The impact of age on vitamin D receptor expression, vitamin D metabolism and cytokine production in ex vivo Rhodococcus equi infection of equine alveolar macrophages.

Rhodococcus equi (R. equi), a pneumonia-causing intracellular bacterium, results in significant morbidity and mortality in young foals, while healthy adult horses rarely develop disease. Survival and replication within alveolar macrophages (AMφ) are the hallmarks of R. equi's pathogenicity. The vitamin D receptor (VDR) and its ligand, the active vitamin D metabolite 1,25(OH)2D, are important in immune responses to intracellular bacteria. The vitamin D/VDR pathway regulates the downstream production of cytokines in infected human AMφ. The immunomodulatory role of the vitamin D/VDR pathway in equine leukocytes is unknown. The objective of the current study was to determine the impact of R. equi infection and age on synthesis of 1,25(OH)2D, VDR expression, and cytokine production in an ex vivo model of R. equi infection in equine AMφ. AMφ were collected from ten healthy foals at 2-, 4- and 8-weeks old and from nine healthy adult horses once via bronchoalveolar lavage. AMφ were mock infected (CONTROL) or infected with a virulent laboratory strain of R. equi for 7 days (INFECTED). VDR expression was determined via RT-qPCR from cell lysates. 1,25(OH)2D and cytokines were measured in cell supernatant by immunoassays. VDR expression was impacted by age (P = 0.001) with higher expression in AMφ from 8-week-old foals than from 2-week-old foals and adults. There was no significant effect of infection in foal AMφ, but in adults, relative VDR expression was significantly lower in INFECTED AMφ compared to CONTROL AMφ (P = 0.002). There was no effect of age or infection on 1,25(OH)2D concentration (P > 0.37). Mean TNFα production was significantly higher from INFECTED compared to CONTROL AMφ from 4- and 8-week-old foals and adults (P < 0.005). Mean IFNγ production was significantly higher from AMφ from foals at 8-weeks-old compared to 2-weeks-old (P = 0.013) and higher from INFECTED AMφ than from CONTROL AMφ in foals at 4-weeks-old and in adults (P < 0.027). The proportion of samples producing IL-1ß and IL-10 was also significantly higher from INFECTED compared to CONTROL AMφ isolated from 4-week-old foals (P < 0.008). Similarly, in adult samples, IL-17 was produced from a greater proportion of INFECTED compared to CONTROL samples (P = 0.031). These data document age-associated changes in VDR expression and cytokine production in equine AMφ in response to R. equi infection. This preliminary investigation supports the need for further research to fully elucidate if the vitamin D pathway has an immunomodulatory role in the horse.

The enteroinsular axis during hospitalization in newborn foals.

The enteroinsular axis (EIA) is an energy regulatory system that modulates insulin secretion through the release of enteroendocrine factors (incretins). Despite the importance of energy homeostasis in the equine neonate, information on the EIA in hospitalized foals is lacking. The goals of this study were to measure serum insulin and plasma incretin (glucose-dependent insulinotropic polypeptide [GIP], glucagon-like peptide-1 [GLP-1] and glucagon-like peptide-2 [GLP-2]) concentrations, to determine the insulin and incretin association, as well as their link to disease severity and outcome in hospitalized foals. A total of 102 newborn foals ≤72 h old were classified into hospitalized (n = 88) and healthy groups (n = 14). Hospitalized foals included septic (n = 55) and sick non-septic (SNS; n = 33) foals based on sepsis scores. Blood samples were collected over 72 h to measure serum insulin and plasma GIP, GLP-1 and GLP-2 concentrations using immunoassays. Data were analyzed by nonparametric methods and univariate logistic regression. At admission, serum glucose and insulin and plasma GIP were significantly lower in hospitalized and septic compared to healthy foals (P < 0.01), while plasma GLP-1 and GLP-2 concentrations were higher in hospitalized and septic foals than healthy and SNS foals, and decreased over time in septic foals (P < 0.05). As a percent of admission values, GLP-1 and GLP-2 concentrations dropped faster in healthy compared to hospitalized foals. Serum insulin concentrations were lower in hospitalized and septic non-survivors than survivors at admission (P < 0.01). Hospitalized foals with serum insulin < 5.8 µIU/mL, plasma GLP-1 >68.5 pM, and plasma GLP-2 >9 ng/mL within 24 h of admission were more likely to die (OR = 4.2; 95% CI = 1.1-16.1; OR = 13.5, 95% CI = 1.4-123.7; OR = 12.5, 95% CI = 1.6-97.6, respectively; P < 0.05). Low GIP together with increased GLP-1 and GLP-2 concentrations indicates that different mechanisms may be contributing to reduced insulin secretion in critically ill foals, including impaired intestinal production (GIP, proximal intestine) and pancreatic endocrine resistance to enhanced incretin secretion (GLP-1, GLP-2; distal intestine). These imbalances could contribute to energy dysregulation in the critically ill equine neonate.

