Digibind Reverses Inhibition of Cellular Rb+ Uptake Caused by Endogenous Sodium Pump Inhibitors Present in Serum and Placenta of Women with Preeclampsia

Hopoate-Sitake, Moana; Adair, Charles; Mason, Lorrie; Torres, Carlos; Kipikasa, Joseph; Graves, Steven W.

doi:10.1177/1933719110385133

Cited by 9 publications

(9 citation statements)

References 47 publications

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“…Previous research by ourselves 27 and others [28][29][30][31][32] had indicated that an SP inhibitor or EDLF exists in placental homogenates, with higher amounts observed in placenta from women having PE. Our initial hypothesis in this study was that the placenta produces such an EDLF.…”

Section: Resultsmentioning

confidence: 99%

“…19 Moreover, recent research also points to EDLFs present in both serum and placenta from women with PE being bound and inactivated by Digibind. 27 Because Digibind recognizes and binds the active EDLF found in PE, we developed an RIA using Digibind as the primary antibody. The assay then measures the same EDLFs endogenous to PE women which it would bind and inactivate as part of Digibind therapy.…”

Section: Endogenous Digitalis-like Factor-specific Immunoassay Employing Digibindmentioning

confidence: 99%

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Increasing Evidence for and Regulation of a Human Placental Endogenous Digitalis-Like Factor

Esplin

Adair

et al. 2012

Reprod. Sci.

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Endogenous digitalis-like factors (EDLFs) appear to be hypertensiogenic and increased in the serum and placenta of women with preeclampsia (PE), a complication of pregnancy. Digibind, an anti-digoxin antibody Fab fragment, reverses in vitro effects of EDLF and in vivo features of PE. We used Digibind in a radioimmunoassay to measure EDLF and compared this to a bio-functional assay of EDLF with good agreement. These methods confirmed that human placenta was a source of EDLF, synthesizing and releasing EDLF into the media of cultured human placental tissue. Ketoconazole, a steroid synthesis inhibitor, and 17-OH progesterone, a possible substrate of steroid synthesis, were shown to inhibit or increase EDLF release respectively, suggesting overlap of synthetic pathways. Abnormalities of PE such as placental hypoxia, increased reactive oxygen species and increased pro-inflammatory cytokines were demonstrated to increase placental EDLF release. These findings strongly support placental production of EDLF with increased release due to features of PE.

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Section: Resultsmentioning

confidence: 99%

Section: Endogenous Digitalis-like Factor-specific Immunoassay Employing Digibindmentioning

confidence: 99%

Increasing Evidence for and Regulation of a Human Placental Endogenous Digitalis-Like Factor

Esplin

Adair

et al. 2012

Reprod. Sci.

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“…Anti-digoxin antibodies interact with a broad range of EDLFs ( 114 ) and have been utilized in both experimental animals and man, with some interesting results ( 87 , 88 , 115 , 116 ). Although the commercial preparation used in most of these studies is no longer available, another commercially available preparation of digoxin antibodies (DigiFab ® ) has similar if not identical cross reactivity with EDLF ( 116 – 118 ). Finally, the ability of individual cardiotonic steroids (CTS) to interfere with the effects of other CTS has added another layer of complexity and suggests another novel approach to the study of and possible therapy of various conditions in which CTS may be involved ( 105 ).…”

Section: Summary In Retrospect and Future Directionsmentioning

confidence: 99%

Endogenous Digitalis-Like Factors: An Overview of the History

Buckalew

2015

Front. Endocrinol.

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The sodium pump is a ubiquitous cell surface enzyme, a Na, K ATPase, which maintains ion gradients between cells and the extracellular fluid (ECF). The extracellular domain of this enzyme contains a highly conserved binding site, a receptor for a plant derived family of compounds, the digitalis glycosides. These compounds inhibit the enzyme and are used in the treatment of congestive heart failure and certain cardiac arrhythmias. The highly conserved nature of this enzyme and its digitalis receptor led to early suggestions that endogenous regulators might exist. Recent examination of this hypothesis emerged from research in two separate areas: the regulation of ECF volume by a natriuretic hormone (NH), and the regulation of peripheral vascular resistance by a circulating inhibitor of vascular Na, K ATPase. These two areas merged with the hypothesis that NH and the vascular Na, K ATPase inhibitor were in fact the same entity, and that it played a causative role in the pathophysiology of certain types of hypertension. The possibility that multiple endogenous digitalis-like factors (EDLFs) exist emerged from efforts to characterize the circulating enzyme inhibitory activity. In this review, the development of this field from its beginnings is traced, the current status of the structure of EDLFs is briefly discussed, and areas for future development are suggested.

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“…Indeed, there is evidence that EDLFs may participate in preeclampsia [8–12]. For that reason we excluded women with preeclampsia from the current study.…”

Section: Commentmentioning

confidence: 99%

Association of cord blood digitalis-like factor and necrotizing enterocolitis

Graves

Esplin

McGee

et al. 2014

American Journal of Obstetrics and Gynecology

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Objective Endogenous digoxin-like factor (EDLF) has been linked to vasoconstriction, altered membrane transport and apoptosis. Our objective was to determine whether increased EDLF in the cord sera of preterm infants was associated with an increased incidence of necrotizing enterocolitis (NEC). Methods Cord sera from pregnant women enrolled in a randomized trial of MgSO4 for fetal neuroprotection were analyzed for EDLF using a red cell Rb+ uptake assay where inhibition of sodium pump-mediated Rb+ transport was used as a functional assay of EDLF. Specimens were assayed blinded to neonatal outcome. Cases (NEC, n=25) and controls (neonates not developing stage 2 or 3 NEC, n=24) were matched by study center and gestational age. None of the women had preeclampsia. Cases and controls were compared using the Wilcoxon test for continuous and the Fisher’s exact test for categorical variables. Conditional logistic regression analysis was used to assess the odds of case versus control by EDLF level. Results Cases and controls were not significantly different for gestational age (GA), race, maternal steroid use, premature rupture of membranes (PPROM) or MgSO4 treatment. In logistic models adjusted for treatment group, race, PPROM and GA, cord sera EDLF was significantly associated with development of NEC (p=0.023). Conclusions These data demonstrated an association between cord sera EDLF and NEC.

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Digibind Reverses Inhibition of Cellular Rb+ Uptake Caused by Endogenous Sodium Pump Inhibitors Present in Serum and Placenta of Women with Preeclampsia

Abstract: These studies evidence EDLF in PE serum. Additionally, PE placentas have high EDLF and may represent a source.

Cited by 9 publications

References 47 publications

Increasing Evidence for and Regulation of a Human Placental Endogenous Digitalis-Like Factor

Increasing Evidence for and Regulation of a Human Placental Endogenous Digitalis-Like Factor

Endogenous Digitalis-Like Factors: An Overview of the History

Association of cord blood digitalis-like factor and necrotizing enterocolitis

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