RESUMEN
BACKGROUND: Right dorsal colitis (RDC) is a nonsteroidal anti-inflammatory drug (NSAID) induced, protein losing enteropathy in horses associated with a high case fatality rate. OBJECTIVES: To describe signalment, NSAID usage, clinical presentations, clinical pathology, ultrasonographic findings, treatments, outcomes, and factors associated with survival in horses diagnosed with RDC. ANIMALS: Thirty-five horses from 7 Australian equine hospitals diagnosed with RDC. METHODS: Retrospective case series. Clinical records of cases were accepted if definitively or presumptively diagnosed by an internist with RDC and had ≥3 of: hypoproteinemia or hypoalbuminemia; diarrhea with negative test results for infectious diseases; colic for which other diseases were excluded or right dorsal colon thickening on ultrasound. Descriptive data analysis was performed for categorical and continuous variables. Univariate binominal logistic regressions were used to assess factors associated with survival. RESULTS: An overdose of NSAIDs occurred in 84% (21/25) cases where dose was known. Common clinical presentations included diarrhea (69%; 22/32), colic (61%; 20/33), and tachycardia (53%, 17/32). Common clinicopathological findings included hypoalbuminemia (83%; 26/31), hypocalcaemia (79%, 23/29), and hyperlactatemia (77%, 14/18). The right dorsal colon wall appeared subjectively thickened in 77% (24/31) cases using ultrasonography. Case fatality rate was 43% (15/35). Odds of survival significantly decreased with increasing heart rate (odds 0.84, 95% CI = 0.71-0.92, P = .01), packed cell volume (odds 0.91, 95% CI 0.82-0.98, P = .05) and abnormal appearance of mucous membranes (odds 0.05, 95% CI 0.005-0.28, P = .001) on hospital presentation. CONCLUSIONS AND CLINICAL IMPORTANCE: An overdose of NSAIDs is common in horses diagnosed with RDC. Serum albumin concentrations should be monitored in horses receiving a prolonged course of NSAIDs. Overall prognosis for RDC remains fair.
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Cólico , Colitis , Enfermedades de los Caballos , Hipoalbuminemia , Animales , Caballos , Estudios Retrospectivos , Cólico/veterinaria , Fenilbutazona/efectos adversos , Hipoalbuminemia/veterinaria , Enfermedades de los Caballos/diagnóstico por imagen , Enfermedades de los Caballos/tratamiento farmacológico , Enfermedades de los Caballos/inducido químicamente , Australia , Colitis/veterinaria , Antiinflamatorios no Esteroideos/uso terapéutico , Diarrea/veterinariaRESUMEN
BACKGROUND: Sirolimus, a mechanistic target of rapamycin inhibitor, suppresses insulin production in other species and has therapeutic potential for hyperinsulinemia in horses. HYPOTHESIS/OBJECTIVE: Determine the pharmacokinetics (PKs) of sirolimus and evaluate its effect on insulin dynamics in healthy and insulin dysregulation (ID) horses. ANIMALS: Eight Standardbred geldings. METHODS: A PK study was performed followed by a placebo-controlled, randomized, crossover study. Blood sirolimus concentrations were measured by liquid chromatography-mass-spectrometry. PK indices were estimated by fitting a 2-compartment model using nonlinear least squares regression. An oral glucose test (OGT) was conducted before and 4, 24, 72, and 144 hours after administration of sirolimus or placebo. Effects of time, treatment and animal on blood glucose and insulin concentrations were analyzed using mixed-effects linear regression. Sirolimus was then administered to 4 horses with dexamethasone-induced ID and an OGT was performed at baseline, after ID induction and after 7 days of treatment. RESULTS: Median (range) maximum sirolimus concentration was 277.0 (247.5-316.06) ng/mL at 5 (5-10) min and half-life was 3552 (3248-4767) min. Mean (range) oral bioavailability was 9.5 (6.8-12.4)%. Sirolimus had a significant effect on insulin concentration 24 hours after a single dose: median (interquartile range) insulin at 60 min (5.0 [3.7-7.0] µIU/mL) was 37 (-5 to 54)% less than placebo (8.7 [5.8-13.7] µIU/mL, P = .03); and at 120 min (10.2 [8.4-12.2] µIU/mL) was 28 (-15 to 53)% less than placebo (14.9 [8.4-24.8] µIU/mL, P = .02). There was minimal effect on glucose concentration. Insulin responses decreased toward baseline in ID horses after 7 days of treatment. CONCLUSION AND CLINICAL IMPORTANCE: Sirolimus decreased the insulinemic response to glucose and warrants further investigation.
