Investigation of glucagon-like peptide-1 response to six oral carbohydrates in ponies.

Glucagon-like peptide-1 (GLP-1), the principal incretin in horses, may play a role in the pathophysiology of insulin dysregulation (ID). This study aimed to describe its concentration in response to three preserved forages and four dynamic tests for ID in ponies. Twelve adult ponies of mixed ID status were given a meal of hay, soaked hay or haylage, an in-feed oral glucose test (OGT), oral sugar test (OST), an oral test using a proprietary breakfast cereal (WEET) or a combined glucose-insulin tolerance test (CGIT) weekly in a randomised cross-over study. Glucose, insulin and GLP-1 concentrations were measured before and following each intervention. Ponies were designated ID or non-ID and insulin resistant (IR) or non-IR according to OGT and CGIT results, respectively. All interventions apart from the CGIT provoked a GLP-1 response within 30 min. The OGT and WEET interventions, (containing the greatest dose of non-structural carbohydrate, 1.06 and 1 g/kg BW, respectively), resulted in a greater area under the curve (AUC) for GLP-1 compared to all other interventions (P < 0.001). No difference in GLP-1 response was detected according to ID or IR status, despite there being strong positive correlations (rs [95 % CI]) between GLP-1 and insulin concentrations measured at individual time points (0.67 [0.62 - 0.71]; P < 0.001) and as AUC (0.66 [0.49-0.79], P < 0.001). These data do not support of the use of GLP-1 as an adjunctive diagnostic test for ID or IR, as defined by conventional intravenous or oral dynamic tests.

Comparison of one novel and four established diagnostic tests for insulin dysregulation in ponies.

Several tests have been advocated for diagnosis of insulin dysregulation (ID). Tests using simple sugars may not reflect the response to naturally ingested carbohydrates. This study aimed to evaluate agreement between the oral glucose test (OGT), the oral sugar test (OST), a novel oral test using a proprietary cereal (WEET), the IV combined glucose-insulin tolerance test (CGIT) and fasted basal insulin (FI) for diagnosis of ID. Each of the five tests above was performed on a group of six normal and six insulin dysregulated mixed-breed ponies in a randomised crossover study. Area under the curve (AUC) and maximum concentration of insulin from OGT, OST and WEET showed strong to very strong bivariate correlations (r = 0.85-0.94, and r = 0.87-0.92, respectively; P ≤ 0.001) and were significantly different between tests (associated with dose of carbohydrate) and between CGIT-positive and -negative ponies. Dichotomous results showed substantial agreement between OST and both WEET (κ = 0.65; P = 0.02) and OGT (κ = 0.67; P = 0.01) and between CGIT and both OST (κ = 0.63; P = 0.03) and OGT (κ = 0.67; P = 0.01), and no agreement between FI, which had low sensitivity, and all other tests (κ = 0.15 - 0.31; P > 0. 05). Palatability of WEET was variable, resulting in one pony being excluded for analysis of WEET data. Further work on development of an oral test using a more palatable feedstuff and appropriate cut-offs or diagnostic thresholds for tests of ID is warranted.

The effect of manually facilitated flexion of the thoracic spine on the interspinous space among horses with impinging dorsal spinous processes of the thoracic vertebrae.

Impinging dorsal spinous processes (IDSP) are typically diagnosed and graded using radiography, during which the effect of the horses' thoracolumbar posture on the interspinous spaces is not commonly considered. Posture can be altered from a spontaneous, relatively extended, or lordotic, position by manual facilitation of thoracic flexion ('thoracic lift'). This study aimed to ascertain if the thoracic vertebral interspinous space distances were increased by using facilitated thoracic flexion to alter the posture in horses diagnosed with IDSP. Seven horses of mixed breed and sex, median age 9.1 years (interquartile range, 7.2-12.4 years), with a diagnosis of thoracic IDSP with no history of spinal surgery, were included in the study. Two sets of radiographs were obtained. The initial set was taken in the horses' spontaneous posture and the second in the manually facilitated flexed posture. Each image was anonymised allowing blinded measurement of the interspinous spaces. Analysis was performed using Hodges-Lehmann median differences estimates. An increase in the median interspinous space distance was achieved after manual facilitation of thoracic flexion at every thoracic intervertebral space (5th-18th thoracic [T] vertebra). The greatest median increase was seen between T7-T8 and T12-T13 (3.1 mm and 3.0 mm, respectively) whereas the lowest median increase was seen between T17-T18 (0.7 mm). In this study, thoracic interspinous space distances could be increased by using manual facilitation to alter the thoracic posture in horses with IDSP, which could affect grading and decision making.