Energy hormone response to fasting-induced dyslipidemia in obese and non-obese donkeys.

Metabolic and endocrine disorders, such as dyslipidemia, are common in donkeys. Negative energy balance due to fasting, stressful conditions, or disease is a major trigger for fat mobilization often leading to dyslipidemia. The hormonal response to fasting has not been well characterized in donkeys. Therefore, this work aimed to study variations in insulin, glucagon, leptin, total adiponectin, ghrelin, and insulin-like growth factor-1 concentrations, insulin-to-glucagon (IGR) and glucagon-to-insulin (GIR) molar ratios, and lipid and carbohydrate parameters during a 66 h fasting period in 8 adult donkeys, and to determine differences depending on body condition. Obese donkeys developed earlier lipid mobilization (increased plasma total triglyceride and total cholesterol concentrations) compared to non-obese donkeys. Plasma glucose and leptin concentrations decreased in obese animals. After 60 h fasting, obese donkeys showed a significant increase in glucagon and decrease in leptin. GIR significantly increased, while insulin and IGR decreased in both groups. These findings support faster lipid mobilization in response to negative energy status in obese donkeys during fasting, which could be linked to greater glucagonemia and could explain the predisposition of these animals to dyslipidemia.

C-terminal telopeptide of type I collagen, osteocalcin, alkaline phosphatase, and parathyroid hormone in healthy and hospitalized foals.

Hypocalcemia is a common finding in critically ill equine patients. Parathyroid hormone (PTH) helps to maintain calcium homeostasis in hypocalcemic patients by promoting renal calcium reabsorption and bone resorption. Increased serum PTH concentrations have been reported in critically ill people and animals, including horses and foals. It is unknown whether increased secretion of PTH is associated with markers of bone turnover in hospitalized foals. The goals of this study were to measure markers of bone resorption (C-terminal telopeptide of type I collagen [CTX-I]) and bone formation (osteocalcin [OCN]; alkaline phosphatase [ALP]) and to determine their association with PTH concentrations, disease severity, and mortality in hospitalized foals. This prospective, multicenter, cross-sectional study was conducted on 75 newborn foals ≤3 d old divided into hospitalized (n = 65; 41 septic; 24 sick nonseptic) and healthy (n = 10) groups. Blood samples were collected on admission to measure serum CTX-I, OCN, and PTH concentrations and ALP activity. Data were analyzed by nonparametric methods and univariate logistic regression. Serum CTX-I and PTH concentrations were significantly higher, whereas OCN concentrations were lower, in septic compared with healthy foals (P < 0.05). Serum ALP activity was not different between groups; however, it was lower in hospitalized and septic foals with low OCN concentrations (P < 0.05). In hospitalized foals, PTH concentrations were positively correlated with CTX-I concentrations and inversely associated with ALP activity (P < 0.05). High CTX-I and low OCN concentrations were associated with disease severity (P < 0.05). Hospitalized nonsurviving foals had significantly lower OCN concentrations compared with survivors (P < 0.05), but CTX-I concentrations were not associated with survival. Hospitalized foals with PTH concentrations >12.4 pmol/L were more likely to die (OR = 1.5; 95% CI = 1.1-4.16; P < 0.05). Elevated PTH and CTX-I together with reduced OCN concentrations and ALP activity in sick foals indicates that bone resorption is increased during critical illness, which may be a compensatory mechanism to correct hypocalcemia or reflect a response to systemic inflammation and metabolic imbalances. Bone resorption could negatively impact skeletal development in the growing foal. Low OCN and high PTH concentrations were predictors of nonsurvival in hospitalized foals.

