Current Pharmaceutical Design - Volume 10, Issue 22, 2004

Developmental toxicology is primarily concerned with adverse effects of environmental and therapeutic exposures to the unborn child. This is the second issue of Current Pharmaceutical Design to focus on this important and controversial area. In line with the previous issue, the emphasis of this set of articles is to discuss emerging aspects in the field. Vitamin A metabolites, and particularly retinoic acid, are essential for norm Read More

The developing limb has been studied extensively and is a useful model to study morphogenesis. During embryogenesis, limb formation is initiated as a budding off from the embryonic lateral body wall. Limb pattern is specified by a series of epithelial-mesenchymal interactions, directing proximodistal, dorsoventral and anteroposterior axes. Vitamin A metabolites, especially retinoic acid, are known to play an important rol Read More

Despite the fact that orofacial clefts represent one of the most common birth defects, the molecular mechanisms by which the embryonic primordia of the midface grow and differentiate are not completely understood. A multiplicity of genes must be expressed and their protein products must interact in a highly orchestrated fashion to affect normal orofacial development. Several families of growth factors have Read More

Elevated maternal homocysteine (Hcys) is a well-established risk factor for embryonic toxicity and the development of congenital defects, particularly neural tube closure defects and neurocristopathies. The mechanisms responsible are unclear but early work has focused on the role of folate metabolism because these defects are greatly reduced by folate supplementation. As a consequence, elevated Hcys is often look Read More

The future chemical policy of the European Union as well as the 7th amendment of the cosmetic directive is calling for the development of alternative tests to animal experimentation for toxicological safety testing. In the field of embryotoxicity one of the most promising in vitro models are based on embryonic stem cells. The embryonic stem cell test has already been validated in comparison to in vivo results in an intern Read More

Phytoestrogens are plant-derived compounds with estrogen-like activities. Certain foods such as soyderived products are known to have high levels of phytoestrogens, and about 25% of commercial infant formulas used in the United States are soy-based. One of the most important phytoestrogens is the isoflavone genistein. Human exposures to genistein occur through normal dietary intake and through the use of g Read More

Nitric oxide (NO) is generated by a family of NO synthase (NOS) enzymes, including endothelial (eNOS), inducible (iNOS) and neuronal (nNOS). NO is an important bioregulator of a wide variety of physiological processes. Recent experimental evidence indicates that inhibition of NO synthesis can lead to teratogenesis. The current review focuses on this aspect of NOS. Exposure of pregnant rodents to non-selective NOS inhibitors, s Read More

Proteinase-activated Receptor 2 (PAR2) is a potential target for the design of drug treatments for vascular diseases. Its unique mechanism of activation by serine proteinases, questions regarding the identities of endogenous agonists and its apparent multiple activities in the vasculature contribute to complex pharmacology. The progress of the pursuit to understand the function of PAR2 relies on the design of short specifi Read More

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily and form heterodimers with retinoid X receptor. To date, three PPARs isoforms have been isolated and termed α, β (or δ), and γ. Although PPARγ is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, it has been recently demonstrat Read More