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Thirty-seven steroid drugs of different types were investigated in silico for their environmental and pharmacokinetic properties (partition between soil and water, bioaccumulation in aquatic organisms, ability to be absorbed from the gastrointestinal tract and to cross biological barriers-skin, blood-brain barrier and placenta) using on-line tools and novel QSAR models. The same drugs were studied by Molecular Docking in the context of their ability to interact with two enzymes-glutathione S-transferase (GST) and human N-acetyltransferase 2 (NAT2), which are involved in the placenta's protective system against harmful xenobiotics. Steroid drugs are released to the environment from households, hospitals, manufacturing plants and farms (e.

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Iron transfer across a functional syncytialized trophoblast monolayer.

Placenta

November 2024

Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland. Electronic address:

Studying iron transfer across trophoblast monolayers is crucial given the significance of iron in maintaining a healthy pregnancy and supporting fetal growth and development. To get insights into the complex mechanism of transplacental iron transfer, we developed a standardized Transwell®-based monolayer model using BeWo (clone b30) cells. Our proposed method is divided into two parts: 1.

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One of the functions of placenta is to protect the fetus against harmful xenobiotics. Protective mechanisms of placenta are based on enzymes, e.g.

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Immunosuppressant drug tacrolimus inhibits HUVEC angiogenesis and production of placental growth factor.

Placenta

January 2025

The Ritchie Centre, Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Clayton, VIC, Australia.

Background: Tacrolimus is a cornerstone of immunosuppression in solid organ transplants, but its use is linked with the development of endothelial dysfunction. Pregnant solid organ transplant recipients are four to six times more likely to develop preeclampsia, which is also associated with endothelial dysfunction. Therefore, this in vitro study investigated the acute effects of tacrolimus on the expression of common angiogenic factors related to preeclampsia, and effects on angiogeneis in primary human tissues.

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Extracellular Vesicles From Preeclampsia Disrupt the Blood-Brain Barrier by Reducing CLDN5.

Arterioscler Thromb Vasc Biol

February 2025

Vascular Physiology Laboratory, Department of Basic Sciences, Universidad del Bío-Bío, Chillán, Chile (H.S., B.I., M.C., F.T., E.E.-G., J.A., C.E.).

Background: The physiopathology of life-threatening cerebrovascular complications in preeclampsia is unknown. We investigated whether disruption of the blood-brain barrier, generated using circulating small extracellular vesicles (sEVs) from women with preeclampsia or placentae cultured under hypoxic conditions, impairs the expression of tight junction proteins, such as CLDN5 (claudin-5), mediated by VEGF (vascular endothelial growth factor), and activation of KDR (VEGFR2 [VEGF receptor 2]).

Methods: We perform a preclinical mechanistic study using sEVs isolated from plasma of pregnant women with normal pregnancy (sEVs-NP; n=9), sEVs isolated from plasma of women with preeclampsia (sEVs-PE; n=9), or sEVs isolated from placentas cultured in normoxia (sEVs-Nor; n=10) or sEVs isolated from placentas cultured in hypoxia (sEVs-Hyp; n=10).

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