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1

Picollo, Camila T., Alexandra A. dos Santos, Ednei L. Antonio, et al. "Digitoxin Attenuates Heart Failure, Reduces Myocardial Hypertrophy, and Preserves the Calcium-Binding Proteins in Infarcted Rats." Journal of Cardiovascular Pharmacology and Therapeutics 25, no. 3 (2019): 265–72. http://dx.doi.org/10.1177/1074248419887708.

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Abstract (sommario):
We previously showed that digitoxin prolongs the survival of rats with heart failure due to myocardial infarction (MI). In this study, we evaluated the effect of digitoxin on myocardial structure, ventricular function, and proteins involved in calcium kinetics. Seventy-two rats with MI >35% of the left ventricle were randomly assigned to 4 treatment groups: sham (n = 15), digitoxin (n = 11), infarction (n = 20), and infarction + digitoxin (n = 26). The rats were assessed 120 days after surgery by echocardiogram, hemodynamics, papillary muscle mechanics, collagen content, cardiomyocyte nucle
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2

Drakenberg, Torbjörn, Peter Brodelius, Deane D. McIntyre, and Hans J. Vogel. "Structural studies of digitoxin and related cardenolides by two-dimensional NMR." Canadian Journal of Chemistry 68, no. 2 (1990): 272–77. http://dx.doi.org/10.1139/v90-037.

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Abstract (sommario):
The 1H and 13C NMR spectra of the cardenolides digitoxigenin, digoxigenin, digitoxin, and mono- and bis-digitoxigenin digitoxosides have been completely assigned by two-dimensional NMR spectroscopy. The techniques used include phase-sensitive COSY, multiple relay COSY, and carbon–proton correlation (HETCOR and HMQC) spectra. Various aspects of the solution conformation of the steroid moiety of digitoxin and digoxigenin could be determined from coupling constants and NOE difference experiments and they are indicative of an all-chair conformation. The carbohydrate rings in digitoxin and the mono
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3

Mukhopadhyay, Rupkatha, Rajkumar Venkatadri, Jenny Katsnelson та Ravit Arav-Boger. "Digitoxin Suppresses Human Cytomegalovirus Replication via Na+, K+/ATPase α1 Subunit-Dependent AMP-Activated Protein Kinase and Autophagy Activation". Journal of Virology 92, № 6 (2018): e01861-17. http://dx.doi.org/10.1128/jvi.01861-17.

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ABSTRACT Host-directed therapeutics for human cytomegalovirus (HCMV) requires elucidation of cellular mechanisms that inhibit HCMV. We report a novel pathway used by cardiac glycosides to inhibit HCMV replication: induction of AMP-activated protein kinase (AMPK) activity and autophagy flux through the Na+,K+/ATPase α1 subunit. Our data illustrate an intricate balance between the autophagy regulators AMPK, mammalian target of rapamycin (mTOR), and ULK1 during infection and treatment with the cardiac glycoside digitoxin. Both infection and digitoxin induced AMPK phosphorylation, but ULK1 was dif
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4

Kragh-Hansen, U. "Relations between high-affinity binding sites of markers for binding regions on human serum albumin." Biochemical Journal 225, no. 3 (1985): 629–38. http://dx.doi.org/10.1042/bj2250629.

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Abstract (sommario):
Binding of warfarin, digitoxin, diazepam, salicylate and Phenol Red, individually or in different pair combinations, to defatted human serum albumin at ligand/protein molar ratios less than 1:1 was studied at pH 7.0. The binding was determined by ultrafiltration. Some of the experiments were repeated with the use of equilibrium dialysis in order to strengthen the results. Irrespective of the method used, all ligands bind to one high-affinity binding site with an association constant in the range 10(4)-10(6) M-1. High-affinity binding of the following pair of ligands took place independently: w
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5

&NA;. "Digitoxin." Reactions Weekly &NA;, no. 1011 (2004): 7. http://dx.doi.org/10.2165/00128415-200410110-00013.

