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

Unmodified synthetic somatostatin, given as a 200-microgram intravenous bolus, plus 200 microgram infused over 3 hours, had no effect on basal plasma insulin and pancreatic glucagon-like immunoreactivity (GLI) levels, both in controls and in patients with chronic pancreatitis. Somatostatin inhibited insulin-hypoglycaemia-induced pancreatic GLI release in controls and in patients with pancreatitis, and prolonged the insulin-induced fall in blood glucose in the patients. Arginine, presumably via insulin release, caused a fall in free fatty acids (FFA) in controls, which was inhibited by somatostatin. Somatostatin abolished the rebound rise in plasma FFA in patients with pancreatitis after insulin-hypoglycaemia. This effect may be related to inhibition of pancreatic GLI release or may be a direct action of somatostatin on lipolysis.
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PMID:The effects of somatostatin on hormonal and metabolic responses in chronic pancreatitis. 89 37

Serial measurements of plasma "true glucagon" (PG) and of glucagon-like immunoreactive materials (GLI) were carried out during and after total resection of the pancreas in a 62-year-old man with calcified pancreatitis. The postoperative course of this patient was uneventful and diabetes was well controlled. PG disappeared from the blood within 30 min after resection of the pancreas. In spite of the evidence that no pancreatic tissue was present in the abdomen, PG was detected again in the blood from 18 hr after total pancreatectomy until the ninth postoperative day. However, plasma PG did not rise following infusion of arginine during the fourteenth postoperative week. After an initial decrease, plasma GLI rose abruptly on the second postoperative day and remained elevated thereafter. The fluctuations of plasma PG and GLI were not parallel.
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PMID:Plasma glucagon after total resection of the pancreas in man. 96 83

The plasma esterolytic activity was measured using benzyol arginine ethyl ester (BAEe) in the peripheral venous blood of patients with acute pancreatitis, normal healthy volunteers and a contrast group of patients with acute intrabdominal inflammations other than acute pancreatitis. The plasma esterolytic activity was significantly elevated in the pancreatitis group. This activity was maximal during the first 48 hours of the illness and remained elevated for a further 8 days thereafter. Aprotinin in a dose of 2000 K.I. u/0-3 ml plasma did not completely inhibit this esterolytic activity, although it resulted in a more substantial inhibition than either ovomucoid or soy bean inhibitor. It is concluded that pancreatic enzymes are released into the circulation during acute pancreatitis and that Aprotinin does not completely inhibit this proteolytic activity. This polyvalent proteinase inhibitor should therefore be administered in much higher dosage than that used hitherto in acute pancreatitis. The plasma esterolytic activity seems to be of diagnostic value in acute pancreatitis.
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PMID:Estimation of plasma esterolytic activity and its in vitro inhibition by proteinase inhibitors during acute pancreatitis in the human. 108 38

The trypsin-inhibiting activity of human serum is lowered upon addition of formaldehyde or acetaldehyde thereto. Acetaldehyde reacts with alpha-1-proteinase inhibitor (alpha 1-PI) to decrease its trypsin-inhibiting ability. Acetaldehyde has only a slight effect on the tryptic hydrolysis of benzoyl-DL-arginine-p-nitroanilide. It did not decrease the inhibitory activity of the Kunitz inhibitor (Aprotinin) or soybean trypsin inhibitor. Since aldehydes form covalent products with primary amines, primary amides, arginine, tyrosine, and tryptophan in protein, as well as methylene bridges thereby crosslinking functional groups, it is proposed that one or more such interactions affect alpha 1-PI activity. It is further suggested that chronically high levels of acetaldehyde, as a metabolic produce of ethanol, may be a contributory factor to the generation of pancreatitis in alcoholics by possibly lowering the effective alpha 1-PI level which is a natural protective element from proteolysis by trypsin.
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PMID:Acetaldehyde decreases the antitryptic activity of alpha 1-proteinase inhibitor. 131 22

