Background: Insulin resistance has been associated with risk of laminitis in horses. Genes coding for proinflammatory cytokines and chemokines are expressed more visceral adipose tissue than subcutaneous insulin-resistant (IR) humans rodents. Hypothesis/Objectives: To investigate depot-specific cytokine chemokine gene expression horses its relationship to insulin sensitivity (SI). Animals: Eleven light breed mares. Methods: Animals were classified as IR (SI = 0.58 ± 0.31 × 10−4 L/min/mU; n...

Medial thickening of the pulmonary arterial wall, secondary to smooth muscle cell (SMC) hyperplasia, is commonly observed in neonatal hypoxic hypertension. Because recent studies have demonstrated existence multiple phenotypically distinct SMC populations within media, we hypothesized that these subpopulations would differ their proliferative responses hypertension and thus contribute selective ways vascular remodeling process. Expression meta-vinculin, a muscle-specific cytoskeletal...

Summary Reasons for performing study : Recent research has indicated that inflammation plays a role in the early stages of laminitis and that, similar to organ failure human sepsis, inflammatory mechanisms may lead downstream events resulting lamellar failure. Characterisation type immune response (i.e. innate vs. adaptive) is essential order develop therapeutic strategies counteract these deleterious events. Objectives To quantitate gene expression pro‐inflammatory cytokines known be...

There is a need to assess the laminar inflammatory response in laminitis model that more closely resembles clinical cases of sepsis-related than black walnut extract (BWE) model.To determine if similar pattern inflammation, characterised by proinflammatory cytokine expression, occurs CHO as has been previously reported for BWE model.Sixteen horses administered 17.6 g starch (85% corn starch/15% wood flour)/kg bwt via nasogastric (NG) tube were anaesthetised either after developing...

Withdrawal seizure prone (WSP) and withdrawal resistant (WRS) mice were genetically selected to express severe or mild handling-induced convulsions (HIC), respectively, after cessation of chronic ethanol (EtOH) vapor inhalation. The studies reported here tested WSP WSR determine whether elevated HIC seen administration acute doses several drugs that depress central nervous system activity. EtOH, pentobarbital, t-butanol, acetaldehyde, diazepam. All initially suppressed in mice. This...

To determine proinflammatory gene expression, endothelial adhesion molecule and matrix metalloproteinase (MMP) concentrations in laminar specimens at 1.5 hours after administration of black walnut extract (BWE) to compare these values with later time points.25 horses.After nasogastric BWE, anesthesia was induced early point (ETP) horses (n = 5), between 3 4 developmental (5), 9 10 acute onset lameness (5). Anesthesia water 2 groups control (3-hour group, n 5; 10-hour 5). Real-time...

Summary Reasons for performing study: The pathophysiological events inhibited by prophylactic digital hypothermia that result in reduction of the severity acute laminitis are unknown. Objectives: To determine if inhibits lamellar inflammatory signalling during development oligofructose (OF) induced laminitis. Methods: Fourteen Standardbred horses were given 10 g/kg bwt OF nasogastric tube with one forelimb (CRYO) continuously cooled immersion ice and water (NON‐RX) at ambient temperature....

Recent research suggested that prophylactic digital cryotherapy (ICE) improved lameness scores, diminished histological changes and early laminar inflammatory signalling in horses following oligofructose administration. In clinical practice, at risk for sepsis-associated laminitis receive ICE. Evidence to support this practice is lacking.To determine factors associated with development of diagnosed colitis, including ICE.Multicentre retrospective case series.Medical records admitted 2...

Background: Insulin resistance (IR) has been widely recognized in humans, and more recently horses, but its underlying mechanisms are still not well understood. The translocation of glucose transporter 4 (GLUT4) to the cell surface is limiting step for uptake insulin‐sensitive tissues. Although downstream signaling pathways regulating GLUT defined, AS160 emerged as a potential key component. In addition, role GLUT12, one most identified GLUTs, during IR unknown. Hypothesis/Objectives: We...

Hyperinsulinaemia has been implicated in the pathogenesis of laminitis; however, laminar cell types responding to insulin remain poorly characterised.To identify expressing receptor (IRc) and/or insulin-like growth factor-1 (IGF-1R); and evaluate effect dietary nonstructural carbohydrate (NSC) on their expression.Mixed-breed ponies (n = 22) received a conditioning hay chop diet (NSC ∼6%); following acclimation, were stratified into lean 11, body condition score [BCS]≤4) or obese BCS ≥7)...

Insulin dysregulation, obesity, and exposure to high-nonstructural carbohydrate (NSC) forage are risk factors for equine metabolic syndrome-associated laminitis (EMSAL); high systemic insulin concentrations in EMSAL proposed induce cellular dysregulation the digital lamellae through activation of insulin-like growth factor-1 receptor.To use a dietary challenge model (DCM) euglycaemic-hyperinsulinaemic clamp (EHC) assess lamellar factor-related signalling.Lamellar phospho (P)-protein...

