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Solar photoexcitation of chromophoric groups in dissolved organic matter (DOM), when coupled to photoreduction of ubiquitous Fe(III)-oxide nanoparticles, can significantly accelerate DOM degradation in near-surface terrestrial systems, but the mechanisms of these reactions remain elusive. We examined the photolysis of chromophoric soil DOM coated onto hematite nanoplatelets featuring (001) exposed facets using a combination of molecular spectroscopies and density functional theory (DFT) computations. Reactive oxygen species (ROS) probed by electron paramagnetic resonance (EPR) spectroscopy revealed that both singlet oxygen and superoxide are the predominant ROS responsible for DOM degradation. DFT calculations confirmed that Fe(II) on the hematite (001) surface, created by interfacial electron transfer from photoexcited chromophores in DOM, can reduce dioxygen molecules to superoxide radicals (â¢O2-) through a one-electron transfer process. 1H nuclear magnetic resonance (NMR) and electrospray ionization Fourier-transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) spectroscopies show that the association of DOM with hematite enhances the cleavage of aromatic groups during photodegradation. The findings point to a pivotal role for organic matter at the interface that guides specific ROS generation and the subsequent photodegradation process, as well as the prospect of using ROS signatures as a forensic tool to help interpret more complicated field-relevant systems.
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Matéria Orgânica Dissolvida , Compostos Férricos , Espécies Reativas de Oxigênio , Superóxidos , FotóliseRESUMO
Thin film deposition from the vapor phase is a complex process involving adatom adsorption, movement, and incorporation into the growing film. Here, we present quantitative experimental data that reveals anion intermixing over long length scales during the deposition of epitaxial Fe2O3 and Cr2O3 films and heterostructures by oxygen-plasma-assisted molecular beam epitaxy. We track this diffusion by incorporating well-defined tracer layers containing 18O and/or 57Fe and measure their redistribution on the nanometer scale with atom probe tomography. Molecular dynamics simulations suggest potential intermixing events, which are then examined via nudged elastic band calculations. We reveal that adatoms on the film surface act to "pull up" subsurface O and Fe. Subsequent ring-like rotation mechanisms involving both adatom and subsurface anions then facilitate their mixing. In addition to film deposition, these intermixing mechanisms may be operant during other surface-mediated processes such as heterogeneous catalysis and corrosion.
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Potomac horse fever (PHF) is a common cause of equine colitis in endemic areas. Until recently, the only causative agent known to cause PHF was Neorickettsia risticii. However, N. findlayensis has been isolated from affected horses. Horses typically become infected upon ingestion of Neorickettsia spp.-infected trematodes within aquatic insects. The most common clinical signs include diarrhea, fever, anorexia, lethargy and colic. The diagnostic test of choice for PHF is PCR of blood and feces. Tetracyclines remain an effective treatment. Supportive care, including fluid therapy, colloid administration, NSAID and anti-endotoxin medication, and digital cryotherapy, is also necessary in some cases.
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Infecções por Anaplasmataceae , Colite , Doenças dos Cavalos , Neorickettsia risticii , Cavalos , Animais , Infecções por Anaplasmataceae/diagnóstico , Infecções por Anaplasmataceae/microbiologia , Infecções por Anaplasmataceae/veterinária , Doenças dos Cavalos/diagnóstico , Colite/veterinária , Diarreia/veterináriaRESUMO
The autocatalytic redox interaction between aqueous Fe(II) and Fe(III)-(oxyhydr)oxide minerals such as goethite and hematite leads to rapid recrystallization marked, in principle, by an atom exchange (AE) front, according to bulk iron isotopic tracer studies. However, direct evidence for this AE front has been elusive given the analytical challenges of mass-resolved imaging at the nanoscale on individual crystallites. We report successful isolation and characterization of the AE front in goethite microrods by 3D atom probe tomography (APT). The microrods were reacted with Fe(II) enriched in tracer 57Fe at conditions consistent with prior bulk studies. APT analyses and 3D reconstructions on cross-sections of the microrods reveal an AE front that is spatially heterogeneous, at times penetrating several nanometers into the lattice, in a manner consistent with defect-accelerated exchange. Evidence for exchange along microstructural domain boundaries was also found, suggesting another important link between exchange extent and initial defect content. The findings provide an unprecedented view into the spatial and temporal characteristics of Fe(II)-catalyzed recrystallization at the atomic scale, and substantiate speculation regarding the role of defects controlling the dynamics of electron transfer and AE interaction at this important redox interface.
