67 research outputs found
DNA repair enzyme expression and differential response to temozolomide in a patient with both glioblastoma and metastatic pancreatic neuroendocrine tumor
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The effect of inhibitors of endogenous opioid degradation, bacitracin, bestatin, captopril, and <scp>D</scp>-phenylalanine, on digoxin-induced arrhythmias in guinea pigs
No full text The purpose of this study was to investigate the effect of inhibition of endogenous opioid degradation on digitalis-induced arrhythmias, utilizing the inhibitors bacitracin, bestatin, captopril, and D-phenylalanine. Guinea pigs, anesthetized with pentobarbital, 50 mg/kg i.p., and breathing spontaneously received intracerebroventricular (i.c.v.) injection of bacitracin (6.8 mg/kg), bestatin (1 mg/kg), captopril (2 mg/kg), D-phenylalanine (1.2 mg/kg) or the diluent, saline. Digitalis arrhythmias were induced by a 50 μg/kg i.v. bolus of digoxin followed by 500 μg∙kg−1∙h−1 i.v. Bacitracin and bestatin, but not captopril or D-phenylalanine, significantly (p < 0.05) altered the relationship between the digoxin dose and the first occurrence of arrhythmias, i.e., digoxin-induced ventricular arrhythmias became manifest at lower digoxin doses. The mean digoxin dose and ED50s, at which arrhythmias first occurred, were significantly (p < 0.05) reduced by bacitracin and bestatin. The findings were similar for fatal arrhythmias, although D-phenylalanine appeared to decrease the digoxin dose at the development of fatal arrhythmias. The opioid antagonist naloxone, in a 50 μg/kg bolus and 50 μg∙kg−1∙h−1 i.c.v., completely prevented these effects of bacitracin and reduced the effect of bestatin. The relationship to arrhythmias could not be ascribed to an effect on blood pressure, as the blood pressure response to digoxin was the same in bestatin, D-phenylalanine, and control groups. To examine whether systemic administration of an inhibitor of opioid degradation had similar effects, a second protocol was selected with systemic administration of bacitracin because it altered the dose effect relationship after i.c.v. administration and systemic concentrations could be readily attained. Bacitracin, in a 13.5 mg/kg i.v. bolus and 135 mg∙kg−1∙h−1 i.v., was followed by 100 μg/kg digoxin i.v. every 15 min. Bacitracin significantly (p < 0.05) reduced the digoxin dose at the development of arrhythmias. This was reversed by naloxone, given as 2 mg/kg i.v. plus 10 mg∙kg−1∙h−1. Thus, these data indicate that inhibitors of degradation of some opioid potentiate digitalis arrhythmias in a manner that is inhibited by naloxone, and provide evidence that implicates a role for endogenous opioids in digitalis arrhythmias.Key words: digitalis arrhythmias, aminopeptidase inhibitors. </jats:p
High Yield of Lynch Syndrome Screening in Pre-Cancerous Colorectal Polyps: A Study of 898 Patients
No full textThe ARRIVE guidelines 2.0: Author checklist.
No full textIntroductionAngiogenin-1 (Ang1) and angiogenin-4 (Ang4) are 14-kDa ribonucleases with potent angiogenic and antimicrobial properties. The role of Ang1 and Ang4 in chronic colitis and colitis-associated cancer has not been previously studied.MethodsWild-type (WT) and angiogenin-1 knock-out (Ang1-KO) C57BL/6 mice were given azoxymethane, a colon carcinogen, 2 days in advance of three cycles of 3.5% dextran sodium sulfate (DSS). Disease activity index (DAI) was recorded, a colonoscopy was performed after each DSS treatment, and mice were euthanized (colitis, recovery, cancer) with tissue evaluated by histopathology. Ang1, Ang4, TNF-α, Il-1F062, IL-6, IL-10, IL-23, IL-33 mRNA levels were analyzed by RT-PCR.ResultsAng1-KO mice exhibited more severe colitis compared to WT mice during both the acute (PAng1-KO mice (PAng4 increased to similar levels in both WT and Ang1-KO mice during colitis and recovery phases, WT mice were distinguished by a significant upregulation of Ang1. Interestingly, despite the reduced colitis, WT mice developed significantly more tumors compared to Ang1-KO mice (PAng1-KO mice, which were also characterized by a 34-fold decrease in Ang4 compared to WT mice and the complete absence of Ang1.ConclusionsIn a mouse model of colitis-associated cancer, Ang1-KO mice develop more severe colitis, but fewer tumors compared to WT mice. Ang1 levels correlate with the severity of colitis and the development of colitis-associated cancer, while Ang4 was upregulated during both colitis and cancer. Ang1 and Ang4 play important regulatory roles in the response to chronic colitis and the development of colitis-associated cancer and may serve as novel therapeutic targets.</div
Support for hMLH1 and MGMT silencing as a mechanism of tumorigenesis in the hyperplastic–adenoma-carcinoma (serrated) carcinogenic pathway in the colon
No full textAng1 and Ang4 differentially affect colitis and carcinogenesis in an AOM-DSS mouse model.
No full textIntroductionAngiogenin-1 (Ang1) and angiogenin-4 (Ang4) are 14-kDa ribonucleases with potent angiogenic and antimicrobial properties. The role of Ang1 and Ang4 in chronic colitis and colitis-associated cancer has not been previously studied.MethodsWild-type (WT) and angiogenin-1 knock-out (Ang1-KO) C57BL/6 mice were given azoxymethane, a colon carcinogen, 2 days in advance of three cycles of 3.5% dextran sodium sulfate (DSS). Disease activity index (DAI) was recorded, a colonoscopy was performed after each DSS treatment, and mice were euthanized (colitis, recovery, cancer) with tissue evaluated by histopathology. Ang1, Ang4, TNF-α, Il-1F062, IL-6, IL-10, IL-23, IL-33 mRNA levels were analyzed by RT-PCR.ResultsAng1-KO mice exhibited more severe colitis compared to WT mice during both the acute (PConclusionsIn a mouse model of colitis-associated cancer, Ang1-KO mice develop more severe colitis, but fewer tumors compared to WT mice. Ang1 levels correlate with the severity of colitis and the development of colitis-associated cancer, while Ang4 was upregulated during both colitis and cancer. Ang1 and Ang4 play important regulatory roles in the response to chronic colitis and the development of colitis-associated cancer and may serve as novel therapeutic targets
Cardiovascular Risk with Non-Steroidal Anti-Inflammatory Drugs: Systematic Review of Population-Based Controlled Observational Studies
No full textThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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