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6

&NA;. "Digitoxin." Reactions Weekly &NA;, no. 1279 (2009): 18. http://dx.doi.org/10.2165/00128415-200912790-00048.

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7

&NA;. "Digitoxin." Reactions Weekly &NA;, no. 801 (2000): 8. http://dx.doi.org/10.2165/00128415-200008010-00020.

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8

Petersen, Maike, Hanns Ulrich Seitz та Ernst Reinhard. "Characterization and Localization of Digitoxin 12 β-Hydroxylase from Cell Cultures of Digitalis lanata EHRH". Zeitschrift für Naturforschung C 43, № 3-4 (1988): 199–206. http://dx.doi.org/10.1515/znc-1988-3-409.

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Abstract (sommario):
The cytochrome P-450-dependent monooxygenase digitoxin 12β-hydroxylase from cell cultures of Digitalis lanata needs NADPH and molecular oxygen and hydroxylates cardiac glycosides with the aglycon of digitoxigenin to the corresponding derivatives of the C-series. Other electron donors cannot replace NADPH. The apparent Km-values are 26 μᴍ for NADPH, 7.1 μᴍ for β-methyldigitoxin and 10 μᴍ for digitoxin. The reaction is inhibited by NADP+ and cytochrome c in a competitive mode. The optimum temperature was at 20 °C. Low concentrations of Mn2+, Mg2+, and EDTA were slightly stimulatory, but there wa
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9

Fardin, Núbia Mantovan, Ednei Luiz Antonio, Jairo Augusto Silva Montemor, Glaucia Luciano da Veiga, Paulo José Ferreira Tucci, and Ruy R. Campos. "Digitoxin improves cardiovascular autonomic control in rats with heart failure." Canadian Journal of Physiology and Pharmacology 94, no. 6 (2016): 643–50. http://dx.doi.org/10.1139/cjpp-2015-0354.

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Abstract (sommario):
The effects of chronic treatment with digitoxin on arterial baroreceptor sensitivity for heart rate (HR) and renal sympathetic nerve activity (rSNA) control, cardiopulmonary reflex, and autonomic HR control in an animal model of heart failure (HF) were evaluated. Wistar rats were treated with digitoxin, which was administered in their daily feed (1 mg/kg per day) for 60 days. The following 3 experimental groups were evaluated: sham, HF, and HF treated with digitoxin (HF + DIG). We observed an increase in rSNA in the HF group (190 ± 29 pps, n = 5) compared with the sham group (98 ± 14 pps, n =
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10

Bonfill, Mercedes, Javier Palazón, Rosa M. Cusidó, M. Teresa Piñol, and Carmen Morales. "Effect of auxin and phenobarbital on the ultrastructure and digitoxin content in Digitalis purpurea tissue culture." Canadian Journal of Botany 74, no. 3 (1996): 378–82. http://dx.doi.org/10.1139/b96-047.

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Abstract (sommario):
Callus derived from Digitalis purpurea hypocotils were grown during a 6-week period on solid Murashige–Skoog medium supplemented with 1 mg/L 6-benzylaminopurine, 0.01 mg/L gibberellic acid and 0.1 mg/L indole-3-acetic acid or α-naphthaleneacetic acid, with or without phenobarbital (40 mg/L). The presence of phenobarbital in the culture medium caused a reduction of the vacuole/cytoplasm ratio. At the same time, the chloroplastic volume fraction decreased in callus tissue cells grown in media supplemented with phenobarbital, while the mitochondrial volume ratio increased. Digitoxin content was e
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11

&NA;. "Digitoxin overdose." Reactions Weekly &NA;, no. 443 (1993): 8. http://dx.doi.org/10.2165/00128415-199304430-00028.

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12

&NA;. "Digitoxin poisoning." Reactions Weekly &NA;, no. 308 (1990): 7. http://dx.doi.org/10.2165/00128415-199003080-00026.

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13

&NA;. "Digitoxin overdose." Reactions Weekly &NA;, no. 365 (1991): 6. http://dx.doi.org/10.2165/00128415-199103650-00026.