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Enfermedades de los Caballos , Insulina , Caballos , Animales , Masculino , Prueba de Tolerancia a la Glucosa/veterinaria , Estudios Cruzados , Glucemia/análisis , GlucosaRESUMEN
BACKGROUND: Endocrinopathic laminitis develops in association with insulin dysregulation, but the role of insulin in the pathogenesis remains unclear. Hyperinsulinemia can cause hypoaminoacidemia, which is associated with integumentary lesions in other species and therefore warrants investigation as a potential mechanism in laminitis. OBJECTIVE: Evaluate plasma amino acid concentrations in the euglycemic-hyperinsulinemic clamp (EHC) and prolonged glucose infusion (PGI) laminitis models. ANIMALS: Sixteen Standardbred horses. METHODS: Prospective experimental study. Plasma amino acid concentrations were measured in samples collected every 6 hours from horses that underwent a 48-hour EHC (n = 8) or 66-hour PGI (n = 8) after a 24- or 6-hour baseline period in EHC and PGI groups, respectively. RESULTS: Fifteen of the 20 measured amino acid concentrations decreased over time in both EHC and PGI horses (P < 0.001). The median percentage change from baseline for these amino acids was: histidine (EHC: 41.5%; PGI: 43.9%), glutamine (EHC: 51.8%; PGI: 35.3%), arginine (EHC: 51.4%; PGI: 41%), glutamic acid (EHC: 52.4%; PGI: 31.7%), threonine (EHC: 62.8%; PGI: 25.2%), alanine (EHC: 48.9%; PGI: 19.5%), proline (EHC: 56.2%; PGI: 30.3%), cystine (EHC: 34.9%; PGI: 31.2%), lysine (EHC: 46.4%; PGI: 27.8%), tyrosine (EHC: 27.5%; PGI: 16.9%), methionine (EHC: 69.3%; PGI: 50.8%), valine (EHC: 50.8%; PGI: 34.4%), isoleucine (EHC: 60.8%; PGI: 38.7%), leucine (EHC: 48.2%; PGI: 36.6%), and phenylalanine (EHC: 16.6%; PGI: 12.1%). CONCLUSIONS AND CLINICAL IMPORTANCE: Hypoaminoacidemia develops in EHC and PGI laminitis models. The role of hypoaminoacidemia in the development of hyperinsulinemia-associated laminitis warrants further investigation.