Management of pituitary pars intermedia dysfunction in practice: A clinical audit.

In horses/ponies with pituitary pars intermedia dysfunction (PPID), pergolide mesylate treatment, with monitoring of therapeutic response, is recommended by contemporaneous literature and equine endocrinologists. However, it is unknown whether these recommendations are adhered to in private practice. This clinical audit aimed to compare treatment and monitoring of PPID cases in veterinary practice against available recommendations. Case data and basal plasma adrenocorticotropic hormone (ACTH) concentrations from all equids tested for PPID between 2012 and 2016 from a single veterinary practice in the UK were obtained. Records were reviewed and information on treatment and monitoring over the subsequent 2-6 years was extracted and compared with published recommendations. After exclusions, the audit population was 480 animals (median age, 20 years). The most common presenting signs were laminitis and/or historical laminitis (51.2%) and hypertrichosis and/or delayed coat shedding (24.5%). Based on seasonally adjusted reference intervals for basal ACTH concentration, 51.7% (n = 248) of animals were classified as positive, 37.1% (n = 178) as negative and 11.3% (n = 54) as equivocal for PPID. Records were available for 459 animals; of which pergolide treatment was initiated in 78.7% (n = 185/235) of positive cases, 19.2% (n = 10/52) of equivocal cases and 6.4% (n = 11/172) of cases classified as negative. Overall, 87.2% (n = 129/148) of cases commenced treatment as per recommendations. Only 77.7% (n = 160/206) of pergolide-treated animals had documented PPID monitoring and of these, only 48.1% (n = 77/160) had follow-up basal ACTH testing in the first 1-3 months following diagnosis. The findings confirm that management of PPID in veterinary practice fell below contemporaneous recommendations, especially for monitoring.

Evaluation of the sensitivity and specificity of basal plasma adrenocorticotrophic hormone concentration for diagnosing pituitary pars intermedia dysfunction in horses: A systematic review.

Measurement of basal adrenocorticotrophic hormone (ACTH) is currently used to diagnose pituitary pars intermedia dysfunction (PPID) in horses, yet a systematic review of the evidence for its use has not been undertaken. This study aimed to systematically review evidence regarding the sensitivity and specificity of the basal ACTH diagnostic test. Electronic databases were systematically searched in January 2019, September 2020 and January 2021, for English language publications published prior to these dates. Screening, data extraction and quality assessment of publications was undertaken by the authors using predefined criteria. Study design, methodology and information reported in included studies were assessed using Standards for Reporting of Diagnostic Accuracy (STARD) checklists. Risk of bias and applicability were appraised using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2) quality assessment tool. Due to identified biases and marked between-study variations, meta-analysis was not undertaken. After removal of duplicates, 415 publications were identified, of which 25 were evaluated in full, with 11 of these meeting inclusion criteria. In most studies, basal ACTH was reported to have good sensitivity (overall median 75.5%; interquartile range [IQR], 64.0-86.5%; range, 36.0-100%) and excellent specificity (overall median, 95.2%; IQR, 84.2-98.9%; range, 63.3-100%). However, QUADAS-2 and STARD assessment highlighted that studies did not utilise optimal study design and/or study populations for the evaluation of a diagnostic test and the majority were subject to bias, or provided insufficient information to fully assess possible biases. Based on this review, basal ACTH performed better at ruling out PPID than detecting it.

