Mark Meyerhoff - Academia.edu (original) (raw)

Papers by Mark Meyerhoff

In this letter, the innate ability of nitric oxide (NO) to inhibit platelet activation/adhesion/t... more In this letter, the innate ability of nitric oxide (NO) to inhibit platelet activation/adhesion/thrombus formation is employed to improve the hemocompatibility and in vivo accuracy of an intravascular (IV) potentiometric PCO 2 (partial pressure of carbon dioxide) sensor. The catheter-type sensor is fabricated by impregnating a segment of dual lumen silicone tubing with a proton ionophore, plasticizer, and lipophilic cation-exchanger. Subsequent filling of bicarbonate and strong buffer solutions and placement of Ag/AgCl reference electrode wires within each lumen, respectively, enables measurement of the membrane potential difference across the inner wall of the tube, with this potential changing as a function of the logarithm of sample PCO 2. The dual lumen device is further encapsulated within a S-nitroso-N-acetyl-DL-penicillamine (SNAP)doped silicone tube that releases physiological levels of NO. The NO releasing sensor exhibits near-Nernstian sensitivity toward PCO 2 (slope = 59.31 ± 0.78 mV/decade) and low drift rates (<2 mV/24 h after initial equilibration). In vivo evaluation of the NO releasing sensors, performed in the arteries and veins of anesthetized pigs for 20 h, shows enhanced accuracy (vs non-NO releasing sensors) when benchmarked to measurements of discrete blood samples made with a commercial blood gas analyzer. The accurate, continuous monitoring of blood PCO 2 levels achieved with this new IV NO releasing PCO 2 sensor configuration could help better manage hospitalized patients in critical care units.

Analytical Chemistry, Oct 1, 1982

Glutathione Reductase Activity. In the presence of excess controlled concentrations of both GSSG ... more Glutathione Reductase Activity. In the presence of excess controlled concentrations of both GSSG and NADPH2, the initial rate of GSH formation was measured from the potential-time graph (mV/min) as a function of glutathione reductase activity (25). Best results were obtained with incubation of a mixture of 2.5 X lo4 M GSSG and the enzyme solutions a t 25 OC in a total volume of 4 mL of 0.1 M Tris-HNOB buffer of pH 8 followed by addition of 2.5 X M NADPH2 after a steady potential was attained. The results obtained under these optimal conditions s h w e d that the initial rate of GSH production is linearly related to the enzyme activity in the range of 0.4-4.0 mIU/mL. The sensitivity (1 (mV/min)/mIU) is high enough to measure the entire range of this activity with a precision of k3%. The method is more simple and sensitive than that previously suggested using a cyclic reaction with the pC02 electrode (26). The detection limit is lower than those reported with many other methods in current use (3, 16, 27).

Acta Biomaterialia, Mar 1, 2017

In separate prior studies, physical topographic surface modification or nitric oxide (NO) release... more In separate prior studies, physical topographic surface modification or nitric oxide (NO) release has been demonstrated to each be an effective approach to inhibit and control bacterial adhesion and biofilm formation on polymeric surfaces. Such approaches can prevent biomaterial-associated infection without causing the antibiotic resistance of the strain. In this work, both techniques were successfully integrated and applied to a polyurethane (PU) biomaterial surface that bears ordered pillar topographies (400/400 nm and 500/500 nm patterns) at the top surface and a S-nitroso-Nacetylpenicillamine (SNAP, NO donor) doped sub-layer in the middle, via a soft lithography twostage replication process. Upon placing the SNAP textured PU films into PBS at 37°C, the decomposition of SNAP within polymer film initiates NO release with a lifetime of up to 10 days at flux levels > 0.5 ×10 −10 mol min −1 cm −2 for a textured polyurethane layer containing 15 wt% SNAP. The textured surface reduces the accessible surface area and the opportunity of bacteriasurface interaction, while the NO release from the same surface further inhibits bacterial growth and biofilm formation. Such dual functionality surfaces are shown to provide a synergistic effect on inhibition of Staphylococcus epidermidis bacterial adhesion that is significantly greater than the inhibition of bacterial adhesion achieved by either single treatment approach alone. Longer term experiments to observe biofilm formation demonstrate that the SNAP doped-textured PU surface can inhibit the biofilm formation for > 28 d and provide a practical approach to improve the biocompatibility of current biomimetic biomaterials and thereby reduce the risk of pathogenic infection.

