Memoria para optar al T?tulo Profesional de M?dico Veterinario / El s?ndrome metab?lico equino (SME) se puede definir como una agrupaci?n de factores de riesgo, asociados a desregulaci?n endocrina y metab?lica, que predicen un mayor riesgo de laminitis. Hoy en d?a, se reconoce que las causas endocrinas de laminitis, principalmente SME y disfunci?n de la pars intermedia, son las principales razones de presentaci?n de ?ste signo cl?nico en la pr?ctica equina. La principal utilidad de comprender la fisiopatolog?a y el concepto de laminitis endocrina, es crear un enfoque dirigido a sus causas, con el objetivo de que se puedan tomar medidas preventivas para reducir su incidencia, en lugar de simplemente actuar frente a los casos despu?s de que hayan demostrado signolog?a cl?nica avanzada. A pesar del ?nfasis inicial que se dio a la resistencia a insulina (RI) como principal causal de este tipo de laminitis, estudios recientes han indicado que la hiperinsulinemia e hiperglicemia resultante de la RI son las responsables y no as?, a la resistencia del tejido del casco a esta hormona. Por lo tanto, una predisposici?n a hiperinsulinemia sin previo consumo de alimento, puede predecir con frecuencia la susceptibilidad a la laminitis. Aunque todos los individuos experimenten una hiperinsulinemia post prandial, ?sta puede magnificarse o manifestarse en ayunas en presencia de ciertos factores como el exceso de adiposidad regional, raza, falta de ejercicio f?sico, edad y sexo. Espec?ficamente, la presencia de obesidad, adem?s de la insulina en exceso, puede ser indicativo de SME y la desatenci?n a su control podr?a resultar en un mayor riesgo de laminitis. Para diagnosticar un ejemplar con este s?ndrome, se describe que es necesario complementar el examen f?sico con pruebas de laboratorio que identifiquen la hiperinsulinemia e hiperglicemia. Dentro de los ex?menes ya existentes para este prop?sito, estudios recomiendan que se realicen mediciones basales y din?micas a la vez, ya que los resultados de una sola prueba pueden ser inconcluyentes para este prop?sito. Una buena estrategia de control de estas alteraciones endocrinas comprende un manejo dietario y ejercicios rutinarios, los cuales, en ciertos casos, pueden ser complementados con un tratamiento farmacol?gico, basado en la utilizaci?n de Metformina y Levotiroxina, medicamentos que han demostrado tener buenos resultados en la regulaci?n de insulina y glucosa en sangre en esta especie. / Equine metabolic syndrome (EMS) can be defined as a group of risk factors, associated with endocrine and metabolic dysregulation, that predict an increased risk of laminitis. Today, it is recognized that the endocrine causes of laminitis, mainly EMS and the pars intermedia dysfunction, are the main reasons for presenting this clinical sign in equine practice. The main usefulness of understanding the pathophysiology and the concept of endocrine laminitis, is to create an approach directed to its causes, with the objective that preventive measures can be taken to reduce its incidence, instead of simply acting in front of cases after have shown advanced clinical signology. Despite the initial emphasis on insulin resistance (IR) as the main cause of this type of laminitis, recent studies have indicated that the hyperinsulinemia and hyperglycemia resulting from IR are responsible, and not the resistance of the hoof tissue to this hormone. Therefore, a predisposition to hyperinsulinemia without prior feed intake can often predict susceptibility to laminitis. Although all individuals experience post-prandial hyperinsulinemia, it can be magnified or manifested during fasting in the presence of certain factors such as excess regional adiposity, race, lack of physical exercise, age and sex. Specifically, the presence of obesity, in addition to excess insulin and glucose, may be indicative of EMS and neglecting their control could result in an increased risk of laminitis. To diagnose a specimen with this syndrome, it is described as necessary to complement the physical examination with laboratory tests that identify hyperinsulinemia and hyperglycemia. Among the existing tests for this purpose, studies recommend that baseline and dynamic measurements of these to be taken at the same time, since the results of a single test may be inconclusive for this purpose. A good strategy to control these endocrine alterations includes a dietary management and routine exercises, which, in certain cases, because of pain in the foot region due to laminitis, can be complemented with a pharmacological treatment, based on the use of Metformin and Levothyroxine, which have shown good results in the regulation of blood insulin and glucose in this species. Key words: Equine