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14

&NA;. "Digitoxin overdose." Reactions Weekly &NA;, no. 487 (1994): 6. http://dx.doi.org/10.2165/00128415-199404870-00023.

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15

&NA;. "Digitoxin overdose." Reactions Weekly &NA;, no. 495 (1994): 6. http://dx.doi.org/10.2165/00128415-199404950-00024.

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16

&NA;. "Digitoxin interaction." Reactions Weekly &NA;, no. 656 (1997): 8. http://dx.doi.org/10.2165/00128415-199706560-00022.

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17

&NA;. "Digitoxin interaction." Reactions Weekly &NA;, no. 666 (1997): 7–8. http://dx.doi.org/10.2165/00128415-199706660-00018.

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18

&NA;. "Digitoxin overdose." Reactions Weekly &NA;, no. 1368 (2011): 16. http://dx.doi.org/10.2165/00128415-201113680-00059.

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19

&NA;. "Digitoxin overdose." Reactions Weekly &NA;, no. 396 (1992): 6. http://dx.doi.org/10.2165/00128415-199203960-00016.

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20

Petersen, M., та H. U. Seitz. "Reconstitution of cytochrome P-450-dependent digitoxin 12β-hydroxylase from cell cultures of foxglove (Digitalis lanata EHRH.)". Biochemical Journal 252, № 2 (1988): 537–43. http://dx.doi.org/10.1042/bj2520537.

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Abstract (sommario):
Cytochrome P-450-dependent digitoxin 12 beta-hydroxylase from cell cultures of foxglove (Digitalis lanata) was solubilized from microsomal membranes with CHAPS (3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulphonic acid). Cytochrome P-450 was separated from NADPH: cytochrome c (P-450) reductase by ion-exchange chromatography on DEAE-Sephacel. NADPH:cytochrome c (P-450) reductase was further purified by affinity chromatography on 2′,5′-ADP-Sepharose 4B. This procedure resulted in a 248-fold purification of the enzyme; on SDS/polyacrylamide-gel electrophoresis after silver staining, only one
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21

Yamamoto, S., G. R. Askew, J. Heiny, H. Masaki, and A. Yatani. "Modulation of pump function by mutations in the first transmembrane region of Na(+)-K(+)-ATPase alpha 1-subunit." American Journal of Physiology-Cell Physiology 270, no. 2 (1996): C457—C464. http://dx.doi.org/10.1152/ajpcell.1996.270.2.c457.

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Abstract (sommario):
The Cys in the first transmembrane region of the Na(+)-K(+)-adenosinetriphosphatase (ATPase) alpha 1-subunit has been shown to be a critical determinant of cardiac glycoside binding. To study the role of this Cys on ion transport activity, we measured pump currents in HeLa cells expressing wild-type or mutant alpha 1-subunit cDNAs. The endogenous ouabainsensitive Na(+)-K(+)-ATPase was selectively inhibited by growing the cells in 0.1 microM ouabain. A Cys-to-Tyr substituted mutant exhibited decreased sensitivity to digitoxin but not digoxin compared with wild type. The decreased affinity for d
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22

Stenzel, R., and B. Reckmann. "Cross-Reactivity of Anti-Digoxin Antibodies with Digitoxin Depends on Tracer Structure." Clinical Chemistry 38, no. 11 (1992): 2228–32. http://dx.doi.org/10.1093/clinchem/38.11.2228.

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Abstract (sommario):
Abstract The most common methods for measuring digoxin concentrations in serum are immunoassays. The prerequisite for exact determination of the digoxin value is an antibody that specifically binds digoxin. Because digitoxin differs from digoxin only in the C-12 hydroxy group, it is difficult to obtain anti-digoxin antibodies that do not cross-react with this compound. During the development of a fluorescence polarization immunoassay (FPIA) for digoxin, we investigated digoxin tracers with different structures. We found that in FPIA the digitoxin cross-reactivity of an antibody could be reduce
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23

Datta, P., E. Sunshine, G. Caldwell, S. Morehouse, J. Peterson, and A. Dasgupta. "107 Interference of digitoxin-like immunoreactive factors in digitoxin immunoassays." Therapeutic Drug Monitoring 19, no. 5 (1997): 574. http://dx.doi.org/10.1097/00007691-199710000-00118.

