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The purpose of this study was to determine the pharmacokinetic profile of intravenous firocoxib in neonatal foals. Six healthy foals were administered 0.09 mg/kg firocoxib intravenously once a day for 7 days. Blood was collected for plasma firocoxib analysis using high-performance liquid chromatography with fluorescence detection at times 0 (day 1 of study only) and 0.08, 0.25, 1, 2, 4, 6, 8, 16 and 24 hr on dose numbers 1, 5 and 7. Blood was also collected immediately prior to doses 3, 4, 5 and 7. Final samples were collected at 36, 48, 72 and 96 hr following the final dose. Noncompartmental analysis using the trapezoidal method with linear interpolation revealed a moderate half-life (15.9 ± 9.1 hr) with a large volume of distribution at steady state (1.79 ± 0.57 L/kg) and a clearance (96.0 ± 59.2 ml h -1  kg -1 ) that was more rapid than that observed in adult horses., (© 2017 John Wiley & Sons Ltd.)

The purpose of this study was to determine the pharmacokinetics and safety profile of firocoxib in neonatal foals. Seven healthy foals were administered 0.1 mg/kg firocoxib orally q24 h for nine consecutive days, commencing at 36 h of age. Blood was collected for firocoxib analysis using high-pressure liquid chromatography with fluorescence detection at 0 (dose #1 only), 0.25, 0.5, 1, 2, 4, 8, 16, and 24 h after doses 1, 5, and 9. For all other doses (2, 3, 4, 6, 7, and 8), blood was collected immediately prior to the next dose (24 h trough). Elimination samples (36, 48, 72, 96, 120, and 144 h) were collected after dose 9. Safety was assessed via physical examinations, body weight measurements, gastroscopy, complete blood count, plasma biochemistry and urinalysis. Firocoxib was rapidly absorbed following oral administration with minimal accumulation after repeat dosing. After the final dose, the terminal half-life was approximately 11 h. Firocoxib was below the limit of detection (<2.5 ng/mL) in plasma 72 h after the final dose. No significant abnormalities were found on blood analyses, urinalysis, or gastroscopy. This study demonstrated that firocoxib is absorbed in neonatal foals with no demonstrable adverse effects after repeated doses of 0.1 mg/kg., (© 2013 John Wiley & Sons Ltd.)

Background: Obesity and hyperinsulinemia increase the risk of laminitis in horses and ponies. In mares, obesity also has been associated with increased circulating concentrations of the proinflammatory cytokine, tumor necrosis factor (TNF)-α. The association of other proinflammatory cytokines with body condition score (BCS) and insulin requires further determination., Hypothesis: Plasma concentrations of TNF, interleukin (IL)-1β, IL-6, and serum amyloid A (SAA) will positively correlate with BCS or insulin or both in horses. Furthermore, inflammatory protein concentrations will correlate with age and variables associated with BCS, including plasma insulin, triglycerides, nonesterified fatty acids, and leptin concentrations., Animals: One hundred and ten mixed light-breed horses, including mares, geldings, and stallions, aged 4-20 years., Methods: Samples were selected from a larger population of plasma samples previously collected during June-July of 2006. Samples were analyzed for TNF, IL-1β, IL-6, and SAA using commercially available ELISAs and simple correlations were used to determine relationships with BCS, insulin, age, and sex., Results: Plasma TNF (P = .047) and IL-6 (P = .021) concentrations were higher in females than males, whereas IL-6 concentrations correlated (P = .001) with age. Plasma SAA concentrations correlated with both insulin (P < .001) and BCS (P = .007)., Conclusions and Clinical Importance: This study provides evidence for factors, including age and sex, that may be associated with plasma concentrations of inflammatory proteins. Concentrations of SAA correlated with BCS and insulin, independent of age or sex. Because BCS and insulin correlate with increased SAA, it is possible that SAA is a component of laminitis pathophysiology., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

The objective of this study was to determine the effects of high and moderate non-structural carbohydrates (NSC) hay on insulin, glucose, triglyceride, and leptin concentrations in overweight Arabian geldings. Eight adult overweight (average BCS 7 [9-point scale]) Arabian geldings were fed each of two orchardgrass hays, high NSC (18% DM) and moderate NSC (12% DM), in a cross over design during two 28-day periods. Body weight and body condition score assessment along with blood sampling to measure insulin, glucose, leptin, and triglyceride concentrations were performed on days 0, 7, 14, 21 and 28 of each period. Effects of hay, period, day, and day*hay on plasma glucose and serum leptin were not detected. Serum insulin was influenced by hay (p = 0.001), day (p = 0.03), and day*hay (p = 0.04). Insulin concentrations were higher on day 7 in the high NSC group (15.6 μIU/ml) than the moderate NSC group (9.5 μIU/ml), but not by day 14 (p = 0.0007). Plasma triglyceride was influenced by period (p = 0.0003), day*period (p < 0.0001), and day*hay (p = 0.02). Hyperinsulinaemia was not observed in the overweight Arabian geldings fed either a moderate or high NSC hay., (© 2011 Blackwell Verlag GmbH.)

