Perspective on Thin Film Waveguides for on-Chip Mid-Infrared Spectroscopy of Liquid Biochemical Analytes
ANALYTICAL CHEMISTRY
Authors: Mittal, Vinita; Mashanovich, Goran Z.; Wilkinson, James S.
Abstract
Miniaturized spectrometers offering low cost, low reagent consumption, high throughput, sensitivity and automation are the future of sensing and have significant applications in environmental monitoring, food safety, biotechnology, pharmaceuticals, and healthcare. Midinfrared (MIR) spectroscopy employing complementary metal oxide semiconductor (CMOS) compatible thin film waveguides and microfluidics shows great promise toward highly integrated and robust detection tools and liquid handling. This perspective provides an overview of the emergence of thin film optical waveguides used for evanescent field sensing of liquid chemical and biological samples for MIR absorption spectroscopy. The state of the art of new material and waveguide systems used for spectroscopic measurements in the MIR is presented. An outlook on the advantages and future of waveguide-based MIR spectroscopy for application in clinical settings for point-of-care biochemical analysis is discussed.
Effect of concurrent organic cation transporter blockade on norepinephrine clearance inhibiting- and antidepressant-like actions of desipramine and venlafaxine
EUROPEAN JOURNAL OF PHARMACOLOGY
Authors: Bowman, Melodi A.; Mitchell, Nathan C.; Owens, W. Anthony; Horton, Rebecca E.; Koek, Wouter; Daws, Lynette C.
Abstract
Depression is a major health problem for which most patients are not effectively treated. This underscores a need to identify new targets for the development of antidepressants with improved efficacy. Studies have shown that blockade of low-affinity/high-capacity transporters, such as organic cation transporters (OCTs) and the plasma membrane monoamine transporter (PMAT), with decynium-22 can produce antidepressant-like effects and inhibit serotonin clearance in brain when the serotonin transporter is pharmacologically or genetically compromised. In vitro studies show that OCTs/PMAT are also capable of norepinephrine transport, raising the possibility that decynium-22 might enhance the antidepressant-like effects of norepinephrine transporter inhibitors. Using in vivo electrochemistry, we show that local administration of decynium-22 into dentate gyrus of hippocampus enhanced the ability of the norepinephrine transporter blocker, desipramine, but not the dual norepinephrine/serotonin transporter blocker venlafaxine, to inhibit norepinephrine clearance. In parallel, systemic administration of decynium-22 (0.32 mg/kg) enhanced the antidepressant-like effects of desipramine (32 mg/kg), but not those of venlafaxine, in the tail suspension test, underscoring the heterogeneous response of mice to antidepressants, including those that share similar mechanisms of action. Systemic administration of normetanephrine, a potent blocker of OCT3, failed to potentiate the antidepressant-like effects of desipramine, suggesting that the actions of decynium-22 to augment the antidepressant-like effects of desipramine are likely mediated by another OCT isoform and/or PMAT. Taken together with existing literature, concurrent blockade of OCTs and/or PMAT merits further investigation as an adjunctive therapeutic for desipramine-like antidepressant drugs.