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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The usefulness of micronutrient antioxidant therapy for recurrent (non-gallstone) pancreatitis has recently been endorsed by a 20-week double-blind double-dummy cross-over trial in 20 patients. Treatment was delivered as two types of tablets, providing daily doses of 600 micrograms organic selenium, 9000 i.u. beta-carotene, 0.54 g vitamin C, 270 i.u. vitamin E and 2 g methionine. We report antioxidant profiles in blood samples collected before entry, at the cross-over stage and upon completion of trial. Baseline serum concentrations of selenium, beta-carotene and vitamin E in the patients were significantly lower than in healthy controls, were unaltered by placebo and normalized by active treatment, but reverted to basal values in the subgroup that received placebo subsequently. The baseline serum concentration of a free radical marker--the 9-cis, 11-trans isomer of linoleic acid--was significantly higher in the patients than in controls, fell inexplicably in the placebo phase and fell further upon active treatment. Discriminant analysis eliminated the overlap in free radical marker and selenium concentrations between control sera on the one hand and baseline or post-placebo samples from the patients on the other: antioxidant treatment normalized the relationship between these biochemical parameters. Subnormal baseline serum levels of S-adenosylmethionine drifted downwards upon active treatment whereas a sharp rise was noted when a relapse of pancreatitis occurred during the placebo phase. The results confirm that adequate exposure to antioxidants in the active treatment phase was associated with amelioration of oxidative stress, and that there was no residual effect 10 weeks after switching over to placebo treatment. Furthermore, the paradoxical behaviour of S-adenosylmethionine may imply that the beneficial effect of micronutrient antioxidants in recurrent pancreatitis is linked with preservation of the methionine trans-sulfuration pathway in pancreatic acinar cells.
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PMID:Antioxidant therapy for recurrent pancreatitis: biochemical profiles in a placebo-controlled trial. 160 43

99 patients affected with acute pancreatitis of different genesis were treated in hospital (necrotizing n = 38, mild form n = 61) from May 1990 to November 1991. Nearly 80% of these illnesses were ethanol-induced, 12% were of biliary origin. 90 patients were submitted to an adjuvant antioxidant therapy with selenium and D-alpha-tocopherol (necrotizing form n = 29, mild form n = 61). The average lethality rate of 34% (1982-1989) fell to 1.1% (1 female patient with biliarily induced pancreatitis). No lethal courses were observed in alcohol-induced, idiopathic, post-traumatic, and post-operative forms. Clinical courses proceeded more easily under adjuvant antioxidant therapy, surgical treatment was not necessary. A treatment at reasonable costs can be made in all general internal wards.
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PMID:[Anti-oxidative therapy of pancreatitis--an 18-month interim evaluation]. 164 22

Malonic dialdehyde as an indirect marker of the lipid peroxidation was found increased in the acute pancreatitis compared with persons of the same age and sex. Its concentrations inversely correlated to those of the serum calcium during the course of the disease and additionally they proved to be indicator of the prognosis. Postulating that the acute pancreatitis must be a "free radical disease", in a randomized clinical study the adjuvant therapy of the acute necrotizing pancreatitis (n = 8) with sodium selenite was carried out in a daily dose of 500 micrograms. The lethality of the control group was 89% (8 out of altogether 9 patients), no patient died in the therapy group. By the selenium therapy within 24 hours a normalization of the serum calcium and a decrease of the increased MDA-values could be achieved. It was concluded that by selenium increased activities of the phospholipid-hydroperoxide-glutathione peroxidase were induced, by means of which a peroxidation protection of membrane fatty acids, an inhibition of the activity of phospholipase A2 and an interruption of the arachidonic acid cascade must have been reached.
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PMID:[Acute pancreatitis--a free radical disease. Decrease in fatality with sodium selenite (Na2SeO3) therapy]. 131 23

Oxidant stress has been proposed as the initiating pathogenetic mechanism in pancreatitis, hence micronutrient antioxidant therapy has been assessed in patients with recurrent attacks and/or constant pancreatic pain. In a 20-week double-blind double-dummy crossover trial active treatment was given as two types of tablets providing daily doses of 600 micrograms organic selenium, 9000 IU beta carotene, 0.54 g vitamin C, 270 IU vitamin E and 2 g methionine. Of 28 patients enrolled, 20 adhered to the full protocol (idiopathic chronic 8, alcoholic chronic 7, idiopathic acute 5). Six patients had an attack whilst on placebo but none whilst on active treatment (P = 0.032). Analysis of visual analogue scoresheets to compare background pain in the 10-week period before entry and during each phase of the trial, using a 10-cm scale for each of 11 best descriptors, endorsed the beneficial effect of active treatment (placebo v baseline, P = 0.073; active v baseline, P less than 0.001; active v placebo, P = 0.049). The same trend emerged from analysis of pain-score diaries by conventional and time series methods. Micronutrient antioxidant therapy thus offers a new approach to the treatment of recurrent (non-gallstone) pancreatitis and/or pancreatic pain.
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PMID:Antioxidant therapy for recurrent pancreatitis: placebo-controlled trial. 210 55