Equine laminitis is a debilitating disease that causes extreme sufferring in afflicted horses and often results in a lifetime of chronic pain. The exact sequence of pathophysiological events culminating in laminitis has not yet been characterized, and this is reflected in the lack of any consistently effective therapeutic strategy. For these reasons, we used a newly developed 21,000 element equine-specific whole-genome oligoarray to perform transcriptomic analysis on laminar tissue from horses with experimentally induced models of laminitis: carbohydrate overload (CHO), hyperinsulinaemia (HI), and oligofructose (OF). Samples were collected during the developmental (DEV) and Obel grade 1 (OG1) stages of laminitis for the CHO model. For the HI model, samples were collected at the Obel grade 2 (OG2) stage. For the OF model, samples were collected at the 12 h and 24 h time points. Appropriate control samples were obtained for all models. This is the first genome-wide transcriptome analysis of laminar tissue using an equine 21,000 70-mer long oligoarray approach in CHO, HI and OF induced laminitis. Overall, we identified the differential expression of genes encoding S100 calcium binding proteins, extracellular matrix proteins, glycoproteins, transporters, olfactory receptors, genes involved in signal transduction, body‟s homeostasis, apoptosis, and immune response. Between CHO and OF models of laminitis, there were more shared genes. We discovered several common differentially expressed genes (i.e., ADAMTS1, CYCS and CXCL14) among all three models that are likely important to the pathogenesis of equine laminitis. We also discovered what appear to be central roles of apoptosis, inflammatory response, and intracellular ion homeostasis molecular processes in CHO and OF models of laminitis. Pathway analysis detected the NOD-like receptor signaling pathway, which is involved in recognition of intracellular bacteria in both the CHO and OF models of laminitis. Genetic network analysis indicated convergent pathway core molecules present in equine acute laminitis: p38 MAPK and NF-κB. Most importantly, our results of overexpression of anti-microbial genes (i.e., DEFB4, PI3, and CXCL14) suggest the central involvement of these genes in the progression of early equine laminitis and will allow refinement of current hypotheses of disease pathogenesis.