Nitric Oxide, Sep 1, 2019

Currently, most antimicrobial topical treatments utilize antibiotics to prevent or treat infectio... more Currently, most antimicrobial topical treatments utilize antibiotics to prevent or treat infection at a wound site. However, with the ongoing evolution of multi-drug resistant bacterial strains, there is a high demand for alternative antimicrobial treatments. Nitric oxide (NO) is an endogenous gas molecule with potent antimicrobial activity, which is effective against a wide variety of bacterial strains. In this study, the potential for creating NO releasing creams containing the naturally occurring NO carrier, Snitrosoglutathione (GSNO), are characterized and evaluated. GSNO is shown to have prolonged stability (>300 days) when mixed and stored within Vaseline at 24°C. Further, enhanced proliferation of NO from GSNO using zinc oxide nanoparticles (ZnO) is demonstrated. Triggering NO release from the GSNO/Vaseline mixture using a commercial zinc oxide-containing cream exhibits first-order NO release kinetics with the highest %NO release over the first 6 h. Significant killing effects against S. aureus, S. epidermidis, and P. aeruginosa are demonstrated for the GSNO/Vaseline/ZnO cream mixtures in a proportional manner dependent upon the concentration of GSNO in the final mixture.

Asaio Journal, Jun 1, 2023

The feasibility of using Nafion tubing on-line to reduce endogenous cation interferences when emp... more The feasibility of using Nafion tubing on-line to reduce endogenous cation interferences when employing enzymes that liberate ammonia/ammonium in conjunction with flow-injection analysis system equipped with an ammonium ion electrode detector was examined. As a model the FIA arrangement was configurated to determine L-glutamine in bioreactor media via the use of immobilized glutaminase.

The size of integrated ion sensors is dictated by the size and spacing of their polymeric membran... more The size of integrated ion sensors is dictated by the size and spacing of their polymeric membranes, which provide the chemical selectivity. The area occupied by an array of these membranes can be significantly reduced through the use of wells (areas separated by barrier walls, into which the membrane solutions are deposited). Screen-printable epoxies are obvious candidates for forming the wells, but their physical and chemical compatibility with polymer-based membranes has not been known. This paper describes a methodology for selecting a screen-printed epoxy well material, and compares 5 perspective materials.

Journal of laboratory chemical education, 2017

In the following experiment, organic chemistry students will gain hands-on experience with ultrav... more In the following experiment, organic chemistry students will gain hands-on experience with ultraviolet-visible and 1 HNMR spectroscopy after synthesizing S-nitroso-N-acetyl-D-penicillamine (SNAP). SNAP is a popular small molecule nitric oxide (NO) donor that has shown promise for biomedical applications. Our group has consistently demonstrated that polymers, such as silicone rubber or polyurethanes, containing SNAP can release NO and use its potent antithrombotic and antimicrobial properties to prevent clot and bacteria biofilm formation. Following the straightforward acid catalyzed synthesis, students will characterize the product with 1 HNMR. Studying SNAP's 1 HNMR spectrum exposes students to a variety of crucial concepts, including chemical shifts, integration, topicity, multiplicity, and coupling constants. Students can also calculate SNAP's molar absorptivity using UV-Vis spectroscopy, and use it to monitor the compound's stability in various environments. The experiment is presented in a manner most appropriate for an undergraduate, second-semester organic laboratory course; however, it can be readily tailored to first-semester students by omitting the 1 HNMR portion. The stability tests are suitable for various environments and durations, allowing the experiment to be used for single or multiple class periods as desired.

Understanding of basic interaction chemistry is a critical step in the development of novel stati... more Understanding of basic interaction chemistry is a critical step in the development of novel stationary phases for separation science. Recently, immobilized tetraphenylporphyrins (TPP; on 5-10 nun silica) have been investigated as novel stationary phases for fullerene, and PAH separations. In the normal phase mode, these columns (both metalated and unmetalated) appear to offer unprecedented selectivities with respect to fullerene separation. Indeed, La@C82, an endohedral metallofullerene, elutes from porphyrin-based column after C{sub 84} and the selectivity for C{sub 70}/C{sub 60} separation is dependent on the pore size of the silica gel onto which the porphyrins; are immobilized (i.e. a{sub C70/C60} increases sequentially with smaller pore size silica). Given the unique 3-dimensional symmetric structures of fullerenes, a retention mechanism is proposed that suggests that p-p interactions of a single fullerene simultaneously with more than one immobilized porphyrin species may occur on the porphyrin-silica stationary phase.

