Evaluation of locking compression plate fixation of the distal phalanx to the hoof wall as a potential therapy for laminitis.

Background: Surgical stabilisation of the distal phalanx (DP) is a potential therapeutic strategy for severe acute laminitis.

Objective: To evaluate the effects of locking compression plate (LCP) fixation of the DP to the dorsal hoof wall.

Study Design: Ex vivo and in vivo experiments.

Effects of an anti-IGF-1 receptor monoclonal antibody on laminitis induced by prolonged hyperinsulinaemia in Standardbred horses.

Currently, there are no registered veterinary drugs for the treatment of endocrinopathic equine laminitis, and although this form of the disease is known to be caused by prolonged hyperinsulinaemia, the mechanism of insulin toxicity is unclear. One possibility is that high concentrations of insulin activate IGF-1 receptors (IGF-1R) in lamellar tissue, leading to uncontrolled cell proliferation and epidermal lamellar dysregulation. An equinized version of a human anti-IGF-1R therapeutic monoclonal antibody (mAb11) was generated to test this theory, using a modification of the prolonged euglycaemic-hyperinsulinaemic clamp technique.

Effects of insulin on IGF-1 receptors in equine lamellar tissue in vitro.

Although it is understood that equine endocrinopathic laminitis can be triggered by high concentrations of insulin, it is unclear whether this represents a direct action on lamellar tissue via insulin receptors (InsR), an interaction with IGF-1 receptors (IGF-1R), or some other, indirect action. This uncertainty is because of the reported scarcity of InsR in lamellar tissue and the low affinity of insulin for equine IGF-1R. In the present study, the effects of insulin and IGF-1 (as a positive control) were examined using lamellar explants isolated from the hooves of healthy horses and incubated in cell culture medium for between 2 min and 48 h.

Lamellar energy metabolism and perfusion in the euglycaemic hyperinsulinaemic clamp model of equine laminitis.

Background: Hyperinsulinaemia is associated with the development of endocrinopathic laminitis; however, the mechanisms remain unclear.

Objectives: Evaluate the effects of hyperinsulinaemia on lamellar energy metabolism and perfusion during laminitis development.

Study Design: In vivo experiment.

An investigation of the equine epidermal growth factor system during hyperinsulinemic laminitis.

Equine laminitis is a disease of the digital epidermal lamellae typified by epidermal cell proliferation and structural collapse. Most commonly the disease is caused by hyperinsulinemia, although the pathogenesis is incompletely understood. Insulin can activate the epidermal growth factor (EGF) system in other species and the present study tested the hypothesis that upregulation of EGF receptor (EGFR) signalling is a key factor in laminitis pathophysiology.

The effect of continuous digital hypothermia on lamellar energy metabolism and perfusion during laminitis development in two experimental models.

Background: Continuous digital hypothermia (CDH) prevents lamellar failure in the euglycaemic hyperinsulinaemic clamp (EHC) and oligofructose (OF) laminitis models, but the mechanisms remain unclear.

Objectives: To evaluate the effects of CDH on lamellar energy metabolism and perfusion in healthy horses and during EHC and OF laminitis models.

Study Design: In vivo experiment.

The effect of different grazing conditions on the insulin and incretin response to the oral glucose test in ponies.

Background: The oral glucose test (OGT) is a useful tool for diagnosing insulin dysregulation (ID) and is somewhat repeatable in ponies under consistent management. This study aimed to determine whether the insulin and incretin responses to an OGT in ponies differed after short-term access to fertilised pasture, compared to unfertilised pasture, by using a randomised, repeated measures study design. Sixteen mixed-breed ponies were classified as severely insulin-dysregulated (SD; post-prandial insulin ≥80 μIU/mL) or not severely insulin-dysregulated (NSD; post-prandial insulin < 80 μIU/mL) using an OGT prior to the study.

Ultrastructural examination of basement membrane pathology in horses with insulin-induced laminitis.