Equine metabolic syndrome (EMS) is a condition of obese horses characterized by insulin resistance, systemic inflammation, and an increased risk of laminitis. The pathogenesis of EMS is thought, in part, to be due to inflammatory proteins produced by adipose tissue. Reducing inflammation may decrease the incidence of laminitis in horses with EMS. Pioglitazone hydrochloride, a thiazolidinedione, has efficacy to reduce obesity associated inflammation in humans. Eight normal, adult, horses were administered 1mg/kg pioglitazone for 14 days, and eight horses served as controls. Physical examination and hematologic variables, transcript abundance of pro-inflammatory cytokines in skeletal muscle and adipose tissue, and circulating concentrations of the acute phase protein, serum amyloid A and pro-inflammatory cytokine, TNF-α were assessed prior to, and following, an LPS infusion (35 ng/kg). The objective was to determine if pre-treatment with pioglitazone would mitigate the development of inflammation and associated clinical markers of inflammation following LPS administration. Lipopolysaccharide administration induced systemic inflammation, as assessed by clinical and hematological aberrations, increased TNF-α, SAA and adipose tissue IL-6 mRNA abundance, however no mitigating effects of pioglitazone were detected. A longer treatment period or higher dose might be indicated for future experiments., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Laminitis is a painful, inflammatory disease of the equine hoof that often results in euthanasia. Elevated plasma insulin concentrations are a predictive factor for laminitis, and in previously healthy horses and ponies, laminitis was induced by infusion of insulin. Thus, we chose to determine if an infusion of insulin would increase plasma concentrations of inflammatory cytokines and cytokine mRNA abundance in subcutaneous adipose tissue, skeletal muscle, and white blood cells. Ten mature Thoroughbred mares received an insulin infusion that elevated plasma insulin concentrations for 6h or an equivalent volume of isotonic saline in a switchback design. Insulin infusion altered plasma concentrations of both TNF (P=0.037) and IL-6 (P=0.044), but did not result in consistent changes to either skeletal muscle or adipose tissue cytokine mRNA. Insulin may be involved in the production of inflammatory cytokines, and this could be a mechanism for insulin increasing the risk of laminitis., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Reasons for Performing Study: F2-isoprostanes have been used extensively to quantify lipid peroxidation in association with risk factors in various diseases. Horses with colic may have intestinal ischaemia and/or inflammation characterised by oxidative stress and increased production of isoprostanes., Objectives: To gather preliminary data regarding the feasibility of using urine F2-isoprostanes and isoprostane metabolites as early screening tools for the presence of gastrointestinal disease requiring surgical intervention in horses and ultimately develop a stall-side test capable of identifying these horses as early as possible for timely referral., Methods: Concentrations of urine isoprostane and isoprostane metabolite were determined by mass spectroscopy and normalised to urine creatinine (Cr) concentrations in urine samples from 42 healthy control horses and 43 horses with gastrointestinal pain or colic., Results: Horses with colic were treated medically (n = 21) or surgically (n = 22). Mean ± s.d. concentrations of urine isoprostane and isoprostane metabolite were significantly higher in horses with colic (2.94 ± 1.69 and 0.31 ± 0.22 ng/mg Cr, respectively), compared to control horses (1.89 ± 1.39 and 0.22 ± 0.08 ng/mg Cr, respectively). Mean urine isoprostane metabolite concentrations were significantly higher in horses undergoing surgery (0.38 ± 0.28 ng/mg Cr) compared to controls and medical colics (0.26 ± 0.11 ng/mg Cr). Nonsurvivors had significantly higher mean urine isoprostane metabolite concentrations (0.47 ± 0.39 ng/mg Cr) than control or surviving colic horses (0.29 ± 0.24 ng/mg Cr)., Conclusions: Measurement of urine isoprostane metabolite concentration may be a useful prognostic indicator in equine colic., Potential Relevance: Urine isoprostane metabolites may aid in early recognition of surgical colic. Isoprostanes are a potential therapeutic target to prevent further systemic and gastrointestinal tissue injury in horses with colic., (© 2011 EVJ Ltd.)