Encyclopedia of Electrochemistry, Aug 27, 2002

ABSTRACT

Abstract Biomedical devices that offer direct vascular access, such as intravascular (IV) cathete... more Abstract Biomedical devices that offer direct vascular access, such as intravascular (IV) catheters, are essential to modern patient care. To improve the hemocompatibility of IV catheters, significant complications associated with thrombus formation and bacterial infections/biofilm formation must be addressed. Current approaches used in the hospital setting to address these issues include use of: (a) systemic anticoagulant treatment or catheters that deliver localized anticoagulants to prevent thrombus formation on catheter surfaces; (b) catheters that contain antibiotics, bacteriophages, biofilm dispersal agents, or Ag+ ion release to prevent bacterial infection/biofilm; or (c) catheter lock solutions for localized delivery of either anticoagulants or antibiotics. Each of these methods have had some success, yet both the blood-material interactions and bacterial biofilm formation remain very serious problems and efforts aimed at devising novel solutions are still needed. Nitric oxide (NO), a naturally produced gas molecule, holds great potential for the development of the next generation of more thromboresistant and antimicrobial catheters because of NO's ability to inhibit platelet activation and prevent bacterial cell proliferation/biofilm formation. This chapter provides an overview of some of the most commonly used approaches for preparing NO release hemocompatible IV catheters, including chemical-based NO releasing catheters, catalyst-based NO generating catheters, and electrochemical-based NO generating catheters.

Proceedings of the International Solid-State Sensors and Actuators Conference - TRANSDUCERS '95, Aug 25, 2005

In our previous work aimed at mass producing chemical sensors, we have used the fabrication techn... more In our previous work aimed at mass producing chemical sensors, we have used the fabrication techniques of semiconductor processing and screen printing, in that work, we showed that high boiling-point solvents (i.e., low evaporation rates) were needed to increase the membrane paste viscosity and thixotropy [1 ]. While this approach achieved a paste with good mechanical properties for screen printing, the resulting sensors for some ions exhibited poor electrochemic~,! perfor.lance in terms of detecfi~n limits and slopes. This paper reports a new technique using a low boiling-point plasticizer, dimethyl phthalate (DMP), to control viscosity in the membrane paste. Use of the plasticizer facilitates screen printing, while maintaining good electrochemical characteristics.

A novel solid-state potentiometric sensing cartridge for detecting the polyanionic anticoagulant ... more A novel solid-state potentiometric sensing cartridge for detecting the polyanionic anticoagulant drug heparin is introduced. The device is based on photocrosslinked decyl methacrylate (DIMA) polyanion-sensitive films covalently immobilized over screen-printed silver epoxy electrodes. The fabrication and optimization of such a sensing arrangement are discussed. In accordance with potentiometric polyion response theory, a sensitive response to heparin can be achieved by decreasing the amounts of ion-exchanger, plasticizer, and crosslinker in the membrane. A novel hydrophilic copolymer can be used as an internal layer to improve EMF reproducibility. Clinical levels of heparin can be detected in as little as 50 /spl mu/L of whole blood.

Clinical Chemistry, Jul 1, 1990

Discrepancies between serum free triiodothyronine and free thyroxin as measured by equilibrium di... more Discrepancies between serum free triiodothyronine and free thyroxin as measured by equilibrium dialysis and analog radioimmunoassays in nonthyroidal illnesses. Clin Chem 1984;30:760-2. 4. Csako G, Zweig MH, Benson C, Ruddel M. On the albumin dependence of measurements of free thyroxin. Technical perfor

Electroanalysis, Jul 29, 2015

Analytical Chemistry, 2004

Nitric oxide generation from porcine kidney slices is assessed using a new planar NO-selective am... more Nitric oxide generation from porcine kidney slices is assessed using a new planar NO-selective amperometric sensor. The planar shape of the sensor allows for direct NO measurements near the surface (10 µm) of renal tissue slices in real time. Renal NO production may be modulated by the addition of L-arginine, arginine homopolymers (R2, R6, R10), and protamine, all of which can potentially transport across cellular membranes and provide a substrate for nitric oxide synthase within kidney parenchyma. Real-time amperometric measurements demonstrate that most L-arginine species can translocate across the cell membrane and rapidly increase NO production. However, no increase in NO generation is observed when the dimer of L-arginine (R2) is added to the solution bathing the tissue, suggesting that this species cannot permeate cell membranes. The degree of enhancement in NO generation observed for L-arginine and the larger peptides depends on the structure and follows the following sequence: R10 (decamer) > protamine > R6 (hexamer) > L-arginine. Protamine and the R10 decamer, especially, induce the largest increases in NO generation owing to their apparent rapid translocation into cells and subsequent cleavage by proteases to create high intracellular levels of L-arginine. The effect of sensor size (for sensor dimensions of 0.15-and 1-mm outer diameters) on the measured surface NO levels is also examined. The larger sensor traps more NO but hinders access of the L-arginine species to the tissue area between the flat distal plane of the sensor and the surface of the kidney slice. The use of such NO-generating peptides may be important in numerous biological systems that depend on NO production, such as ischemia-reperfusion injury and thrombogenesis.

