Relationship Between Methadone, Selective Serotonin Reuptake Inhibitors, and Neonatal Abstinence Syndrome.

OBJECTIVE: To compare incidence and severity of neo- natal abstinence syndrome (NAS) in neonates exposed to methadone and selective serotonin reuptake inhibitors (SSRIs) with neonates ex- posed to methadone alone. STUDY DESIGN: Retro- spective cohort study of women on methadone main- tenance with live births be- tween January 1, 2003, and December 31, 2009, at a tertiary care hospital. Data were abstracted from electronic medical records, exclud- ing cases of multiple gestations and lack of neonatal abstinence score documentation. Data analysis included Mann-Whitney U, Fisher's exact test, a receiver operat- ing characteristic curve, and a scatter diagram. RESULTS: A total of 91 cases comprised our study population, with 85 (93.4%) assigned to the methadone- only group and 6 (6.6%) assigned to the methadone and SSRIs group. NAS incidence was not significantly different between the methadone/SSRI group and the methadone group (5/6 [83.3%] vs. 43/85 [50.6%], p=0.21). However, severity of NAS (median 14.0 vs. 10.0, p=0.04) and neonatal intensive care unit stay were significantly higher and longer in the methadone/ SSRI group. CONCLUSION: While currently neonates exposed to SSRIs are not screened for NAS, health care providers may need to pay closer attention to the effects of SSRIs on neonates.

Electrochemical analysis of azurin thermodynamic and adsorption properties at monolayer-protected cluster film assemblies - evidence for a more homogeneous adsorption interface.

Thermodynamic and adsorption properties of protein monolayer electrochemistry (PME) are examined for Pseudomonas aeruginosa azurin (AZ) immobilized at an electrode modified with a networked film of monolayer-protected clusters (MPCs) to assess if nanoparticle films of this nature offer a more homogeneous adsorption interface compared to traditional self-assembled monolayer (SAM) modified electrodes. Specifically, electrochemistry is used to assess properties of surface coverage, formal potential, peak broadening, and electron transfer (ET) kinetics as a function of film thickness. The modification of a surface with dithiol-linked films of MPCs (Au(225)C6(75)) provides a more uniform binding interface for AZ that results in voltammetry with less peak broadening (<110mV) compared to SAMs (>120-130mV). Improved homogeneity of the MPC interface for protein adsorption is confirmed by atomic force microscopy imaging that shows uniform coverage of the gold substrate topography and by electrochemical analysis of film properties during systematic desorption of AZ, which indicates a more homogeneous population of adsorbed protein at MPC films. These results suggest MPC film assemblies may be used in PME to provide greater molecular level control of the protein adsorption interface, a development with applications for strategies to study biological ET processes as well as the advancement of biosensor technologies.

Distance dependence of electron transfer kinetics for azurin protein adsorbed to monolayer protected nanoparticle film assemblies.

The distance dependence and kinetics of the heterogeneous electron transfer (ET) reaction for the redox protein azurin adsorbed to an electrode modified with a gold nanoparticle film are investigated using cyclic voltammetry. The nanoparticle films are comprised of nonaqueous nanoparticles, known as monolayer-protected clusters (MPCs), which are covalently networked with dithiol linkers. The MPC film assembly serves as an alternative adsorption platform to the traditional alkanethiolate self-assembled monolayer (SAM) modified electrodes that are commonly employed to study the ET kinetics of immobilized redox proteins, a strategy known as protein monolayer electrochemistry. Voltammetric analysis of the ET kinetics for azurin adsorbed to SAMs of increasing chain length results in quasi-reversible voltammetry with significant peak splitting. We observed rate constants (k degrees (ET)) of 12-20 s(-1) for the protein at SAMs of shorter alkanethiolates that decays exponentially (beta = 0.9/CH(2) or 0.8/A) at SAMs of longer alkanethiolates (9-11 methylene units) or an estimated distance of 1.23 nm and is representative of classical electronic tunneling behavior over increasing distance. Azurin adsorbed to the MPC film platforms of increasing thickness results in reversible voltammetry with very little voltammetric peaks splitting and nearly negligible decay of the ET rate over significant distances up to 20 nm. The apparent lack of distance dependence for heterogeneous ET reactions at MPC film assemblies is attributed to a two-step mechanism involving extremely fast electronic hopping through the MPC film architecture. These results suggest that MPC platforms may be used in protein monolayer electrochemistry to create adsorption platforms of higher architecture that can accommodate greater than monolayer protein coverage and increase the Faradaic signal, a finding with significant implications for amperometric biosensor design and development.