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)

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

We have previously demonstrated a direct relationship between the activity of the arachidonic acid cascade in vivo and the extent of cellular damage following several types of experimental injury. Since phospholipase activity has been shown to regulate arachidonic acid availability, we tested the ability of circulating phospholipase A2 (PLA2) of pancreatic origin to stimulate prostanoid production or induce cellular injury in the isolated, perfused rabbit liver. Experimental conditions were similar to those present during pancreatitis or early splanchnic artery occlusion shock. The administration of PLA2 at a rate of 100 U/min for 10 min resulted in enhanced rates of thromboxane B2 and 6-ketoprostaglandin F1 alpha release between 1 and 5 min into the infusion period. No changes in hepatic perfusion pressure, vascular resistance, wet tissue weight, or release of lactic dehydrogenase or acid phosphatase into the effluent were observed in either vehicle or PLA2-treated livers. This indicates that cellular injury was not a factor in the prostanoid release. These data suggest that circulating PLA2 can directly stimulate de novo prostanoid synthesis in noninjured tissues. Thus, enhanced plasma prostanoid concentrations in intact animals during periods or regional cellular injury may be due in part to circulating PLA2 released from damaged tissues.
 ...
PMID:Phospholipase A2 stimulated release of prostanoids from the isolated, perfused rabbit liver: implications in regional cellular injury. 733 80

The purpose of this study was to determine the effect of superoxide dismutase (SOD) on canine experimental pancreatitis. Pancreatitis was induced by retrograde biliary juice injection (0.5 ml/kg) to accessory pancreatic duct. Twenty-one mongrel dogs were divided into two groups, i.e. control (untreated) group (n = 13) and SOD-treated group (n = 8). In SOD-treated group, SOD 5000 units/kg was administered from celiac artery immediately after onset of pancreatitis. Xanthine oxidase (XOD), malondialdehyde (MDA), phospholipase (PL), and SOD were assayed from pancreatic tissue 1 and 3 hours after onset of pancreatitis. Serum amylase, elastase I, calcium, and WBC were assayed for 7 days after onset of pancreatitis. XOD and MDA levels were increased in untreated group, and not significantly changed in treated group with statistical difference. PL levels were increased after onset of pancreatitis in both groups and SOD levels were not changed even in treated group. No statistical difference was seen in PL and SOD levels between two groups. Increase of XOD levels suggests continuous generating of free radical species from pancreatic tissue, and SOD inhibits this increase. Increase of PL level was not improved by SOD. Serum laboratory findings and survival rates were not improved by SOD treatment.
 ...
PMID:[Role of free radicals on canine bile-induced pancreatitis and effect of superoxide dismutase]. 766 54

Acute pancreatitis remains a serious illness. Most patients with persisting organ failure have necrotizing rather than interstitial pancreatitis. Necrotizing pancreatitis can be distinguished from interstitial pancreatitis on incremental dynamic bolus CT scan. Infected necrosis can be diagnosed by guided percutaneous aspiration with Gram stain and culture. The treatment is surgical debridement. Patients with sterile necrosis associated with organ failure may have a high mortality rate. It remains unclear at present whether such patients should be treated by early surgical debridement or continuation of medical therapy. Measures that may be helpful in the future in reducing morbidity and mortality include the use of newer inhibitors of proteases and phospholipase-A2, inhibitors of other mediators of inflammation, and methods to improve the microcirculation of the pancreas.
 ...
PMID:Acute pancreatitis: medical and surgical management. 804 17