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Enfermedades del Pie , Pezuñas y Garras , Enfermedades de los Caballos , Hiperinsulinismo , Aminoácidos , Animales , Enfermedades del Pie/veterinaria , Enfermedades de los Caballos/etiología , Caballos , Hiperinsulinismo/veterinaria , Estudios ProspectivosRESUMEN
BACKGROUND: Supporting limb laminitis (SLL) is suspected to be caused by lamellar ischaemia as a consequence of increased mechanical load. OBJECTIVES: Examine the effects of prolonged preferential weight bearing (PWB) on lamellar perfusion and metabolism. STUDY DESIGN: In vivo experiment. METHODS: Microdialysis probes were inserted in the lamellar and sublamellar dermis of one forelimb in 13 Standardbred horses. In six horses, a platform shoe (contralateral forelimb) was used to induce increased load on the microdialysis-instrumented forelimb (PWB). The remaining seven horses were controls (CON). All horses were housed in stocks with limb weight distribution logged continuously for 92 hours. Microdialysate was collected and analysed every 4 hours for glucose, lactate, pyruvate, and lactate to pyruvate ratio (L:P). Microdialysis urea clearance was used to estimate lamellar perfusion. Data were analysed using a mixed-effects linear regression model. RESULTS: Median [IQR] load on the microdialysis-instrumented limb was equivalent to 38.7% bwt. [37.3-40.3] in PWB and 27.3% bwt. [26.6-28] in CON. Limb offloading frequency increased in CON (P < .001) but not PWB (P = .2). Lamellar microdialysate glucose decreased in PWB (P < .001) and CON (P = .004), however, the rate of decrease was higher in PWB (P = .007). Lamellar L:P increased in PWB (P < .001) and peaked at 196 [79-656], whereas L:P did not change over time in CON (P = .6) and peaked at 42 [41-49]. Lamellar urea clearance decreased in PWB (P < .001) but not in CON (P = .3). Sublamellar L:P and urea clearance did not change over time in either group (P > .05). MAIN LIMITATIONS: The PWB model may not be representative of naturally occurring SLL. CONCLUSIONS: Evidence of lamellar ischaemia (increased L:P and decreased urea clearance) was detected exclusively in the lamellar dermis of PWB feet subjected to persistently increased load. Lamellar ischaemia is a consequence of increased mechanical load and likely contributes to the development of SLL.
Asunto(s)
Enfermedades del Pie , Pezuñas y Garras , Enfermedades de los Caballos , Animales , Metabolismo Energético , Enfermedades del Pie/veterinaria , Caballos , Inflamación/veterinaria , Perfusión/veterinaria , Soporte de PesoRESUMEN
Prudent use of antimicrobials is paramount to slow the development of resistance and for successful treatment. The use of cumulative antibiograms will allow evidence-based antimicrobial selection with consideration of local resistance patterns. We generated a "first-isolate-per-patient" cumulative antibiogram for a regional equine referral hospital. Bacterial organisms cultured from horses between 2011 and 2018, sample origin, antimicrobial susceptibilities, and multidrug-resistant (MDR) status were tabulated. Of 1,176 samples, 50% were culture positive. Overall, 93 of 374 (25%) were MDR. Of the MDR isolates, 11 (12%) were susceptible to high-importance antimicrobials only (as defined by the Australian Strategic and Technical Advisory Group on antimicrobial resistance). ß-hemolytic streptococci were uniformly susceptible to penicillin (76 of 76); 17 of 20 (85%) non-ß-hemolytic Streptococcus spp. were susceptible to penicillin. Despite veterinary-specific challenges in constructing an antibiogram, our study provides an exemplar of the clinical utility of regional-, farm-, or hospital-specific cumulative antibiograms for evidence-based empirical antimicrobial selection by veterinarians prior to susceptibility result availability.