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Thiamine is a vital co-factor for several anti-inflammatory and antioxidant processes that are critical for mitigation of sepsis-associated inflammation, but pharmacokinetic (PK) analysis has not been reported in horses. We hypothesized that IV thiamine hydrochloride (TH) at increasing dosages would result in corresponding increases in plasma thiamine concentrations without causing adverse effects. A randomized cross-over study was performed in 9 healthy horses that each received TH at 5, 10, and 20 mg/kg IV. Blood was collected immediately prior to drug administration and at several time points thereafter. High-performance liquid chromatography with mass spectrometry was used to quantify thiamine concentrations at each time point. Non-compartmental PK methods showed that IV TH resulted in supraphysiologic plasma concentrations with a short half-life (0.77-1.12 h) and no adverse clinical signs were observed. The terminal rate constant decreased as the dosage increased (p < .0001) and clearance significantly decreased at the 20 mg/kg dosage (p = .0011). The area under the curve (AUC) increased in a non-linear fashion. These findings suggest that thiamine follows non-linear elimination kinetics in horses, which is likely due to saturation of renal elimination. Future studies are needed to identify therapeutic plasma concentrations and develop thiamine dosing recommendations for horses.
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Tiamina , Administração Intravenosa/veterinária , Animais , Área Sob a Curva , Estudos Cross-Over , Meia-Vida , CavalosRESUMO
BACKGROUND: Ascorbic acid (AA) is an antioxidant that might be beneficial for adjunctive treatment of sepsis in horses. The optimal dose and effects on oxidative status are unknown. HYPOTHESIS: Ascorbic acid administration will increase plasma AA concentrations and decrease determinants of reactive oxygen metabolites (dROM), basal and stimulant-induced intraerythrocytic reactive oxygen species (ROS) concentrations, and stimulant-induced neutrophil ROS production, and increase plasma antioxidant capacity (PAC) in a dose-dependent manner. ANIMALS: Eight healthy horses. METHODS: Randomized placebo-controlled crossover study. Each horse received 4 single-dose IV treatments including AA at 25, 50, and 100 mg/kg and saline (placebo) with each treatment separated by ≥1 week. Blood was collected at baseline, 2 and 6 hours for assessment of plasma dROM and PAC via photometer, intraerythrocytic ROS by flow cytometry, and stimulant-induced neutrophil ROS by a fluorometric assay. Plasma AA concentrations were measured by high-performance liquid chromatography/electrochemical detection. RESULTS: Ascorbic acid at 100 mg/kg resulted in decreased dROM 2 hours after treatment (P = .03, 95% CI 5.51-121.2, point estimate 63.3). There was no effect of AA on basal or stimulant-induced intraerythrocytic ROS (P = .88, 95% CI -0.156 to 0.081, point estimate -0.037; P = .93, 95% CI -0.123 to 0.112, point estimate -0.006, respectively), basal or stimulant-induced neutrophil ROS (P ≥ .12, 95% CI -644.9 to 56.2, point estimate -294.4), or PAC (P ≥ .64, 95% CI -1567 to 463.4, point estimate -552.0) at any dose or timepoint. Plasma AA concentrations increased in a dose-dependent manner. CONCLUSIONS AND CLINICAL IMPORTANCE: High-dose administration of AA might provide antioxidant benefits in horses.