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In order to investigate the early ultrastructural lesions at the first sign of lameness in the oligofructose (OF) model of laminitis, the disease was induced in four horses, while another four horses were sham-treated controls. Minor lesions were detected in lamellar samples examined by light microscopy. Examination by transmission electron microscopy (TEM) showed excessive waviness, breaks and separation of portions of lamellar basement membrane (BM) in the treated horses. There was also disintegration and disappearance of hemidesmosomes (HD) and epidermal basal cell (EBC) cytoskeleton, and an increase in the distance between the EBC plasmalemma and the centre of the BM. A link was thus established between the first clinical signs of lameness and ultrastructural changes in the lamellar dermo-epidermal interface. This implied that pathogenesis was underway well before clinical signs (24 h) and that successful therapy would need to be instituted earlier than previously considered. Earlier therapy may be facilitated if delivery of efficacious drugs to the foot was achievable. A treatment modality that delivered effective concentrations of anti laminitic drugs to the target organ (the epidermal lamellae) was thus an objective of this study. Hoof lamellar tissue from five ponies treated with prolonged euglycaemic hyperinsulinaemia and four control (sham-treated) ponies were harvested and processed for TEM. Lamellae from treated ponies showed attenuation and elongation of secondary epidermal lamellae (SEL), HD number reduction and infiltration of leukocytes. Unlike carbohydrate induced laminitis in horses, there was no global separation at the lamellar dermal/epidermal interface in ponies. Two unique lamellar lesions found in this induction model was mitosis among EBCs and thickening of the BM, not normally characteristic of acute laminitis. The pathophysiology of hyperinsulinaemic laminitis remains unresolved but if insulin, delivered directly to the foot, induced laminitis several pathophysiological questions would be answered. In particular, it would emphasise the laminitogenic potential of insulin alone in the pathogenesis of laminitis. It also allows the treatment foot to be compared with the remaining three that act as internal controls. A modality that delivered drugs like insulin to the target organ (the epidermal lamellae) was needed and was an objective of this study. A microdialysis (MD) method, based on continuous sampling of the lamellar extracellular fluid (ECF), was developed to monitor lamellar drug concentrations. MD probes were implanted in the hoof lamellar tissue of six normal Standardbred horses under local anaesthesia. A bolus intravenous (IV) dose (5 mg/kg BWT) of gentamicin sulfate was injected into the jugular vein. MD and blood samples were collected at different time points during 24 h, and calibrated and analyzed using an ELISA method for gentamicin. During the first 8 h, the concentration of gentamicin was significantly higher in blood than lamellar ECF, a result that is reversed when lamellar MD is repeated during IO infusion of gentamicin. The results showed that this modestly invasive method was a useful tool to monitor changes in the lamellar ECF during drug delivery or during laminitis development. Knowledge of the anatomy and dynamics of blood circulation in the equine foot is fundamental to understand laminitis pathophysiology. Using histology, decalcification, diaphanization, computed tomography (CT), micro CT and gelatin-India Ink vascular perfusion, the normal anatomy of the dorsal part of distal phalanx (DP) and its vascular relationship to hoof lamellae was characterised. The results showed a close relationship between the distal phalangeal and lamellar circulations and raised the possibility of accessing the lamellar circulation via the DP and the possibility that IO perfusion (IOP) of the DP could deliver drugs to the lamellae. IOP of the DP with methyl methacrylate (MMA) corrosion casting material resulted in filling of the lamellar and sublamellar vascular network and incomplete filling of lamellar capillaries. Perfusion of common digital artery with a suspension of barium sulfate resulted in filling of lamellar arteries but not capillaries. Perfusion of the common digital vein resulted in filling of lamellar veins but not capillaries. Perfusion with barium sulfate partitioned veins from arteries because particle size prevented entry into capillaries. IOP with barium sulfate filled only veins revealing that vascular egress from the DP was venous. This study showed that a retrograde venous connection exists between the DP and lamellar circulations with the potential for lamellar drug delivery. Intra-arterial (IA) and IO infusion results using gelatin-India Ink were markedly improved when cadaver limbs were subjected to cyclic loading within the physiological range. Without loading lamellar capillaries failed to fill no matter what the injection pressure. Cyclic loading cadaver limbs 6 times resulted in complete lamellar capillary filling and suggested that cyclic limb loading contributed to perfusion of lamellar capillaries normally in horses. To evaluate IO delivery of drugs to hoof lamellae in the standing, conscious horse, gentamicin solution (25 mg/mL) was slowly infused (20 µL/min) through an IO bone screw. Lamellar ECF was collected via a lamellar MD probe and blood was collected from the jugular vein. Gentamicin was 50-100 times more concentrated in lamellar ECF than in blood. This study introduces a potential method for delivery of drugs into the lamellar tissue in the standing, conscious horse. Laminitis pathology occurs before clinical signs and can be induced by insulin as well as enteric OF overload. Thus therapy delivered to the target of laminitis, the hoof lamellae, has an improved chance of success if delivered promptly, safely and at high concentrations. A validated drug delivery and lamellar analysis system that achieves these criteria, was the discovery of this project and is now available to combat laminitis.

Thesis (Ph. D.) University of Missouri-Columbia, 2006. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on July 31, 2007) Includes bibliographical references.

Thesis (M.S.)--Oregon State University, 2007. / Printout. Includes bibliographical references (leaves 67-72). Also available on the World Wide Web.

The aim of the thesis is by evaluating diagnoses of veterinary clinics and surgery farrier to determine the effect on the incidence of the disease in thoroughbred his age, gender, class performance and genotype.