Pioglitazone is a thiazolidinedione class of antidiabetic agent with proven efficacy in increasing insulin sensitivity in humans with noninsulin-dependent diabetes mellitus, a syndrome of insulin resistance sharing similarities with equine metabolic syndrome. The purpose of this study was to determine the pharmacokinetics of pioglitazone in adult horses following multiple oral dose administration. Pioglitazone hydrochloride (1 mg/kg) was administered orally for 11 doses at 24-h intervals, and plasma samples were collected. Initially, a pilot study was performed using one horse; and thereafter the drug was administered to six horses. Samples were analyzed by liquid chromatography with tandem mass spectrometry, and pharmacokinetic parameters were calculated using noncompartmental modeling. The maximum plasma concentration was 509.1 ± 413.5 ng/mL achieved at 1.88 ± 1.39 h following oral administration of the first dose, and 448.1 ± 303.5 ng/mL achieved at 2.83 ± 1.81 h (mean ± SD) following the eleventh dose. Apparent elimination half-life was 9.94 ± 4.57 and 9.63 ± 5.33 h after the first and eleventh dose, respectively. This study showed that in healthy horses, pioglitazone administered at a daily oral dose of 1 mg/kg results in plasma concentrations and total drug exposure approximating, but slightly below, those considered therapeutic in humans., (© 2010 Blackwell Publishing Ltd.)

Background: Obesity and insulin resistance increase the risk of laminitis in horses. Pioglitazone (PG) is an insulin-sensitizing drug used in humans that is absorbed after oral administration to horses., Hypothesis: PG treatment will increase insulin sensitivity and transcript abundance of glucose and lipid transporters in adipose and skeletal muscle tissues., Animals: Sixteen lean, healthy horses., Methods: Eight horses were administered PG (1 mg/kg bodyweight PO) for 12 days before induction of insulin resistance through IV administration of lipopolysaccharide (LPS). Treated and untreated controls (CN; n = 8) were subjected to testing of peripheral insulin sensitivity and biopsies of both subcutaneous (nuchal ligament) adipose tissue and skeletal muscle before and after treatment, and 24 hours after LPS administration., Results: PG treatment did not improve basal insulin sensitivity (CNs: 1.4 ± 0.3, PG-treated: 1.9 ± 1.3; P > .4) or mitigate LPS-induced insulin resistance (CNs: 0.4 ± 0.3, PG-treated: 0.4 ± 0.3); however, transcript abundance of glucose and lipid transporters was altered in both skeletal muscle and subcutaneous adipose tissue., Conclusions and Clinical Importance: Either a higher dose or longer treatment period might be required for physiological effects to be observed. PG is a novel therapeutic agent requiring further investigation in horses in order to determine treatment efficacy., (Copyright © 2011 by the American College of Veterinary Internal Medicine.)

Objective: To measure the ascorbic acid (AA) concentration in bronchoalveolar lavage fluid (BALF) and cellular glutathione peroxidase (cGPx) activity in RBCs and WBCs from peripherally obtained blood and in cells from BALF to determine whether differences existed between the 2 major redox systems in recurrent airway obstruction (RAO)-affected and -nonaffected (control) horses and between systemic and local pulmonary responses in the glutathione redox system., Animals: 16 adult horses in pairs: 8 healthy (control) and 8 RAO-affected horses., Procedures: Physical examination data and biological samples were collected from horses before (remission), during, and after (recovery) environmental challenge with dusty straw and hay. At each stage, BALF cell AA concentration and RBC, WBC, and BALF cell cGPx activity were measured., Results: Compared with control horses, RAO-affected horses had significantly higher cGPx activity in RBCs at all points and in WBCs during remission and challenge. The BALF cell cGPx activity was higher in RAO-affected horses during recovery than during remission The BALF cell AA concentration did not differ significantly in control horses at any point, but total and free AA concentrations were significantly lower in RAO-affected horses during the challenge period than during remission and recovery periods., Conclusions and Clinical Relevance: High cGPx activity suggested this redox system was upregulated during exposure to dusty straw and hay to combat oxidative stress, as AA was depleted in RAO-affected horses. The relative delay and lack of comparative increase in cGPx activity within the local environment (represented by BALF cells), compared with that in RBCs and WBCs, might contribute to disease in RAO-affected horses.

A 14-year-old male alpaca had refractory pleural effusion. The cause of the effusion was not apparent either radiographically or sonographically, or following a pleural fluid cytologic examination. Using computed tomographic (CT) examination, a dorsal paravertebral mass was identified and similar masses were found in the cranial mediastinum, retroperitoneal space, and adjacent to the hepatic entry of the portal vein. The histopathologic diagnosis was multicentric T-cell lymphoma. CT examination may prove to be a valuable imaging modality in the localization and staging of neoplasia in new world camelids.

The lipogenic capacities of equine liver and adipose tissue explants were investigated in vitro. Preference for glucose or acetate as the primary carbon source for de novo fatty acid synthesis was determined using (14)C labeled substrates. Additional aims included determining the relative contribution of NADPH generating pathways to reducing equivalent generation and comparing the lipogenic activity of two adipose depots, mesenteric and subcutaneous harvested from the crest region of the neck. Mesenteric adipose tissue had greater lipogenic activity than subcutaneous adipose tissue, and liver tissue showed minimal (14)C incorporation into fatty acids, indicating a low hepatic lipogenic capacity. Acetate was found to be the primary carbon source for fatty acid synthesis due to both the appearance of the (14)C label in the lipid fraction and the low activity of ATP-citrate lyase. Finally, the pentose phosphate and isocitrate dehydrogenase enzymes contributed to NADPH production in equine adipose tissue., (2009 Elsevier Inc. All rights reserved.)