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Bacterias/aislamiento & purificación , Caballos/microbiología , Pruebas de Sensibilidad Microbiana/veterinaria , Animales , Bacterias/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple , Hospitales Veterinarios/estadística & datos numéricos , Pruebas de Sensibilidad Microbiana/estadística & datos numéricos , QueenslandRESUMEN
BACKGROUND: Diagnosis of pituitary pars intermedia dysfunction (PPID) is problematic because of large variations in ACTH concentrations. HYPOTHESIS/OBJECTIVES: Compare the test characteristics of baseline and post-thyrotropin-releasing hormone (TRH) stimulation plasma ACTH concentrations in horses using diagnostic cutoff values (DCOVs) and reference intervals (RIs) and determine the clinical consequences of using each method. ANIMALS: One hundred six mature horses: 72 control cases and 34 PPID cases. METHODS: Prospective case-controlled study. Horses underwent monthly TRH stimulation tests. Diagnostic cutoff values were determined monthly by receiver operating characteristic curves using the Youden index. Reference intervals were determined monthly by a robust method. For each case age, sex and body condition score (BCS) were recorded. RESULTS: Baseline ACTH concentrations varied by month (P < .001) with significant "month × age" (P = .003), "month × sex" (P = .003), and "month × BCS" (P = .007) effects. Baseline ACTH concentrations were accurate to diagnose PPID (0.91 ± 0.06) with DCOVs increasing the test sensitivity (0.61 ± 0.21 to 0.87 ± 0.05, P = .002) and RI increasing test specificity (0.85 ± 0.12 to 0.98 ± 0.01, P = .01). Thyrotropin-releasing hormone stimulation improved test accuracy (0.91 ± 0.06 to 0.97 ± 0.03, P = .004). CONCLUSIONS AND CLINICAL IMPORTANCE: ACTH concentrations follow a circannual rhythm and vary with physiological factors. As using DCOVs increases the ability to detect mild cases and using RI decreases the risk of unnecessary treatments, ACTH concentrations should be interpreted within a specific clinical context. The TRH stimulation test improves the diagnosis of PPID.
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Enfermedades de los Caballos , Enfermedades de la Hipófisis , Adenohipófisis Porción Intermedia , Hormona Adrenocorticotrópica/metabolismo , Animales , Enfermedades de los Caballos/diagnóstico , Caballos , Enfermedades de la Hipófisis/diagnóstico , Enfermedades de la Hipófisis/veterinaria , Estudios Prospectivos , Hormona Liberadora de TirotropinaRESUMEN
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. Healthy Standardbred horses were infused for 48 h with 0.9% saline (negative-control, n = 6), a combination of insulin (4.5 mIU/kgBW/min) and a variable infusion of 50% glucose to maintain euglycaemia (positive-control, n = 6), or insulin and glucose, preceded by a low dose of mAb11 (20 mg), designed to treat one foot only and delivered by retrograde infusion into one forelimb (mAb-treated, n = 7). Maximum insulin concentrations were 502 ± 54.4 and 435 ± 30.4 µIU/mL in the positive-control and mAb11-treated groups, respectively (P = 0.33). While the control group remained healthy, all the insulin-treated horses developed laminitis within 30 h, as judged by clinical examination, foot radiographs and histological analysis. Some effects of insulin were not attenuated by the antibody, however, relative to the positive-control group, horses treated with mAb11 showed less sinking of the distal phalanx (P < 0.05) and milder histological changes, with markedly less elongation at the tips of the secondary epidermal lamellae (P < 0.05). These differences were apparent in both front feet and were statistically significant when the values for both feet were combined. The results confirm that IGF-1R may have a role in insulin-induced laminitis and suggest that mAb11 warrants further research as a potential agent to prevent or treat the disease.