Evaluation of dynamic testing for pituitary pars intermedia dysfunction diagnosis in donkeys.

BACKGROUND: Endocrine disorders are common in donkeys. Pituitary pars intermedia dysfunction (PPID) is thought to be a frequent disturbance in donkeys due to their longevity. However, information on PPID dynamic testing in donkeys is lacking. OBJECTIVES: The objective of this study was to evaluate the previously described guidelines for PPID diagnosis in horses in donkeys with suspicion of PPID. STUDY DESIGN: Prospective experimental study. METHODS: Eighty donkeys were evaluated for PPID suspicion based on clinical signs and baseline adrenocorticotropic hormone (ACTH) concentrations. Six mix-breed donkeys (one jack and five non-pregnant jennies) fulfilling inclusion criteria were subjected to dexamethasone suppression test (DST), thyrotropin-releasing hormone stimulation test (TRH) and combined DST-TRH challenge. Tests were interpreted according to guidelines for PPID diagnosis in horses. RESULTS: Donkeys fulfilling inclusion criteria were diagnosed with PPID by TRH stimulation test (six of six). Both DST (three of six) and DST-TRH (4/6) challenges failed to detect those animals and showed conflicting results. Similarly, cortisol basal concentrations were not consistent with PPID suspicion. MAIN LIMITATIONS: Characterisation of seasonal and geographical location effect on baseline ACTH concentrations and response to TRH is compelling in this species. Further studies with a larger number of donkeys are needed. CONCLUSIONS: This is the first study in donkeys to evaluate common dynamic tests used for PPID diagnosis in horses. Preliminary results agree with the guidelines for PPID diagnosis in horses and baseline ACTH measurement followed by TRH challenge are recommended tests for diagnosis of PPID in donkeys.

Effect of intravenous glucose and combined glucose-insulin challenges on energy-regulating hormones concentrations in donkeys.

Metabolic disorders are highly prevalent in donkeys. Differences in energy regulatory hormones and glucose dynamic testing, including the intravenous glucose tolerance test (IVGTT) and combined glucose-insulin test (CGIT), have been documented between donkeys and horses. The aims of this study were to characterise the insulin:glucagon (IGR) and glucagon:insulin (GIR) molar ratios, at baseline and in response to the IVGTT and CGIT in healthy donkeys, and to determine their correlation with endocrine (leptin, ghrelin and adiponectin) and morphometric variables. Median values and interquartile ranges (IQRs) for IGR and GIR in 49 healthy adult donkeys were 1.5 (IQR, 1.0-1.8) and 0.7 (IQR 0.5-0.9), respectively. IVGTT and CGIT were each performed on eight donkeys, while dynamic testing was performed on six donkeys due to loss of two donkeys from the study. IVGTT induced an increase in IGR (and a decrease in GIR) from 15 to 180min after the onset of the test, but had no effect on leptin, adiponectin or ghrelin concentrations. CGIT resulted in a significant elevation in IGR (and a decrease in GIR) from 15 to 120min after the onset of the test. Plasma leptin concentrations increased significantly at 240min. No correlations were found between ratios, hormones and morphometric measurements. The findings support differences between donkeys and horses, which are likely to be related to proportionally higher glucagon compared to insulin concentrations in donkeys, and may be relevant to disorders related to energy dysregulation in donkeys, including metabolic syndrome and dyslipidaemias.

The FGF-23/klotho axis and its relationship with phosphorus, calcium, vitamin D, PTH, aldosterone, severity of disease, and outcome in hospitalised foals.