Objective-To determine whether a limited sampling time method based on serum iohexol clearance (Cl(iohexol)) would yield estimates of glomerular filtration rate (GFR) in clinically normal horses similar to those for plasma creatinine clearance (Cl(creatinine)). Animals-10 clinically normal adult horses. Procedures-A bolus of iohexol (150 mg/kg) was administered IV, and serum samples were obtained 5, 20, 40, 60, 120, 240, and 360 minutes after injection. Urinary clearance of exogenous creatinine was measured during three 20-minute periods. The GFR determined by use of serum Cl(iohexol) and plasma Cl(creatinine) was compared with limits of agreement plots. Results-Values obtained for plasma Cl(creatinine) ranged from 1.68 to 2.69 mL/min/kg (mean, 2.11 mL/min/kg). Mean serum Cl(iohexol) was 2.38 mL/min/kg (range, 1.95 to 3.33 mL/min/kg). Limits of agreement plots indicated good agreement between the methods. Conclusions and Clinical Relevance-Use of serum Cl(iohexol) yielded estimates of GFR in clinically normal adult horses similar to those for plasma Cl(creatinine). This study was the first step in the evaluation of the use of serum Cl(iohexol) for estimating GFR in adult horses.

This article is presented with two main goals: (1) to provide equine clinicians with a resource for identifying types of serum tests available and (2) to outline briefly the necessary sample type, assay principle, and relative strengths and weakness of the various methods. Specific etiologies are presented and grouped by clinical diagnosis categories, along with brief comments concerning each disorder and its relevant diagnostic assays. This organization provides an abstracted list of infectious disorders commonly considered for the various clinical presentations and a summary of available serologic tests for narrowing the differential diagnosis list. The reader is also provided with a list of specific laboratories that perform the diagnostic assay for the mentioned disorders.

Immunodeficiencies are characterized as primary (genetic) or secondary (acquired). Primary immunodeficiencies are relatively uncommon; however, clinically, they present a significant challenge to the practitioner, especially if the underlying disorder goes unrecognized. Secondary immunodeficiencies may present at any age, but failure of passive transfer in neonatal foals is most commonly encountered. This article provides a general overview of clinical signs and diagnosis of primary and secondary immunodeficiencies currently recognized in horses.

Activation of the host response to infection, the "acute-phase response," is a highly organized physiologic reaction that includes changes in concentrations of plasma acute-phase proteins (APPs). The APPs are increasingly being used as markers for prognosis and monitoring response to therapy along with general determinants of equine health. Use of APPs in veterinary medicine is becoming more widespread as more commercial diagnostic kits are being validated. This article reviews the salient features of APPs and examines their current application and potential utility in equine inflammatory disorders.

Blood smear examination in a 4-day-old alpaca revealed massive erythrocyte parasitism by Mycoplasma haemolamae. Blood collected from both the nonparasitemic dam and the cria were positive for M. haemolamae by polymerase chain reaction (PCR) analysis. These findings suggest in utero transmission of M. haemolamae in camelids, even when the dam is not parasitemic.

Reasons for Performing Study: Colic is a serious disease syndrome in horses. Much of the mortality is associated with ischaemic-injured intestine during strangulating obstruction, yet there is limited understanding of the associated molecular events. Identification of differentially expressed genes during ischaemic injury should expand our understanding of colic and may lead to novel targeted therapeutic approaches in the future., Objective: To isolate and identify differentially expressed genes in equine jejunum following a 2 h ischaemic event compared to normally perfused jejunum., Methods: Suppressive subtractive hybridisation was used to clone genes that are differentially expressed in equine jejunum injured by 2 h of complete ischaemia as compared to time-matched control jejunal tissues. Expression of selected clones was further evaluated by northern blot analysis., Results: Of the 384 clones selected, 157 were confirmed to possess cDNAs corresponding differentially expressed genes by dot blot analysis. Two genes, fatty acid binding protein 2 and calcium-activated chloride channel 4 were further confirmed to be differentially expressed by northern blot analysis., Conclusions: Suppressive subtractive hybridisation can be used to detect changes in expression of a broad array of genes, as confirmed by northern blot analysis of selected genes., Potential Relevance: These initial results have identified a pool of equine intestinal epithelial genes that are differentially expressed following a 2 h ischaemic event. In particular, genes indicative of deranged metabolic activity and those potentially involved in early repair events were identified and may ultimately provide clues as to the nature of epithelial ischaemic injury in horses.

