Transfer of Heparin Across the Human Perfused Placental Lobule

Bajoria, Rekha; Contractor, S.F.

doi:10.1111/j.2042-7158.1992.tb07073.x

Cited by 26 publications

(7 citation statements)

References 45 publications

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“…This was attributed to its high polarity and hydrophilicity and not to its molecular size because drugs with similar molecular weights cross the placenta freely (Reynolds & Knott 1989). Similarly, many investigators have shown that the rate of transfer of polar molecules such as chlorazepate and cimetidine depend upon their hydrophilicity rather than on their molecular weight, and occurs through the hypothetical water-filled pores of the membrane (Illsley et a1 1985;Ching et a1 1987;Bajoria & Contractor 1992).…”

Section: Discussionmentioning

confidence: 99%

“…The dual closed-circuit perfusion of isolated lobules of human term placenta was established with placentae obtained after vaginal or caesarean deliveries after 37 weeks of gestation. The perfusion of the isolated lobule was commenced within 10-15 rnin at 37°C under optimum physiological conditions of oxygenation, pressure, flow, osmotic pressure and pH (Bajoria & Contractor 1992). Closed-circuit perfusion of the foetalplacental circulations was established by cannulating the chorionic artery and vein with a perfusion pressure of 40-50 mmHg and a venous outflow of 6-9 mL min-I.…”

Section: Placental Perjksion Techniquementioning

confidence: 99%

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Effect of the Size of Liposomes on the Transfer and Uptake of Carboxyfluorescein by the Perfused Human Term Placenta

Bajoria

Contractor

1997

Journal of Pharmacy and Pharmacology

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The effect of the size of liposomes on the uptake and transfer of the low molecular-weight, hydrophilic and polar molecule carboxyfluorescein has been determined across the perfused human term placenta. Carboxyfluorescein-encapsulated neutral liposomes of three different sizes were prepared from equimolar concentrations of lecithin and cholesterol. Size distribution, encapsulation efficiency and stability of liposomes in blood-based media were determined. The concentration of carboxyfluorescein was measured spectrophotometrically. The transplacental transfer and placental uptake of free carboxyfluorescein (control data) were respectively 1.9 +/- 0.2 and 5.0 +/- 0.7% of initial dose. The placental uptake and foetal concentration of carboxyfluorescein were significantly increased by small liposomes (P < 0.05), and reduced by large (0.82 +/- 0.13%; P < 0.05) and multilamellar liposomes (0.32 +/- 0.11%). There was a negative correlation between liposome size and transplacental transfer (y = -0.53 + 0.9x; r = 0.96; P < 0.001; n = 24) and placental uptake of carboxyfluorescein (y = -5.9 + 6.5x; r = 0.84; P < 0.001; n = 24). The study indicates that placental uptake and transfer rate of liposomal carboxyfluorescein were dependant upon the size of liposomes.

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Section: Discussionmentioning

confidence: 99%

Section: Placental Perjksion Techniquementioning

confidence: 99%

Effect of the Size of Liposomes on the Transfer and Uptake of Carboxyfluorescein by the Perfused Human Term Placenta

Bajoria

Contractor

1997

Journal of Pharmacy and Pharmacology

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“…With a therapeutic application of rhEPO for the treatment of chronic anemia of the mother during pregnancy an effect on fetal tissues seems unlikely. Specific binding sites for EPO to the syncytiotrophoblast of the placenta [5] ** BAJORIA and CONTRACTOR [2] *** MALEK et al: [14] J. Perinat. Med.…”