Translating research into practice: Adoption of endocrine diagnostic testing in cases of equine laminitis.

Research demonstrating insulin's causal role in endocrinopathic laminitis has greatly advanced understanding of equine laminitis. However, the degree to which this knowledge has been translated into clinical practice has not been assessed. This two-part study aimed to investigate veterinary surgeons' current diagnostic approach to laminitis, whether this had changed over time, and the impact of diagnosing an endocrinopathy on laminitis case management and outcome. Two cross-sectional online surveys of equine veterinary surgeons working within the UK were undertaken. The first study population comprised 141 veterinary surgeons, who had graduated a median of 8 years previously. Overall, 83.6% of respondents (n = 117/140) had changed their diagnostic approach to laminitis since graduating, primarily through increasing use of endocrine testing (88.7%; n = 86/97). Ninety-nine percent (n = 140/141) performed endocrine diagnostic test(s) for some or all laminitis cases at initial and/or subsequent examinations. The second study had 120 participating veterinary surgeons, ≥76% of whom considered diagnosing underlying endocrine diseases greatly influenced their laminitis case management. Where an endocrinopathy was identified, 75.0% (n = 90/120) considered that client communication regarding laminitis was facilitated, and ≥67% considered that treating the endocrinopathy was effective in reducing laminitis recurrence. This study demonstrates successful translation of research knowledge into equine practice, with the vast majority of veterinary surgeons adopting endocrine diagnostic testing within their routine approach to laminitis cases. Respondents perceived that this change in diagnostic approach has resulted in improvements in several non-clinical and clinical healthcare outcomes, including client communication and reduction in recurrent laminitis episodes.

Efficacy of pergolide for the management of equine pituitary pars intermedia dysfunction: A systematic review.

Pergolide, a dopamine agonist, is commonly administered to manage pituitary pars intermedia dysfunction (PPID), a progressive neurodegenerative disease prevalent in aged horses. However, available evidence regarding pergolide's efficacy in improving clinical and endocrine parameters is limited. The aim of this systematic review was to assess published literature and evaluate evidence regarding whether pergolide treatment results in improvement of clinical signs and/or adrenocorticotrophic hormone (ACTH) concentration compared to no treatment or other unlicensed treatments. Systematic searches of electronic databases were undertaken in April 2019, repeated in August and October 2019, and updated in July 2020. English language publications published prior to these dates were included. Screening, data extraction and quality assessment of publications was undertaken individually by the authors using predefined criteria and subsequently cross-checked. Modified critically appraised topic data collection forms were used to extract data. Due to marked between-study variations, meta-analysis was not undertaken. After removal of duplicate records; 612 publications were identified, of which 129 abstracts were screened for eligibility and 28 publications met criteria for inclusion in the review. Most studies were descriptive case series, cohort studies or non-randomised, uncontrolled field trials. Despite marked variation in study populations, case selection, diagnostic protocols, pergolide dose, follow-up period and outcome measures, in the vast majority of the included studies, pergolide was reported to provide overall clinical improvement in >75% of cases. However, reported improvements in individual clinical signs varied widely. A reduction in plasma ACTH concentrations was reported in 44-74% of cases, while normalisation to within reported reference intervals occurred in 28-74% of cases.

Comparison of fasted basal insulin with the combined glucose-insulin test in horses and ponies with suspected insulin dysregulation.