The effect of recombinant equine IL-1beta (EqIL-1beta) on steady-state mRNA levels of equine articular chondrocytes in high-density monolayer culture was investigated using a customized cDNA array analysis. Total RNA samples isolated from chondrocytes cultured in media alone or with the addition of 1 ng/ml EqIL-1beta for 1-, 3-, and 6-h durations of exposure were reverse transcribed, radiolabeled, and hybridized to a customized 380-target cDNA array. Means of duplicate log base 2 transformed hybridization signals were normalized to equine glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mean signal intensities. Differentially expressed transcripts were identified using a two-stage mixed linear analysis of variance model (Statistical Analysis Software, Cary, NC). A time-dependent pattern was observed in the number of transcripts increased > or =two-fold in response to EqIL-1beta after 1, 3 and 6h (1, 2 and 109 transcripts, respectively). At 6 h of EqIL-1beta stimulation, signal intensities for 88 cDNA targets with purported function in processes related to cell cycle, intracellular signaling, transcription, translation, extracellular matrix turnover, and inflammation, as well as a number of cDNAs lacking homology to previously reported cDNA sequences, were increased >two-fold and were associated with p<0.05. Principal component analysis identified a vector component ( approximately 10% of the total variation) corresponding to a potential EqIL-1beta co-regulation of cell cycle associated gene transcription. These results support and expand our existing comprehension of the complex role of IL-1 in modulated chondrocyte gene expression and suggest the involvement of specific target gene up-regulation and activation of downstream inflammatory cascade mediators. This study adds to the current understanding of the molecular events associated with an IL-1 induced inflammation and pathobiologic processes that may be associated with the development of equine osteoarthritis.

Objective: To assess changes in systemic hydration, concentrations of electrolytes in plasma, hydration of colonic contents and feces, and gastrointestinal transit in horses treated with IV fluid therapy or enteral administration of magnesium sulfate (MgSO4), sodium sulfate (NaSO4), water, or a balanced electrolyte solution., Animals: 7 horses with fistulas in the right dorsal colon (RDC)., Procedure: In a crossover design, horses alternately received 1 of 6 treatments: no treatment (control); IV fluid therapy with lactated Ringer's solution; or enteral administration of MgSO4, Na2SO4, water, or a balanced electrolyte solution via nasogastric intubation. Physical examinations were performed and samples of blood, RDC contents, and feces were collected every 6 hours during the 48 hour-observation period. Horses were muzzled for the initial 24 hours but had access to water ad libitum. Horses had access to hay, salt, and water ad libitum for the last 24 hours., Results: Enteral administration of a balanced electrolyte solution and Na2SO4 were the best treatments for promoting hydration of RDC contents, followed by water. Sodium sulfate was the best treatment for promoting fecal hydration, followed by MgSO4 and the balanced electrolyte solution. Sodium sulfate caused hypocalcemia and hypernatremia, and water caused hyponatremia., Conclusions and Clinical Relevance: Enteral administration of a balanced electrolyte solution promoted hydration of RDC contents and may be useful in horses with large colon impactions. Enteral administration of either Na2SO4 or water may promote hydration of RDC contents but can cause severe electrolyte imbalances.

Objective: To assess changes in systemic hydration, concentrations of plasma electrolytes, hydration and physical properties of colonic contents and feces, and gastrointestinal transit in horses with access to large amounts of grain., Animals: 6 horses with right dorsal colon (RDC) fistulas., Procedure: In a crossover design, horses were alternately fed 1 of 3 diets: orchard grass hay ad libitum after being adapted to this diet for at least 5 days, orchard grass hay ad libitum and 4.55 kg of grain offered every 12 hours after being adapted to orchard grass hay ad libitum for at least 5 days, or orchard grass hay ad libitum and 4.55 kg of grain offered every 12 hours after being adapted to this diet for at least 5 days. Physical examinations were performed and samples of blood, colonic contents, and feces were collected every 6 hours during a 48-hour observation period., Results: Grain ingestion had several effects, including changes in the concentrations of electrolytes in plasma; RDC contents became more homogenous, dehydrated, foamy, and less dense; RDC contents flowed spontaneously when the cannula was opened; RDC contents expanded when heated in an oven; and feces became fetid and less formed. Horses did not have any clinical signs of colic, endotoxemia, or laminitis., Conclusions and Clinical Relevance: Changes observed in the colonic contents and feces may be explained by the large amounts of hydrolyzable carbohydrates provided by grain. Access to large amounts of grain may increase the risk of tympany and displacement of the large intestine.