Abstract Objective —To study expression of interleukin-1beta (IL-1β) in the digital laminae horses prodromal stage experimentally induced laminitis. Animals —8 healthy adult with no signs Procedure —Black walnut extract was administered via nasogastric tube to 4 horses, and water remaining (controls). Complete blood counts physical examinations were performed every 30 minutes after administration black or water. General anesthesia when total WBC count decreased by 30% given 3 hours control...

Abstract Objective —To evaluate the pharmacokinetic-pharmacodynamic parameters of enrofloxacin and a low dose amikacin administered via regional IV limb perfusion (RILP) in standing horses. Animals —14 adult Procedures —Standing horses (7 horses/group) received either (1.5 mg/kg) or (250 mg) RILP (involving tourniquet application) 1 forelimb. Samples interstitial fluid (collected implanted capillary ultrafiltration devices) from bone marrow (BMIF) third metacarpal overlying subcutaneous...

Abstract Objective —To compare the levels of mRNA expression cycooxygenase (COX)-1 and COX-2 in digital laminae normal horses developmental stages laminitis experimentally induced by administration black walnut extract (BWE). Sample Population —Samples extracted from 5 control at onset leukopenia after BWE. Procedure —Specimens were collected anesthetized prior to euthanasia. Expression COX-1 affected was evaluated via realtime quantitative polymerase chain reaction techniques. Results...

Background:Recent reports indicate increased amounts of mRNA from inflammation‐related genes in the prodromal stage laminitis. Hypothesis:Cyclooxygenase‐1 (COX‐1) and cyclooxygenase‐2 (COX‐2) undergo distinct patterns expression equine laminae developmental (DEV) acute clinical (LAM) Animals:Horses selected an outbred population were placed into 1 4 groups: DEV (n = 5), CON‐3h (control group for DEV, n LAM 5) CON‐10h LAM, 5). Methods:Laminar skin samples obtained (1) animals either...

Background: Laminar inflammation is one of the earliest events in equine laminitis. Calprotectin (CP), a Damage‐Associated Molecular Pattern protein, overexpressed inflammatory conditions human skin. Hypothesis: CP laminar epidermis horses with black walnut extract (BWE)‐induced Animals: Twenty adult horses. Methods: Experimental study. Horses were allocated to 4 groups. BWE was administered 3 groups, which sampled 1.5, 3, and 12 hours (LAM) later. visualized by immunohistochemistry....

While there is evidence of laminar leukocyte infiltration in black walnut extract (BWE)-induced laminitis, no such for carbohydrate overload (CHO) laminitis.To assess presence leukocytes and signs epidermal stress/injury the tissue from horses with CHO-induced laminitis.Twenty-four adult horses.Immunohistochemistry myeloid cell markers calprotectin (CP) monocyte-specific marker (CD163) was performed on sections obtained 2 groups CHO model: developmental time point (DTP) group (n = 6) onset...

Summary Reasons for performing study Prophylactic digital hypothermia reduces the severity of acute laminitis experimentally but there is no evidence its efficacy as a treatment once lameness has already developed. Objectives To investigate therapeutic effects hypothermia, applied after onset lameness, in an experimental model. Study design Randomised, controlled (within subject), blinded, trial. Methods Eight Standardbred horses underwent induction using oligofructose Once was detected at...

Summary Reasons for performing study : The mediators and signalling cascades important in the initiation of laminitis remain unclear. We therefore wanted to explore genes overall mechanisms that play an role developmental stage laminitis. Objective To use a broad genomic screening technique identify novel are differentially regulated equine lamellae during period Methods Differential mRNA display (DRD) was performed discover genes, real‐time quantitative polymerase chain reaction (RT‐qPCR)...

Thickening of peripheral pulmonary arteries (PA) in the hypertensive neonate has been well described morphologically, but less is known regarding role cell proliferation either normal or neonatal PA. Thus we studied DNA synthetic indices tunica media and adventitia four different sizes/generations PA normoxic calves (n = 15) exposed to hypobaric hypoxia during first 14 days life. were determined by incorporation thymidine analogue bromodeoxyuridine (BrdU). Hemodynamic studies confirmed a...

Summary Reasons for study : Xanthine oxidase (XO)‐dependent production of superoxide anion and hydrogen peroxide, a characteristic ischaemia‐reperfusion injury, may contribute to the development equine laminitis. Objective To determine levels XO antioxidant enzymes (catalase, dismutase [SOD]) in digital laminae normal horses (CON) developmental stage laminitis using black walnut extract (BWE) model. Methods Healthy (n = 12) were administered BWE (BWE group, n 6), or water (CON 6) through...