Ketamine immunomodulation during endotoxemia

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file."August 2007"Includes bibliographical references.Thesis (M.S.) University of Missouri-Columbia 2007.Dissertations, Academic -- University of Missouri--Columbia -- Veterinary medicine and surgery.[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Previous studies have shown that ketamine attenuates endotoxin (LPS)-induced production of tumor necrosis factor (TNF)-[alpha] in murine models. Because TNF-[alpha] is a key mediator of the systemic and pulmonary inflammatory response to infection, we hypothesized that ketamine would ameliorate LPS-induced acute lung injury (ALI) in rats and prevent the hemodynamic and immunologic alterations in dogs. Forty male CD rats were divided into 4 treatment groups: control, ketamine, LPS and LPS+ ketamine. Rats were euthanized at either 1 or 6 hours after LPS administration for determination of serum TNF-[alpha] activity or pulmonary evaluation. Ketamine treatment blunted LPSinduced serum TNF-[alpha] activity but did not ameliorate the pulmonary histopathologic changes associated with endotoxemia. For the second study, nine dogs were randomized to either ketamine or placebo treatment groups in a cross-over design. At 30 min, LPS was administered. Heart rate (HR), systolic arterial blood pressure (SAP), plasma TNF-[alpha] activity and white blood cell (WBC) counts were evaluated. Dogs in the ketamine group had significantly lower HR and peak plasma TNF-[alpha] activity after LPS administration versus placebo. There were no differences detected between treatment groups for SAP or white blood cell counts. Based on these data, while ketamine ameliorates TNF-[alpha] production in rats and dogs, it is unlikely to have a clinically important impact on the development of acute lung injury, perturbations in WBC count or SAP during Gram negative sepsis

Effects of Orally Administered Resveratrol on TNF, IL-1β, Leukocyte Phagocytic Activity and Oxidative Burst Function in Horses: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Study

Resveratrol, a phytophenol, is a commonly used equine nutraceutical supplement touted to exert anti-inflammatory effects. The effect of orally administered resveratrol on tumor necrosis factor (TNF), interleukin-1β (IL-1β), leukocyte phagocytic activity or oxidative burst function have not been reported in horses. The objective of this study was to determine the effects of a commercially available, orally administered resveratrol product on innate immune functions in healthy adult horses. Whole blood was collected from 12 horses prior to and following 3 weeks of treatment with either the manufacturer’s recommended dose of resveratrol or placebo. Phagocytosis, oxidative burst and pathogen associated molecular pattern (PAMP) motif-stimulated leukocyte production of TNF and IL-1β were compared pre- and post-treatment between treatment groups. Phagocytosis and oxidative burst capacity were evaluated via flow cytometry. Tumor necrosis factor and IL-1β were measured using cytotoxicity and ELISA assays, respectively. There were no significant differences in phagocytosis, oxidative burst or stimulated TNF or IL-1β production between resveratrol and placebo treatment groups. Orally administered resveratrol at a routinely recommended dose for a duration of 3 weeks did not significantly affect phagocytic activity, oxidative burst function or PAMP-stimulated leukocyte cytokine production

Serum vitamin D concentration in hospitalized critically ill dogs

DOI of related article: 10.1371/journal.pone.0194062.Citation of related article: Jaffey JA, Backus RC, McDaniel KM, DeClue AE (2018) Serum vitamin D concentrations in hospitalized critically ill dogs. PLoS ONE 13(3): e0194062. https://doi.org/10.1371/journal.pone.0194062Abstract of related article: Hypovitaminosis D has been extensively documented in critically ill humans. However, whether or not critically ill dogs have alterations in vitamin D concentrations remains unconfirmed. The primary aims of our study were to compare serum 25-hydroxycholecalciferol [25(OH)D] concentrations in critically ill dogs with healthy control dogs, determine the prognostic utility of serum 25(OH)D concentration as a biomarker in critically ill dogs, and to assess if serum 25(OH)D concentrations in critically ill dogs are associated with length of stay in the intensive care unit or illness severity. Serum concentrations of 25(OH)D together with a range of other clinical, biochemical, and hematological parameters, were measured in 99 dogs within 24 hours of admission to the Intensive Care Unit (ICU). Critically ill dogs (P = 0.001) and dogs with sepsis (P = 0.002) had significantly lower serum 25(OH)D concentrations compared to healthy control dogs. In addition, serum 25(OH)D concentration was an independent predictor of in-hospital and 30 day survival. Using a cut-off of 33 ng/mL, serum 25(OH)D concentrations had excellent sensitivity (0.94; 95% CI, 0.71–1.00), but poor specificity (0.41; 95% CI, 0.31–0.53) for detection of survival. Serum 25(OH)D concentrations were inversely associated with acute patient physiologic and laboratory evaluation (APPLE) fast score but were not associated with ICU length of stay. Hospitalized dogs with critical illness have decreased serum 25(OH)D concentrations compared to healthy dogs and can be used to predict survival in this cohort

Immune response to C. novyi-NT immunotherapy

Abstract Clostridium novyi-NT (CVN-NT) spores germinate in hypoxic regions of tumors and have successfully cured induced neoplasia in mouse models and resulted in objective tumor responses in naturally developing neoplasia in the dog. The objective of this pilot, descriptive, prospective, clinical investigation, was to evaluate and describe the immune response to CNV-NT spores to better understand which immune pathways might play a role in the response to this bacteriolytic immunotherapy. Intratumoral injection of CNV-NT spores result in increased phagocytosis and NK cell-like function after treatment. Intravenous injection of CNV-NT spores resulted in increased LPS-induced TNF-α production, LTA-induced IL-10 production and NK cell-like function post-treatment. Increased NK cell-like function was sustained to 28 (intratumoral) or 56 (intravenous) days post-treatment, and increased phagocytic function was sustained to 28 days post-treatment suggesting that CNV-NT spores induce longer-term immune cell function changes. Future investigations evaluating long-term immune system changes and associations between immune function and tumor remission rates should include evaluation of these pathways

Receiver-operating characteristic (ROC) curve and dot plot comparing the diagnostic sensitivity and 1-specificity of serum 25(OH)D concentration for determining survival 30 days after discharge.

<p>(A) The diagonal red line represents the reference line. (B) The horizontal red line represents the optimal serum 25(OH)D concentration cutoff of 30 ng/ml.</p

Mentation score [37].

<p>Adapted from Hayes et al., 2010.</p

Box and whiskers plot comparing serum 25(OH)D concentrations in survivor and non-survivor critically ill dogs.

<p>The boxes represent the 25th and 75th quartiles with the horizontal line representing the median. The whiskers represent the range of the data. The black circles represent results for individual dogs. (A) Dogs that survived (n = 82) to discharge had significantly greater serum 25(OH)D concentration than non-survivors (n = 17). (B) Dogs that were alive (n = 23) 30 days after discharge had significantly greater serum 25(OH)D concentrations than non-survivors (n = 70).</p