BACKGROUND: Fibroblast growth factor-23 (FGF-23) and klotho are key regulators of vitamin D and parathyroid hormone (PTH) synthesis as well as phosphorus and calcium homeostasis; however, information on the FGF-23/klotho axis in healthy and hospitalised foals is lacking. OBJECTIVES: The aims of this study were to measure serum FGF-23 and klotho concentrations and determine their association with serum phosphorus, total calcium (TCa), vitamin D metabolite [25(OH)D, 1,25(OH)2 D], PTH, and aldosterone concentrations, disease severity, and mortality in hospitalised foals. STUDY DESIGN: Prospective, multicentre, cross-sectional study. METHODS: A total of 91 foals ≤72 h old were classified as hospitalised (n = 81; 58 septic; 23 sick non-septic [SNS]) and healthy (n = 10). Blood samples were collected on admission. Hormone concentrations were determined by immunoassays. RESULTS: Serum FGF-23, PTH, phosphorus, and aldosterone concentrations were higher while klotho, 25(OH)D, 1,25(OH)2 D, and TCa concentrations were lower in septic and SNS compared to healthy foals (P<0.05). In hospitalised and septic foals, increased FGF-23 and aldosterone concentrations were associated with high phosphorus and PTH but not with TCa and vitamin D metabolite concentrations. Hospitalised foals with the highest FGF-23 and lowest klotho concentrations were more likely to die (odds ratio (OR): 3.3; 95% confidence interval (CI): 1.1-10.3 and OR: 3.1; CI: 1.1-8.0, respectively). MAIN LIMITATIONS: Blood gas, ionised calcium, blood culture information not being available for many foals, and use of the sepsis score to classify hospitalised foals. CONCLUSIONS: Imbalances in the FGF-23/klotho axis may contribute to mineral dyshomeostasis and disease progression in critically ill foals. Elevated FGF-23 and reduced klotho, together with high phosphorus and PTH concentrations suggests FGF-23 resistance. FGF-23 and klotho are good markers of disease severity and likelihood of mortality in hospitalised foals. Aldosterone may influence phosphorus and PTH dynamics in hospitalised foals. Routine measurement of phosphorus concentrations in sick foals is recommended.

Preliminary investigation of orally administered benazepril in horses with left-sided valvular regurgitation.

BACKGROUND: Despite the paucity of data available, orally administered angiotensin-converting enzyme (ACE) inhibitors are empirically used in horses with valvular regurgitation. OBJECTIVE: Evaluate the echocardiographic and hormonal changes in response to oral benazepril in horses with left-sided valvular regurgitation. STUDY DESIGN: Prospective, randomised double-blind, placebo-controlled trial. METHODS: Horses with mitral valve (MR) and/or aortic valve regurgitation (AR) received oral benazepril (n = 6) at a dosage of 1 mg/kg q 12 h or a placebo (n = 5) for 28 days. Echocardiography was performed before drug administration and after 28 days of treatment. Plasma renin activity, serum ACE activity, angiotensin II concentration, aldosterone concentration and biochemical variables were measured before drug administration and after 7 and 28 days of treatment. RESULTS: Relative to baseline, horses treated with benazepril had statistically significant reduction in left ventricular internal diameter in systole (mean difference between groups = -0.97 cm; 95% CI = -1.5 to -0.43 cm), aortic sinus diameter (-0.31 cm; -0.54 to -0.07 cm), and percentage of the aortic annulus diameter occupied by the base of the AR jet (-17.05%; -31.17 to -2.93%) compared with horses receiving a placebo. In addition, horses treated with benazepril had a significantly greater increase in cardiac output (11.95 L/min; 1.17-22.73 L/min) and fractional shortening (7.59%; 3.3-11.88%) compared with horses receiving a placebo. Despite profound serum ACE inhibition, renin activity and concentrations of angiotensin II and aldosterone were not significantly different between treatment groups or among time points. MAIN LIMITATIONS: Very small sample size and short treatment period. CONCLUSIONS: Treatment with oral benazepril resulted in statistically significant echocardiographic changes that might indicate reduced cardiac afterload in horses with left-sided valvular regurgitation. Additional studies with a larger sample size will be necessary to determine if administration of benazepril is beneficial in horses with valvular regurgitation. The Summary is available in Spanish - see Supporting Information.

Effect of Intravenous Administration of Cobalt Chloride to Horses on Clinical and Hemodynamic Variables.