Elevated phospholipase A2 activities in serum were measured in patients suffering from acute pancreatitis or various inflammatory diseases. The photometric phospholipase A assay of Hoffmann & Neumann (Klin. Wochenschr. 67 (1989) 106-109) was combined with immunoabsorption by different monoclonal antibodies directed against pancreatic phospholipase A2. Pancreatic phospholipase A2 was purified from human duodenal juice. Monoclonal antibodies were prepared by fusion of spleen cells from immunized mice with P3X63-Ag8-653 myeloma cells. Samples with phospholipase A2 activity were incubated in monoclonal antibody-coated microtitre plates. Phospholipase A2 activities were determined in the monoclonal antibody-treated samples as well as in control samples. The method allows the determination of the fraction of human phospholipase A2 isoenzymes in various biological materials. For pancreatic phospholipase A2 the specific binding capacity was about 60-80%, the unspecific binding was 5-30%. Practically no cross-reactivity was seen with partially purified serum phospholipase A2, with recombinant platelet phospholipase A2, or with the sera of patients with non-pancreatic diseases. In conclusion, the present study confirmed the presence of pancreatic phospholipase A2 in human duodenal juice and in the ascites of necrotizing pancreatitis. However, pancreatic isoenzyme was absent in non-pancreatic inflammatory diseases. Therefore, elevated phospholipase activities in non-pancreatic inflammatory diseases cannot be attributed to the pancreas.
 ...
PMID:Differentiation of human phospholipase A2 isoenzymes in serum and other body fluids with use of monoclonal antibodies. 831 67

A previous report has shown that undernutrition reduces the mortality of acute experimental pancreatitis probably by decreasing pancreatic enzyme content. Cerulein in physiological doses reduces the enzyme content of the pancreas without any harmful effect on the organ. The aim of the present study was to asses the effect of acute reduction of pancreatic enzyme content on the outcome of acute pancreatitis. Two groups of male Wistar rats weighing 230-250 g were studied: group I, 12-h fasted animals, and group II, ad libitum-fed animals who received cerulein at the inframaximal dose (0.2 microgram kg-1 h-1) for 2 h. Cerulein administration resulted in the reduction of the pancreatic contents of chymotrypsinogen (71%), trypsinogen (55%), proelastase (60%), amylase (62%) and cathepsin B (45%) (P < 0.05). However, no significant reduction in pancreatic phospholipase content was observed. Acute pancreatitis was induced in group I after 12-h fasting and in group II at the end of cerulein infusion by retrograde injection o 0.5 ml of 2.5% Na+ taurocholate into the pancreatic duct. Ascites volume and the degree of histologically observed lesions were similar in both groups, but 72-h mortality was 56% in the control group (10/ 18) and 23% (5/22) in the cerulein group (P < 0.05). We speculate that the reduction of pancreatic enzyme content may exert its beneficial effect in acute pancreatitis by decreasing the quantity of pancreatic enzymes reaching the circulation and consequently their pathogenic effects.
 ...
PMID:Reduction of pancreatic enzyme content and mortality in experimental acute pancreatitis in rats. 852 May 45

Alcohol abuse and gallstones are the most important factors in the pathogenesis of acute pancreatitis. Other factors are less frequent, and in some patients one is unable to identify any risk factor. Even in the most frequent forms of alcoholic or biliary pancreatitis little is known about the cellular and molecular mechanisms which lead to severe pancreatitis. New experimental studies have shown that many biochemical and morphological events are similar in different experimental models of pancreatitis as well as in human disease. These changes include intracellular premature activation of trypsin, blockade of luminal enzyme secretion and appearance of intracellular vacuoles. Although activated trypsin triggers the activation of other proteases, it is not trypsin but other proteases (e.g. elastase, chymotrypsin and phospholipase) which damage the pancreatic acinar cell. These pathogenetic findings may lead to the development of inhibitors which more effectively inhibit the latter cell-toxic proteases and may thereby help to improve the therapy.
 ...
PMID:[Current aspects in the pathogenesis of acute pancreatitis]. 917 94