Asunto(s)
Enfermedades de los Caballos/tratamiento farmacológico , Hiperinsulinismo/tratamiento farmacológico , Insulina/metabolismo , Receptor IGF Tipo 1/inmunología , Animales , Anticuerpos Antiidiotipos/inmunología , Anticuerpos Antiidiotipos/farmacología , Anticuerpos Monoclonales/farmacología , Proliferación Celular/efectos de los fármacos , Epidermis/efectos de los fármacos , Glucosa/metabolismo , Enfermedades de los Caballos/inmunología , Caballos , Hiperinsulinismo/inmunología , Hiperinsulinismo/patología , Hiperinsulinismo/veterinaria , Insulina/inmunología , Receptor IGF Tipo 1/antagonistas & inhibidoresRESUMEN
BACKGROUND: Continuous digital hypothermia (CDH) prevents lamellar failure in the euglycemic hyperinsulinemic clamp (EHC) model of laminitis, but the protective mechanisms are unclear. HYPOTHESIS/OBJECTIVES: To determine if CDH inhibits lamellar inflammatory signaling in the EHC model of laminitis. ANIMALS: Eight Standardbred horses. METHODS: Prospective experimental study. Horses underwent an EHC, with 1 forelimb treated with CDH and the other kept at ambient temperature (AMB). Horses were euthanized 48 hours after initiation of the EHC and lamellar tissue was analyzed via polymerase chain reaction (pro-inflammatory cytokine and chemokine genes-CXCL1, CXCL6, CXCL8, IL-6, MCP-1, MCP-2, IL-1ß, IL-11, cyclooxygenase 1 and 2, tumour necrosis factor-alpha [TNF-α], E-selectin, and intercellular adhesion molecule-1 [ICAM-1]) and immunoblotting (phosphorylated and total signal transducer and activator of transcription 1 [STAT1] and STAT3). RESULTS: Compared to AMB, lamellar messenger ribonucleic acid (mRNA) concentrations of CXCL6 (P =.02), CXCL8 (P = .008), IL-6 (P = .008), IL-1ß (P = .008), IL-11 (P = .008), and cyclooxygenase-2 (P = .008) were decreased in CDH. Cyclooxygenase-1 (P = .008) was increased in CDH, while CXCL1 (P = .15), MCP-1 (P = .05), MCP-2 (P = .46), TNF-α (P = .05), E-selectin (P = .15), and ICAM-1 (P = .15) mRNA were not significantly different. Compared to AMB, lamellar concentration of total STAT3 protein was decreased in CDH (P < .001), but there was no change in phosphorylated STAT3 (P-STAT3 [S727] P = .19; P-STAT3 [Y705] P = .05). There was no change in lamellar concentrations of total STAT1 (P = .75) or phosphorylated STAT1 (P-STAT1 [S727], P = .25; P-STAT1 [Y701], P = .64). CONCLUSIONS AND CLINICAL IMPORTANCE: These data add further support for the use of CDH as a first aid treatment for severe acute laminitis associated with hyperinsulinemia in horses.
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Enfermedades del Pie/veterinaria , Pezuñas y Garras/patología , Enfermedades de los Caballos/inducido químicamente , Hipotermia Inducida/veterinaria , Inflamación/veterinaria , Animales , Citocinas/genética , Citocinas/metabolismo , Enfermedades del Pie/inducido químicamente , Enfermedades del Pie/fisiopatología , Regulación de la Expresión Génica , Técnica de Clampeo de la Glucosa/veterinaria , Enfermedades de los Caballos/fisiopatología , Caballos , Hiperinsulinismo/veterinaria , Inflamación/inducido químicamente , Inflamación/fisiopatología , Masculino , Estudios Prospectivos , Transducción de SeñalRESUMEN
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. METHODS: Archived samples were used from Standardbred geldings that received no treatment (CON) (n = 8) or underwent EHC (n = 8) or OF (n = 6) laminitis models. Both forelimbs were instrumented with a lamellar microdialysis system, and one forelimb was cooled (CDH) with the other maintained at ambient temperature (AMB). Microdialysate was collected every 6 hours and analysed for glucose, lactate and pyruvate concentrations and lactate to pyruvate ratio (L:P). Microdialysis urea clearance was used to estimate lamellar tissue perfusion. Data were analysed using a mixed-effects linear regression model. RESULTS: Glucose did not change in CDH limbs relative to AMB in CON (P = .3), EHC (P = .3) or OF (P = .6) groups. There was a decrease in lactate (P < .001) and pyruvate (P < .01) in CDH limbs relative to AMB in all groups. L:P decreased in CON CDH relative to CON AMB (P < .001) but was not different in EHC (P = .6) and OF (P = .07) groups. Urea clearance decreased in CDH limbs relative to AMB in CON (P = .002) and EHC (P < .001), but not in OF (P = .4). MAIN LIMITATIONS: The EHC model may not mimic natural endocrinopathic laminitis. CONCLUSIONS: CDH caused a marked decrease in lamellar glucose metabolism (CON, EHC and OF) and perfusion (CON and EHC) without affecting lamellar glucose concentration. Although cellular energy failure is not a primary pathophysiological event in EHC and OF laminitis models, CDH may act by limiting energy supply to pathologic cellular processes whilst preserving those critical to lamellar homoeostasis.