Previous studies on pancreatic calculi (PC) from alcoholic pancreatitis and our recent studies on calculi from tropical pancreatitis have shown them to consist mainly of CaCO3 with minute quantities of Mg. However, no attempt was made to look for other elements in PC. This is because of the difficulty in obtaining adequate samples of PC, coupled with the technical limitations in analyzing multi-elements from small samples. In this study, our aim was to analyze the major, minor and trace elements of PC from different parts of the world. DC plasma emission spectroscopy, a modern method that permits determination of multiple elements from small samples, was used in elemental analysis. We identified 17 elements in addition to calcium. Selenium was looked for but was absent. It was interesting that the elemental composition of PC in four patients from different geographical areas with divergent etiological factors remained the same. Absence of Se is of interest, as Se deficiency is associated with pancreatic fibrosis in experimental animals and it is often noted in chronic alcoholics and the malnourished. This preliminary study emphasizes the need for analysis of the elemental composition of pancreatic juice in normals and in conditions predisposing to chronic pancreatitis, to understand lithogenesis and possibly also the etiology of, at least, some types of pancreatitis.
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PMID:DC plasma emission spectroscopic analysis of pancreatic calculi. 368 Oct 37

Coronary artery bypass grafting (CABG) carries a high risk of acute pancreatitis. We report a pilot study to investigate whether pre-existing oxidative stress might underlie this susceptibility, in that a burst of free radical activity not only accompanies the reperfusion stage of CABG but seems to be a pivotal step in the pathogenesis of pancreatitis. Samples of peripheral venous blood were obtained on the morning of surgery from 8 consecutive patients (age, median and range, 62, 35-70 years) with > 75% stenosis in at least three coronary vessels and a further 8 (64, 49-70 years) who had received 1200 mg allopurinol in divided doses in the previous 48 h: the results were compared with profiles of 8 healthy controls (56, 50-60 years) with normal exercise ECG. None of the patients or controls currently smoked cigarettes and the majority drank alcohol on a social basis. Compared with controls, untreated patients had lower levels of glutathione (P < 0.001) and ascorbate (P < 0.05) in plasma, alpha-tocopherol (vitamin E as molar ratio of cholesterol, P < 0.025 and beta-carotene (P < 0.05) in serum. There was no difference in serum selenium levels, but values in patients and controls were lower than in younger controls from this area (P < 0.02). Samples from the patients contained higher concentrations of lipid peroxides than control samples (P < 0.25) but there was no evidence of excessive isomerisation of linoleic acid or oxidation of ascorbate and erythrocytes showed normal ATP and energy charge with no increase in membrane lipid peroxidisability. Treatment with allopurinol did not alter this pattern, such that the ratio of oxidised to total glutathione in plasma was higher among the 16 patients than 8 controls (P < 0.025). Habitually inadequate intakes are the best explanation for the patients' deficits in aqueous phase antioxidants; prescribed low cholesterol diets would exacerbate any prior insufficiency of lipid-phase antioxidants. Correction of these deficits during the months leading up to surgery should reduce the risk of CABG-induced acute pancreatitis.
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PMID:A pilot study of blood antioxidant and free radical marker profiles in patients awaiting coronary artery bypass grafting. 885 65

Cardiac-related death of HIV-positive patients is not rare. The etiology of AIDS-associated dilated cardiomyopathies often remains unknown, even at autopsy. We report an observation associated to a severe deficit in selenium. The patient had been diagnosed as HIV-positive 2 years before. He presented Pneumocystis carinii pneumonia then Cryptococcus meningitis. Two months later he was hospitalized for pancreatitis and cachexia. He presented global heart failure that lead to death. No microorganism was found in myocardium at autopsy but plasma selenium was dramatically decreased (24 micrograms/L). The deficit in selenium has been associated to a dilated cardiomyopathy in non-AIDS patients. HIV-positive patients have an early decrease in plasma selenium, this concentration is dramatically decreased in malnourished patients. Selenium deficit might be the cause of some of the AIDS-related dilated cardiomyopathies and selenium supplementation might be useful in these patients.
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PMID:[Dilated cardiomyopathy and selenium deficiency in AIDS. Apropos of a case]. 936 39