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24

Zeng, Jing, Guangfei Sun, Ruobin Wang, et al. "Gold-catalyzed diversified synthesis of 3-aminosugar analogues of digitoxin and digoxin." Organic Chemistry Frontiers 4, no. 12 (2017): 2450–54. http://dx.doi.org/10.1039/c7qo00648a.

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25

Chou, Jou-Chun, Jie-Hau Li, Chih-Chieh Chen, Chien-Wei Chen, Ho Lin, and Paulus S. Wang. "Inhibitory Effects of Digoxin and Digitoxin on Cell Growth in Human Ovarian Cancer Cell Line SKOV-3." Integrative Cancer Therapies 20 (January 2021): 153473542110026. http://dx.doi.org/10.1177/15347354211002662.

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Abstract (sommario):
Background: Cardiac glycosides (CGs) possess a chemical structure similar to steroids, and are inhibitors of the sodium potassium pump. An anti-tumor effect of CGs in breast and prostate cancers has been reported, but the effect of CGs on ovarian cancer is still unclear. Aims: In this study, the effects of CGs on proliferation, cytotoxicity and cell cycle of ovarian cancer cell line (SKOV-3) have been investigated. Procedure: The cell proliferation and cytotoxicity were detected by MTT assay and LDH activity assay, respectively. CGs, at concentrations higher than IC50, decreased cell prolifera
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26

Dasgupta, Amitava, Anita E. Vega, Alice Wells, and Pradip Datta. "Sensitive Methods for Determination of Free Digitoxin Concentration Using Digitoxin Immunoassays: Demonstration of Elevated Free Digitoxin Concentration Caused by Digitoxin–Phenytoin Interaction by Applying These New Techniques." Therapeutic Drug Monitoring 21, no. 6 (1999): 625. http://dx.doi.org/10.1097/00007691-199912000-00008.

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27

Schneider, A. W., H. J. Gilfrich, and L. Fechler. "Thrombozytopenie bei Digitoxin-Intoxikation." DMW - Deutsche Medizinische Wochenschrift 117, no. 09 (2008): 337–40. http://dx.doi.org/10.1055/s-2008-1062317.

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28

Maier, Ch, and K. D. Kolenda. "Digitoxin bei hepatorenaler Insuffizienz." DMW - Deutsche Medizinische Wochenschrift 108, no. 39 (2008): 1475–80. http://dx.doi.org/10.1055/s-2008-1069770.

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29

Fu, Yu Wan, Hua Sun, Yan Jun Shen, Xi Chen, and Min Wang. "Biotransformation of Digitoxin by Aspergillus Ochraceus." Advanced Materials Research 343-344 (September 2011): 1281–84. http://dx.doi.org/10.4028/www.scientific.net/amr.343-344.1281.

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Abstract (sommario):
Biotransformations of natural products have great potential for preparation of lead compounds. In this paper, the biotransformation of digitoxin (1) with Aspergillus ochraceus afforded two products, identified as digitoxigenin (2) and sarmentogenin (3) by HR-MS, 1H-NMR and 13C-NMR.
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30

&NA;. "Digitoxin: overdosing in the elderly." Reactions Weekly &NA;, no. 883 (2002): 7. http://dx.doi.org/10.2165/00128415-200208830-00007.

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31

Wang, Hua-Yu Leo, Wenjun Xin, Maoquan Zhou, Todd A. Stueckle, Yon Rojanasakul, and George A. O'Doherty. "Stereochemical Survey of Digitoxin Monosaccharides." ACS Medicinal Chemistry Letters 2, no. 1 (2010): 73–78. http://dx.doi.org/10.1021/ml100219d.