Fasting horses for measurement of basal serum insulin concentration (fasting insulin; FI) has been recommended to standardise testing for insulin dysregulation (ID), yet limited data exist comparing it to dynamic tests. This study aimed to compare FI with the combined glucose-insulin test (CGIT) in horses suspect for ID. We hypothesised that FI would have poor sensitivity for detecting ID compared to CGIT using conventional cut-offs. Records were retrieved from CGITs performed in horses fasted for approximately 8h. Serum insulin and glucose concentrations were measured before and for 150min following an IV bolus of glucose followed by insulin. Correlations between FI and CGIT values were assessed. Youden's index analysis was used to determine the optimal cut-off for FI. Logistic regression and Mann-Whitney U tests were used to determine factors affecting the results. CGITs (n=130) from 62 horses were evaluated. Compared to CGIT, sensitivity and specificity of FI for diagnosis of ID were 14.6% and 100% at a cut-off of 20µIU/mL and 63.4% and 87.2% at a cut-off of 5.2µIU/mL, respectively. FI was significantly correlated with insulin at 45min (rs=0.66) and 75min (rs=0.72); area under the curve for insulin (AUCinsulin; rs=0.67); glucose at 45min (rs=0.53); and AUCglucose (rs=0.50). Obesity was significantly associated with increased odds of a positive CGIT and horses with a positive CGIT were significantly older (P<0.05). In conclusion, FI correlated well with CGIT results and had adequate sensitivity and specificity at lower cut-offs, despite poor sensitivity at conventional cut-off values. Further research to derive cut-off values relevant to the fasting period is warranted.

Prevalence of owner-reported ocular problems and veterinary ocular findings in a population of horses aged ≥15 years.

BACKGROUND: Previous studies suggest that ocular disease is common among aged horses but owners may fail to identify or underestimate their clinical relevance. OBJECTIVES: To document the prevalence of owner-reported ocular disease in horses aged ≥15 years. In a subset of these horses, to document ophthalmic findings from veterinary examination and compare with owner-reported ocular disease, and to determine risk factors for veterinary ophthalmic findings. STUDY DESIGN: Cross-sectional study. METHODS: Owners of aged horses completed a survey on management, clinical signs and medical history. Risk factors for the presence of ocular disease as reported by the owner were determined. A subset of these horses underwent an ophthalmological examination. Risk factors for the presence of ocular disease detected during this examination were determined. Agreement between owner-reported data and veterinary ophthalmic findings was assessed. RESULTS: Abnormal ocular findings were detected in 287/327 horses aged ≥15 years that underwent a complete ophthalmic examination, whereas the presence of ocular disease as reported by the horse-owners was only 3.3%. Agreement between owner-reported ocular disease and results of the veterinary examination was low for all categories analysed. An owner-reported history of ocular discharge was associated with increased odds of veterinary-reported diminished vision. Increasing age was associated with increased odds of the presence of an eye abnormality (any) and cataracts. Appaloosa horses had increased odds of cataract compared with other breeds. Horses in work were less likely to have an eye abnormality. MAIN LIMITATIONS: Volunteer bias may have influenced our results with owners of sick horses or those more concerned about their horses more likely to volunteer at the initial recruitment phase. CONCLUSIONS: This study showed a high prevalence of ocular lesions in aged horses which was not reflected in owner-reported disease. This has highlighted problems in obtaining information on ocular conditions from horse-owners.

Epidemiology of pituitary pars intermedia dysfunction: A systematic literature review of clinical presentation, disease prevalence and risk factors.

Pituitary pars intermedia dysfunction (PPID) is caused by an age-related degenerative disease of dopaminergic neurones. Despite its importance in equine practice, available information regarding its epidemiology is limited. This systematic review aimed to assess published literature to evaluate available evidence regarding the clinical presentation, prevalence and risk factors for PPID in horses and ponies. Electronic database searches were undertaken using a range of terms, and English language publications published prior to August 2016 were included. Both authors independently reviewed screened papers for inclusion, extracted data, and assessed the quality of reporting using predefined criteria. Data were extracted using modified critically appraised topic data collection forms. Meta-analysis was not undertaken due to marked between-study variations. Following removal of duplicate records, of 358 published papers yielded by the search, 97 abstracts were screened for eligibility and 29 publications meeting inclusion criteria were included in the review. Most studies reviewed were case series or cross-sectional studies, with considerable variation in study populations and PPID case definition. Hypertrichosis and/or other hair coat abnormalities, laminitis and epaxial muscle wastage or muscle atrophy are the most frequently reported clinical signs, with prevalence of these signs increasing with increasing horse age. The most robust prevalence estimates for PPID were 21.2% in horses and ponies aged ≥15 years and 2.9% amongst the general equine population. Findings regarding breed and sex predispositions were equivocal and only increasing age has been identified as a significant risk factor for PPID.