Orientador: Luiz Carlos Marques / Banca: Thaís Helena Constantino Patelli / Banca: Lúcia Helena Rodrigues / Banca: Daniela Gomes da Silva / Banca: Luís Guilherme de Oliveira / Resumo: Este estudo avaliou o uso da termografia infravermelha e do exame radiológico digital como ferramentas de diagnóstico precoce da laminite em ovinos com acidose ruminal subaguda induzida experimentalmente e os efeitos da ingestão prolongada de alta proporção de alimento concentrado sobre as variáveis clínicas e laboratoriais. Foram utilizadas sete ovelhas adultas, com cânulas ruminais permanentes, que não tiveram prévio contato com alimento concentrado. Para a indução da acidose ruminal, incluiu-se ao volumoso, diariamente, 10% de alimento concentrado até atingir 80%, porcentagem mantida até completarem 19 semanas. A observação dos sinais de diarreia deu-se do quarto ao 22º dia e de laminite do quinto ao 24º dia. O fluido ruminal foi predominantemente líquido, de odor ácido e coloração amarelada. Observou-se elevação inicial nos valores da frequência cardíaca, tempo de sedimentação e flotação no fluido ruminal, plaquetas, neutrófilos segmentados, AST, FA, GGT, cálcio ionizado, magnésio, glicose, ureia, triglicérides e bilirrubinas indireta e total. No início do experimento, notou-se redução da frequência respiratória, linfocitopenia, monocitopenia, hipocalcemia, hipofosfatemia, hiponatremia, hipoproteinemia e hipocolesterolemia. A frequência de movimentos ruminais, o tempo de redução do azul de metileno, os níveis sanguíneos de creatinina, bilirrubina direta, lactato e CK foram reduzidos, enquanto as médias de temperatura, peso e escore corporal, eosinófilos, albumina, cloretos e potássio no sangue aumentaram durante todo o período de observação. Redução do pH ruminal ocorreu nos primeiros dias, a despeito de sua manutenção acima de 5,5 durante as 19 semanas de observação. Mecanismos compensatórios respiratórios e metabólicos, principalmente a acidificação da urina, mantiveram o pH sanguíneo dentro dos limites fisiológicos considerados... / Abstract: This study evaluated the use of infrared termography and digital radiologic examination as early diagnostic tools for laminitis in sheep with experimentally induced subacute ruminal acidosis, and the effects of long-term ingestion of a high concentrate diet on clinical and laboratory variables. Seven adult ewes with permanent rumen cannula were used, which did not have any previous ingestion of concentrate feed. For the induction of ruminal acidosis, it was added to the roughage, 10% of concentrate feed until reach 80%, percentage held to the end of the 19-week experiment. Diarrhea signs were observed from fourth to 22nd day and laminitis from fifth to 24th day. Ruminal fluid was predominantly liquid, sour-smelling and yellowish. Initial increases of heart rate, sedimentation and flotation time, platelets, segmented neutrophils, AST, ALP, GGT, ionized calcium, magnesium, glucose, urea, triglycerides, indirect and total bilirubin were noted. At the beginning of the experiment, there was reduction of respiratory rate, lymphocytopenia, monocytopenia, hypocalcemia, hypophosphatemia, hyponatremia, hypoproteinemia, and hypocholesterolemia. Ruminal movement rate, methylene blue reduction time, creatinine, direct bilirubin, lactate and CK blood levels decreased, while body temperature, weight and score, eosinophils, albumin, chloride and potassium blood levels increase throughout the period. Ruminal pH reduction occurred within the first days, despite its maintenance above 5.5 during the 19 weeks. Respiratory and metabolic mechanisms, mainly urine acidification, remained the blood pH between physiologic limits for sheep. Sixteen protein fractions were separated by electrophoresis, among them eight proteins of unknown functions, identified by their molecular weights. Most acute phase proteins and the immunoglobulins identified in the electrophoretic fractionation varied throughout the observation ... / Doutor

No description available.