Objective: To determine whether pharmacokinetic analysis of data derived from a single i.v. dose of iohexol could be used to predict creatinine clearance and evaluate simplified methods for predicting serum clearance of iohexol with data derived from 2 or 3 blood samples in clinically normal foals., Animals: 10 healthy foals., Procedure: Serum disposition of iohexol and exogenous creatinine clearance was determined simultaneously in each foal (5 males and 5 females). A 3-compartment model of iohexol serum disposition was selected via standard methods. Iohexol clearance calculated from the model was compared with creatinine clearance. Separate limited-sample models were created with various combinations of sample times from the terminal slope of the plasma versus time profile for iohexol. Correction factors were determined for the limited-sample models, and iohexol clearance calculated via each method was compared with exogenous creatinine clearance by use of method comparison techniques., Results: Mean exogenous creatinine clearance was 2.17 mL/min/kg. The disposition of iohexol was best described by a 3-compartment open model. Mean clearance value for iohexol was 2.15 mL/min/kg and was not significantly different from mean creatinine clearance. A method for predicting serum iohexol clearance based on a 2-sample protocol (3- and 4-hour samples) was developed., Conclusions and Clinical Relevance: Iohexol clearance can be used to predict exogenous creatinine clearance and can be determined from 2 blood samples taken after i.v. injection of iohexol. Appropriate correction factors for adult horses and horses with abnormal glomerular filtration rate need to be determined.

Objective: To determine concentrations of IgA and IgG subclasses in serum, colostrum, milk, and nasal wash samples of adult horses and foals., Animals: Seven 2-year-old Welsh ponies, 27 adult mixed-breed horses, and 5 Quarter Horse mares and their foals., Procedure: Serum was obtained from ponies and adult horses. Colostrum and milk were obtained from mares and serum and nasal wash samples from their foals immediately after parturition and on days 1, 7, 14, 28, 42, and 63. Nasal wash samples were also obtained from 23 adult horses. Concentrations of immunoglobulins were determined by use of inhibition ELISA. To determine transfer of maternal isotypes to foals, concentrations in colostrum and milk were compared with those in foal serum. Serum half-lives of isotypes in foals were also determined., Results: IgGb was the most abundant isotype in serum and colostrum from adult horses, whereas IgA was the predominant isotype in milk. The major isotype in nasal secretions of adult horses and foals > or = 28 days old was IgA, but IgGa and IgGb were the major isotypes in nasal secretions of foals < or = 14 days old. Serum half lives of IgGa, IgGb, IgG(T), and IgA in foals were 176, 32, 21, and 3.4 days, respectively., Conclusions and Clinical Relevance: The early immunoglobulin repertoire of neonatal foals comprised IgGa, IgG(T), and IgA; endogenous synthesis of IgGb could not be detected until 63 days after birth. The restricted repertoire of immunoglobulins in foals may influence humoral immune responses to vaccination.

Objective: To evaluate healing of pinch-grafted wounds on the distal aspect of the limbs of ponies bandaged with equine amnion or a standard nonadherent wound dressing material., Animals: 6 ponies., Procedure: A 2.5x2.5-cm full-thickness section of skin was removed from the dorsal aspect of each limb at the midpoint of the metacarpus or metatarsus. Six days later, wounds were grafted with partial-thickness pinch grafts. Half the wounds were bandaged with amnion, and the other half were bandaged with a nonadherent dressing. Bandages were changed every 3 days until wound healing was complete. At each bandage change, numbers of grafts lost were recorded, and wounds were measured., Results: Percentage of grafts lost from wounds bandaged with amnion was not significantly different from percentage lost from wounds bandaged with the nonadherent dressing. Median healing time for wounds bandaged with amnion (30 days) was significantly less than median healing time for wounds bandaged with the nonadherent dressing (39 days). All wounds were healed by day 45., Conclusions and Clinical Relevance: Results suggest that amnion can be used for bandaging pinch-grafted wounds on the distal aspect of the limbs of ponies.

Tumors of the equine respiratory tract occur infrequently. An accurate diagnosis of neoplasia of the respiratory tract is critical because the prognosis is usually grave. The clinical signs and diagnostic procedures are discussed for tumors of the nasal and paranasal sinuses, nasopharynx/larynx, guttural pouch and thorax including lung, pleura, and thymus.

Objective: To determine pharmacokinetic variables that describe disposition of ketoprofen after its i.v. administration to foals < 24 hours old., Animals: 6 healthy foals (1 male and 5 females); mean age, 12.5 (range, 8.5 to 17) hours at time of dose administration., Procedure: Ketoprofen was administered i.v. to foals at a dosage of 2.2 mg/kg of body weight. Ketoprofen concentration in plasma samples was analyzed, using high-performance liquid chromatography. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined times during a 48-hour period. Samples were centrifuged, and plasma was frozen at -70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by use of Akaike's information criterion analysis., Results: Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance (normalized for body weight) was significantly lower than that determined for adult horses. Volume of distribution (normalized for body weight) was larger than that determined for adult horses. Mean (harmonic) plasma half-life for healthy foals < 24 hours old was 4.3 hours., Clinical Relevance: Although additional factors, such as dehydration or sepsis, must be considered on a case-by-case basis, the dose of ketoprofen administered to foals < 24 hours old should be different from the dose administered to adult horses. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to produce comparable therapeutic concentrations; longer dose intervals, based on clinical response, would be necessary to avoid drug toxicity.

