Current Pharmaceutical Design - Volume 15, Issue 25, 2009

The principal aim of this special issue is to critically and translationally review the pathophysiology of bilirubin-induced neurological disease (BIND). Understanding the mechanisms of BIND can point the way to new diagnostic methods to predict the development of acute BIND and to prevent and treat it more effectively. Kernicterus is a rare disease of the nervous system, seen mostly in severely jaundiced neonates; its incidence is Read More

Unconjugated bilirubin (UCB), the principal mammalian bile pigment, is the end product of heme catabolism. Both belong to the superfamily of tetrapyrrolic compounds that serve multiple biological functions in animals and plants. Its six internal hydrogen bonds give UCB a unique structure responsible for its physico-chemical properties and biological effects. Like many weakly-polar, poorly-soluble compounds, UCB is transpo Read More

The ATP-Binding Cassette (ABC) superfamily is the largest transporter family known to translocate a wide variety of exogenous and endogenous substrates across cell membranes. In this chapter we review the potential role of three ABC proteins in the transport of unconjugated bilirubin (UCB). These transporters are MRP1, MRP3 and PGP (MDR1). MRP1 is expressed at high levels in most epithelia, usually at the basolater Read More

The endothelium of the brain microvessels and the choroid plexus epithelium form highly specialized cellular barriers referred to as blood-brain interfaces through which molecular exchanges take place between the blood and the neuropil or the cerebrospinal fluid, respectively. Within the brain, the ependyma and the pia-glia limitans modulate exchanges between the neuropil and the cerebrospinal fluid. All these interfaces Read More

Unconjugated bilirubin (UCB) is the major degradation product of the heme catabolism. UCB is a potent antioxidant molecule as well as an indirect pro-oxidant generator. Growing evidence suggests that its major cellular effects are mediated by inhibiting proliferation in cancer cell lines and eliciting cytotoxicity, particularly in neurons and glial cells. Here we describe studies showing that alteration of the redox status and gen Read More

Hyperbilirubinemia is a common condition in neonatal life, where elevated levels of unconjugated bilirubin (UCB) may lead to adverse neurologic outcomes, namely in the presence of inflammatory features. In this review, we summarize recent concepts on UCB damage to brain cells and associated neuroinflammation research. Exposure of astrocytes and microglia to UCB initiates an inflammatory response with the releas Read More

Severe unconjugated hyperbilirubinemia, seen mainly in neonates, may cause kernicterus and death. Conventional treatment for severe unconjugated hyperbilirubinemia consists of phototherapy and exchange transfusion. Phototherapy, however, has several known disadvantages while exchange transfusion is associated with a significant morbidity, and even mortality. These harmful effects indicate the need to dev Read More

The American Academy of Pediatrics has proposed guidelines for treating term/near term infants with hyperbilirubinemia based primarily on maintaining the total serum bilirubin concentration (TSB) below a “critical” level of 25 mg/dL (426 μmol/L). We estimated the sensitivity and specificity of this critical TSB using patient data from published reports. A TSB >25 mg/dL is recorded in about 92% of term/near term in Read More

Virus infection and oncogenesis are two tightly linked processes. Some viruses are endowed with a direct transforming capability and infection activates inflammation that, in turn, favours tumor progression. Also, both inflammation and tumor trigger (and are strongly dependent from) angiogenesis. Finally, some oncogenic viruses release “virokines” that contribute to the development of virus-associated tumors. At a m Read More

Dendrimers represent a class of novel polymers having unique molecular architectures characterized by their well-defined structure, with a high degree of molecular uniformity, low polydispersity and properties that make them attractive materials for the development of nanomedicines. The dendrimer drug delivery can be achieved by coupling a drug through one of two approaches. Hydrophobic drugs can be complexed with Read More

Malaria continues to devastate much of the tropics and sub-tropics in spite of the availability of a number of antimalarial drugs. Part of this problem is due to the disadvantages of the drugs in use, which include (depending on the drug) side effects, reduced efficacy due to resistance, and high cost. Multiple traditional and novel approaches to the discovery and design of new antimalarial agents are likely to be required to furnish Read More