Phospholipase-A2 has been suggested as having a role in the pathophysiology of acute pancreatitis. The inhibition of phospholipase-A2 was studied in vitro using 17 pharmacological agents in the search for a specific therapy for acute pancreatitis. The inhibitory effect was tested using an isotopic assay system with 2-palmitoyl-(1-14C)-labelled dipalmitoyl phosphatidylcholine as a substrate and 10 microliters of serum from patients with acute necrotizing pancreatitis as an enzyme source. Among all agents tested, anti-inflammatory drugs inhibited enzyme activity most significantly: indomethacin (9.0 x 10(-3) mol l-1) decreased the phospholipase-A2 activity to one- tenth. The weak inhibitory effect could also be demonstrated using a lower concentration of 2 x 10(-5) mol l-1, which can be achieved after intravenous administration of 50 mg of this drug. The other drugs inhibited the enzyme activity at concentrations higher than those achieved after intravenous injections in clinical use. Diclofenac (3.1 x 10(-2) mol l-1) reduced the phospholipase-A2 activity by 93%, ketoprofen (2.0 x 10(-2) mol l-1) or chlorpromazine (1.4 x 10(-2) mol l-1) by 90%, tobramycin (1.7 x 10(-2) mol l-1) by 84%, doxycycline (9.0 x 10(-3) mol l-1) by 61%, dexamethasone (1.7 x 10(-3) mol l-1) by 62%, methylprednisolone (3.8 x 10(-2) mol l-1) by 50%, and pindolol (1.0 x 10(-4) mol l-1) by 59%. A weak inhibition of phospholipase-A2 activity was demonstrated by betamethasone, bupivacaine, digoxin, hydrocortisone, lidocaine, metoprolol, propranolol, and vancomycin. Indomethacin proved the most potent of the tested agents in inhibiting phospholipase-A2 activity in serum from patients with acute pancreatitis and should be further studied in vivo.
 ...
PMID:Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro. 927 65

The authors reveal and discuss the role of novel biochemical parameters in early diagnosis of acute pancreatitis and assessment of the severity of the disease. These biochemical parameters, beside routinely used amilase and lipase, might enable us to early identify those patients who are at risk of developing severe form of pancreatitis or complications. These parameters include trypsinogen activation peptide (TAP), C-reactive protein (CRP, tripsinogen-2, procalcitonin, phospholipase-A2 (PLA2), carboxypeptidase activation peptide (CAPAP) and interleukin-6 and 8 (IL-6, IL-8). Although these markers are still not incorporated in routine clinical practice, IL-6, IL-10, procalcitonin and trypsinogen activation peptide seem to have a good chance to be used as a new biochemical markers in assessment of severity and prognosis of acute pancreatitis.
 ...
PMID:[Biochemical markers in assessment of severity and prognosis of acute pancreatitis]. 2312 Aug 47

P-21-activated kinases (PAKs) are serine/threonine kinases comprising six isoforms divided in two groups, group-I (PAK1-3)/group-II (PAK4-6) which play important roles in cell cytoskeletal dynamics, survival, secretion and proliferation and are activated by diverse stimuli. However, little is known about PAKs ability to be activated by gastrointestinal (GI) hormones/neurotransmitters/growth-factors. We used rat pancreatic acini to explore the ability of GI-hormones/neurotransmitters/growth-factors to activate Group-I-PAKs and the signaling cascades involved. Only PAK2 was present in acini. PAK2 was activated by some pancreatic growth-factors [EGF, PDGF, bFGF], by secretagogues activating phospholipase-C (PLC) [CCK, carbachol, bombesin] and by post-receptor stimulants activating PKC [TPA], but not agents only mobilizing cellular calcium or increasing cyclic AMP. CCK-activation of PAK2 required both high- and low-affinity-CCK1-receptor-state activation. It was partially reduced by PKC- or Src-inhibition, but not with PI3K-inhibitors (wortmannin, LY294002) or thapsigargin. IPA-3, which prevents PAK2 binding to small-GTPases partially inhibited PAK2-activation, as well as reduced CCK-induced ERK1/2 activation and amylase release induced by CCK or bombesin. This study demonstrates pancreatic acini, possess only one Group-I-PAK, PAK2. CCK and other GI-hormones/neurotransmitters/growth-factors activate PAK2 via small GTPases (CDC42/Rac1), PKC and SFK but not cytosolic calcium or PI3K. CCK-activation of PAK2 showed several novel features being dependent on both receptor-activation states, having PLC- and PKC-dependent/independent components and small-GTPase-dependent/independent components. These results show that PAK2 is important in signaling cascades activated by numerous pancreatic stimuli which mediate their various physiological/pathophysiological responses and thus could be a promising target for the development of therapies in some pancreatic disorders such as pancreatitis.
...
PMID:Gastrointestinal hormones/neurotransmitters and growth factors can activate P21 activated kinase 2 in pancreatic acinar cells by novel mechanisms. 2597 36


<< Previous 1 2 3 Next >>