Section: Resultsmentioning

confidence: 99%

Lack of permeability of the human placenta for erythropoietin

Schneider¹,

Malek²

1995

Jpme

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Measurements of erythropoietin in fetal blood obtained by cordocentesis or in umbilical cordblood and maternal blood have shown a lack of correlation indicating an independent regulation of EPO concentration in fetal and maternal compartments. There is a good correlation between amniotic fluid EPO concentration in fetal blood levels. Fetal EPO concentration therefore might serve as an indicator of chronic fetal hypoxia with fetal EPO production being responsive to tissue hypoxia early on in pregnancy. The lack of human placental permeability for EPO was further investigated using a dual in vitro perfusion system of an isolated cotyledon in freshly delivered term placentae. With recirculation of both circuits trace amounts of EPO (0.04% of the amount added to the maternal compartment) were transferred to the fetal side during 4-5 hours of perfusion. This transfer is comparable to the rate determined in the same experiments for albumine, and the biological significance of this very slow transfer is questionable. A very low rate of diffusion across the human placenta has also been shown for dextran, horseradish peroxidase and heparin using an in vitro perfusion system. The only exception among macromolecules are immunoglobulines G, which towards the end of pregnancy are transferred by an Fc-receptor mediated transcellular mechanism from the mother to the fetus. It is concluded, that there is no easy exchange of EPO across the human placenta between maternal and fetal compartments. Changes in EPO concentration in the fetal compartment therefore could serve as indicator of fetal hypoxia. A therapeutic application of EPO in the mother for the treatment of chronic anemia would not have any effect on fetal tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Erythropoietin was measured using the Human Erythropoietin Quantikine IVD ELISA Kit (R&D Systems, Minneapolis, USA) according to the supplier's instructions. Permeability of antipyrine and creatinine was calculated according to the equation P = C fet /(weight cot ×[AUC mat −AUC fet ]) with C fet to be the concentration in the fetal circuit at the end of perfusion, AUC mat the area under the concentration-time curve (AUC) in the maternal circuit, AUC fet the AUC in the fetal circuit, and weight cot the wet weight of the cotyledon [37]. The hCG release was calculated as described [38].…”

Section: Methodsmentioning

confidence: 99%

Antibody-Dependent Transplacental Transfer of Malaria Blood-Stage Antigen Using a Human Ex Vivo Placental Perfusion Model

et al. 2009

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Prenatal exposure to allergens or antigens released by infections during pregnancy can stimulate an immune response or induce immunoregulatory networks in the fetus affecting susceptibility to infection and disease later in life. How antigen crosses from the maternal to fetal environment is poorly understood. One hypothesis is that transplacental antigen transfer occurs as immune complexes, via receptor-mediated transport across the syncytiotrophoblastic membrane and endothelium of vessels in fetal villi. This hypothesis has never been directly tested. Here we studied Plasmodium falciparum merozoite surface protein 1 (MSP1) that is released upon erythrocyte invasion. We found MSP1 in cord blood from a third of newborns of malaria-infected women and in >90% following treatment with acid dissociation demonstrating MSP1 immune complexes. Using an ex vivo human placental model that dually perfuses a placental cotyledon with independent maternal and fetal circuits, immune-complexed MSP1 transferred from maternal to fetal circulation. MSP1 alone or with non-immune plasma did not transfer; pre-incubation with human plasma containing anti-MSP1 was required. MSP1 bound to IgG was detected in the fetal perfusate. Laser scanning confocal microscopy demonstrated MSP1 in the fetal villous stroma, predominantly in fetal endothelial cells. MSP1 co-localized with IgG in endothelial cells, but not with placental macrophages. Thus we show, for the first time, antibody-dependent transplacental transfer of an antigen in the form of immune complexes. These studies imply frequent exposure of the fetus to certain antigens with implications for management of maternal infections during pregnancy and novel approaches to deliver vaccines or drugs to the fetus.

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Transfer of Heparin Across the Human Perfused Placental Lobule

Cited by 26 publications

References 45 publications

Effect of the Size of Liposomes on the Transfer and Uptake of Carboxyfluorescein by the Perfused Human Term Placenta

Effect of the Size of Liposomes on the Transfer and Uptake of Carboxyfluorescein by the Perfused Human Term Placenta

Lack of permeability of the human placenta for erythropoietin

Antibody-Dependent Transplacental Transfer of Malaria Blood-Stage Antigen Using a Human Ex Vivo Placental Perfusion Model

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