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Enfermedades del Pie/veterinaria , Pezuñas y Garras , Enfermedades de los Caballos , Hipotermia/veterinaria , Animales , Metabolismo Energético , Caballos , Inflamación/veterinaria , Masculino , Modelos TeóricosRESUMEN
We describe herein the clinical, endoscopic, computed tomography (CT), pathologic, and microbiologic features of an infection caused by an under-recognized fungal pathogen, Flavodon flavus, in a 25-y-old Australian Quarter Horse. The horse had a unilateral obstructive nasal mass, resulting in stertor and dyspnea. On endoscopy, the mass was tan, multinodular, and completely obstructed the nasal passage. CT analysis revealed a large, soft tissue-attenuating and partially mineralized mass in the right nasal passage and dorsal-conchofrontal sinus, expanding into adjacent paranasal sinuses with associated bone lysis and rhinosinusitis. Histopathology of the mass on 2 occasions revealed suppurative inflammation initially, and pyogranulomatous inflammation subsequently. The inflammatory reaction surrounded numerous spherical fungal structures (~60-80 µm diameter) that stained positively on periodic acid-Schiff and Grocott methenamine silver stains. PCR for the fungal internal transcribed spacer 1 and 2 regions followed by Sanger sequencing on a cultured isolate identified the agent as F. flavus, which has only been reported previously as pathogenic in one horse in the United States, to our knowledge. Previous reports described this fungus as a nonpathogenic, environmental commensal fungus associated with insects and plants.
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Basidiomycota/aislamiento & purificación , Enfermedades de los Caballos/microbiología , Micosis/veterinaria , Rinitis/veterinaria , Sinusitis/veterinaria , Animales , Australia , Femenino , Caballos , Humanos , Masculino , Micosis/microbiología , Senos Paranasales , Reacción en Cadena de la Polimerasa , Rinitis/microbiología , Sinusitis/microbiología , Tomografía Computarizada por Rayos XRESUMEN
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. METHODS: Eight Standardbred horses were instrumented with a microdialysis probe in the lamellae of a forelimb. A 24 hours baseline period (BASELINE) was followed by 48 hours of a continuous euglycaemic hyperinsulinaemic clamp (EHC) from 24 to 72 hours (CLAMP). Microdialysate was collected every 6 hours and analysed for glucose, lactate and pyruvate concentrations and lactate-to-pyruvate ratio (L:P). Microdialysis urea clearance was used to estimate lamellar tissue perfusion. Archived microdialysis samples from six identically instrumented Standardbred horses served as controls (CON). Variables were compared over time and between EHC and CON horses using a mixed-effects linear regression model. RESULTS: Glucose concentration decreased during the CLAMP period in CON and EHC horses (P < .001), but there was no difference between CON and EHC (P > .9). Lactate concentration increased during the CLAMP period in CON and EHC horses (P < .001), however, the rate of increase was significantly higher in EHC horses relative to CON (P = .014). There was a relative increase in pyruvate concentration in EHC horses compared with CON during the CLAMP period (P = .03). L:P increased significantly in CON horses during the CLAMP period (P < .001) but not in EHC (P = .1). Urea clearance did not change in CON (P = .9) or EHC (P = .05) during the CLAMP, but did increase in EHC relative to CON (P = .02). MAIN LIMITATIONS: The effects of microdialysis probe implantation on perfusion and metabolism remain unclear. The EHC model may not mimic natural endocrinopathic laminitis. CONCLUSIONS: Laminitis developed without evidence of lamellar hypoperfusion or energy stress. Therapies to improve perfusion are unlikely to affect the initial development of endocrinopathic laminitis.