Objective: To determine pharmacokinetic variables that describe the disposition of flunixin after i.v. administration of flunixin meglumine to foals < 24 hours old., Animals: 6 healthy foals, 2 males and 4 females (mean age, 11.6 hours; range, 6 to 22.5 hours)., Procedure: Flunixin (as flunixin meglumine) was administered to foals at a dosage of 1.1 mg/kg of body weight. Flunixin concentration in plasma samples was analyzed, using gas chromatography/mass spectroscopy. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined intervals over a 48-hour period. Samples were centrifuged, and plasma was frozen at -70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by Akaike's information criterion analysis., Results: Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance was significantly lower than that determined for older foals and adult horses. Volume of distribution was larger than that determined for adults. Mean plasma half-life for healthy foals < 24 hours old was 8.5 hours., Conclusions and Clinical Relevance: Although additional factors (eg, dehydration or sepsis) must be considered on a case-by-case basis, flunixin meglumine should be administered differently to foals < 24 hours old, compared with adults. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to induce comparable therapeutic concentrations; longer dose intervals, on the basis of clinical response, would be necessary to avoid drug toxicity.

The objectives of this study were to: (1) develop a technique to analyze the in vitro cytotoxic activity of lymphocytes from adult horses against equine herpesvirus-1 (EHV-1) infected allogenic equine dermal fibroblasts (EDF); (2) evaluate the ability of a 72-h in vitro incubation with interleukin-2 (IL-2) to enhance the lymphocytic cytolytic activity against EHV-1 infected EDF; (3) compare the cytotoxic activity of lymphocytes isolated from pregnant mares and non-pregnant mares against EHV-1 infected EDF; (4) ascertain if any correlations existed between the percent cytotoxicity and percentage of lymphocytes phenotypically identified by five different mouse-anti-equine monoclonal antibodies; and (5) determine if any correlation existed between virus-neutralizing antibody titers and the percent cytotoxicity. Results of the study indicate that in vitro cytotoxic activity of equine lymphocytes against EHV-1 infected allogenic fibroblasts can be measured with a standard 4-h 51Cr release assay. This activity was enhanced by an in vitro incubation with IL-2. The cytolytic activity of freshly isolated lymphocytes was greater for non-pregnant than pregnant mares. However, after IL-2 stimulation the cytolytic activity was greater for lymphocytes from pregnant mares. A positive correlation was not detected between the percentage of phenotypically identified cells and the percent cytotoxicity, although several negative correlations were present. This suggests that the cytotoxic activity was either not mediated by any of the phenotypically identified cell populations or that the activity was

Single doses (2.2 mg/kg of body weight) of phenylbutazone (PBZ) were administered IV to 6 neonatal horses (5 to 17 hours old at time of dosing). Plasma concentrations of PBZ and its metabolite oxyphenbutazone were monitored serially for 120 hours after drug administration. Pharmacokinetic variables were calculated, using 1- and 2-compartment open models. Descriptive equations from the best model for each foal were then used to derive model-independent variables describing PBZ disposition. Median volume of distribution at steady-state was 0.274 L/kg (range, 0.190 to 0.401 L/kg). Median terminal half-life was 7.4 (6.4 to 22.1) hours, and median total plasma clearance of PBZ for foals in this study was 0.018 L/kg/h (range, 0.013 to 0.038 L/kg/h). Volume of distribution was larger, half-life was longer, and total clearance was lower, compared with similar values reported for administration of PBZ to adult horses.

The pharmacokinetics of pentoxifylline (P) and its alcohol metabolite I (MI) were determined after administration of intravenous pentoxifylline, sustained release pentoxifylline tablets (Trental), and crushed pentoxifylline tablets in corn syrup, to five healthy adult horses. Pharmacokinetics were evaluated in a model-independent manner. After intravenous administration, pentoxifylline was rapidly eliminated (mean residence time 1.09 +/- 0.67 h), had a large steady-state volume of distribution (2.81 +/- 1.16 l/kg), and high clearance (3.06 +/- 1.05 l/kg/h). Oral absorption of pentoxifylline from both dose forms varied considerably between individuals. Times to peak concentration ranged from 1-10 h for either dose form. There was no difference in relative bioavailability (F') between whole (0.98 +/- 0.30) and crushed Trental tablets. Ratios between areas under the curve (AUC) for pentoxifylline and MI were different following administration of oral versus intravenous doses. This finding suggests that route of administration may affect the metabolic profile of pentoxifylline. Given the extreme differences in absorption characteristics between individuals in this study, recommendations are not made as to appropriate dose, dose interval, or dose form for administration of pentoxifylline to horses.