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32

Ochs, H., and G. Bodem. "Arzneimittelinteraktion zwischen Digitoxin und Chinidin?" DMW - Deutsche Medizinische Wochenschrift 107, no. 17 (2009): 673–74. http://dx.doi.org/10.1055/s-0029-1236743.

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33

Middeke, M., C. Remien, G. Lohmöller, H. Holzgreve, and N. Zöllner. "Interaction between tamoxifen and digitoxin?" Klinische Wochenschrift 64, no. 22 (1986): 1211. http://dx.doi.org/10.1007/bf01728465.

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34

Deluca, Mónica E., Alicia M. Seldes та Eduardo G. Gros. "The 14β-Hydroxylation in the Biosynthesis of Cardenolides in Digitalis purpurea. The Role of 3β-Hydroxy-5β-pregn-8(14)-en-20-one". Zeitschrift für Naturforschung C 42, № 1-2 (1987): 77–78. http://dx.doi.org/10.1515/znc-1987-1-213.

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Abstract (sommario):
Abstract Labelled 3β-hydroxy-5β-pregnan-20-one was incorporated by Digitalis purpurea plants into digitoxin while 3β-hydroxy-5β-pregn-8(14)-en-20-one was not. This result excluded the intermediary role of the latter compound as precursor of cardenolides in the mentioned plant.
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35

Datta, Pradip, and Amitava Dasgupta. "Interference From Digitoxin-like Immunoreactive Factors Reduced in a New Monoclonal Chemiluminescent Digitoxin Assay." Therapeutic Drug Monitoring 20, no. 6 (1998): 663–68. http://dx.doi.org/10.1097/00007691-199812000-00014.

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36

Baryal, Kedar N., Surya Adhikari та Jianglong Zhu. "Catalytic Stereoselective Synthesis of β-Digitoxosides: Direct Synthesis of Digitoxin and C1′-epi-Digitoxin". Journal of Organic Chemistry 78, № 24 (2013): 12469–76. http://dx.doi.org/10.1021/jo4021419.

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37

Cai, Hongyi, Hua-Yu L. Wang, Rajkumar Venkatadri, et al. "Digitoxin Analogues with Improved Anticytomegalovirus Activity." ACS Medicinal Chemistry Letters 5, no. 4 (2014): 395–99. http://dx.doi.org/10.1021/ml400529q.

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38

Deluca, Mónica E., Alicia M. Seldes, and Eduardo G. Gros. "Biosynthesis of digitoxin in Digitalis purpurea." Phytochemistry 28, no. 1 (1989): 109–11. http://dx.doi.org/10.1016/0031-9422(89)85019-8.

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39

Baryal, Kedar N., Surya Adhikari та Jianglong Zhu. "ChemInform Abstract: Catalytic Stereoselective Synthesis of β-Digitoxosides: Direct Synthesis of Digitoxin and C1′-epi-Digitoxin." ChemInform 45, № 10 (2014): no. http://dx.doi.org/10.1002/chin.201410212.

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40

Cha, Kyungman, Byung Hak So, and Won Jung Jeong. "Bufotoxin poisoning that showed the sign of acute digitalis overdose in the patient of Kyushin® intoxication." Hong Kong Journal of Emergency Medicine 27, no. 3 (2018): 180–84. http://dx.doi.org/10.1177/1024907918807526.

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Abstract (sommario):
Introduction: Kyushin® is a widely used herbal medicine in East Asia for heart failure. Toad venom in present in Kyushin®, which has positive inotropic effect as digitoxin. Case presentation: An 81-year-old, female patient presented with decreased mental status after overdose of Kyushin®. The first electrocardiogram showed junctional tachycardia with 142/min, suddenly dropped to 27/min and followed by ventricular fibrillation. After one cycle of CPR, spontaneous circulation returned but junctional bradycardia, tachycardia, and ventricular fibrillation appeared. After six times of defibrillatio
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41

Thong, B., S. J. Soldin, and C. A. Lingwood. "Lack of specificity of current anti-digoxin antibodies, and preparation of a new, specific polyclonal antibody that recognizes the carbohydrate moiety of digoxin." Clinical Chemistry 31, no. 10 (1985): 1625–31. http://dx.doi.org/10.1093/clinchem/31.10.1625.

