Placenta, defined

Benzodiazepines readily pass from the mother to fetus through the placenta (117). There may be a risk of congenital malformations, particularly oral cleft, if a pregnant woman takes a benzodiazepine during the first trimester, but the data are inconsistent across drugs (alprazolam having the most clearly defined risk), and any overall effect is probably small (27,28). The risk of benzodiazepine-induced birth defects thus remains uncertain (118), despite two cases of fetal-alcohol syndrome reported after benzodiazepine exposure alone (119). 

Another, more recent, example is enzyme therapy for Gaucher s disease, an inborn error of metabolism, treated with Ceredase. The therapy, which requires more than a ton of placenta annually to extract and make the drug, can cost as much as S500,000 per year per person, depending on the dosage needed. A 1996 National Institutes of Health technology assessment panel addressed issues in diagnosis and treatment of the disease and concluded that despite the success of enzyme therapy, treatment is limited by the cost. The panel reported that it was imperative to define the appropriate clinical indications for treatment and to determine the lowest effective initial and maintenance doses (43). 

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]. 

Poly(ADP-ribose) synthetase is a chromatin-bound enzyme which, in the presence of DNA, catalyzes polymerization of the ADP-ribose moiety of NAD to form a protein-bound homopolymer, poly(ADP-ribose) (1). The enzyme is automodified during the reaction. It has been shown that the enzyme consists of three functional domains for DNA-binding, automodification, and NAD-binding (2-4). The enzyme has recently been purified from human placenta and characterized (4, 5). To study the structure and function of the enzyme in more detail we have prepared monoclonal antibodies to the placental enzyme (6, 7). The present study defines three monoclonal antibodies to human poly(ADP-ribose) synthetase and shows that one of the antibodies which binds to the NAD binding domain inhibits the enzyme activity. 

The mechanism for the transport of lead through the placenta is not well defined. There are several reasons for suggesting it may be a matter of simple diffusion from maternal to fetal circulation (Goyer 1990). For one,... 

In addition to its archetypical members, uteroferrin and bovine spleen add phosphatase, the class of purple add phosphatases includes proteins isolated from rat bone and. spleen spleens of patients with Gaucher s disease or leukemic reticuloen-dotheliosis equine uterine flushings bovine cortical bone giant ceU tumors human placenta and microorganisms . The plant enzymes include an Fe-Zn phosphatase from red kidney beans and an Fe-Fe or Mn(in) protein from sweet potato tubers . Although less well-defined and more heterogeneous than their mammalian counterparts, the color and iron content of the plant enzymes warrant their designation as purple acid phosphatases. 

---