Persistent hypercoagulability in dogs envenomated by the European adder (Vipera berus berus)

Background Envenomation by the European adder, Vipera berus berus (Vbb), is a medical emergency. The overall in vivo haemostatic effects of pro- and anticoagulant components in Vbb venom, and the downstream effects of cellular injury and systemic inflammation, are unclear. Objectives To longitudinally describe the global coagulation status of dogs after Vbb envenomation and compare to healthy controls. A secondary aim was to investigate differences between dogs treated with and without antivenom. Methods Citrated plasma was collected at presentation, 12 hours (h), 24 h, 36 h and 15 days after bite from 28 dogs envenomated by Vbb, and from 28 healthy controls at a single timepoint. Thrombin generation (initiated with and without exogenous phospholipids and tissue factor), thrombin-antithrombin (TAT)-complexes and the procoagulant activity of phosphatidylserine (PS)-expressing extracellular vesicles (EVs), expressed as PS-equivalents, were measured. Results At presentation the envenomated dogs were hypercoagulable compared to controls, measured as increased thrombin generation, TAT-complexes and PS-equivalents. The hypercoagulability decreased gradually but compared to controls thrombin generation and PS-equivalents were still increased at day 15. The discrepancy in peak thrombin between envenomated dogs and controls was greater when the measurement was phospholipid-dependent, indicating that PS-positive EVs contribute to hypercoagulability. Lag time was shorter in non-antivenom treated dogs, compared to antivenom treated dogs <24 h after envenomation. Conclusions Hypercoagulability was measured in dogs up to 15 days after Vbb envenomation. Dogs treated with antivenom may be less hypercoagulable than their non-antivenom treated counterparts. Thrombin generation is a promising diagnostic and monitoring tool for Vbb envenomation.publishedVersio

Immunohistochemical expression of β-catenin, Ki67, CD3 and CD18 in canine colorectal adenomas and adenocarcinomas

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Ambulatory Electrocardiography and Serum Cardiac Troponin I Measurement in 21 Dogs Envenomated by the European Adder (Vipera Berus)

Background: Envenomation by the European adder (Vipera berus) is common in dogs in Europe. Cardiac arrhythmias occur but clinical studies of envenomated dogs are limited. Objectives: To describe arrhythmias in dogs within 48 hours of envenomation, and investigate associations between arrhythmia grade, serum troponin I (cTnI), and snakebite severity score (SS score). Animals: Twenty-one client-owned dogs bitten by V berus. Methods: Prospective cohort study of envenomated dogs. Ambulatory electrocardiograms were recorded from presentation to 48 hours after snakebite, and arrhythmias graded 0 to 3 based on frequency and severity. Serum cTnI was measured at presentation, 12 hours, 24 hours, 36 hours, and 14 days after bite. An SS score of 1 to 3 was recorded at admission and based on clinical examination. Results: All dogs survived. Twelve dogs (57%) developed arrhythmias, all of which were ventricular in origin. Severe complex ventricular arrhythmias (VAs) were observed in 6 dogs (29%). Eighty-one percent of dogs (n = 17) had increased cTnI concentrations at 1 or more time points. Dogs that developed arrhythmias had significantly higher concentrations of cTnI at 12 hours (1.67 [0.04-32.68] versus 0.03 [0.01-0.052]; P = .002), 24 hours (1.88 [0.2-14.23] versus 0.06 [0.01-2.06]; P = .009), and 36 hours (3.7 [0.02-16.62] versus 0.06 [0.01-1.33]; P = .006) after bite compared to those that did not. Contingency table analysis showed that SS score was not significantly associated with arrhythmia grade (P = .9).publishedVersio

Ambulatory Electrocardiography and Serum Cardiac Troponin I Measurement in 21 Dogs Envenomated by the European Adder (Vipera Berus)

Background: Envenomation by the European adder (Vipera berus) is common in dogs in Europe. Cardiac arrhythmias occur but clinical studies of envenomated dogs are limited. Objectives: To describe arrhythmias in dogs within 48 hours of envenomation, and investigate associations between arrhythmia grade, serum troponin I (cTnI), and snakebite severity score (SS score). Animals: Twenty-one client-owned dogs bitten by V berus. Methods: Prospective cohort study of envenomated dogs. Ambulatory electrocardiograms were recorded from presentation to 48 hours after snakebite, and arrhythmias graded 0 to 3 based on frequency and severity. Serum cTnI was measured at presentation, 12 hours, 24 hours, 36 hours, and 14 days after bite. An SS score of 1 to 3 was recorded at admission and based on clinical examination. Results: All dogs survived. Twelve dogs (57%) developed arrhythmias, all of which were ventricular in origin. Severe complex ventricular arrhythmias (VAs) were observed in 6 dogs (29%). Eighty-one percent of dogs (n = 17) had increased cTnI concentrations at 1 or more time points. Dogs that developed arrhythmias had significantly higher concentrations of cTnI at 12 hours (1.67 [0.04-32.68] versus 0.03 [0.01-0.052]; P = .002), 24 hours (1.88 [0.2-14.23] versus 0.06 [0.01-2.06]; P = .009), and 36 hours (3.7 [0.02-16.62] versus 0.06 [0.01-1.33]; P = .006) after bite compared to those that did not. Contingency table analysis showed that SS score was not significantly associated with arrhythmia grade (P = .9)

Serial serum creatinine, SDMA and urinary acute kidney injury biomarker measurements in dogs envenomated by the European adder (Vipera berus)

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Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome

Background: Meconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a piglet MAS model. Additionally, we showed ex vivo that meconium-induced inflammation was dependent on complement and Toll-like receptors. Objectives: To assess the efficacy of the combined inhibition of complement (C5) and CD14 on systemic inflammation induced in a forceful piglet MAS model. Methods: Thirty piglets were randomly allocated to a treatment group receiving the C5-inhibitor SOBI002 and anti-CD14 (n = 15) and a nontreated control group (n = 15). MAS was induced by intratracheal meconium instillation, and the piglets were observed for 5 h. Complement, cytokines, and myeloperoxidase (MPO) were measured by ELISA. Results: SOBI002 ablated C5 activity and the formation of the terminal complement complex in vivo. The combined inhibition attenuated the inflammasome cytokines IL-1β and IL-6 by 60 (p = 0.029) and 44% (p = 0.01), respectively, and also MPO activity in the bronchoalveolar fluid by 42% (p = 0.017). Ex vivo experiments in human blood revealed that the combined regimen attenuated meconium-induced MPO release by 64% (p = 0.008), but there was only a negligible effect with single inhibition, indicating a synergic cross-talk between the key molecules C5 and CD14. Conclusion: Combined inhibition of C5 and CD14 attenuates meconium-induced inflammation in vivo and this could become a future therapeutic regimen for MAS