Insulinaemic and glycaemic responses to three forages in ponies.

Reduction of the hyperinsulinaemic response to feeding is central to the management of insulin dysregulation (ID). The aim of this study was to compare insulinaemic and glycaemic responses to soaked hay, dry hay and haylage in ponies. Twelve ponies of mixed breeds were maintained under identical management conditions. A randomised four-way crossover trial was conducted, in which fasted animals were fed a meal of 0.25% body weight as dry matter intake soaked hay, dry hay or haylage, or administered an oral glucose test (OGT). Blood glucose and serum insulin concentrations were measured before and at 2h following OGT, and regularly for 5h following forage meals. Median and interquartile range (IQR) area under the curve (AUC) for insulin (AUCi) was greater for haylage (median 6495; IQR 17352) vs. dry hay (2932; IQR 5937; P=0.019) and soaked hay (1066; IQR 1753; P=0.002), and greater for dry hay vs. soaked hay (P=0.002). The AUC for glucose (AUCg) was lower for soaked hay (1021; IQR 99) vs. dry hay (1075; IQR 105; P=0.002) and haylage (1107; IQR 221; P=0.003). Six ponies were classified as having ID based on the OGT. AUCi was greater in ID vs. non-ID ponies after all forages. In contrast, there was no detectable effect of ID status on AUCg. On an equivalent dry matter basis, soaked hay produced the lowest insulinaemic and glycaemic responses to feeding, while haylage produced the highest responses. The insulinaemic effects of all forages were greater in ponies with ID. These data support the practice of soaking hay with water to reduce postprandial insulinaemic responses in ponies.

Paradigm shifts in understanding equine laminitis.

Laminitis, one of the most debilitating conditions of all equids, is now known to be the result of several systemic disease entities. This finding, together with other recent developments in the field of laminitis research, have provoked a rethink of our clinical and research strategies for this condition. First, laminitis is now considered to be a clinical syndrome associated with systemic disease (endocrine disease, sepsis or systemic inflammatory response syndrome, SIRS) or altered weight bearing rather than being a discrete disease entity. Next, laminitis associated with endocrine disease (endocrinopathic laminitis) is now believed to be the predominant form in animals presenting (primarily) for lameness. Third, the designation of laminitis as a primary and severe basement membrane pathology now requires revision. Instead, current data now proposes a variable subclinical phase associated with gross changes in the hoof capsule, with stretching and elongation of the lamellar cells an early and key event in the pathophysiology. These findings have fuelled new mechanistic hypotheses and research directions that will be discussed, together with their implications for future clinical management.

Comparison of two blood sampling techniques for the determination of coagulation parameters in the horse: Jugular venipuncture and indwelling intravenous catheter.

BACKGROUND: Evaluation of coagulation status is an important component of critical care. Ongoing monitoring of coagulation status in hospitalised horses has previously been via serial venipuncture due to concerns that sampling directly from the intravenous catheter (IVC) may alter the accuracy of the results. Adverse effects such as patient anxiety and trauma to the sampled vessel could be avoided by the use of an indwelling IVC for repeat blood sampling. OBJECTIVES: To compare coagulation parameters from blood obtained by jugular venipuncture with IVC sampling in critically ill horses. STUDY DESIGN: Prospective observational study. METHODS: A single set of paired blood samples were obtained from horses (n = 55) admitted to an intensive care unit by direct jugular venipuncture and, following removal of a presample, via an indwelling IVC. The following coagulation parameters were measured on venipuncture and IVC samples: whole blood prothrombin time (PT), fresh plasma PT and activated partial thromboplastin time (aPTT) and stored plasma antithrombin activity (AT) and fibrinogen concentration. D-dimer concentration was also measured in some horses (n = 22). Comparison of venipuncture and IVC results was performed using Lin's concordance correlation coefficient. Agreement between paired results was assessed using Bland Altman analysis. RESULTS: Correlation was substantial and agreement was good between sample methods for all parameters except AT and D-dimers. MAIN LIMITATIONS: Each coagulation parameter was tested using only one assay. Sampling was limited to a convenience sample and timing of sample collection was not standardised in relation to when the catheter was flushed with heparinised saline. CONCLUSIONS: With the exception of AT and D-dimers, coagulation parameters measured on blood samples obtained via an IVC have clinically equivalent values to those obtained by jugular venipuncture.