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Antioxidantes , Ácido Ascórbico , Cavalos , Animais , Ácido Ascórbico/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Estudos Cross-Over , Estresse Oxidativo , Vitaminas , Oxigênio , Administração Intravenosa/veterináriaRESUMO
Gram-negative bacterial septicemia is mediated through binding of lipopolysaccharide (LPS) to mammalian toll-like receptor protein 4 (TLR4). TLR4 and its cognate protein, myeloid differentiation factor 2 (MD2) form a heterodimeric complex after binding LPS. This complex induces a cascade of reactions that results in increased proinflammatory cytokine gene expression, including TNFα, which leads to activation of innate immunity. In horses, the immune response to LPS varies widely. To determine if this variation is due to differences in TLR4 or MD2, DNA from 15 healthy adult horses with different TNFα dynamics after experimental intravenous LPS infusion was sequenced across exons of TLR4 and MD2. Haplotypes were constructed for both genes using all identified variants. Four haplotypes were observed for each gene. No significant associations were found between either TNFα baseline concentrations or response to LPS and haplotype; however, there was a significant association (P value = 0.0460) between the baseline TNFα concentration and one MD2 missense variant. Three-dimensional structures of the equine TLR4-MD2-LPS complex were built according to haplotype combinations observed in the study horses, and the implications of missense variants on LPS binding were modeled. Although the sample size was small, there was no evidence that variation in TLR4 or MD2 explains the variability in TNFα response observed after LPS exposure in horses.
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Lipopolissacarídeos , Receptor 4 Toll-Like , Animais , Cavalos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Antígeno 96 de Linfócito/metabolismo , Receptores Toll-Like/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Mamíferos/metabolismoRESUMO
Organic macromolecules exert remarkable control over the nucleation and growth of inorganic crystallites during (bio)mineralization, as exemplified during enamel formation where the protein amelogenin regulates the formation of hydroxyapatite (HAP). However, it is poorly understood how fundamental processes at the organic-inorganic interface, such as protein adsorption and/or incorporation into minerals, regulates nucleation and crystal growth due to technical challenges in observing and characterizing mineral-bound organics at high-resolution. Here, atom probe tomography techniques were developed and applied to characterize amelogenin-mineralized HAP particles in vitro, revealing distinct organic-inorganic interfacial structures and processes at the nanoscale. Specifically, visualization of amelogenin across the mineralized particulate demonstrates protein can become entrapped during HAP crystal aggregation and fusion. Identification of protein signatures and structural interpretations were further supported by standards analyses, i.e., defined HAP surfaces with and without amelogenin adsorbed. These findings represent a significant advance in the characterization of interfacial structures and, more so, interpretation of fundamental organic-inorganic processes and mechanisms influencing crystal growth. Ultimately, this approach can be broadly applied to inform how potentially unique and diverse organic-inorganic interactions at different stages regulates the growth and evolution of various biominerals.
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Using the equine infectious anemia virus (EIAV) lentivirus model system, we previously demonstrated protective effects of broadly neutralizing immune plasma in young horses (foals) with severe combined immunodeficiency (SCID). However, in vivo selection of a neutralization-resistant envelope variant occurred. Here, we determined the protective effects of purified immunoglobulin with more potent broadly neutralizing activity. Overall, protection correlated with the breadth and potency of neutralizing activity in vitro. Four of five SCID foals were completely protected against homologous challenge, while partial protection occurred following heterologous challenge. These results support the inclusion of broadly neutralizing antibodies in lentivirus control strategies.
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Anticorpos Neutralizantes/imunologia , Anemia Infecciosa Equina/prevenção & controle , Doenças dos Cavalos/prevenção & controle , Imunoglobulinas/imunologia , Vírus da Anemia Infecciosa Equina/imunologia , Imunodeficiência Combinada Severa/veterinária , Animais , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/imunologia , Anemia Infecciosa Equina/imunologia , Anemia Infecciosa Equina/virologia , Doenças dos Cavalos/imunologia , Doenças dos Cavalos/virologia , Cavalos , Imunoglobulinas/administração & dosagem , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/virologiaRESUMO
OBJECTIVE: To report history, clinical examination findings, clinicopathologic findings, diagnostic test results, treatment, and outcome in horses with a novel idiopathic hepatitis syndrome. ANIMALS: 13 client-owned horses. PROCEDURES: Medical records of horses that were presented with fever and increased blood liver enzyme activity over a 16-month period were reviewed (December 1, 2020, to April 1, 2022). Collected data included signalment, history, clinical and clinicopathologic findings, diagnostic test results, treatment, clinical progression, and short-term outcome. RESULTS: Affected horses were presented between December and April of each of the 2 seasons investigated. The majority of horses developed cyclic fevers over the course of 3 weeks, during which time histologic evidence of hepatitis was observed. Histologic lesions included hepatic necrosis, neutrophilic to lymphohistiocytic inflammation, biliary epithelial injury, and portal fibrosis. Systemic inflammation was evidenced by increased serum amyloid A concentration and leukon changes. No horse developed signs of hepatic insufficiency, and all horses clinically recovered. Return of serum activity of GGT to within the reference range occurred within 16 weeks in most horses. Histologic lesions remained evident up to 27 weeks after initial presentation in 1 horse. CLINICAL RELEVANCE: Although an etiologic agent has not been identified, an apparently seasonal equine hepatitis syndrome was characterized by fever, systemic inflammation, increased liver enzyme activity, and histologic evidence of hepatitis. An infectious cause is suspected on the basis of histology and outcome.