Immune system dysfunction and immunoglobulin deficiency was diagnosed in a 2-year-old horse with disseminated lymphosarcoma. Prolonged (35 days) parenteral nutrition was delivered to support the horse during a period in which immune function studies could be performed. Correction of nutritional compromise by use of parenteral nutrition did not correct the immunoglobulin deficiency, and results of lymphocyte phenotype testing did not indicate abnormal proportions of leukocytes. Lymphoblast transformation studies were suggestive of a circulating immunosuppressive factor in the horse's serum. Normal cell function was detected when the cells were stimulated in precolostral equine serum.

To determine whether road transport affected pulmonary phagocyte activity, 7 healthy Thoroughbred horses were shipped 1,160 kilometers over 36 hours. Fluid collected by bronchoalveolar lavage (BAL) 12 hours, and 7 and 14 days after transport was analyzed. Results were compared to those from the same horses pre-transport, and 7 non-transported control horses that had BAL performed at the same times as the transported horses. Of cells recovered with BAL the percentage of viable pulmonary alveolar macrophages (PAMs) declined from 90.0 +/- 0.9% pre-transport to 80.0 +/- 3.7% by 2 weeks post transport. Although the ability of PAMs to inhibit the growth of Staphylococcus epidermidis had decreased by 2 weeks post-transport (19.2 +/- 3.7% vs. 8.8 +/- 2.3% inhibition) this could not be attributed to transport as a similar effect occurred in the control group. In contrast, the ability of PAMs to phagocytose sheep erythrocytes labelled with rabbit anti-erythrocyte antibodies increased from 74.0 +/- 8.1% to 92.3 +/- 1.5% by 12 hours post-transport. As all variables were unchanged or only mildly altered following transport, we conclude that this form of transport did not alter the PAM functions we assessed.

Bovine whey samples were evaluated by use of lymphocyte-transformation tests to determine their effect on lymphocyte blastogenesis. Whey samples from mammary glands with clinical mastitis strongly inhibited DNA synthesis and blastogenesis in lymphocytes stimulated with mitogens or dividing because of bovine leukemia virus infection. Whey samples from apparently healthy glands either did not inhibit lymphocyte DNA synthesis or inhibited it to a lesser degree than did whey from mastitic glands. Degree of inhibition was dose-dependent. The molecules causing inhibition were noncytotoxic and underwent minimal binding to the lymphocytes. Inhibitory molecules were susceptible to various proteolytic and glycolytic enzymes, indicating a glycoprotein-like structure. Whey inhibited incorporation of thymidine if it was in the cell cultures during the early stages of stimulation. Incubation of lymphocytes in whey that inhibited thymidine incorporation did not affect DNA synthesis in subsequent culturing of the same cells without whey. Degree of inhibition was affected by the method of whey preparation.

Sixty milk whey samples prepared from quarters of five cows with a history of mastitis were tested for their ability to inhibit DNA synthesis in mitogen-stimulated lymphocytes. The inhibitory activity was compared with milk SCC, electrical conductivity, pH, and the number of colony-forming bacteria in the milk. Milk whey contained factors that inhibited DNA synthesis in cultured lymphocytes. Inhibition of mitogen-induced DNA synthesis increased with the clinical severity of mastitis and with increased values of indirect indicators of mastitis. The increases in inhibition and electrical conductivity were delayed past the increases in SCC. Milk whey (10 microliters) from quarters with clinical mastitis and from quarters with SCC greater than 900,000 inhibited 96 to 100%, 84 to 100%, and 69 to 100% of DNA synthesis in 3-d cultures of lymphocytes stimulated with Concanavalin A, phytohemagglutinin P, and pokeweed mitogen, respectively. The numbers of colony-forming bacteria correlated least with the inhibitory activity.

We surveyed the whole blood selenium status of a randomly sampled population of horses from 4 contiguous counties in northern Maryland. Two hundred and two horses from 74 farms were sampled. Whole blood selenium levels greater than or equal to 0.100 parts per million (ppm) were considered adequate; blood levels less than 0.100 ppm were considered marginal or deficient. The average blood selenium concentration of the horses sampled was 0.137 ppm, with a standard deviation of 0.041 ppm. Blood selenium concentrations ranged from 0.050-0.266 ppm. Thirty-eight of 202 horses (18.8%) had a selenium level less than or equal to 0.099 ppm. Twenty-one of 74 farms (28.4%) had at least 1 horse with a selenium level less than or equal to 0.099 ppm. Animal husbandry practices had a significant influence on selenium status. Horses were more prone to having an abnormal selenium status if they were either maintained on pasture or used infrequently, or if their diet did not include mineral and vitamin supplements.