Polymer, Jul 1, 2021

Abstract Controllable delivery of nitric oxide (NO) platforms have attracted considerable attenti... more Abstract Controllable delivery of nitric oxide (NO) platforms have attracted considerable attention for biomedical/therapeutic applications. Poly(n-butyl methacrylate) is one of the most widely explored biomedical materials as a primer and is used in manufacturing the commercial XIENCE family of coronary stents. Herein we report the preparation of NO-releasing poly(n-butyl methacrylate) (PBMA) films via incorporation of S-nitroso-N-acetylpenicillamine (SNAP) within, and explore the NO-releasing profiles of such films under physiological conditions. Specifically, the total NO-release time of PBMA films doped with SNAP can reach up to 75 d, and the total leaching of SNAP is extremely low (∼2.2%, based on HPLC-MS measurements). The surface morphology of SNAP-doped PBMA films indicates the formation of needle-like crystalline SNAP particles, which is further confirmed by the PXRD data. Based on element mapping, SNAP is found to be homogenously distributed within the PBMA polymer phase. Moreover, the antimicrobial and anti-biofilm properties of the NO-releasing PBMA polymer films are demonstrated using E. coli, P. aeruginosa, S. aureus, and S. epidermidis bacterial strains over 7 d periods. These results suggest that the controllable release of NO using PBMA films could be useful for therapeutic or biomedical device applications. Moreover, the corresponding data would also contribute to the exploration of the controllable drug release property using PBMA as the polymer matrix during the manufacture of biomedical stents.

Colloids and Surfaces B: Biointerfaces, Aug 1, 2020

The blood compatibility of various intravascular (IV) devices (e.g., catheters, sensors, etc.) is... more The blood compatibility of various intravascular (IV) devices (e.g., catheters, sensors, etc.) is compromised by activation of platelets that can cause thrombus formation and device failure. Such devices also carry a high risk of microbial infection. Recently, nitric oxide (NO) releasing polymers/devices have been proposed to reduce these clinical problems. CD47, a ubiquitously expressed transmembrane protein with proven anti-inflammation/anti-platelet properties when immobilized on polymeric surfaces, is a good candidate to complement NO release in both effectiveness and longevity. In this work, we successfully appended CD47 peptides (pepCD47) to the surface of biomedical grade polyurethane (PU) copolymers. SIRPα binding and THP-1 cell attachment experiments strongly suggested that the pepCD47 retains its biological properties when bound to PU films. In spite of the potentially high reactivity of NO toward various amino acid residues in CD47, the efficacy of surface-immobilized pepCD47 to prevent inflammatory cell attachment was not inhibited after being subjected to a high flux of NO for three days, demonstrating excellent compatibility of the two species. We further constructed a CD47 surface immobilized silicone tubing filled with NO releasing S-nitrosoglutathione/ascorbic acid (GSNO/AA) solution for synergistic biocompatibility evaluation. Via an ex vivo Chandler loop model, we demonstrate for the first time that NO release and CD47 modification could function synergistically at the blood/material interface and produce greatly enhanced anti-inflammatory/anti-platelet effects. This concept should be readily implementable to create a new generation of thromboresistant/antimicrobial implantable devices.

ACS Sensors, Jan 23, 2017

Two facile, robust, and universal methods by which various polymeric quaternary ammonium salts (p... more Two facile, robust, and universal methods by which various polymeric quaternary ammonium salts (polyquaterniums (PQs)) can be quantified and characterized using simple potentiometric polymeric membrane polyion sensitive electrodes as detectors are described. The two methods are: a) direct detection with polycation sensitive membrane electrodes based on the sodium salt of dinonylnaphthalene sulfonate (DNNS-), and b) indirect detection using polyanion sensors based on tridodecylmethylammonium chloride (TDMAC) and dextran sulphate (DS) as a titrant to complex the various polyquaternary species (four different PQs: PQ-2, PQ-6, PQ-10, and poly(2-methacryloxyethyltrimethylammonium) chloride (PMETAC)). Direct detection yields information regarding the charge density of the polycationic species. For the titration method, a series of polyanion sensors doped with TDMAC are used to follow a potentiometric titration of a PQ species using a syringe pump to deliver the titrant. This indirect detection method is more reliable and yields limits of detection in the ppm range for the four PQs examined. The titration method is further explored for detecting excess levels of PQ-6, a common flocculating agent for municipal water supply systems, within the purified water emitted by the Ann Arbor, MI, drinking water treatment plant.