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Doenças dos Cavalos , Hepatopatias , Animais , Cavalos , Hospitais Veterinários , Estações do Ano , Hospitais de Ensino , Hepatopatias/veterinária , Inflamação/veterinária , Doenças dos Cavalos/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: A systemic and dysregulated immune response to infection contributes to morbidity and mortality associated with sepsis. Peripheral blood-derived mesenchymal stromal cells (PB-MSC) mitigate inflammation in animal models of sepsis. Allogeneic PB-MSC administered IV to horses is well-tolerated but therapeutic benefits are unknown. HYPOTHESIS: After IV lipopolysaccharide (LPS) infusion, horses treated with PB-MSC would have less severe clinical signs, clinicopathological abnormalities, inflammatory cytokine gene expression, and oxidative stress compared to controls administered a placebo. ANIMALS: Sixteen horses were included in this study. METHODS: A randomized placebo-controlled experimental trial was performed. Sixteen healthy horses were assigned to 1 of 2 treatment groups (1 × 109 PB-MSC or saline placebo). Treatments were administered 30 minutes after completion of LPS infusion of approximately 30 ng/kg. Clinical signs, clinicopathological variables, inflammatory cytokine gene expression, and oxidative stress markers were assessed at various time points over a 24-hour period. RESULTS: A predictable response to IV LPS infusion was observed in all horses. At the dose administered, there was no significant effect of PB-MSC on clinical signs, clinicopathological variables, or inflammatory cytokine gene expression at any time point. Antioxidant potential was not different between treatment groups, but intracellular ROS increased over time in the placebo group. Other variables that changed over time were likely due to effects of IV LPS infusion. CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of allogeneic PB-MSC did not cause clinically detectable adverse effects in healthy horses. The dose of PB-MSC used here is unlikely to exert a beneficial effect in endotoxemic horses.
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Endotoxemia , Doenças dos Cavalos , Células-Tronco Mesenquimais , Animais , Citocinas/genética , Citocinas/metabolismo , Endotoxemia/veterinária , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Infusões Intravenosas/veterinária , Lipopolissacarídeos , Células-Tronco Mesenquimais/metabolismoRESUMO
Vaccines preventing HIV-1 infection will likely elicit antibodies that neutralize diverse strains. However, the capacity for lentiviruses to escape broadly neutralizing antibodies (NAbs) is not completely understood, nor is it known whether NAbs alone can control heterologous infection. Here, we determined that convalescent immune plasma from a horse persistently infected with equine infectious anemia virus (EIAV) neutralized homologous virus and several envelope variants containing heterologous principal neutralizing domains (PND). Plasma was infused into young horses (foals) affected with severe combined immunodeficiency (SCID), followed by challenge with a homologous EIAV stock. Treated SCID foals were protected against clinical disease, with complete prevention of infection occurring in one foal. In three SCID foals, a novel neutralization-resistant variant arose that was found to preexist at a low frequency in the challenge inoculum. In contrast, SCID foals infused with nonimmune plasma developed acute disease associated with high levels of the predominant challenge virus. Following transfer to an immunocompetent horse, the neutralization-resistant variant induced a single febrile episode and was subsequently controlled in the absence of type-specific NAb. Long-term control was associated with the presence of cytotoxic T lymphocytes (CTL). Our results demonstrate that immune plasma with neutralizing activity against heterologous PND variants can prevent lentivirus infection and clinical disease in the complete absence of T cells. Importantly, however, rare neutralization-resistant envelope variants can replicate in vivo under relatively broad selection pressure, highlighting the need for protective lentivirus vaccines to elicit NAb responses with increased breadth and potency and/or CTL that target conserved epitopes.
