Oxidative Stress, Proton Fluxes, and Chloroquine/Hydroxychloroquine Treatment for COVID-19

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as treatments for COVID-19. These drugs have been studied for many decades, primarily in the context of their use as antimalarials, where they induce oxidative stress-killing of the malarial parasite. Less appreciated, however, is evidence showing that CQ/HCQ causes systemic oxidative stress. In vitro and observational data suggest that CQ/HCQ can be repurposed as potential antiviral medications. This review focuses on the potential health concerns of CQ/HCQ induced by oxidative stress, particularly in the hyperinflammatory stage of COVID-19 disease. The pathophysiological role of oxidative stress in acute respiratory distress syndrome (ARDS) has been well-documented. Additional oxidative stress caused by CQ/HCQ during ARDS could be problematic. In vitro data showing that CQ forms a complex with free-heme that promotes lipid peroxidation of phospholipid bilayers are also relevant to COVID-19. Free-heme induced oxidative stress is implicated as a systemic activator of coagulation, which is increasingly recognized as a contributor to COVID-19 morbidity. This review will also provide a brief overview of CQ/HCQ pharmacology with an emphasis on how these drugs alter proton fluxes in subcellular organelles. CQ/HCQ-induced alterations in proton fluxes influence the type and chemical reactivity of reactive oxygen species (ROS)

The pursuit of isotopic and molecular fire tracers in the polar atmosphere and cryosphere

We present an overview of recent multidisciplinary, multi-institutional efforts to identify and date major sources of combustion aerosol in the current and paleoatmospheres. The work was stimulated, in part, by an atmospheric particle \u27sample of opportunity\u27 collected at Summit, Greenland in August 1994, that bore the 14C imprint of biomass burning. During the summer field seasons of 1995 and 1996, we collected air filter, surface snow and snowpit samples to investigate chemical and isotopic evidence of combustion particles that had been transported from distant fires. Among the chemical tracers employed for source identification are organic acids, potassium and ammonium ions, and elemental and organic components of carbonaceous particles. Ion chromatography, performed by members of the Climate Change Research Center (University of New Hampshire), has been especially valuable in indicating periods at Summit that were likely to have been affected by the long range transport of biomass burning aerosol. Univariate and multivariate patterns of the ion concentrations in the snow and ice pinpointed surface and snowpit samples for the direct analysis of particulate (soot) carbon and carbon isotopes. The research at NIST is focusing on graphitic and polycyclic aromatic carbon, which serve as almost certain indicators of fire, and measurements of carbon isotopes, especially 14C, to distinguish fossil and biomass combustion sources. Complementing the chemical and isotopic record, are direct \u27visual\u27 (satellite imagery) records and less direct backtrajectory records, to indicate geographic source regions and transport paths. In this paper we illustrate the unique way in which the synthesis of the chemical, isotopic, satellite and trajectory data enhances our ability to develop the recent history of the formation and transport of soot deposited in the polar snow and ice

Repetitions in beta-integers

Classical crystals are solid materials containing arbitrarily long periodic repetitions of a single motif. In this paper, we study the maximal possible repetition of the same motif occurring in beta-integers -- one dimensional models of quasicrystals. We are interested in beta-integers realizing only a finite number of distinct distances between neighboring elements. In such a case, the problem may be reformulated in terms of combinatorics on words as a study of the index of infinite words coding beta-integers. We will solve a particular case for beta being a quadratic non-simple Parry number.Comment: 11 page

Synthesis and Characterization of Thermally and Chemically Gelling Injectable Hydrogels for Tissue Engineering