The traditional ductal model for the development of chronic pancreatitis leaves many questions unanswered and it has not facilitated management. An alternate philosophy centres on the acinar cell as the site of mounting oxidant stress, usually as a result of steady exposure to xenobiotics that induce cytochrome P450 mono-oxygenases while depleting glutathione: ductal changes are regarded as secondary, disease-compounding manifestations of the oxidant environment. Within this framework each burst of oxidant stress jeopardises exocytosis, to trigger an attack of pancreatitis by interfering with the methionine-to-glutathione transsulphuration pathway, which interacts closely with ascorbate and selenium. The resulting diversion of free radical oxidation products into the pancreatic interstitium causes mast cells to degranulate, thereby provoking inflammation, the activation of nociceptive axon reflexes, and profibrotic interactions.
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PMID:A framework for the aetiogenesis of chronic pancreatitis. 983 31

The Manchester 'oxidant stress' hypothesis for the development of pancreatitis accommodates published information on both chronic pancreatitis and acute pancreatitis. Oxidant stress, mainly from reactive xenobiotic metabolites, is perceived as the pivotal pre-morbid problem in chronic pancreatitis and, by depleting glutathione, targets the exocytosis mechanism of the pancreatic acinar cell. Inhalation exposure to petrochemical products is identified as an independent risk factor in patients at Manchester Royal Infirmary, where some 50% of patients referred have non-alcoholic disease. This paper describes the development of antioxidant therapy, using supplements of methionine, vitamin C and selenium, and its validation in a placebo-controlled trial, followed by a retrospective cross-sectional study in 94 consecutive patients for an average of 30 months. Antioxidant therapy emerges as a safe and effective medical alternative to surgery for painful chronic pancreatitis.
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PMID:Chronic pancreatitis at Manchester, UK. Focus on antioxidant therapy. 983 34

The present work critically reviews the evidence for an involvement of free radicals in the pathophysiology of acute pancreatitis and the potential of treatment with antioxidants and scavenger substances. Data originating from clinical trials, experimental pancreatitis studies and in vitro investigations are included. Enhanced free radical activities and increased concentrations of lipid peroxides in plasma and tissue have been found in both patients and experimental animals with acute pancreatitis. The individual contribution of possible sources of free radicals (e.g., invading inflammatory cells, xanthine oxidase, cytochromes P450, nitric oxide synthase) is not yet clear, however. Since prophylactic administration of antioxidants diminished, in particular, pancreatic edema formation, free radicals seem to play an important role in the genesis of edema in acute pancreatitis. An involvement of free radicals in the pathogenesis of pancreatic necrosis could not yet be proven. Thus, no antioxidant treatment has proven useful for therapy of fulminant pancreatitis in animals to date. However, in severe acute pancreatitis characterized by death occurring after 12-18 hours, the seleno-organic compound Ebselen, which has a glutathione peroxidase-like activity, and the membrane permeable ascorbic acid derivative CV-3611 have been demonstrated to be effective. To date, controlled clinical studies have failed to demonstrate the therapeutic efficacy of antioxidant selenium or glutathione precursor supplementation. Therefore, further controlled clinical trials are needed to determine whether supplements of antioxidants can alter the clinical course of acute pancreatitis. Since the nitric oxide radical may even protect the pancreas, a purely negative discussion of the role of free radicals on the pancreas is not justified. The actual role of free radicals in acute pancreatitis, i.e. serving the body's defense against infection, being an epiphenomenon of the inflammatory process without pathophysiological relevance, or having true pathogenic significance, is not yet clear. Lipid peroxidation may perhaps not be the cause but rather the sequel of pancreatic inflammation and may likely reflect the severity of the systemic inflammatory response rather than that of pancreatic parenchyma damage. In vitro, exposure of isolated pancreatic acinar cells to oxidative stress caused rapid cell damage and death. Such knowledge from cellular studies might help to plan therapeutical trials to evaluate potentially effective therapies in the experimental animal, as well as in patients suffering from pancreatitis. Thus, to further clarify the role of oxidative stress in acute pancreatitis, an integrated approach is needed, including investigations at various biological levels, from isolated cells or even organelles to laboratory animals and, finally, clinical studies in man.
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PMID:Oxidative stress in acute pancreatitis. 1057 39


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