Placenta barrier

HCH also penetrates the placenta barrier [A96, A101]. Complications during pregnancy occurred 1.5 times more frequently in the 213 women whose blood contained HCH than in the 89 women with no signs of this insecticide (78.3% and 58.4% respectively). It is especially significant that twice as many women with HCH in their blood spontaneously miscarried during the first trimester as those without HCH (7.5% and 3.4% respectively). Causal factors included disruptions in prenatal fetal development, and disruptions in women s hormonal systems under the effect of HCH [A96]. Postpartum complications in women who had HCH in their blood were 2.5... 

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],... 

Distribution, including accumulation of an absorbed substance, will be the same irrespective of the route of administration. However, distribution and accumulation at the site of apphcation (inhalation, oral, dermal) may depend on the route of administration. In such cases, local accumulation may occur and may be responsible for tissue damage. In these cases, systemic toxicokinetics of the substance may be of limited relevance for the risk assessment. It is generally not cmcial for risk assessment to determine the precise tissue distribution profile for a substance. In certain special cases, however, specific tissue distribution studies may assist or even be essential for the interpretation of available toxicological data. For example, it may be of interest to know whether the substance will cross the blood-brain barrier, the placenta barrier, or will accumulate in specific tissues. 

Vancomycin can cause red-man syndrome consisting of diffuse flushing, presumably mediated by histamine-release. This problem can be prevented by limiting the infusion rate. The most serious adverse reactions are ototoxicity and nephrotoxicity. The toxicity for both organ systems is potentiated by aminoglycosides. Vancomycin will cross the placenta barrier and has the potential to cause fetal ototoxicity. 

The second set of parameters are compound specific and will determine its transport over barriers (e.g., between gut and blood, blood and tissues), its biotransformation, and its excretion. Most of the transport parameters can be described as partition coefficients [20] and are strongly determined by the compound s physicochemical parameters, lipophilicity and volatility being the most important ones. However, the role of transporter proteins present in cellular membranes and responsible for the partitioning over specific barriers needs special attention, e.g., in the gut, the kidney, and at the blood-brain barrier [22], the blood placenta barrier, and the liver-bile interface [23]. 

Given the role of specific transporters for which prediction models are not (yet) available, the measurement of partitioning is necessary in many cases. For a number of situations systems are available to measure transport. One well-defined model for estimating the parameters for oral uptake is the Caco-2 cell system [30, 31]. Other systems exist for the blood-brain barrier [32] and the blood-placenta barrier [33]. 

P-glycoprotein (P-gp, Table 8.2) plays an important role in determining drug distribution of many important drug candidates. P-gp substrates generally have reduced oral drug absorption and enhanced renal and biliary excretion. Limiting the exposure of xenobiotics to P-gp at the blood-brain barrier and placenta] barrier may also be important considerations. The rapid identification of P-gp substrates or... 

In addition to this nonlinear relationship for the blood-brain barrier permeation of imidazolines, many other nonlinear lipophilicity relationships have been derived for buccal and gastrointestinal absorption, skin permeation, as well as blood-brain and blood-placenta barrier permeation (e.g., Eqs. (58) to (62) Fig. 7 [59,60,63,64] Barbiturates permeation through an organic membrane ... 

Various drugs permeation of blood-placenta barrier ... 

On the other hand, it is widely accepted that isoflavones can freely pass the placenta barrier and in humans isoflavone concentrations in the neonate are similar to those in the maternal plasma. It has been reported that isoflavones at concentrations found in a standard, natural-ingredient diet may affect the sexual differentiation of female rats in the uterus [7, 44],... 

Bursa (1996) studied the population consisted of 40 pregnant women (living in the Silesia district over 10 years and non-professionally exposed to heavy metals) and their 40 newborns, who had perinatal period problems (mainly respiratory effort). The concentrations of cadmium in whole maternal blood and in cord blood of their newborns with different birth weight (BW) are shown in Table 20. The author concluded, that the placenta barrier between mothers and babies exist only in relation to cadmium transfer, independently of birth weight. 

Chloroprocaine (N,N -diethylaminoethyl 4-amino-2-chlorobenzoate) is a very short-acting, amino ester-type local anesthetic used to provide regional anesthesia by infiltration as well as by peripheral and central nerve block, including lumbar and caudal epidural blocks. The presence of a chlorine atom ortho to the carbonyl of the ester function increases its rate of hydrolysis by plasma cholinesterase at least threefold compared to procaine and benzocaine. Thus, chloroprocaine may be used in maternal and neonatal patients with minimal placental passage of chloroprocaine. The lower plasma cholinesterase activity in the maternal epidural space must still have sufficient activity for degrading chloroprocaine and, thus, not allowing it to cross the placenta barrier. 

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