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)

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

Glutathione S-transferase activity increased in rats with acute pancreatitis: 2.2 times on day 2, 2-fold on day 4, and 1.5 times on day 10. Inducers of microsomal enzymes aroclor 1254 and phenobarbital notably inhibited glutathione S-transferase activity in animals with experimental pancreatitis on days 2-4 of the disease (3.1-2.5 times in comparison with sham-operated induced animals). Hence, the activity of enzymes of phase II of liver xenobiotic metabolism is altered in acute pancreatitis.
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PMID:Glutathione S-transferase activity in the liver in acute pancreatitis at various terms of disease and during treatment with inducers. 1097 50

Conjugation of xenobiotic alcohols with endogenous fatty acids is considered one of the mechanisms of their retention in the target organs. A number of fatty acid esters of alcohol's detected in the human tissues were found to be toxic in vivo and in vitro. Non-oxidative metabolism of ethanol resulting in the formation of fatty acid ethyl esters (FAEEs) appears to be one of the major pathways of ethanol disposition in the pancreas during chronic alcohol abuse, and could be associated with pancreatitis. In most cases, pancreatic damage occurs in alcoholics preceding the onset of clinical pancreatitis. Early markers of ethanol-induced pancreatitis could be important for early prevention of such injury. Although FAEEs have been implicated in the ethanol-induced pancreatitis, mechanism(s) of such injury is not well understood. Studies by others and by our own group have shown that plasma levels of FAEEs correlate well with plasma/blood alcohol concentration. FAEE synthase is known to catalyze the formation of FAEEs. The activity of FAEE synthase was found highest in the pancreas. Excessive synthesis of FAEEs during chronic alcohol abuse in the pancreas may be associated with pancreatic injury as supported by in vivo and cell culture studies. Human studies correlating plasma FAEE levels with that of markers of pancreatic injury could be important in developing markers of ethanol-induced toxicity. Although toxicity of exogenously administered FAEEs is shown in vivo and in vitro, the toxicity associated with endogenously formed FAEEs has not been studied. Therefore, studies regarding the role of endogenously formed FAEEs could be important in understanding the mechanism of ethanol-induced pancreatitis.
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PMID:Fatty acid ethyl esters and ethanol-induced pancreatitis. 1193 65

The time-related metabolic effects of 1-cyano-2-hydroxy-3-butene (CHB, crambene), a naturally occurring nitrile and experimental model toxin causing exocrine pancreatitis, have been investigated in rats using high-resolution NMR spectroscopy of urine and serum in combination with pattern recognition analysis. Rats were administered CHB subcutaneously in two doses, 15 mg/kg dose (n = 10) and 150 mg/kg (n = 10), and conventional histopathology and clinical chemistry assessments were performed. Urine samples were collected at - 16 and 0, 8, 24, 48, 72, 96, 120, 144 and 168 h postdosing and serum samples were collected at 48 and 168 h postdosing; these were analyzed using a range of 1D and 2D NMR spectroscopic methods. The metabolic profile perturbations seen throughout the time-course of the study are described, and the application of the spectral correlation technique Statistical TOtal Correlation SpectroscopY (STOCSY) to detect both structural and novel toxicological connectivities between xenobiotic and endogenous metabolite signals is illustrated for the first time. As a result, it is suggested that the STOCSY approach may be of wider application in the identification of toxic versus nontoxic metabolites in drug metabolism studies.
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PMID:Metabonomic investigations into the global biochemical sequelae of exposure to the pancreatic toxin 1-cyano-2-hydroxy-3-butene in the rat. 1963 9

For good performance in clinical and forensic toxicology, it is important to be aware of the signs and symptoms related to xenobiotic exposure since they will assist clinicians to reach a useful and rapid diagnosis. This manuscript highlights and critically analyses clinical and forensic imaging related to ethanol abuse. Here, signs that may lead to suspected ethanol abuse, but that are not necessarily related to liver disease are thoroughly discussed regarding its underlying mechanisms. This includes flushing and disulfiram reactions, urticaria, palmar erythema, spider telangiectasias, porphyria cutanea tarda, "paper money skin", psoriasis, rhinophyma, Dupuytren's contracture, multiple symmetrical lipomatosis (lipomatosis Lanois-Bensaude, Madelung's disease), pancreatitis-related signs, black hairy tongue, gout, nail changes, fetal alcohol syndrome, seborrheic dermatitis, sialosis and cancer.
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PMID:Clinical and forensic signs related to ethanol abuse: a mechanistic approach. 2427 40

Environmental toxicants such as dioxins and polycyclic aromatic carbons are risk factors for pancreatitis and pancreatic cancer. These toxicants activate aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, of which activation regulates many downstream biological events, including xenobiotic metabolism, inflammation, and cancer cell growth and transformation. Here, we identified that environmental toxicant-activated AHR increased expression of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in pancreatic cancer cells and pancreatic tissues. The MALAT1 is a long noncoding (lnc) RNA which interacts with Enhancer of Zeste 2 (EZH2), a histone methyltransferase with epigenetic silencer activity, and the MALAT1-EZH2 interaction increased its epigenetic silencing activity. In contrast, AHR antagonist, CH223191 or resveratrol, counteracted the AHR-mediated MALAT1 induction and MALAT1-enahnced EZH2 activity. Collectively, these results revealed a novel pathway of how environmental exposure leads to epigenetic alteration via activation of AHR-MALAT1-EZH2 signaling axis under pancreatic tissue- and cancer cell-context.
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PMID:Regulation of a long noncoding RNA MALAT1 by aryl hydrocarbon receptor in pancreatic cancer cells and tissues. 3290 Apr 87