Bilistick: a low-cost point-of-care system to measure total plasma bilirubin.

BACKGROUND: Severe neonatal hyperbilirubinemia, with consequent encephalopathy, remains a common cause of morbidity and death in many regions of the world. Poor access to clinical laboratory resources and screening programs to measure plasma bilirubin levels is a major contributor to delayed treatment in developing countries, and the cost of existing point-of-care screening instruments precludes their dissemination. OBJECTIVES: We are evaluating the accuracy of a low-cost, minimally invasive point-of-care system (Bilistick) requiring a 25-µl blood sample that could be used in low-resource environments to evaluate patients with neonatal jaundice. METHODS: We compared plasma bilirubin levels in divided blood samples by clinical laboratories and by Bilistick at two medical centers serving term and near-term newborns from ethnically different populations. RESULTS: 118 neonates with bilirubin levels ranging from 24.8 to 501.0 µmol/l were analyzed. The mean bilirubin concentration (±SD) was 215.6 ± 85.5 µmol/l for Bilistick and 226.1 ± 86.4 µmol/l by laboratory determination. Pearson's correlation coefficient between all paired results was 0.961, and the Bland-Altman analysis showed a mean difference of 10.3 µmol/l with a 95% interval of agreement of -38.0 to 58.7 µmol/l. CONCLUSION: Bilistick is a minimally invasive method for measuring total bilirubin concentration over a wide range of values and should provide an affordable and accurate system for pre-discharge and follow-up screening of jaundiced infants, particularly in low-resource environments.

The role of ABC transporters in protecting cells from bilirubin toxicity.

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 basolateral membrane. Among a multiplicity of substrates, MRP1 mediates the ATP-dependent cellular export of UCB, and its role has been demonstrated in protecting cells from UCB toxicity. MRP3 is an organic anion transporter whose major substrates are GSH conjugates of organic compounds. Among the MRP family members, MRP3 shares the highest degree of amino acid homology with MRP1. Although the hepatic expression of MRP3 has been reported to be up-regulated by bilirubin and bilirubin glucuronides, it is unknown whether MRP3 is also involved in the transport of UCB. PGP is expressed in organs involved in the elimination of endo- and xenobiotics and UCB is one of these substrates. Since the Km of PGP for UCB is well above pathophysiological levels of Bf, it remains uncertain whether it has a role in protecting against UCB cytotoxicity.

Role of multidrug resistance-associated protein 1 expression in the in vitro susceptibility of rat nerve cell to unconjugated bilirubin.

Nerve cell injury by unconjugated bilirubin (UCB) has been implicated in brain damage during neonatal hyperbilirubinemia, particularly in the preterm newborn. Recently, it was shown that UCB is a substrate for the multidrug resistance-associated protein 1 (Mrp1), an ATP-dependent efflux pump, which may decrease UCB intracellular levels. To obtain a further insight into the role of Mrp1 in the increased vulnerability of immature cells to UCB, we evaluated the mRNA and the protein levels of Mrp1 throughout differentiation in primary cultures of rat neurons and astrocytes. Furthermore, in order to provide supportive evidence for the role of Mrp1 in the protection of nerve cells from UCB-induced effects, we evaluated cell susceptibility to UCB when Mrp1 was inhibited with MK571 ((E)-3-[[[3-[2-(7-chloro-2-quinolinyl) ethenyl]phenyl]-[[3-dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid). The results are the first to demonstrate that Mrp1 is expressed in neurons and that both mRNA and protein levels of Mrp1 increase with cell differentiation. Additionally, inhibition of Mrp1 was associated with an increase in UCB toxic effects, namely cell death, cell dysfunction, and secretion of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, as well as of glutamate. These results point to a novel role of Mrp1 in the susceptibility of premature babies to UCB encephalopathy, and provide a startup point for the development of a new therapeutic strategy.

The effectiveness and practicality of occupational stress management interventions: a survey of subject matter expert opinions.

Stress management (SM) subject matter experts (SMEs) evaluated 6 widely used occupational SM interventions (relaxation, physical fitness, cognitive restructuring, meditation, assertiveness training, and stress inoculation) on the basis of 10 practicality criteria and 7 effectiveness objectives. Relaxation was evaluated overall as the most practical intervention, while meditation and stress inoculation were judged as the least practical. Physical fitness was chosen to be the most effective intervention, while both meditation and assertiveness training were rated overall as the least effective. The findings also revealed that the SMEs considered history of success and duration of effect, rather than "relevance to program objectives," as the most important factors when selecting SM interventions. Incongruence between effectiveness ratings and actual choices of interventions are discussed.