The role of Leptospira spp. in horses affected with recurrent uveitis in the UK.

BACKGROUND: Equine recurrent uveitis (ERU) is a common cause of ocular pain and blindness in horses. Leptospira spp. have been commonly implicated in the pathophysiology of ERU in mainland Europe and the USA. No recent studies have been carried out in the UK, but Leptospira is reported not to be a major factor in the aetiology of ERU in the UK. OBJECTIVES: To establish the prevalence of Leptospira-associated ERU in the UK and to identify the serovars involved in these cases; to compare serum vs. aqueous humour antibody levels in cases and controls in order to confirm the diagnosis of Leptospira-associated ERU, and to assess the usefulness of serology alone as a confirmatory test for Leptospira-associated ERU in the UK. STUDY DESIGN: Case-control study. METHODS: Eyes enucleated for clinical reasons in ERU-affected horses were collected. Blood and aqueous humour were obtained to determine antibody levels against a variety of Leptospira serovars and C-values (aqueous humour value/serum value) were calculated. In addition, eyes, blood and aqueous humour were obtained from control cases for comparison. Histopathology was performed in all eyes to confirm uveitis in each case. Differences in seroprevalences between ERU and control cases and between Leptospira- and non-Leptospira-associated ERU cases were calculated. RESULTS: A total of 30 ERU and 43 control eyes were analysed. Of the ERU eyes, only two had a C-value of >4 (prevalence of Leptospira-associated uveitis: 6.7%). Serovars hardjo and javanica were detected. There was no difference in seroprevalence between horses with uveitis and control cases (65.5% and 41.9%, respectively; P = 0.11) or between Leptospira- and non-Leptospira-associated uveitis cases (100% and 63.0%, respectively; P = 0.52). MAIN LIMITATIONS: The study was limited by low case numbers. Eyes were presented at different stages of disease. The only test used to detect Leptospira was the microscopic agglutination test. CONCLUSIONS: Leptospira-associated ERU is uncommon in the UK. Serology alone may not help to definitively diagnose Leptospira-associated uveitis in this country.

Evaluation of a Chemiluminescent Immunoassay for Measurement of Equine Insulin.

BACKGROUND: Many diagnostic tests for insulin dysregulation use reference intervals established with an insulin radioimmunoassay (RIA) that is no longer available. A chemiluminescent immunoassay (CLIA) is commonly used for the measurement of serum insulin concentration in clinical practice but requires further validation, especially at clinically relevant reference intervals. OBJECTIVES: To evaluate the CLIA for measurement of equine insulin and compare it to the previously validated, but now unavailable RIA. SAMPLES: Equine serum samples (n = 78) from clinical and experimental studies. METHODS: In this experimental study, performance of the CLIA was evaluated using standard variables, including comparison with the RIA. Continuous and binary outcomes were analyzed. RESULTS: The CLIA showed good intra-assay (coefficient of variation [CV], 1.8-2.4%) and interassay (CV, 3-7.1%) precision. Acceptable recovery on dilution (100 ± 10%) was achieved only at dilutions <1:1. Recovery on addition was acceptable. Comparison of the CLIA and RIA showed strong positive correlation (r = 0.91-0.98), with fixed and proportional bias. At 3 diagnostic cutoffs, sensitivity of CLIA compared with RIA ranged from 67 to 100% and specificity from 96 to 100%. CONCLUSIONS AND CLINICAL IMPORTANCE: The CLIA is a highly repeatable assay which is suitable for within- and between-horse comparisons. Dilution of high concentration samples should be performed with charcoal-stripped serum (CSS) and at the lowest dilution factor possible. At concentrations commonly used for diagnosis of insulin dysregulation (≤100 µIU/mL), results from the CLIA tend to be lower than from the RIA and should be interpreted accordingly. Further standardization of equine insulin assays is required.