BACKGROUND: Cobalt chloride (CoCl2 ) is administered to racehorses to enhance performance. The purpose of this study was to evaluate the clinical, cardiovascular, and endocrine effects of parenterally administered CoCl2 . OBJECTIVES: To describe the effects of weekly intravenous doses of CoCl2 on Standardbred horses. ANIMALS: Five, healthy Standardbred mares. METHODS: Prospective, randomized, experimental dose-escalation pilot. Five Standardbred mares were assigned to receive 1 of 5 doses of CoCl2 (4, 2, 1, 0.5, or 0.25 mg/kg) weekly IV for 5 weeks. Physical examination, blood pressure, cardiac output, and electrocardiography (ECG) were evaluated for 4 hours after administration of the first and fifth doses. Blood and urine samples were collected for evaluation of cobalt concentration, CBC and clinical chemistry, and hormone concentrations. RESULTS: All mares displayed pawing, nostril flaring, muscle tremors, and straining after CoCl2 infusion. Mares receiving 4, 2, or 1 mg/kg doses developed tachycardia after dosing (HR 60-126 bpm). Ventricular tachycardia was noted for 10 minutes after administration of the 4 mg/kg dose. Increases in systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) occurred after administration of all doses (4, 2, 1, 0.5, and 0.25 mg/kg). Profound hypertension was observed after the 4 mg/kg dose (SAP/DAP, MAP [mmHg] = 291-300/163-213, 218-279). Hemodynamics normalized by 1-2 hours after administration. ACTH and cortisol concentrations increased within 30 minutes of administration of all CoCl2 doses, and cardiac troponin I concentration increased after administration of the 4 and 2 mg/kg doses. CONCLUSIONS AND CLINICAL IMPORTANCE: The degree of hypertension and arrhythmia observed after IV CoCl2 administration raises animal welfare and human safety concerns.

Steroids, steroid precursors, and neuroactive steroids in critically ill equine neonates.

Hypothalamic-pituitary-adrenal axis (HPAA) dysfunction has been associated with sepsis and mortality in foals. Most studies have focused on cortisol, while other steroids have not been investigated. The objectives of this study were to characterise the adrenal steroid and steroid precursor response to disease and to determine their association with the HPAA response to illness, disease severity, and mortality in hospitalised foals. All foals (n=326) were classified by two scoring systems into three categories: based on the sepsis score (septic, sick non-septic [SNS] and healthy) and the foal survival score (Group 1: 3-18%; Group 2: 38-62%; Group 3: 82-97% likelihood of survival). Blood concentrations of adrenocorticotropic hormone (ACTH) and steroids were determined by immunoassays. ACTH-cortisol imbalance (ACI) was defined as a high ACTH/cortisol ratio. Septic foals had higher ACTH, cortisol, progesterone, 17α-OH-progesterone, pregnenolone, and androstenedione concentrations as well as higher ACTH/cortisol, ACTH/progesterone, ACTH/aldosterone, and ACTH/DHEAS ratios than SNS and healthy foals (P<0.01). Foals with DHEAS of 0.4-5.4ng/mL were more likely to have ACI (OR=2.5). Foals in Group 1 had higher ACTH, aldosterone, progesterone, and cortisol concentrations as well as ACTH/cortisol, ACTH/progesterone, and ACTH/DHEAS ratios than foals in Groups 2 and 3 (P<0.01). High progesterone concentrations were associated with non-survival and the cutoff value below which survival could be predicted was 23.5ng/mL, with 75% sensitivity and 72% specificity. In addition to cortisol, the response to the stress of illness in foals is characterised by the release of multiple adrenal steroids. DHEAS and progesterone were good predictors of HPAA dysfunction and outcome in hospitalised foals.