The third phalanx of the equine digit is suspended within the hoof capsule by a specialized interdigitating dermoepidermal layer called the lamellae, which fails during laminitis. Pathology of the basement membrane (BM), which interfaces epidermis and dermis, is evident during acute laminitis. However, BM damage appears to be less prevalent in ponies with the insulin-associated form of laminitis.

A "modified Obel" method for the severity scoring of (endocrinopathic) equine laminitis.

Background: Laminitis is a common equine disease characterized by foot pain, and is commonly diagnosed using a five-grade Obel system developed in 1948 using sepsis-related cases. However, endocrinopathic laminitis is now the most common form of the disease and clinical signs may be mild, or spread across two Obel grades. This paper describes a modified method which assigns scores to discreet clinical signs, providing a wider scale suitable for use in a research setting.

Insulin and incretin responses to grazing in insulin-dysregulated and healthy ponies.

Background: Supraphysiological insulin and incretin responses to a cereal-based diet have been described in horses and ponies with insulin dysregulation (ID). However, the hormonal responses to grazing have not yet been described.

Objectives: To determine if there is a difference in the insulin and incretin responses to grazing pasture between insulin-dysregulated and healthy ponies.

The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies.

There are no registered veterinary drugs for treating insulin dysregulation and preventing insulin-associated laminitis in horses. Velagliflozin is a sodium-glucose co-transport 2 inhibitor that reduces renal glucose reabsorption, promotes glucosuria, and consequently, decreases blood glucose and insulin concentrations. This study aimed to determine if velagliflozin reduced hyperinsulinemia and prevented laminitis in insulin-dysregulated ponies fed a challenge diet high in non-structural carbohydrates (NSC).

Sweet taste receptor inhibitors: Potential treatment for equine insulin dysregulation.

Hyperinsulinemia is a major risk factor for equine laminitis, a debilitating and painful foot condition. Sweet taste receptor (T1R2/3) inhibitors have been used to reduce the insulin and glucose responses to oral carbohydrates in other species. However, their effect in horses has not been investigated.

Effect of Continuous Digital Hypothermia on Lamellar Inflammatory Signaling When Applied at a Clinically-Relevant Timepoint in the Oligofructose Laminitis Model.

Background: Although continuous digital hypothermia (CDH) protects lamellae from injury in the oligofructose (OF) model of sepsis-related laminitis (SRL), conflicting results exist from these studies regarding effects of CDH on lamellar inflammatory events.

Hypothesis/objectives: To determine the effect of CDH on lamellar inflammatory events in normal and OF-treated horses when instituted at a clinically relevant time point (onset of clinical signs of sepsis in this model).

Animals: Standardbred geldings (n = 15) aged 3-11 years were used.

The oral glucose test predicts laminitis risk in ponies fed a diet high in nonstructural carbohydrates.

The aim of this study was to investigate the relationship between laminitis development in ponies and insulin/glucose concentrations in response to the oral glucose test (OGT) and a dietary challenge high in nonstructural carbohydrates (NSCs). After undergoing an OGT (1 g dextrose/kg BW in feed), 37 ponies with 2-h serum insulin concentrations ranging from 22 to 1,133 μIU/mL were subjected to a diet challenge period (DCP), consuming 12 g NSC/kg BW/d for up to 18 d. Insulin and glucose responses were measured on day 2 of the DCP.

Effect of Delayed Digital Hypothermia on Lamellar Inflammatory Signaling in the Oligofructose Laminitis Model.

Background: In the oligofructose (OF) model of sepsis-related laminitis (SRL), digital hypothermia ("cryotherapy") initiated before the onset of clinical signs is reported not only to limit lamellar injury, but also to cause marked inhibition of lamellar inflammatory signaling.

Hypothesis/objectives: Because hypothermia also has been reported to be protective when not initiated until the onset of lameness in the OF model of SRL, we hypothesized that the lamellar protection conferred by hypothermia is caused by local lamellar inhibition of inflammatory signaling as described when hypothermia was initiated earlier in the disease process.

Animals: Eight Standardbred geldings aged 3-11 years with no lameness and no abnormalities of the feet detectable by gross or radiographic examination.

Sustained, Low-Intensity Exercise Achieved by a Dynamic Feeding System Decreases Body Fat in Ponies.