Novel, injectable hydrogels were developed that solidify through a dual-gelation, physical and chemical, mechanism upon preparation and elevation of temperature to 37°C. A thermogelling, poly(N-isopropylacrylamide)-based macromer with pendant epoxy rings and a hydrolyticallydegradable polyamidoamine-based diamine crosslinker were synthesized, characterized, and combined to produce in situ forming hydrogel constructs. Network formation through the epoxyamine reaction was shown to be rapid and facile, and the progressive incorporation of the hydrophilic polyamidoamine crosslinker into the hydrogel was shown to mitigate the often problematic tendency of thermogelling materials to undergo significant post-formation gel syneresis. The results suggest that this novel class of injectable hydrogels may be attractive substrates for tissue engineering applications due to the synthetic versatility of the component materials and beneficial hydrogel gelation kinetics and stability

A critical evaluation of interlaboratory data on total, elemental, and isotopic carbon in the carbonaceous particle reference material, NIST SRM 1649a

Because of increased interest in the marine and atmospheric sciences in elemental carbon (EC), or black carbon (BC) or soot carbon (SC), and because of the difficulties in analyzing or even defining this pervasive component of particulate carbon, it has become quite important to have appropriate reference materials for intercomparison and quality control. The NIST "urban dust" Standard Reference Material? SRM 1649a is useful in this respect, in part because it comprises a considerable array of inorganic and organic species, and because it exhibits a large degree of (14C) isotopic heterogeneity, with biomass carbon source contributions ranging from about 2 % (essentially fossil aliphatic fraction) to about 32 % (polar fraction). A primary purpose of this report is to provide documentation for the new isotopic and chemical particulate carbon data for the most recent (31 Jan. 2001) SRM 1649a Certificate of Analysis. Supporting this is a critical review of underlying international intercomparison data and methodologies, provided by 18 teams of analytical experts from 11 institutions. Key results of the intercomparison are: (1) a new, Certified Value for total carbon (TC) in SRM 1649a; (2) 14C Reference Values for total carbon and a number of organic species, including for the first time 8 individual PAHs; and (3) elemental carbon (EC) Information Values derived from 13 analytical methods applied to this component. Results for elemental carbon, which comprised a special focus of the intercomparison, were quite diverse, reflecting the confounding of methodological-matrix artifacts, and methods that tended to probe more or less refractory regions of this universal, but ill-defined product of incomplete combustion. Availability of both chemical and 14C speciation data for SRM 1649a holds great promise for improved analytical insight through comparative analysis (e.g., fossil/ biomass partition in EC compared to PAH), and through application of the principle of isotopic mass balance.Carrie, L. A., Benner, B. A., Kessler, J. D., Klinedinst, D. B., Klouda, G. A., Marolf, J. V., . . . Schmid, H. (2002). A Critical Evaluation of Interlaboratory Data on Total, Elemental, and Isotopic Carbon in the Carbonaceous Particle Reference Material, NIST SRM 1649a. Journal of Research of the National Institute of Standards and Technology, 107(3), 279-298

Oxidative Stress, Proton Fluxes, and Chloroquine/Hydroxychloroquine Treatment for COVID-19

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as treatments for COVID-19. These drugs have been studied for many decades, primarily in the context of their use as antimalarials, where they induce oxidative stress-killing of the malarial parasite. Less appreciated, however, is evidence showing that CQ/HCQ causes systemic oxidative stress. In vitro and observational data suggest that CQ/HCQ can be repurposed as potential antiviral medications. This review focuses on the potential health concerns of CQ/HCQ induced by oxidative stress, particularly in the hyperinflammatory stage of COVID-19 disease. The pathophysiological role of oxidative stress in acute respiratory distress syndrome (ARDS) has been well-documented. Additional oxidative stress caused by CQ/HCQ during ARDS could be problematic. In vitro data showing that CQ forms a complex with free-heme that promotes lipid peroxidation of phospholipid bilayers are also relevant to COVID-19. Free-heme induced oxidative stress is implicated as a systemic activator of coagulation, which is increasingly recognized as a contributor to COVID-19 morbidity. This review will also provide a brief overview of CQ/HCQ pharmacology with an emphasis on how these drugs alter proton fluxes in subcellular organelles. CQ/HCQ-induced alterations in proton fluxes influence the type and chemical reactivity of reactive oxygen species (ROS)