Fibroblast Growth Factor-23 Concentration in Dogs with Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with hyperphosphatemia, decreased vitamin D metabolite concentrations, and hyperparathyroidism. This syndrome is known as CKD-mineral bone disorder (CKD-MBD). Recently, it has been shown that an increase in fibroblast growth factor-23 (FGF-23) concentration is an early biomarker of CKD in people. It is an independent risk factor for both progression of renal disease and survival time in humans and cats with CKD. Information about FGF-23 in healthy dogs and those with CKD is lacking. OBJECTIVES: To measure FGF-23 concentration in dogs with different stages of CKD and determine its association with factors involved in CKD-MBD, including serum phosphorus and parathyroid hormone (PTH) concentrations. A secondary aim was to validate an ELISA for measurement of plasma FGF-23 concentration in dogs. ANIMALS: Thirty-two client-owned dogs with naturally occurring CKD and 10 healthy control dogs. METHODS: Prospective cross-sectional study. An FGF-23 ELISA was used to measure plasma FGF-23 concentration in dogs and their association with serum creatinine, phosphorus, calcium, and PTH concentrations. RESULTS: Plasma FGF-23 concentrations increased with severity of CKD and were significantly different between IRIS stages 1 and 2 versus stages 3 and 4 (P < .0001). Increases in FGF-23 concentrations were more frequent than hyperparathyroidism or hyperphosphatemia in this cohort. Serum creatinine and phosphorus concentrations were the strongest independent predictors of FGF-23 concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma FGF-23 concentrations increase in dogs with CKD as disease progresses. Plasma FGF-23 concentrations appear to be useful for further study of the pathophysiology of CKD-MBD in dogs.

Association of Vitamin D Metabolites with Parathyroid Hormone, Fibroblast Growth Factor-23, Calcium, and Phosphorus in Dogs with Various Stages of Chronic Kidney Disease.

BACKGROUND: Hypovitaminosis D is associated with progression of renal disease, development of renal secondary hyperparathyroidism (RHPT), chronic kidney disease-mineral bone disorder (CKD-MBD), and increased mortality in people with CKD. Despite what is known regarding vitamin D dysregulation in humans with CKD, little is known about vitamin D metabolism in dogs with CKD. OBJECTIVES: The purpose of our study was to further elucidate vitamin D status in dogs with different stages of CKD and to relate it to factors that affect the development of CKD-MBD, including parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), calcium, and phosphorus concentrations. METHODS: Thirty-seven dogs with naturally occurring CKD were compared to 10 healthy dogs. Serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2 D], and 24,25-dihydroxyvitamin D [24,25(OH)2 D], and PTH and FGF-23 concentrations were measured. Their association with serum calcium and phosphorus concentrations and IRIS stage was determined. RESULTS: Compared to healthy dogs, all vitamin D metabolite concentrations were significantly lower in dogs with International Renal Interest Society (IRIS) stages 3 and 4 CKD (r [creatinine]: -0.49 to -0.60; P < .05) but not different in dogs with stages 1 and 2 CKD. All vitamin D metabolites were negatively correlated with PTH, FGF-23, and phosphorus concentrations (r: -0.39 to -0.64; P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: CKD in dogs is associated with decreases in all vitamin D metabolites evaluated suggesting that multiple mechanisms, in addition to decreased renal mass, affect their metabolism. This information could have prognostic and therapeutic implications.

Temporal and Spatial Analysis of the New World Screwworm (Cochliomyia hominivorax) in Darien and Embera, Panama (2001-2011).

Larvae (maggots) of Cochliomyia hominivorax, the New World Screwworm fly, are voracious consumers of living flesh that have a negative economic impact by decreasing productivity, predisposing to other pathogens, and, in severe cases, causing death of domestic livestock. Screwworm caused extensive financial losses to the livestock industry in North America prior to its eradication. Sterile insect technique (SIT) was used to eradicate screwworm throughout North and Central America and continues to be the main tool to control it in eastern Panama. The goal of this study was to evaluate the temporal and spatial trends of screwworm myiasis cases reported in the Province of Darien and Comarca Embera (border with Colombia), Panama, from 2001 to 2011. We hypothesized that screwworm cases would vary seasonally and be spatially clustered near Colombia as a result of effective eradication strategies in Panama and the presence of an autochthonous population of flies in western Colombia. Temporal and spatial data were retrieved from COPEG-USDA records (Panama) and analysed by anova, Ripley's K function, discrete Poisson spatial statistic scan and Getis-Ord Gi*. No significant temporal trend was found, but cases were spatially distributed in four clusters. One cluster of cases occurred from 2001 to 2003 and was considered a focal temporal and spatial cluster. One cluster occurred in 2001 and 2007 indicating more rare outbreaks in an area with fewer cattle. The two remaining clusters contained cases from 2004 to 2011 and 2001 to 2011 suggesting regular breaks in the control barrier due to occasional failures of the SIT programme, difficulties implementing border quarantine strategies, livestock smuggling or the movement of infested wildlife.