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Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anemia Infecciosa Equina/imunologia , Soros Imunes/imunologia , Vírus da Anemia Infecciosa Equina/imunologia , Animais , Cavalos , Vírus da Anemia Infecciosa Equina/genética , Imunodeficiência Combinada Severa/complicações , Linfócitos T Citotóxicos/imunologiaRESUMO
BACKGROUND: Oxidative stress refers to the accumulation of reactive oxygen species (ROS). Most assays for ROS detection are costly, laborious, and usually use indirect markers. The use of 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) is a possible alternative. This substance becomes a fluorochrome when oxidized by ROS, with the resultant fluorescence proportional to ROS concentration. Erythrocytes are highly exposed to ROS, resulting in cell damage and consequently impaired oxygen delivery. The effects of this exposure in physiologic and pathologic conditions necessitate an improvement in ROS detection methods. OBJECTIVE: We aimed to validate intraerythrocytic ROS detection by flow cytometry using DCHF-DA in healthy horses. METHODS: Erythrocytes from 31 healthy horses were isolated, incubated with DCFH-DA, and either left unstimulated or stimulated with hydrogen peroxide (H2 O2 ). For specificity, each cellular component of blood was separated and plotted according to its size and complexity. Samples were run in triplicate for intra-assay precision and five consecutive times for inter-assay repeatability. Stability was determined by analyzing the same sample up to 48 hours after blood collection. The acceptable coefficient of variation (CV) was ≤20%. RESULTS: The intra-assay CV was 1.7% and 13.3%, and the inter-assay CV was 4.8% and 17.8% for unstimulated and stimulated samples, respectively. Unstimulated and stimulated samples were stable for up to 48 and 24 hours, respectively. Stimulated samples had greater fluorescence than unstimulated samples (P < .0001). CONCLUSIONS: This flow cytometric assay demonstrated adequate specificity, precision, and stability and is, therefore, a promising technique with multiple applications for studying oxidative stress in horses.
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Peróxido de Hidrogênio , Estresse Oxidativo , Animais , Citometria de Fluxo/veterinária , Fluoresceínas , Cavalos , Espécies Reativas de OxigênioRESUMO
BACKGROUND: Immunological mechanisms involved in the pathogenesis of mild to moderate equine asthma (MEA) are not completely understood. There are limited data on bronchoalveolar lavage fluid (BALF) and blood inflammatory cytokine profiles in racehorses with MEA, and the effect of racing on inflammatory cytokines is unknown. HYPOTHESIS/OBJECTIVES: We hypothesized that inflammatory cytokine gene expression in BALF and resting blood would be higher in racehorses with lower airway inflammation compared to healthy controls, and that gene expression in blood collected immediately post-race would be increased compared to resting blood in racehorses with lower airway inflammation. ANIMALS: 38 racing Thoroughbreds (samples: 30 resting blood, 22 post-race BALF, 41 post-race blood). METHODS: Prospective observational study. Inflammatory cytokine gene expression was determined in resting blood, post-race BALF and post-race blood from racehorses with lower airway inflammation and controls. RESULTS: Lower airway inflammation was diagnosed in 79 % of racehorses (23 % neutrophilic, 67 % mastocytic, and 10 % mixed). There was no difference in gene expression in BALF or resting blood between racehorses with lower airway inflammation and controls. IL-8 gene expression was higher in post-race blood compared to resting peripheral blood, regardless of disease (p = 0052). BALF neutrophil proportions increased with increasing IL-1ß gene expression in all sample types (p = 0.0025). BALF mast cell proportions increased with increasing TNF-α gene expression in post-race blood (p = 0.015). CONCLUSIONS AND CLINICAL IMPORTANCE: Lower airway inflammation was common in a population of racehorses without respiratory signs or exercise intolerance. Exercise alone increased peripheral blood IL-8 gene expression. Inflammatory cytokine gene expression was not increased in BALF or resting blood in horses with subclinical lower airway inflammation, precluding its diagnostic utility in clinical practice.
