Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper presents the application of a newly developed noninvasive system (PISA; Phase-Invariant Signature Algorithm) in the early detection and quantification of the effects of glucagon on the ouaban-induced electrophysiological disturbances in the heart of the dog. Three doses (20, 30, and 40 migrograms/kg) of ouabain were administered intravenously to each of six anesthetized dogs and broadband ECGs were recorded on FM tape for 100 min. The records were analyzed for PISA signatures and indexes at 20, 40, 60, 80, and 100 min after ouabain administration. There were dose-dependent increases in the PISA indexes. Ouabain (20 micrograms/kg) did not produce any observable changes in the conventional ECG, although it produced significant increases in the PISA indexes. In a second group sox dogs, glucagon (50 micrograms/kg) was administered intravenously 20 min after ouabain (40 micrograms/kg) administration and the ECGs, both conventional and for PISA analysis, were recorded for a further period of 80 min. Glucagon reversed the effects of ouabain on the PISA indexes. These indicate that the PISA method has the capability of early detection and quantitication of drug-induced cardiac disorder.
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PMID:Studies on the effects of glucagon on ouabain-induced cardiac disorders using the PISA method. 739 36

Modulation of the DNA repair pathway is an emerging target for the development of anticancer drugs. DNA interstrand cross-links (ICLs), one of the most severe forms of DNA damage caused by anticancer drugs such as cisplatin and mitomycin C (MMC), activates the Fanconi anemia (FA)/BRCA DNA repair pathway. Inhibition of the FA/BRCA pathway can enhance the cytotoxic effects of ICL-inducing anticancer drugs and can reduce anticancer drug resistance. To find FA/BRCA pathway inhibitory small molecules, we established a cell-based high-content screening method for quantitating the activation of the FA/BRCA pathway by measuring FANCD2 foci on DNA lesions and then applied our method to chemical screening. Using commercial LOPAC1280 chemical library screening, ouabain was identified as a competent FA/BRCA pathway inhibitory compound. Ouabain, a member of the cardiac glycoside family, binds to and inhibits Na(+)/K(+)-ATPase and has been used to treat heart disease for many years. We observed that ouabain, as well as other cardiac glycoside family members--digitoxin and digoxin--down-regulated FANCD2 and FANCI mRNA levels, reduced monoubiquitination of FANCD2, inhibited FANCD2 foci formation on DNA lesions, and abrogated cell cycle arrest induced by MMC treatment. These inhibitory activities of ouabain required p38 MAPK and were independent of cellular Ca(2+) ion increase or the drug uptake-inhibition effect of ouabain. Furthermore, we found that ouabain potentiated the cytotoxic effects of MMC in tumor cells. Taken together, we identified an additional effect of ouabain as a FA/BRCA pathway-inhibiting chemosensitization compound. The results of this study suggest that ouabain may serve as a chemosensitizer to ICL-inducing anticancer drugs.
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PMID:Ouabain, a cardiac glycoside, inhibits the Fanconi anemia/BRCA pathway activated by DNA interstrand cross-linking agents. 2412 20