Placenta membranes

Absorption Distribution Metabolism Excretion GI tract, lungs, skin Storage in tissues (plasma proteins, liver and kidney, fat, bone), blood-brain barrier, passage across the placenta, membrane permeability Liver, lungs, kidney, brain, phase I, phase II metabolism Urinary, fecal, exhalation, milk, sweat, sahva... 

Mothers of preterm infants were also more likely than mothers of full-term infants to have obstetrical complications at the time of delivery. Eighty percent of mothers of preterm infants had three or more obstetrical complications. Possible complications included premature labor, oremature rupture of membranes, prolonged rupture of membranes, Caesarean section, chorioamnionitis, and marginal placenta abruption. In contrast, only one mother of a full-term infant developed obstetrical complications during the perinatal period. 

Steroid hormones are produced by the adrenal cortex, testes, ovaries, and placenta. Synthesized from cholesterol, these hormones are lipid soluble therefore, they cross cell membranes readily and bind to receptors found intracellularly. However, because their lipid solubility renders them insoluble in blood, these hormones are transported in the blood bound to proteins. Furthermore, steroid hormones are not typically preformed and stored for future use within the endocrine gland. Because they are lipid soluble, they could diffuse out of the cells and physiological regulation of their release would not be possible. Finally, steroid hormones are absorbed easily by the gastrointestinal tract and therefore may be administered orally. 

Campbell, F.M., Gordan, M.J., Taffasse, S. and Dutta-Roy, A.K. (1995) Plasma membrane fatty acid-binding protein from human placenta identification and characterization. Biochemical and Biophysical Research Communications 209, 1011-1017. 

Recently, Prasad et al. cloned a mammalian Na+-dependent multivitamin transporter (SMVT) from rat placenta [305], This transporter is very highly expressed in intestine and transports pantothenate, biotin, and lipoate [305, 306]. Additionally, it has been suggested that there are other specific transport systems for more water-soluble vitamins. Takanaga et al. [307] demonstrated that nicotinic acid is absorbed by two independent active transport mechanisms from small intestine one is a proton cotransporter and the other an anion antiporter. These nicotinic acid related transporters are capable of taking up monocarboxylic acid-like drugs such as valproic acid, salicylic acid, and penicillins [5], Also, more water-soluble transporters were discovered as Huang and Swann [308] reported the possible occurrence of high-affinity riboflavin transporter(s) on the microvillous membrane. 

Within the OAT family, OAT4 is the only transporter expressed at appreciable levels in both the placenta and in the kidney [54]. The membrane localization of OAT4 within these tissues has not been examined. Steroid sulfates, and ochratoxinA are efficient transport substrates of OAT4, whereas PAH is weakly transported [54]. The functional importance of OAT4 in regulating placental permeability and renal drug elimination is currently unknown. 

Mesobilirubin-XIIIa labelled with 13C in two propionic acid 13COOH groups, 90, has been synthesized75 in 11% overall yield from K13CN in 10 steps shown in equation 34. 90, a model compound not found in nature, is to be used to study the conformation of bilirubin in solution76 or when bound to proteins or in membranes to understand its ability to cross several selective physiological barriers such as placenta and blood-brain barrier... 

Kim et al. (67) P. placenta Polyclonal antiserum was produced to P. placenta extracellular metabolites red spruce and birch were degraded by P. placenta using the soil-block procedure degraded wood-block samples were prepared for TEM and the immunoelectron localization of wood-degrading enzymes Extracellular membrane structures (matrix) were observed surrounding hyphae, which degraded spruce and birch wood the matrix labeled positively with antisera produced to P. placenta extracellular metabolites... 

Mercuric salts weakly penetrate the placenta barrier however, they can accumulate in placenta [26-29], foetal membranes and amniotic fluid [30], In mice, mercuric chloride (1.5 mg per kg) injected on day 14 of gestation resulted in 0.14% of the injected mercury being transferred to foetal tissues 4 days later [27],... 

The biogenic amines are the preferred substrates of MAO. The enzyme comes in two flavors, MAO-A and MAO-B, both of which, like FMO, rely on the redox properties of FAD for their oxidative machinery. The two isoforms share a sequence homology of approximately 70% (81) and are found in the outer mitochondrial membrane, but they differ in substrate selectivity and tissue distribution. In mammalian tissues MAO-A is located primarily in the placenta, gut, and liver, while MAO-B is predominant in the brain, liver, and platelets. MAO-A is selective for serotonin and norepinephrine and is selectively inhibited by the mechanism-based inhibitor clorgyline (82). MAO-B is selective for /1-phcncthylaminc and tryptamine, and it is selectively inhibited by the mechanism-based inhibitors, deprenyl and pargyline (82) (Fig. 4.32). Recently, both MAO-A (83) and MAO-B (84) were structurally characterized by x-ray crystallography. 

However, only the extracellular domains immediately adjacent to the cell membrane and the (32 microglobulin peptide have clear homology with the immunoglobulin domains. The al and ct2 segments of class I and the al and (31 domains in class II have quite an unusual structure. Class I molecules are present on virtually every cell in the body, the most notable exception being the syncytial trophoblast of the placenta. Class II expression is far more restricted B cells, dendritic cells which present antigen to T cells, and macrophage express abundant class II molecule on their surfaces. However, most other tissues can be induced to express class II molecules under the influence of soluble mediators such as 7-interferon. 

In the last decade, several investigations were performed with regard to in vitro reconstruction of corneal epithelium for transplantation. Meanwhile, many studies have also been reported, dealing with the cultivation and transplantation of corneal epithelium grown on amniotic membranes (i.e., the innermost membrane of the placenta), fibrin gels, or temperature-responsive culture dishes [83-85], However, none of these models has been examined for suitability as a model for drug absorption studies. 

Primarily to elucidate transporter localization and function, vesicles enriched in trophoblast apical or basolateral membranes have frequently been utilized. To give a few instances, they have been used to investigate P-gp-mediated transport, mechanisms of transport of cationic compounds, drug interactions with nutrient transport, and differences in amino acid transport in pathological conditions of the placenta [36, 40-42], Briefly, for preparation of microvillus membrane vesicles the cord, amniochorion and decidua are removed from placenta, and the tissue cut on the maternal side. The mince is stirred to loosen... 

It needs to be mentioned here that there remains some controversy over the placental expression of P-gp as a function of gestational age. An immunohis-tochemical study done by Macfarland et al. showed that P-gp was localized to the microvillous border of trophoblasts in first trimester placenta, but not in term placenta [85], Subsequent studies refuted this to show that MDR1 mRNA is present throughout pregnancy [94], More recently, enzyme-linked immunosorbent assay (ELISA) performed in syncytial microvillous membrane showed that P-gp protein expression in early gestational age placenta is about... 

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