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Asma Induzida por Exercício/veterinária , Asma/veterinária , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/genética , Doenças dos Cavalos/genética , Inflamação/veterinária , Animais , Asma/genética , Asma/imunologia , Asma/metabolismo , Asma Induzida por Exercício/genética , Asma Induzida por Exercício/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Expressão Gênica , Doenças dos Cavalos/metabolismo , Cavalos , Inflamação/genética , Inflamação/imunologia , Mastócitos/imunologia , Neutrófilos/imunologia , Esforço Físico/imunologia , EsportesRESUMO
Recent discovery of superconductivity in Nd0.8Sr0.2NiO2 motivates the synthesis of other nickelates for providing insights into the origin of high-temperature superconductivity. However, the synthesis of stoichiometric R 1-x Sr x NiO3 thin films over a range of x has proven challenging. Moreover, little is known about the structures and properties of the end member SrNiO3 Here, we show that spontaneous phase segregation occurs while depositing SrNiO3 thin films on perovskite oxide substrates by molecular beam epitaxy. Two coexisting oxygen-deficient Ruddlesden-Popper phases, Sr2NiO3 and SrNi2O3, are formed to balance the stoichiometry and stabilize the energetically preferred Ni2+ cation. Our study sheds light on an unusual oxide thin-film nucleation process driven by the instability in perovskite structured SrNiO3 and the tendency of transition metal cations to form their most stable valence (i.e., Ni2+ in this case). The resulting metastable reduced Ruddlesden-Popper structures offer a testbed for further studying emerging phenomena in nickel-based oxides.
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The objective was to compare the analgesic efficacy of ketorolac tromethamine (KT) and two other nonsteroidal anti-inflammatory drugs (NSAIDs), including flunixin meglumine (FM) and phenylbutazone (PB), using a heart bar shoe (HBS) model of reversible foot lameness in horses. Nine adult horses were used in a blinded, randomized, placebo-controlled crossover study. After induction of left front limb lameness using a modified HBS model, one of three NSAIDs (KT, 2.0 mg/kg IV; FM, 1.1 mg/kg IV; PB, 4.4 mg/kg IV) or saline (placebo) was administered IV as a single dose. Lameness was assessed every 30 minutes for 2 hours, then every hour up to 12 hours using both a lameness grading scale (lameness score; LS) and a body-mounted inertial sensor system (lameness locator; LL). High-performance liquid chromatography and mass spectrometry were used to measure plasma drug concentration at various time points. There was no difference in percent reduction of LS or LL value between KT and any other group, or between FM and placebo. The PB group showed a significantly higher percentage in LS reduction than the placebo and FM groups. The mean percent reduction in LL value was greater for the PB group than that for the placebo and FM groups. Plasma drug concentration was similar among horses for each drug at each time point, with drug concentrations decreasing over time. Thus, variation in plasma drug concentration did not influence lameness reduction for any drug. Ketorolac tromethamine was not superior to FM or PB in reducing lameness using a HBS model.
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Doenças dos Cavalos , Cetorolaco , Animais , Clonixina/análogos & derivados , Estudos Cross-Over , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Coxeadura Animal/tratamento farmacológico , Dor/veterinária , FenilbutazonaRESUMO
The mechanism by which nonsteroidal anti-inflammatory drugs mitigate pain caused by a heart bar shoe (HBS) model of lameness is unknown. The purpose of this study was to determine if this HBS model of lameness induces inflammation in horses. Five healthy adult horses from a university teaching herd were enrolled. A custom HBS was applied to the left front foot of each horse, followed by induction of the American Association of Equine Practitioners Lameness Score of 4. Inflammatory markers including serum amyloid A (SAA) concentration, local venous tumor necrosis factor alpha and prostaglandin E2 (PGE2) concentrations, and foot temperature were measured before lameness induction and 1, 3, and 13 hours after lameness induction. Lameness induction using the HBS model did not significantly increase production of plasma SAA, tumor necrosis factor alpha, or PGE2 concentrations at measured time points. Immediately and 1 hour after lameness induction, dorsal coronary band temperatures were higher in the left front foot compared with the right front foot, but there was no difference at 3 or 13 hours. In conclusion, the HBS model did not induce inflammation as assessed by select inflammatory markers, suggesting that the HBS model induces mechanical rather than inflammatory pain. This should be considered when using the HBS model to assess analgesic drugs in horses.
