Laminar Inflammatory Gene Expression in the Carbohydrate Overload Model of Equine Laminitis

Leise, Britta S.; Johnson, Philip J.; Faleiros, Rafael Resende; Black, Samuel J.; Belknap, James K.

doi:10.1016/j.jevs.2010.01.030

Cited by 23 publications

(68 citation statements)

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“…Porém existem evidências de que o processo inϐlama-tório que precede a doença é sistêmico, e não apenas local, com ativação de leucócitos sanguíneos (Hurley et al 2006). Leise et al (2011) observaram que ocorre aumento da expressão genética de diversos fatores inϐlamatórios, como as interleucinas IL-1β, IL-6 e a ciclooxigenase 2, em equinos após a indução de laminite por administração de carboidrato. Contribuindo também para esta hipótese, o estudo de Visser & Pollitt (2011c) demonstrou que a degradação do colágeno tipo IV, presente no tecido laminar do casco, ocorre em outros locais do organismo de um cavalo com laminite, como pele e estômago, o que sugere fator desencadeante sistêmico para a doença.…”

Section: Resultsunclassified

Lipocalina associada à gelatinase de neutrófilos (NGAL) e calprotectina no tecido laminar de equinos após obstrução jejunal, tratados ou não com hidrocortisona

Laskoski

Valadão

Vasconcelos³

et al. 2012

Pesq. Vet. Bras.

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Section: Resultsunclassified

Lipocalina associada à gelatinase de neutrófilos (NGAL) e calprotectina no tecido laminar de equinos após obstrução jejunal, tratados ou não com hidrocortisona

Laskoski

Valadão

Vasconcelos³

et al. 2012

Pesq. Vet. Bras.

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“…This protocol was designed to counter the developmental phase (6-30h after carbohydrate administration) when the major pro-inflammatory cytokine expression. (Leise et al 2011, Visser & Pollitt 2011, chemokines (Faleiros et al 2011b), and leukocyte immigration (Faleiros et al 2011a, Visser & Pollitt 2011 begin in the lamellae.…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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“…are present at the onset of lameness in horses with CHO induced laminitis (Ingvastlarsson et al 1992;Belknap et al 2007;Leise et al 2011;Kwon et al 2013). Cytokines can regulate protease expression and activation, and may be involved in initiating the excessive protease activation that occurs during laminitis development (Mauviel 1993).…”

Section: Theories On Laminitis Pathogenesismentioning

confidence: 99%

“…Several key steps in laminitis pathophysiology have been elucidated, resulting in identification of drugs that may prevent laminitis (anti-laminitis drugs (ALDs)). Potential therapeutic targets involved in sepsisrelated laminitis include inflammation (Belknap, Giguere et al 2007;Leise, Faleiros et al 2011;Leise, Watts et al 2012;Tadros, Frank et al 2012), proteolytic enzyme activation (Pollitt, Pass et al 1998;Visser and Pollitt 2012;Wang, Pawlak et al 2012) and destabilization of the laminar epidermal:dermal junction by Wnt-pathway dysregulation (Wang, Pawlak et al 2013). Activation of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, MMP-13 and MMP-14, have been implicated in laminitis pathophysiology Visser and Pollitt 2012;Wang et al 2012, Wang et al 2014.…”

Section: Introductionmentioning

confidence: 99%

Drug delivery to equine digital lamellar tissue

Underwood¹

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Laminitis, a serious and debilitating disease of the equine foot, is a significant cause of wastage in the equine industry. There is no scientifically validated treatment and laminitis prophylaxis is currently limited to digital cryotherapy. Several key steps in laminitis pathophysiology have been elucidated, resulting in identification of drugs that may prevent laminitis (anti-laminitis drugs (ALDs)). Many of these pharmaceuticals are not suitable for systemic delivery but may be amenable to either local or nanoparticle delivery mechanisms.The aim of this thesis was to evaluate local, systemic and nanoparticle delivery mechanisms, using the matrix metalloproteinase (MMP) inhibitor marimastat, to establish a method of drug delivery that yields sustained therapeutic lamellar concentrations for experimental and potential clinical use. In order to establish marimastat concentrations necessary for inhibition of lamellar MMPs, zymography was performed using lamellar homogenates incubated in increasing concentrations of marimastat. Based on this assay, target marimastat concentrations of 177 ng/mL were set (the concentration necessary to inhibit 90% of lamellar MMP-2 and MMP-9).

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Laminar Inflammatory Gene Expression in the Carbohydrate Overload Model of Equine Laminitis

Cited by 23 publications

References 0 publications

Lipocalina associada à gelatinase de neutrófilos (NGAL) e calprotectina no tecido laminar de equinos após obstrução jejunal, tratados ou não com hidrocortisona

Lipocalina associada à gelatinase de neutrófilos (NGAL) e calprotectina no tecido laminar de equinos após obstrução jejunal, tratados ou não com hidrocortisona

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

Drug delivery to equine digital lamellar tissue

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