Laminar Leukocyte Accumulation in Horses with Carbohydrate Overload‐Induced Laminitis

Faleiros, Rafael Resende; Johnson, Philip J.; Nuovo, Gerard J.; Messer, Nat T.; Black, Samuel J.; Belknap, James K.

doi:10.1111/j.1939-1676.2010.0650.x

Cited by 57 publications

(78 citation statements)

References 24 publications

(36 reference statements)

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“…However, the epidermis and basement membrane PAS grades were consistently low (2 to 3) compared to other studies of carbohydrate overload models (Faleiros et al 2011a, Visser & Pollitt 2011 reported extensive epidermal cell detachment from the basement membrane (corresponding to score 5) 48 h after administering the same oligofructose dose. Similarly, in a cornstarch model using the same PAS grade system, PAS scores between 3 and 4 occurred in 50% of subjects between 20 and 48h (Faleiros et al 2011a).…”

Section: Discussionmentioning

confidence: 66%

“…Feet were biopsied sequentially, and the forefeet were biopsied at the later time points (36 and 72h) because they are more prone to developing laminitis lesions. A prior study revealed significant variability in the carbohydrate overload-induced laminitis lesions between samples obtained from a single hoof (Faleiros et al 2011a); therefore, three samples were taken from each hoof.…”

Section: Discussionmentioning

confidence: 99%

“…The sections were scored using a histological grading system for assessing lamellar degradation (Faleiros et al 2011a). All sections were scored by an investigator blinded to the collection times and treatment groups.…”

Section: Methodsmentioning

confidence: 99%

“…Despite recent evidence indicating leukocyte involvement in laminitis development (Black et al 2006, Hurley et al 2006, Loftus et al 2007, Stewart et al 2009, Faleiros et al 2009b, Faleiros et al 2011a, and the therapeutic potential of DF1681B for neutrophil migration in rodents, this drug has not yet been studied in horses.…”

Section: Introductionmentioning

confidence: 99%

“…Dermal-epidermal junction collapse is common in laminitis of numerous etiologies, but the initial event triggering the structural failure remains poorly understood (Katz & Bailey 2012). Multiple studies propose resident leukocyte activation in the lamella and leukocytic infiltration from the bloodstream, associated with systemic inflammatory response syndrome (SIRS), as probable mechanisms that initiate structural failure (Black et al 2006, Hurley et al 2006, Loftus et al 2007, Stewart et al 2009, Faleiros et al 2009b, Faleiros et al 2011a. Increased pro-inflammatory cytokine expression (mainly IL-1β and IL-6), as well as CXC and CCR chemokines, during the developmental stage, indicates that these molecules may play an important role in leukocyte migration in the early events of laminitis , Faleiros et al 2009a, Leise et al 2011, Faleiros et al 2011b, Visser et al 2011).…”

Section: Introductionmentioning

confidence: 99%

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Histologic and inflammatory lamellar changes in horses with oligofructose-induced laminitis treated with a CXCR1/2 antagonist

et al. 2016

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RESUMO.-[Alterações histológicas e inflamatórias no tecido laminar de equinos submetidos ao modelo de laminite por oligofrutose e tratados com um antagonista para CXCR1/2.] A expressão de quimiocinas e a infiltração de leucócitos no tecido laminar são característicos de laminite aguda de equinos. O presente estudo avaliou o efeito terapêutico da administração intravenosa de DF1681B , um antagonista seletivo para CXCR1 e CXCR2 (receptores de quimiocinas), em um modelo de laminite equina por oligofrutose. Utilizaram-se doze cavalos sem raça definida, compreendendo quatro machos e oito fêmeas não gestantes, com idade (média ±SD) 7±3,5 anos, pesando 305±35kg e com uma pontuação média de condição corporal de 5±1/9. Os indivíduos elegíveis eram clinicamente saudáveis, sem história prévia de claudicação relacionados ao casco. Após administração de oligofrutose (10g/kg por sonda nasogás-trica), os animais foram divididos em dois grupos: tratado (30mg/kg de DF1681B intravenosa, 6, 12, 18 e 24h após a oligofrutose) e não tratado, que recebeu placebo. Bióp-sias laminares foram realizadas antes e 12, 36 e 72h após a administração de oligofrutose. As amostras foram coradas com ácido periódico de Schiff (PAS) e classificadas de 0-6 de acordo com alterações nas células epidérmicas e na membrana basal. Também determinaram-se as expressões gênicas de IL-1β, CXCL1 e IL-6 por RT-PCR. Testes paramé-tricos e não paramétricos foram utilizados para comparar os momentos em cada grupo (P<0,05). Estatisticamente, os graus PAS e as expressões de IL-1β e IL-6 se elevaram após a indução no grupo não tratado, mas se mantiveram cons- With the hypothesis that blocking chemokine signaling can ameliorate acute laminitis, the aim was to evaluate the therapeutic effect of intravenous DF1681B, a selective antagonist for CXCR1 and CXCR2 (chemokine receptors), in an oligofructose equine laminitis model. To twelve mixed breed clinically healthy hoses with no previous history of hoof-related lameness was administered oligofructose (10g/kg given by nasogastric tube) and divided into two groups: treated (intravenous DF1681B at 30mg/kg 6, 12, 18, and 24h after oligofructose) and non-treated groups. Laminar biopsies were performed before and 12, 36, and 72h after administering oligofructose. Samples were stained with periodic acid-Schiff (PAS) and scored from 0 to 6 according to epidermal cell and basal membrane changes. The IL-1β, IL-6, and CXCL1 RNA expressions were determined by RT-PCR. Parametric and non--parametric tests were used to compare times within each group (P<0.05). The PAS grades and IL-1β and IL-6 RNA expression increased in the non-treated group, but remained constant in the treated horses. In conclusion, DF1681B therapy reduced laminar inflammation and epidermal deterioration in treated horses. CXCR1/2 blockage should be considered therapeutically for equine acute laminitis. tantes nos cavalos tratados. Em conclusão, a terapia por DF1681B reduziu a inflamação laminar e a deterioração epidérmica em equinos submetidos ao modelo de intoxicaç...

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%