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Casco e Garras , Doenças dos Cavalos , Dor , Analgésicos/uso terapêutico , Animais , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Coxeadura Animal/etiologia , Dor/etiologia , Dor/veterináriaRESUMO
BACKGROUND: Sepsis is associated with ascorbic acid (AA) depletion and critical illness-related corticosteroid insufficiency (CIRCI) in humans. HYPOTHESES: Intravenous infusion of lipopolysaccharide (LPS) would (a) decrease endogneous AA concentrations, (b) induce CIRCI and (c) administration of a combination of AA and hydrocortisone (HC) would have decreased indices of inflammation compared to either drug alone. ANIMALS: Thirty-two healthy horses. METHODS: Randomized placebo-controlled experimental trial. Horses were assigned to 1 of 4 groups (saline, AA and HC, AA only, or HC only). Treatments were administered 1 hour after completion of LPS infusion. Clinical signs, clinicopathological variables, pro-inflammatory cytokine gene expression and production, and plasma AA concentrations were assessed at various time points. Serum cortisol concentrations and ACTH stimulation tests were used to detect CIRCI. RESULTS: There was no effect of drug on clinical signs or pro-inflammatory cytokine gene expression or production compared to controls at any time point. Administration of AA was associated with higher blood neutrophil counts 6 hours after LPS infusion (11.01 ± 1.02 K/µl) compared to other groups (8.99 ± 0.94 K/µL; P < .009). Adminstration of HC was associated with higher blood neutrophil counts 12 hours after LPS infusion (10.40 ± 0.75 K/µl) compared to other groups (6.88 ± 0.68 K/µl; P < .001). Serum cortisol increased from 5.11 ± 1.48 µg/dL before LPS administration to 9.59 ± 1.83 µg/dL 1 h after completion of LPS infusion (T1) without an effect of treatment (P = 0.59). CONCLUSIONS AND CLINICAL IMPORTANCE: Ascorbic acid and HC appeared to protect against LPS-induced neutrophil depletion and could be considered as adjunctive therapy in horses with endotoxemia.
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Ácido Ascórbico/uso terapêutico , Endotoxemia , Doenças dos Cavalos , Hidrocortisona/uso terapêutico , Animais , Citocinas/genética , Endotoxemia/tratamento farmacológico , Endotoxemia/veterinária , Doenças dos Cavalos/induzido quimicamente , Doenças dos Cavalos/tratamento farmacológico , Cavalos , LipopolissacarídeosRESUMO
PURPOSE: To undertake a systematic process of verification of consumer accounts of alleged genetic discrimination. METHODS: Verification of incidents reported in life insurance and other contexts that met the criteria of genetic discrimination, and the impact of fear of such treatment, was determined, with consent, through interview, document analysis and where appropriate, direct contact with the third party involved. The process comprised obtaining evidence that the alleged incident was accurately reported and determining whether the decision or action seemed to be justifiable and/or ethical. RESULTS: Reported incidents of genetic discrimination were verified in life insurance access, underwriting and coercion (9), applications for worker's compensation (1) and early release from prison (1) and in two cases of fear of discrimination impacting on access to genetic testing. Relevant conditions were inherited cancer susceptibility (8), Huntington disease (3), hereditary hemochromatosis (1), and polycystic kidney disease (1). In two cases, the reversal of an adverse underwriting decision to standard rate after intervention with insurers by genetics health professionals was verified. The mismatch between consumer and third party accounts in three life insurance incidents involved miscommunication or lack of information provision by financial advisers. CONCLUSION: These first cases of verified genetic discrimination make it essential for policies and guidelines to be developed and implemented to ensure appropriate use of genetic test results in insurance underwriting, to promote education and training in the financial industry, and to provide support for consumers and health professionals undertaking challenges of adverse decisions.