The effects of dose and diet on the pharmacodynamics of omeprazole in the horse.

BACKGROUND: Conflicting data are presented in the current literature regarding the efficacy of omeprazole for suppressing gastric acidity in the horse. OBJECTIVES: The objective of this study was to investigate the duration of intraday acid suppression achieved with two doses of omeprazole under two different dietary conditions. STUDY DESIGN: A four-way crossover design. METHODS: Six adult Thoroughbred horses instrumented with percutaneous gastrotomy tubes were used. Intragastric pH was measured for continuous 23 h periods (08.00-07.00 h) for six consecutive days (Days 0-5). Baseline data was recorded on Day 0 and omeprazole administered on Days 1-5. Two doses (1 mg/kg and 4 mg/kg bwt per os once a day) and two diets (a high grain/low fibre [HG/LF] and ad libitum hay [HAY)] diet) were studied. Data for the percent (%) time pH was above 4 (%tpH>4) and median intraday pH was reported for two measurement locations and analysed using generalised estimating equations. RESULTS: An effect of both diet and dose was evident with mean %tpH>4 and the mean of the median intraday pHs typically higher at the higher (4 mg/kg bwt) dose and in HG/LF diet. The overall efficacy of omeprazole in raising intragastric pH was good under the HG/LF conditions but relatively poor in the HAY diet. A cumulative effect of dosing, not previously reported in the horse, was observed. CONCLUSIONS: The overall efficacy of omeprazole in raising ventral gastric pH was less than previously reported. Both dose and diet may play a role in the efficacy of omeprazole in the horse. Therefore, the use of singular dosing recommendations that encompass all horse types and management conditions may not be appropriate and dosing recommendations that take into account the diet of the horse may be advantageous.

The effects of dose and diet on the pharmacokinetics of omeprazole in the horse.

This study aimed to investigate the effect of diet and dose on the pharmacokinetics of omeprazole in the horse. Six horses received two doses (1 and 4 mg/kg) of omeprazole orally once daily for 5 days. Each dose was evaluated during feeding either a high-grain/low-fibre (HG/LF) diet or an ad libitum hay (HAY) diet in a four-way crossover design. Plasma samples were collected for pharmacokinetic analysis on days 1 and 5. Plasma omeprazole concentrations were determined by ultra-high pressure liquid chromatography-mass spectrometry. In horses being fed the HG/LF diet, on day 1, the area under the curve (AUC) and maximal plasma concentration (Cmax ) were higher on the 4 mg/kg dose than on the 1 mg/kg dose. The AUC was higher on day 5 compared to day 1 with the 4 mg/kg dose on the HG/LF diet. On days 1 and 5, the AUC and Cmax were higher in horses being fed the HG/LF diet and receiving the 4 mg/kg dose than in horses being fed the HAY diet and receiving the 1 mg/kg dose. These findings suggest that both dose and diet may affect pharmacokinetic variables of omeprazole in the horse.

Treatment of equine metabolic syndrome: A clinical case series.