Transcutaneous direct current cardioversion in a foal with lone atrial fibrillation.

There are rare published reports of atrial fibrillation (AF) in foals, all of which are associated with structural heart disease or within the adaptive period of newborns. This report describes a 3-month-old Thoroughbred filly with AF and a structurally normal heart on echocardiography. Medical cardioversion of the foal's AF was attempted with three 20mg/kg doses of quinidine sulfate therapy without success. Timed, transcutaneous, direct current cardioversion was successfully performed using adhesive patches on the midthorax in conjunction with intravenous procainamide at a total dose of 20mg/kg. A normal sinus rhythm was maintained through discharge from the hospital and at recheck 5 months after cardioversion. Transcutaneous direct current cardioversion presents a feasible alternative to quinidine sulfate or transvenous electrical cardioversion in young or lower body weight equids.

Evaluation of Four Diagnostic Tests for Insulin Dysregulation in Adult Light-Breed Horses.

BACKGROUND: Several tests have been evaluated in horses for quantifying insulin dysregulation to support a diagnosis of equine metabolic syndrome. Comparing the performance of these tests in the same horses will provide clarification of their accuracy in the diagnosis of equine insulin dysregulation. OBJECTIVES: The aim of this study was to evaluate the agreement between basal serum insulin concentrations (BIC), the oral sugar test (OST), the combined glucose-insulin test (CGIT), and the frequently sampled insulin-modified intravenous glucose tolerance test (FSIGTT). ANIMALS: Twelve healthy, light-breed horses. METHODS: Randomized, prospective study. Each of the above tests was performed on 12 horses. RESULTS: Minimal model analysis of the FSIGTT was considered the reference standard and classified 7 horses as insulin resistant (IR) and 5 as insulin sensitive (IS). In contrast, BIC and OST assessment using conventional cut-off values classified all horses as IS. Kappa coefficients, measuring agreement among BIC, OST, CGIT, and FSIGTT were poor to fair. Sensitivity of the CGIT (positive phase duration of the glucose curve >45 minutes) was 85.7% and specificity was 40%, whereas CGIT ([insulin]45 >100 µIU/mL) sensitivity and specificity were 28.5% and 100%, respectively. Area under the glucose curve (AUCg0-120 ) was significantly correlated among the OST, CGIT, and FSIGTT, but Bland-Altman method and Lin's concordance coefficient showed a lack of agreement. CONCLUSIONS: Current criteria for diagnosis of insulin resistance using BIC and the OST are highly specific but lack sensitivity. The CGIT displayed better sensitivity and specificity, but modifications may be necessary to improve agreement with minimal model analysis.

Association of aldosterone and arginine vasopressin concentrations and clinical markers of hypoperfusion in neonatal foals.

REASONS FOR PERFORMING STUDY: Critically ill foals often present to veterinary hospitals with impaired organ perfusion which can be demonstrated by increased blood L-lactate concentrations. As a compensatory mechanism to low blood pressure and electrolyte abnormalities, aldosterone and arginine vasopressin (AVP) are released to restore organ perfusion and function. Several studies have investigated the ability of blood L-lactate concentrations to predict severity of disease and outcome in critically ill human patients, adult horses and foals. However, information on the aldosterone and AVP response to hypoperfusion and its association with L-lactate concentrations in neonatal foals is limited. OBJECTIVES: To determine the association between clinical hypoperfusion and endocrine markers of reduced tissue perfusion in normo- and hypoperfused foals. STUDY DESIGN: Prospective, multicentre, cross-sectional observational study. METHODS: Blood samples were collected on admission from 72 clinically hypoperfused, 110 normoperfused (73 hospitalised and 37 healthy) foals of ≤4 days of age. Foals were considered clinically hypoperfused if they had L-lactate concentrations ≥2.5 mmol/l and one of the 3 following findings: heart rate >120 beats/min, packed cell volume (PCV) >0.44 l/l or azotaemia (increased creatinine and blood urea nitrogen [BUN]). Blood concentrations of aldosterone and AVP were determined by radioimmunoassays. RESULTS: Aldosterone, AVP, creatinine and BUN concentrations and heart rate, PCV and blood osmolality were higher in clinically hypoperfused compared with normoperfused foals (P<0.05). Risk of hypoperfusion increased with the presence of hypothermic extremities (OR = 5.26) and with each one unit increase in albumin concentrations (OR = 3.5) (P<0.05). The proposed admission L-lactate cut-off value above which nonsurvival could be reliably predicted in hospitalised foals was 10.6 mmol/l with 82% of sensitivity and 74% of specificity. CONCLUSIONS: Hyperaldosteronaemia and hypervasopressinaemia as well as hypothermic extremities and increased albumin concentrations are potent predictors of hypoperfusion in hospitalised foals.

