@article{shropshire_johnson_olver_2020, title={Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein-losing nephropathy}, ISBN={1939-1676}, DOI={10.1111/jvim.15694}, abstractNote={Abstract Background Dogs with protein‐losing nephropathy (PLN) are treated with antiplatelet drugs for thromboprophylaxis but no standardized method exists to measure drug response. It is also unknown if clopidogrel metabolite concentrations [CM] differ between healthy and PLN dogs. Objectives Assess response to aspirin or clopidogrel in PLN dogs using platelet aggregometry (PA) and compare [CM] between healthy and PLN dogs. Animals Six healthy and 14 PLN dogs. Methods Platelet aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and saline was performed in healthy dogs at baseline and 1‐week postclopidogrel administration to identify responders or nonresponders. A decrease of ≥60% for ADP or ≥30% for AA at 1 or 3 hours postpill was used to define a responder. At 1 and 3 hours postclopidogrel, [CM] and PA were measured in healthy and PLN dogs. Platelet aggregometry was performed in PLN dogs at baseline, 1, 6, and 12 weeks after clopidogrel or aspirin administration. Results In PLN dogs receiving clopidogrel, PA differed from baseline at all time points for ADP but not for AA at any time point. Most dogs responded at 1 or both time points except for 1 dog that showed no response. For PLN dogs receiving aspirin, no differences from baseline were observed at any time point for either ADP or AA. No differences in [CM] were found at either time point between healthy and PLN dogs. Conclusions and Clinical Importance Platelet aggregometry may represent an objective method to evaluate response to clopidogrel or aspirin treatment and PLN dogs appear to metabolize clopidogrel similarly to healthy dogs.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Shropshire, Sarah and Johnson, Tyler and Olver, Christine}, year={2020} }
 @article{johnson_wells_bell_nielsen_olver_2019, title={Carbon monoxide releasing molecule enhances coagulation and decreases fibrinolysis in canine plasma exposed to Crotalus viridis venom in vitro and in vivo}, volume={125}, ISSN={["1742-7843"]}, DOI={10.1111/bcpt.13242}, abstractNote={Carbon monoxide releasing molecule‐2 (CORM‐2), an emerging therapeutic in human medicine, enhances plasmatic coagulation and attenuates fibrinolysis in vitro in human, rabbit and horse plasma and ameliorates hypocoagulation and hyperfibrinolysis secondary to venom exposure in human plasma in vitro. Fibrinogenases in rattlesnake venom cause decreased clot strength, and in the presence of tissue plasminogen activator (tPA) in vitro, a markedly increased rate of clot lysis. CO interacts with a haem group on fibrinogen, changing its configuration so that the fibrin clot is strengthened and more resistant to fibrinolysis. We hypothesized that CORM‐2 enhances coagulation and attenuates fibrinolysis in canine plasma exposed to C viridis venom. We measured the effects of C viridis venom on clot strength, rates of coagulation and fibrinolysis in both pooled canine plasma and plasma from individual naturally envenomed dogs, with and without CORM‐2, using thromboelastography (TEG). We tested venom effects on coagulation using tissue factor (TF) activated TEG and on both coagulation and fibrinolysis using TF‐activated TEG with added tPA. We found that 17.9 µg/mL of venom causes a mean 26.4% decrease in clot strength, a 61.8% decrease in maximum rate of thrombus generation, 75% faster clot lysis, a 226% increase in maximum rate of lysis and a 92% decrease in total clot life span (CLS). CORM‐2 ameliorated these effects, increasing CLS in the presence of venom by 603%. Additionally, we showed that CORM‐2 has similar effects in vitro on plasma from naturally envenomed dogs, showing promise as an adjunct therapy for snake envenomation.}, number={4}, journal={BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY}, author={Johnson, Tyler E. and Wells, Raegan J. and Bell, Amy and Nielsen, Vance G. and Olver, Christine S.}, year={2019}, month={Oct}, pages={328–336} }
 @article{johnson_mach_grove_kelly_van cott_blum_2018, title={Secretion and fusion of biogeochemically active archaeal membrane vesicles}, volume={16}, ISSN={["1472-4669"]}, DOI={10.1111/gbi.12306}, abstractNote={Microbes belonging to the genus Metallosphaera oxidize sulfidic minerals. These organisms thrive at temperature extremes and are members of the archaeal phylum Crenarchaeota. Because they can employ a lithoautotrophic metabolism, energy availability likely limits their activity raising questions about how they conduct biogeochemical activity. Vesicles are membrane encapsulated structures produced by all biological lineages but using very different mechanisms. Across the Crenarchaeota, it has been proposed that a eukaryotic‐like Endosomal Sorting Complex Required for Transport system promotes formation of these structures but in response to unknown signals and for undefined purposes. To address such questions, Metallosphaera sedula vesicle formation and function were studied under lithoautotrophic conditions. Energy deprivation was evaluated and found to stimulate vesicle synthesis while energy excess repressed vesicle formation. Purified vesicles adhered rapidly to the primary copper ore, chalcopyrite, and formed compact monolayers. These vesicle monolayers catalyzed iron oxidation and solubilization of mineralized copper in a time‐dependent process. As these activities were membrane associated, their potential transfer by vesicle fusion to M. sedula cells was examined. Fluorophore‐loaded vesicles rapidly transferred fluorescence under environmentally relevant conditions. Vesicles from a related archaeal species were also capable of fusion; however, this process was species‐specific as vesicles from different species were incapable of fusion. In addition, vesicles produced by a copper‐resistant M. sedula cell line transferred copper extrusion capacity along with improved viability over mutant M. sedula cells lacking copper transport proteins. Membrane vesicles may therefore play a role in modulating energy‐related traits in geochemical environments by fusion‐mediated protein delivery.}, number={6}, journal={GEOBIOLOGY}, author={Johnson, Tyler B. and Mach, Collin and Grove, Ryan and Kelly, Robert and Van Cott, Kevin and Blum, Paul}, year={2018}, month={Nov}, pages={659–673} }