REASONS FOR PERFORMING STUDY: Treatment of equine metabolic syndrome (EMS) is essential to improve insulin sensitivity and reduce the risk of laminitis. Calorie restriction and increased exercise are the mainstays of treatment but there is potential for poor owner compliance. OBJECTIVES: To determine whether significant weight loss accompanied by improvements in measures of insulin sensitivity can be achieved in horses and ponies with EMS managed by their owners in their normal environment under veterinary guidance. STUDY DESIGN: Retrospective clinical case series. METHODS: Horses and ponies attending 2 university hospitals for investigation and treatment of suspected EMS were eligible for inclusion in the study. Animals underwent a clinical examination, basal and dynamic endocrine testing; those with pituitary pars intermedia dysfunction (PPID) were excluded. Owners were given individually tailored diet and exercise programmes to follow for between 3 and 6 months. After the treatment period, clinical examination and endocrine tests were repeated and results compared to the initial assessment. RESULTS: Nineteen animals were recruited to the study, 17 with a history of laminitis. All animals showed a reduction in body condition score (P<0.001) and 18/19 had a reduction in bodyweight (P<0.001) between assessments. There were significant (P<0.05) reductions in basal insulin, insulin at 45 min during a combined glucose insulin tolerance test (CGIT), time for blood glucose concentration to return to baseline during a CGIT and mean area under the glucose curve. CONCLUSIONS: A diet and exercise programme tailored to the needs of the individual animal and implemented by the owner results in weight loss accompanied by improvements in insulin sensitivity.

Lamellar pathology in horses with pituitary pars intermedia dysfunction.

REASONS FOR PERFORMING STUDY: Hoof lamellar pathology in horses with pituitary pars intermedia dysfunction (PPID) has not been described previously. OBJECTIVES: To describe the histomorphometry and pathological lesions in hoof lamellar tissue of animals that had PPID with or without concurrent laminitis, with reference to age-matched controls. We hypothesised that lamellar lesions consistent with laminitis would be associated with PPID, even in animals without current or historical laminitis. STUDY DESIGN: Prospective case-control study. METHODS: Mid-dorsal hoof histological sections were obtained post mortem from the forelimbs of 16 PPID-affected animals either with (n = 6) or without laminitis (n = 10) and 10 age- and breed-matched controls. Sections were examined by a blinded veterinary pathologist. The length and width of 10 primary epidermal lamellae were measured using image analysis software. The morphology and pathology of primary and secondary epidermal lamellae were then typed or graded in axial, middle and abaxial regions. Fasting serum insulin, plasma adrenocorticotropin and blood glucose concentration were measured from blood samples taken prior to euthanasia. RESULTS: All animals with PPID and laminitis had fasting hyperinsulinaemia (median 74.1 miu/l, interquartile range 49.9-349.5 miu/l) whereas PPID animals without laminitis had serum insulin concentrations below the upper limit of the reference range (<20 miu/l). Lamellar pathology in PPID animals with laminitis was variable in severity and unrelated to the reported duration of laminitis (range 2 months-5 years). Most lesions were located abaxially within the lamellar tissue and included increased length and width of the lamellae, chronic abnormal keratinisation, interlamellar epidermal bridging and cell death with more acute lamellar tearing in some cases. The lamellae of PPID animals without laminitis were normal referent to the relevant control group. CONCLUSIONS: Whether PPID and hyperinsulinaemia have a causal inter-relationship or not, it may only be the hyperinsulinaemia that is associated with lamellar morphological alteration and pathology consistent with laminitis.

Pharmacokinetics and bioequivalence testing of five commercial formulations of omeprazole in the horse.

Omeprazole is widely used in the treatment of equine gastric ulcer syndrome. To date, little is known about the relative pharmacokinetics of the different formulations making comparisons between products difficult. The objectives of the study were to investigate the relative pharmacokinetics of five commercially available formulations of omeprazole in the horse and to test for bioequivalence of four of the formulations using one of the formulations as a reference standard. Twelve mature Thoroughbred horses were fasted for 16 h then administered 2 g of each formulation in a cross-over design. Serial blood samples were collected and plasma omeprazole concentration was determined by ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS). No significant differences were present between three of the formulations and the reference formulation, while the fourth formulation had a lower Cmax and longer Tmax than the reference formulation. Bioequivalence against the reference formulation could not be demonstrated for any of the formulations tested. The findings of the study suggested that the method of protection utilised by different formulations of omeprazole (enteric-coated granules vs. buffering) does not significantly alter the pharmacokinetics of the drug. Further work to establish bioequivalence is needed before direct comparisons can be drawn between different formulations.