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Enfermedades del Pie/veterinaria , Pezuñas y Garras , Enfermedades de los Caballos , Animales , Metabolismo Energético , Técnica de Clampeo de la Glucosa/veterinaria , Caballos , Inflamación/veterinariaRESUMEN
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. Ultrafiltration probes were placed in both forefeet of five horses to collect lamellar interstitial fluid as lamellar ultrafiltrate (LUF). Marimastat solution (3.5 mg/mL) containing lidocaine (20 mg/mL) was infused by IOIDP at 0.15 mL/min for 12 h. After a 12 h wash-out, marimastat (3.5 mg/mL) and lidocaine were infused by constant rate infusion (CRI) at 0.15 mL/min for 12 h. LUF, plasma and lamellar tissue marimastat concentrations were quantified using UPLC-MS. Zymography was used to establish the inhibitory concentrations of marimastat for equine lamellar matrix metalloproteinases (MMPs). Data were analysed non-parametrically. There was no difference between the steady-state marimastat concentration in lamellar ultrafiltrate (LUF[M]) during IOIDP (139[88-497] ng/mL) and CRI (136[93-157] ng/mL). During IOIDP, there was no difference between marimastat concentrations in the treated foot (139[88-497] ng/mL), the untreated foot (91[63-154] ng/mL) and plasma (101[93-118] ng/mL). LUF[M] after IOIDP and CRI were >IC50 of lamellar MMP-2 and 9, but below the concentration considered necessary for in vivo laminitis prevention. Lamellar drug delivery during IOIDP was inconsistent and did not achieve higher lamellar marimastat concentrations than CRI. Modification or refinement of the IOIDP technique is necessary if it is to be consistently effective.
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Enfermedades del Pie/veterinaria , Enfermedades de los Caballos/tratamiento farmacológico , Ácidos Hidroxámicos/administración & dosificación , Infusiones Intraóseas/veterinaria , Infusiones Intravenosas/veterinaria , Inhibidores de la Metaloproteinasa de la Matriz/administración & dosificación , Animales , Femenino , Pezuñas y Garras , Caballos , Ácidos Hidroxámicos/uso terapéutico , Masculino , Inhibidores de la Metaloproteinasa de la Matriz/uso terapéuticoRESUMEN
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. A technique for placing ultrafiltration probes was developed in vitro using 15 cadaver limbs. Subsequently, lamellar ultrafiltration probes were placed in one forelimb in six living horses. Interstitial fluid was collected continuously from the probes as ultrafiltrate for 4 (n = 4) or 14 days (n = 2). The rate of ultrafiltrate collection was calculated every 12 h. Biochemical analyses were performed on ultrafiltrate collected on night 1 (12-24 h post-implantation) and night 4 (84-96 h post-implantation). Sections surrounding the probe and control tissue from the contralateral limb were harvested, stained with H&E and Masson's trichrome and scored based on the tissue response to the probe. Ultrafiltration probes were placed in the lamellar tissue in all six horses. Ultrafiltrate was collected from these probes at 55 (30-63) µL/h (median [interquartile range]). Fluid production decreased significantly with time from night 3 onwards (P < 0.05). There was no significant change in the constituents of the ultrafiltrate between nights 1 and 4 (P > 0.05). The technique was well tolerated. This study demonstrates that ultrafiltration can be used to sample equine digital lamellar interstitial fluid, and has potential for measuring lamellar drug levels.
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Cromatografía Líquida de Alta Presión/veterinaria , Pezuñas y Garras/química , Caballos/metabolismo , Preparaciones Farmacéuticas/análisis , Ultrafiltración/veterinaria , Animales , Líquido Extracelular/química , Cojera Animal/etiología , Cojera Animal/fisiopatología , Masculino , Dimensión del Dolor/veterinaria , Factores de TiempoRESUMEN
A 9-day-old Thoroughbred filly was presented for diarrhea and lethargy. Diagnostic test results were compatible with severe renal dysfunction. Diffuse cystic lesions of both kidneys were identified on ultrasonographic examination. Postmortem examination confirmed the presence of multiple renal cysts. Congenital nephropathy compatible with bilateral diffuse cystic renal dysplasia was diagnosed.
