Current Pharmaceutical Design - Volume 13, Issue 29, 2007

The papers in this special issue of Current Pharmaceutical Design cover a wide spectrum of relevant and fascinating topics in the area of developmental and reproductive toxicology. There is increasing evidence that small gaseous molecules, such as dioxygen, carbon monoxide, nitric oxide and hydrogen sulphide, serve important roles in modulating a variety of physiological responses, including those involved in develo Read More

Dioxygen (O2) is an exogenously supplied gas with a number of properties that make it valuable as a biological source of energy and as a result much of life has become dependent on this molecule. Nitric oxide (NO), carbon dioxide (CO) and hydrogen sulfide (H2S) are small molecules that are sometimes in a gaseous state and that can be either exogenously or endogenously supplied. The chemistry of these four molecules Read More

Drugs blocking the potassium current IKr, either as an intended pharmacologic effect (eg antiarrhythmics dofetilide and almokalant) or as an unwanted side-effect (eg antihistamine astemizole, propulsive drug cisapride, antidepressive drugs and macrolide antibiotics) are potential human teratogens. It is the contention of this paper that the existing repeat dose regimen used in teratology studies to fulfil regulatory require Read More

Many human-made chemicals are called endocrine disruptors (EDs) because they have the potential to disrupt endocrine functions in exposed organisms. Many EDs can disrupt hormonal homeostasis by interfering with hormone receptor recognition, binding and activation, while others act by still unknown mechanisms. Among the EDs specifically affecting the female reproductive system, those with steroidogenic/antisteroid Read More

Environmental toxicants comprise a number of man-made organic chemicals which may resist metabolism or their metabolites may persist in the environment and accumulate in the food chain. Some of these persistent chemicals are carried over long distances via the atmospheric transport and can have biological effects in fish, wildlife and humans. In this review the relationship between structure of these chemicals, their m Read More

All-trans retinoic acid (atRA) is the transcriptionally active product of vitamin A and induces gene expression via specific receptors at nM concentrations. Essential enzymes that regulate the local levels of atRA are the CYP26 members of the cytochrome P450 family, which catabolize atRA. Compounds that have been designed to inhibit these enzymes are known as Retinoic Acid Metabolic Blocking Agents (RAMBAs). Tr Read More

Cubilin and megalin are multiligand receptors that mediate uptake of extracellular ligands. Their function has extensively been studied in the kidney where they play a key role in vitamin B12 and vitamin D homeostasis. Amnionless is a plasma membrane protein that binds to cubilin in various epithelia; the interaction cubilin-amnionless in the gut is crucial for dietary vitamin B12 uptake. Studies in patients with gene defects in t Read More

Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilitie Read More