Background: Obesity in horses is increasing in prevalence and can be associated with insulin insensitivity and laminitis. Current treatment strategies for obesity include dietary restriction and exercise. However, whether exercise alone is effective for decreasing body fat is uncertain.

Microdialysis measurements of equine lamellar perfusion and energy metabolism in response to physical and pharmacological manipulations of blood flow.

Reasons For Performing Study: A suitable method for evaluating lamellar perfusion changes and their metabolic consequences is currently lacking.

Objectives: To examine perfusion changes in lamellar tissue using serial microdialysis measurements of urea clearance and energy metabolites.

Study Design: Randomised, controlled (within subject) experimental trial.

Distribution of technetium-99m PEG-liposomes during oligofructose-induced laminitis development in horses.

Liposomes are phospholipid nanoparticles used for targeted drug delivery. This study aimed to determine whether intravenous liposomes accumulate in lamellar tissue during laminitis development in horses so as to assess their potential for targeted lamellar drug delivery. Polyethylene-glycol (PEG) coated liposomes were prepared according to the film hydration method and labelled using (99m)Tc-hexamethyl-propylene-amine-oxime.

Intraosseous infusion of the distal phalanx compared to systemic intravenous infusion for marimastat delivery to equine lamellar tissue.

No validated laminitis drug therapy exists, yet pharmaceutical agents with potential for laminitis prevention have been identified. Many of these are impractical for systemic administration but may be effective if administered locally. This study compared intraosseous infusion of the distal phalanx (IOIDP) with systemic intravenous constant rate infusion (CRI) to determine which was more effective for lamellar marimastat delivery.

An abattoir survey of equine dental abnormalities in Queensland, Australia.

Objective: A cadaver study to estimate the prevalence of dental disorders in horses presented at an abattoir in Queensland, Australia.

Methods: Cadaver heads at a Queensland abattoir were examined for the presence of dental abnormalities and categorised into age groups. The prevalence of abnormalities was analysed by binomial observation of observed proportion, Pearson's Chi-square test or Fisher's exact correlation test.

The suspensory apparatus of the distal phalanx in normal horses.

Reasons For Performing Study: The suspensory apparatus of the distal phalanx (SADP) is functionally and clinically important.

Objectives: To investigate SADP form and function and the microanatomy of its insertion zone.

Study Design: Descriptive gross and microanatomy.

Regional intravenous limb perfusion compared to systemic intravenous administration for marimastat delivery to equine lamellar tissue.

Pharmaceutical agents with potential for laminitis prevention have been identified. Many of these, including the MMP inhibitor marimastat, are impractical for systemic administration. This study compared local delivery of marimastat by regional limb perfusion (RLP) to systemic intravenous bolus dosing (SIVB), and established whether RLP results in local lamellar drug delivery.

Microdialysis measurements of lamellar perfusion and energy metabolism during the development of laminitis in the oligofructose model.

Reasons For Performing Study: Failure of lamellar energy metabolism, with or without ischaemia, may be important in the pathophysiology of sepsis-associated laminitis.

Objectives: To examine lamellar perfusion and energy balance during laminitis development in the oligofructose model using tissue microdialysis.

Study Design: In vivo experiment.

Ultrafiltration of equine digital lamellar tissue.

There are no experimentally validated pharmacological means of preventing laminitis; however, locally acting pharmaceutical agents with the potential to prevent laminitis have been identified. Demonstrating therapeutic drug concentrations in lamellar tissue is essential for evaluating the efficacy of these agents. The aim of this study was to develop an experimental technique for repeatedly sampling lamellar interstitial fluid.

The effect of weightbearing and limb load cycling on equine lamellar perfusion and energy metabolism measured using tissue microdialysis.

Reasons For Performing Study: Lamellar perfusion is thought to be affected by weightbearing and limb load cycling; this may be critical in the development of supporting limb laminitis.

Objectives: To document the effects of unilateral weightbearing and altered limb load cycling on lamellar energy metabolism and perfusion.

Study Design: Randomised, controlled (within subject), experimental trial.