We examined the protective effect of human pancreatic secretory trypsin inhibitor (PSTI), a specific trypsin inhibitor secreted from pancreatic acinar cells into the pancreatic duct, on cerulein-induced acute pancreatitis in conscious rats. The protective effect of human PSTI-RS, an analogue of PSTI with Arg-44 to Ser substitution which has a longer half-life in vitro, was also examined. Intraperitoneal administration of a pharmacological dose of cerulein to conscious rats induced acute pancreatitis, characterized by light microscopy as cellular disorganization of the acini and interstitial edema. Intravenous infusion of human PSTI (10, 50 or 250 micrograms/rat/h) into rats with cerulein-induced acute pancreatitis decreased their pancreatic wet weight and plasma amylase concentration. It also caused a dose-dependent decrease in vacuoles in acinar cells and interstitial edema. Human PSTI-RS, which has a longer half-life in vivo, was more effective than native PSTI at the same dose rate (10 micrograms/rat/h) in reducing pancreatitis. These results suggest that human PSTI may have a beneficial effect on acute pancreatitis.
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PMID:Protective effect of human pancreatic secretory trypsin inhibitor on cerulein-induced acute pancreatitis in rats. 145 47

The metabolic response to injury occurs after a diverse group of surgical injuries including major surgical intervention, shock, infection, and sources of inflammation such as pancreatitis. The response is mediated by the macroendocrine system, the autonomic nervous system, and the cell-cell communication system. The clinical manifestations include now well-described clinical, physiologic, and metabolic characteristics. The approach of aggressive source control, invasive circulatory resuscitation, and nutrition/metabolic support has been associated with an overall reduction in morbidity and mortality. In those patients who do not respond to this approach, the disease process progresses to multiple organ failure syndrome with its associated high mortality. Altering the route of feeding, preventing single nutrient and generalized nutrient deficiency, and reducing nosocomial infections with selective gut decontamination have not significantly altered the course or outcome of the disease process in this latter group of patients with persistent hypermetabolism. The available data support the position that this persistent hypermetabolism represents abnormal metabolic regulation resulting in persistence of the inflammatory response with associated suppression of the immune defenses. A number of research approaches are being taken to understand and modulate this abnormal state of regulation. Because of the role of specific nutrients in these regulatory processes, beyond their role in classic nutrition support, nutrients such as arginine n-3 polyunsaturated fatty acids, and RNA are being evaluated for their ability to modulate inflammation and to improve immune function. Preliminary results are encouraging.
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PMID:Nutrient modulation of inflammatory and immune function. 170 26

Human pancreatic colipase is secreted as the inactive form procolipase. Activation involves tryptic cleavage of an N-terminal pentapeptide Ala-Pro-Gly-Pro-Arg (APGPR) which is known as procolipase activation peptide (CLAP). N-terminally haptenised synthetic APGPR was used to generate specific C-terminally directed anti-APGPR antibodies. The antiserum was used to develop a competitive enzyme linked immunosorbent assay (ELISA) specific for free CLAP with a detection limit of 12 nmol/l and an intra-assay coefficient of variation (CV) of 3.28% and an inter-assay CV of 5.82%. The release of immunoreactive CLAP from human pancreatic juice and chicken pancreas upon trypsinisation was demonstrated, as well as the absence of reactivity of the antisera with procolipase from which the CLAP is released. APGPR was found to be unstable in biological fluids. Immunoreactivity is rapidly lost with half life of 5 min and 4 h in human serum and urine respectively. This loss of reactivity can be significantly slowed by the addition of 20 mmol/l Zinc ions (Zn2+), while ethylenediaminetetra-acetic acid (EDTA) and other protease inhibitors were ineffective. In serum the moiety responsible for loss of immunoreactivity was found to have an estimated molecular mass of 200,000-300,000 Da. CLAP assay specifically reports procolipase activation and may help elucidate the mechanism of satiety as well as contribute to the recognition and understanding of the role of procolipase activation in diseases states such as pancreatitis.
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PMID:Development of enzyme-linked immunosorbent assay for free human pro-colipase activation peptide (APGPR). 177 64