Characterization of the intravenous glucose tolerance test and the combined glucose-insulin test in donkeys.

Glucose-insulin dynamic challenges such as the intravenous glucose tolerance test (IVGTT) and combined glucose-insulin test (CGIT) have not been described in donkeys. The objectives of this study were (1) to characterize the IVGTT and CGIT in healthy adult donkeys, and (2) to establish normal glucose-insulin proxies. Sixteen donkeys were used and body morphometric variables obtained each. For the IVGTT, glucose (300 mg/kg) was given IV. For the CGIT, glucose (150 mg/kg) followed by recombinant insulin (0.1 IU/kg) were administered IV. Blood samples for glucose and insulin determinations were collected over 300 min. In the IVGTT the positive phase lasted 160.9 ± 13.3 min, glucose concentration peaked at 323.1 ± 9.2 mg/dL and declined at a rate of 1.28 ± 0.15 mg/dL/min. The glucose area under the curve (AUC) was 21.4 ± 1.9 × 10(3) mg/dL/min and the insulin AUC was 7.2 ± 0.9 × 10(3) µIU/mL/min. The positive phase of the CGIT curve lasted 44 ± 3 min, with a glucose clearance rate of 2.01 ± 0.18 mg/dL/min. The negative phase lasted 255.9 ± 3 min, decreasing glucose concentration at rate of -0.63 ± 0.06 mg/dL/min, and reaching a nadir (33.1 ± 3.6 mg/dL) at 118.3 ± 6.3 min. The glucose and insulin AUC values were 15.2 ± 0.9 × 10(3) mg/dL/min and 13.2 ± 0.9 × 10(3) µIU/mL/min. This is the first study characterizing CGIT and IVGTT, and glucose-insulin proxies in healthy adult donkeys. Distinct glucose dynamics, when compared with horses, support the use of species-specific protocols to assess endocrine function.

Animal Models of Bone Metastasis.

Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone.

Energy-related parameters and their association with age, gender, and morphometric measurements in healthy donkeys.

Donkeys are commonly afflicted by endocrine and metabolic disturbances but few studies have investigated endocrine variables involved in energy regulation and their association with morphometric indices, age or gender in this species. Hemostatic and clinical differences have been demonstrated between horses and donkeys, so to consider both species as metabolically and endocrinologically similar could lead to misdiagnosis. In this study, plasma concentrations of glucose, triglycerides and endocrine factors involved in energy homeostasis (insulin, glucagon, leptin, adiponectin, ghrelin and insulin-like growth factor [IGF]-1) were measured and their association with morphometric variables (body condition score, neck scoring and body mass index), gender and age was determined in 62 healthy donkeys. In addition, a neck scoring system specific for donkeys was developed. Insulin, glucagon, leptin and IGF-1 concentrations were found to be similar between donkeys and other species, but adiponectin and active ghrelin were lower in donkeys than horses. Donkeys with larger neck scores and body mass indices had higher triglyceride, leptin and IGF-1 concentrations. A sexual dimorphism was observed on all morphometric measurements and plasma glucose concentrations independent of adiposity. Younger animals had lower morphometric measurements and triglyceride and leptin concentrations.