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Abstract

Objective—To compare whole-body phenylalanine kinetics and the abundance of factors in signaling pathways associated with skeletal muscle protein synthesis and protein breakdown between horses with pituitary pars intermedia dysfunction (PPID) and age-matched control horses without PPID.

Animals—12 aged horses (6 horses with PPID and 6 control horses; mean age, 25.0 and 25.7 years, respectively).

Procedures—Plasma glucose, insulin, and amino acids concentrations were determined before and 90 minutes after feeding. Gluteal muscle biopsy samples were obtained from horses 90 minutes after feeding, and the abundance and activation of factors involved in signaling pathways of muscle protein synthesis and breakdown were determined. The next day, horses received a priming dose and 2 hours of a constant rate infusion of 13C sodium bicarbonate followed by a priming dose and 4 hours of a constant rate infusion of 1-13C phenylalanine IV; whole-body protein synthesis was determined.

Results—Plasma glucose and insulin concentrations were higher after feeding than they were before feeding for both groups of horses; however, no significant postprandial increase in plasma amino acids concentrations was detected for either group. Phenylalanine flux, oxidation, release from protein breakdown, and nonoxidative disposal were not significantly different between groups. No significant effect of PPID status was detected on the abundance or activation of positive or negative regulators of protein synthesis or positive regulators of protein breakdown.

Conclusions and Clinical Relevance—Results of this study suggested that whole-body phenylalanine kinetics and the postprandial activation of signaling pathways that regulate protein synthesis and breakdown in muscles were not affected by PPID status alone in aged horses.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine the pharmacokinetics, bioavailability, and pharmacological effects of cannabidiol (CBD) in senior horses.

ANIMALS

8 university-owned senior horses.

PROCEDURES

In this randomized, crossover study, horses were assigned to receive either a single oral dose of 2 mg/kg CBD in oil or a single IV dose of 0.1 mg/kg CBD in DMSO between August 10 and September 4, 2020. Blood samples were collected before and then 0.5, 1, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, and 264 hours after CBD administration. Serum biochemical analyses and CBCs were performed. Plasma concentrations of CBD and its metabolites were determined with the use of liquid chromatography-tandem mass spectrometry.

RESULTS

Concentrations of CBD and metabolites (7-COH CBD and 7-COOH CBD) were detected in all plasma samples up to 8 hours after dosing (oral and IV), with 7-COOH CBD being the most predominant metabolite. Pharmacokinetic results for CBD oral dosing at 2 mg/kg were mean ± SD half-life of 7.22 ± 2.86 hours, maximum concentration of 18.54 ± 9.80 ng/mL, and time to maximum concentration of 2.46 ± 1.62 hours. For both oral and IV administrations, 7-COOH CBD did not fall below the limit of quantification for the times reported. Oral bioavailability for CBD was 7.92%. There was no meaningful effect of CBD on results for CBC, serum biochemical analyses, or vital signs for any horse.

CLINICAL RELEVANCE

Pharmacokinetics and bioavailability of CBD in senior horses were determined, and there were no adverse effects of administering either the oral or IV dose of CBD evaluated.

Open access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of advanced age on whole-body protein synthesis and activation of the mechanistic target of rapamycin (mTOR) signaling pathway in skeletal muscle of horses.

Animals—Six 22- to 26-year-old (aged) and six 7- to 14-year-old (mature) horses.

Procedures—Whole-body protein synthesis was measured with a 2-hour primed constant infusion of 13C sodium bicarbonate, followed by a 4-hour primed constant infusion of 1-13C phenylalanine. After the infusions, a biopsy specimen was obtained from a gluteus medius muscle and activation of protein kinase B (Akt), p70 riboprotein S6 kinase (S6K1), riboprotein S6 (rpS6), and eukaryotic initiation factor 4E binding protein 1 (4EBP1) was determined with western immunoblot analysis. For all horses, inflammatory cytokine expression in muscle and blood samples was measured with quantitative real-time PCR analysis.

Results—Advanced age had no effect on whole-body protein synthesis or the phosphorylation of Akt, rpS6, and 4EBP1; however, muscle specimens of aged horses had 42% lower phosphorylation of S6K1 than did those of mature horses. Aged and mature horses had similar inflammatory cytokine expression in muscle and blood samples.

Conclusions and Clinical Relevance—The lower S6K1 activation for aged horses, compared with that for mature horses, could be indicative of low rates of muscle protein synthesis in aged horses. However, advanced age had no effect on any other indicators of whole-body or muscle protein synthesis or on measures of systemic or muscle inflammation, which suggested that protein metabolism and subsequently requirements may not differ between healthy mature and aged horses.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To perform lipidomic analysis of surfactant and plasma from asthmatic and healthy horses.

ANIMALS

30 horses with clinical signs of asthma and 30 age-matched control horses.

PROCEDURES

Detailed history, physical examination, CBC, and bronchoalveolar lavage fluid (BALF) cytologies were obtained. Asthmatic horses were grouped based on their BALF inflammatory profile: severe equine asthma (SEA), mild equine asthma with neutrophilic airway inflammation (MEA-N), or mild equine asthma with eosinophilic airway inflammation (MEA-E). Each asthma group was assigned its own age-matched control group. Lipidomic analysis was completed on surfactant and plasma. Surfactant protein D (SP-D) concentrations were measured in serum and BALF.

RESULTS

SEA surfactant was characterized by a phospholipid deficit and altered composition (increased ceramides, decreased phosphatidylglycerol, and increased cyclic phosphatidic acid [cPA]). In comparison, MEA-N surfactant only had a decrease in select phosphatidylglycerol species and increased cPA levels. The plasma lipidomic profile was significantly different in all asthma groups compared to controls. Specifically, all groups had increased plasma phytoceramide. SEA horses had increased plasma cPA and diacylglycerol whereas MEA-N horses only had increased cPA. MEA-E horses had increases in select ceramides and dihydrocermides. Only SEA horses had significantly increased serum SP-D concentrations.

CLINICAL RELEVANCE

The most significant surfactant alterations were present in SEA (altered phospholipid content and composition); only mild changes were observed in MEA-N horses. The plasma lipidomic profile was significantly altered in all groups of asthmatic horses and differed among groups. Data from a larger population of asthmatic horses are needed to assess implications for diagnosis, prognosis, and treatment.

Open access
in American Journal of Veterinary Research