In insulin dependent diabetes mellitis (IDDM) beta cell destruction is associated with infiltration of the pancreatic islets by T lymphocytes and macrophages. Cytokine products from the infiltrating immunocytes not only have powerful immunoregulatory actions but also are capable of impairing islet cell functions and have thus been postulated to assume a central role in mediating anti-beta cell immunity and beta cell destruction. In an effort to explore further the role of cytokines in the pathogenesis of IDDM, we examined clinical, metabolic and pathological features of NOD/Wehi mice injected intraperitoneally with multiple doses of IFN-gamma and/or TNF-alpha. Blood glucose profiles were not significantly altered by injection of cytokines alone or in combination. Except for a hypoglycaemic rebound in mice injected with TNF-alpha, arginine stimulation tests revealed no disturbances in islet secretory function in cytokine injected mice. Compared with vehicle and cytokines alone, injection of IFN-gamma + TNF-alpha was associated with a variety of clinical and pathological changes including abdominal distention, piloerection, ascites, oedema, thymic atrophy, splenic enlargement and pancreatic distention. Histological examination of the pancreas in these mice revealed moderate to severe pancreatitis which included focal haemorrhagic necrosis, oedema and polymorphonuclear and mononuclear cell infiltration. The islets in these mice appeared normal morphologically and when stained for insulin. The injection of IFN-gamma + TNF-alpha, and to a lesser extent TNF-alpha alone, was associated with a significant reduction in the severity of insulitis. Examination of pancreatic MHC-class I and class II molecule expression revealed in mice given IFN-gamma + TNF-alpha, as compared with controls, significant and uniform induction of both these molecules on ductal and acinar cells; low level MHC-class II expression was also detectable on beta cells in these mice. MHC-class I molecules which were expressed at high levels by beta cells in control mice did not appear to change following administration of the cytokines alone or in combination. We conclude that despite their immunostimulatory actions in vitro and in other models in vivo, systemic administration of the cytokines IFN-gamma and/or TNF-alpha to NOD/Wehi mice does not activate or enhance, and may actually suppress, anti-beta cell immunity in this model.
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PMID:Reduction in insulitis following administration of IFN-gamma and TNF-alpha in the NOD mouse. 190 36

There are several forms of the enzyme phospholipase A2 (PLA2) in human tissues. In the pancreas the enzyme is produced as a zymogen, pro-phospholipase A2 (pro-PLA2). The active form is generated upon proteolytic cleavage of the N-terminal prophospholipase A2 activation peptide (PLAP), with the sequence Asp-Ser-Gly-Ile-Ser-Pro-Arg (DSGISPR). Antisera specific for free PLAP were produced by immunization with the synthetic peptide, N-terminally conjugated to bovine thyroglobin. Affinity purified antibodies were used to develop a radioimmunoassay with a detection limit of 5 nmol/L. Competitive inhibition studies with amino-terminally truncated sequences showed that, at least, the C-terminal pentapeptide (GISPR) was required for significant inhibition. Anti-PLAP antibodies did not react with native human pancreatic homogenate (a source of pro-PLA2). A large immunoreactive signal was generated upon trypsinization, which coeluted with synthetic PLAP when chromatographed on Sephadex-G25. Likewise, Sephadex-G50 chromatograph fractions of the untrypsinized homogenate reacted with the antibodies only after trypsinization. The immunoreactive signal appeared at a molecular weight of 14,500 which corresponds to the reported molecular weight of pancreatic pro-PLA2. This demonstrates that the assay is specific for the free peptide and reports pro-PLA2 activation. PLAP assay may therefore contribute to the study of the role of the PLA2 activation event in disease states such as pancreatitis.
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PMID:Detection of human pancreatic pro-phospholipase A2 activation using an immunoassay for the free activation peptide DSGISPR. 195 54

After an acute episode of pancreatitis, a 63-year-old man was found to have a pancreatic glucagonoma. The tumor was resected without evidence of metastases. Three years later he had symptoms of uncontrolled diabetes, no skin lesions, and diarrhea and was found to have a pancreatic pseudocyst and multiple hepatic metastases. Glucagon concentrations were raised but were suppressible by glucose and somatostatin and responded to arginine stimulation. He was treated for 6 months with octreotide (Sandostatin), which reduced his symptoms; the pseudocyst resolved, but liver metastases continued to grow. Although spontaneous resolution of the pseudocyst is possible, this case appears to illustrate differences in sensitivity of endocrine and exocrine tissues to suppression by Sandostatin.
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PMID:Somatostatin analogue in treatment of coexisting glucagonoma and pancreatic pseudocyst: dissociation of responses. 216 87


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