side effects were noticed.
 ...
PMID:Phospholipase A2 inhibitors and their possible clinical use in the treatment of acute pancreatitis. 677 62

The incidence of pancreatitis in bacterial enterocolitis is disputed. Two cases of young patients with S. enteritidis-induced enterocolitis and markedly elevated amylase and lipase blood levels are described. In both patients there were neither clinical nor ultrasonographic signs of pancreatitis. Furthermore, both had increased intestinal permeability for oral 51Cr-EDTA, a condition discussed as "leaky gut" in other publications. In one patient enzyme levels and 51Cr-EDTA resorption became rapidly normal, while in the other the values remained elevated after a 7-month interval with stool culture negative. Enhanced intestinal absorption of 51Cr-EDTA (mw 391) suggests--but does not definitely prove--an inflammatory response of the mucosa leading to increased intestinal permeability, which in turn may allow resorption of amylase (mw 62,000), lipase (43,000) or other macromolecules. Performance of a 51Cr-EDTA resorption test may be helpful in cases of clinical uncertainty.
 ...
PMID:[Pseudopancreatitis in entero-invasive salmonellosis]. 769 Jan 54

We have developed an enzyme-linked immunosorbent assay (ELISA) for the specific quantification of alpha 2-macroglobulin-trypsin complex-like substance (MTLS). To exclude artifacts in measured values of MTLS, the conditions for collection of blood samples are critical. In the present study, we have determined the optimal conditions for blood collection and investigated the role of MTLS as a clinical tool for diagnosis in pancreatitis. Results obtained are as follows: (1) MTLS levels of all sera were more than 10-fold higher than the corresponding plasma; (2) MTLS levels of heparinized plasma were the lowest among plasma with three anticoagulants (sodium citrate, sodium EDTA and heparin); (3) some kinds of blood collection tubes containing heparin were not suitable for the sampling; (4) MTLS values of plasma obtained by blood collection tubes containing Trasylol and sodium EDTA were demonstrated more stable and lower than those obtained by heparin tubes; and (5) under these conditions, we can exclude elevation of MTLS values caused by inappropriate blood sampling and find the time course of the elevation reflecting clinical course of a patient with acute pancreatitis and a patient after endoscopic retrograde cholangiopancreatography (ERCP). The optimal conditions for collection of blood samples were as follows. Blood sampling should be performed by blood collection tubes containing Trasylol (50 microliters/ml blood) and sodium EDTA (1.5 mg/ml blood). The samples were immediately stored at 4 degrees C and centrifuged at 3,000 rpm for 15 min. The plasma were stored in plastic tubes at 4 degrees C until assayed.
 ...
PMID:Optimal conditions for collection of blood samples for assay of alpha 2-macroglobulin-trypsin complex-like substance (MTLS). 888 1

Mutations Arg(117) --> His and Asn(21) --> Ile in human trypsinogen-I have been recently associated with hereditary pancreatitis (HP). The Arg(117) --> His substitution is believed to cause pancreatitis by stabilizing trypsin against autolytic degradation, while the mechanism of action of Asn(21) --> Ile has been unknown. In an effort to understand the effect(s) of this mutation, Thr(21) in the highly homologous rat trypsinogen-II was replaced with Asn or Ile, and the recombinant zymogens and their active trypsin forms were studied. Kinetic parameters of all three trypsins were comparable, and the active enzymes suffered autolysis at similar rates, indicating that neither catalytic properties nor proteolytic stability of trypsin are influenced by mutations at position 21. When incubated at pH 8.0, 37 degrees C, pure zymogens underwent autoactivation with concomitant trypsinolytic degradation in a Ca(2+)-dependent fashion. Thus, in the presence of 5 mM Ca(2+), autoactivation and digestion of the zymogens after Arg(117) and Lys(188) were observed, while in the presence of 1 mM EDTA autoactivation and cleavage at Lys(188) were reduced, and zymogenolysis at the Arg(117) site was enhanced. Overall rates of zymogen degradation in [Asn(21)]- and [Ile(21)]trypsinogens were higher in Ca(2+) than in EDTA, while [Thr(21)]trypsinogen demonstrated inverse characteristics. Remarkably, both in the presence and absence of Ca(2+), [Ile(21)]trypsinogen exhibited significantly higher stability against autoactivation and proteolysis than zymogens with Asn(21) or Thr(21). The observations suggest that autocatalytic trypsinogen degradation may be an important defense mechanism against excessive trypsin generation in the pancreas, and trypsinogen stabilization by the Asn(21) --> Ile mutation plays a role in the pathogenesis of HP.
 ...
PMID:Hereditary pancreatitis-associated mutation asn(21) --> ile stabilizes rat trypsinogen in vitro. 1051 42


1 2 Next >>