Dysplasie rénale kystique diffuse bilatérale chez une pouliche Thoroughbred âgée de 9 jours. Une pouliche Thoroughbred âgée de 9 jours a été présentée pour de la diarrhée et de la léthargie. Les résultats des tests diagnostiques étaient compatibles avec une dysfonction rénale grave. Des lésions kystiques diffuses des deux reins ont été identifiées à l'échographie. L'examen postmortem a confirmé la présence de kystes rénaux multiples. Une néphropathie congénitale compatible avec la dysplasie rénale kystique diffuse bilatérale a été diagnostiquée.(Traduit par Isabelle Vallières).
Asunto(s)
Enfermedades de los Caballos/patología , Enfermedades Renales Quísticas/veterinaria , Animales , Animales Recién Nacidos , Femenino , Caballos , Enfermedades Renales Quísticas/patologíaAsunto(s)
Infecciones por Ascaridida/veterinaria , Enfermedades de los Caballos/diagnóstico , Obstrucción Intestinal/veterinaria , Perforación Intestinal/veterinaria , Animales , Infecciones por Ascaridida/complicaciones , Infecciones por Ascaridida/diagnóstico , Infecciones por Ascaridida/patología , Ascaridoidea , Femenino , Enfermedades de los Caballos/etiología , Enfermedades de los Caballos/parasitología , Enfermedades de los Caballos/patología , Caballos , Obstrucción Intestinal/parasitología , Obstrucción Intestinal/patología , Perforación Intestinal/diagnóstico , Perforación Intestinal/etiología , Perforación Intestinal/patologíaRESUMEN
Fecal samples were collected to establish the apparent prevalence of Clostridium difficile shedding in Standardbred and Thoroughbred racehorses housed at 4 racetracks and 2 breeding facilities, and in horses admitted to a referral large animal clinic. Forty-one (7.59%) of 540 racetrack horses, seven (5.83%) of 120 breeding farm horses, and four (4.88%) out of 82 horses admitted to the referral clinic were culture-positive for C. difficile. An overall fecal culture prevalence of 7.01% for C. difficile was identified in 742 fecal samples. PCR-ribotyping and toxin gene identification was performed and seventeen 17 PCR-ribotypes were identified among the 52 C. difficile isolates.
Asunto(s)
Derrame de Bacterias , Clostridioides difficile/aislamiento & purificación , Heces/microbiología , Caballos/microbiología , Animales , Toxinas Bacterianas/genética , Clostridioides difficile/clasificación , Clostridioides difficile/genética , Enterocolitis Seudomembranosa/epidemiología , Enterocolitis Seudomembranosa/microbiología , Enterocolitis Seudomembranosa/veterinaria , Femenino , Enfermedades de los Caballos/epidemiología , Enfermedades de los Caballos/microbiología , Masculino , Ontario/epidemiología , Reacción en Cadena de la Polimerasa/veterinaria , Prevalencia , Ribotipificación/veterinariaRESUMEN
The aim of this study was to determine if hypoxia and the hypoxia mimetic cobalt chloride regulate the activity of matrix metalloproteinase (MMP)-2 and -9 in cultures of equine hoof keratinocytes. These effects were assessed in primary cultures of laminar keratinocytes using gelatin zymography. Incubation of keratinocytes with cobalt chloride significantly increased the levels of active MMP-2 compared to untreated controls. Hypoxia significantly increased the expression of active MMP-2 and -9 in keratinocyte cultures. This up-regulation was observed after 6h and peaked at 24h. The study findings provide novel evidence of a potential link between hypoxia within the hoof and up-regulation of MMPs which may in turn result in damage to the lamellar basement membrane.