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Abstract (sommario):
Abstract Current immunoassays for digoxin do not distinguish digoxin from its glycosidic metabolites. We have synthesized a novel digoxin/bovine serum albumin conjugate via reductive ozonolysis of the lactone ring such that the carbohydrate moiety of digoxin remains intact. Antibodies raised against this conjugate show minimal cross reactivity to digoxigenin, bisdigitoxide, monodigitoxide, digoxigenin, and digitoxin. With this antibody, digoxin can be measured in the presence of these metabolites.
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42

Datta, P., L. Xu, S. Malik, et al. "Effect of antibody specificity on results of selected digoxin immunoassays among various clinical groups." Clinical Chemistry 42, no. 3 (1996): 373–79. http://dx.doi.org/10.1093/clinchem/42.3.373.

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Abstract (sommario):
Abstract We examined the specificity of three automated digoxin immunoassays (Abbott TDxFLx Digoxin II assay, Baxter-Dade Stratus II Digoxin assay, and Ciba Corning ACS Digoxin assay) applied without modification to (a) sera from 229 digoxin-free patients in 12 cohorts associated with nonspecific or endogenous digoxin-like immunoreactive factor (DLIF) interference, and (b) drug-free serum supplemented with the major metabolites and analogs of digoxin. We observed three patterns of apparent digoxin results among the DLIF samples: one common to kidney and liver failure patients, where TDx and St
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43

Hintsche, Rainer, and Rudolf Megges. "Konformation der Digitoxosereste des Digitoxins in Lösung." Zeitschrift für Chemie 26, no. 12 (2010): 439–41. http://dx.doi.org/10.1002/zfch.19860261210.

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44

MØLSTAD, P., and M. ABDELNOOR. "Digitoxin-associated mortality in acute myocardial infarction." European Heart Journal 12, no. 1 (1991): 65–69. http://dx.doi.org/10.1093/oxfordjournals.eurheartj.a059827.

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45

Storstein, Liv, and Marit Johnsgård. "STUDIES ON DIGITALIS 15. BIOAVAILABILITY OF DIGITOXIN." Acta Medica Scandinavica 209, S645 (2009): 91–95. http://dx.doi.org/10.1111/j.0954-6820.1981.tb02606.x.

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46

Lohman, Joseph J. H. M., Piet M. Hooymans, Marli L. P. Koten, Maurice T. J. M. Verhey, and Frans W. H. M. Merkus. "Effect of heparin on digitoxin protein binding." Clinical Pharmacology and Therapeutics 37, no. 1 (1985): 55–60. http://dx.doi.org/10.1038/clpt.1985.11.

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47

Kuhlmann, J., and J. Pabst. "Eiweißbindung und Hydroxylierungsrate von Digitoxin bei Niereninsuffizienz." DMW - Deutsche Medizinische Wochenschrift 107, no. 41 (2008): 1551–55. http://dx.doi.org/10.1055/s-2008-1070164.

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48

Peters, U., T. Risler, B. Grabensee, U. Falkenstein, and J. Kroukou. "Interaktion von Chinidin und Digitoxin beim Menschen*." DMW - Deutsche Medizinische Wochenschrift 105, no. 13 (2008): 438–42. http://dx.doi.org/10.1055/s-2008-1070683.

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49

L�er, S., H. Scholz, I. Buschmann, M. Thoenes, and T. Meinertz. "Digitoxin intoxication during concomitant use of amiodarone." European Journal of Clinical Pharmacology 54, no. 1 (1998): 95–96. http://dx.doi.org/10.1007/s002280050427.

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50

Brock, Axel. "Binding of Digitoxin to Human Serum Proteins: Influence of pH on the Binding of Digitoxin to Human Albumin." Acta Pharmacologica et Toxicologica 36, no. 1 (2009): 13–24. http://dx.doi.org/10.1111/j.1600-0773.1975.tb00767.x.

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