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1.
Animals (Basel) ; 14(13)2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38997975

RESUMEN

With the increase in popularity of utilizing cannabidiol (CBD) for human ailments, owners are actively interested in the possible utilization of cannabinoid products for their pets. The evaluation of CBD-rich hemp as an anti-anxiolytic, anti-inflammatory, immunomodulator, and anti-epileptic supplement has been assessed in previous studies in dogs, with adverse events such as ataxia or lethargy noted. In this study, the utilization of CBD-rich hemp was assessed at two concentrations to ascertain the impact on behavior as well as the tolerability of the medication given in a typically recommended dose and then twice that dose. Eighteen dogs were utilized in a randomized, double-blinded, placebo-controlled, 3 × 3 designed study. Each group of six dogs was provided placebo, 2 mg/kg, and 4 mg/kg of a cannabidiol/cannabidiolic acid (CBD/CBDA)-rich hemp in two-week intervals with one-week washout periods between each treatment period. Throughout the 10-week treatment period, student evaluations were performed, simulating clients' subjective assessments. Improvements in anxiety-related behavior and adverse events related to lethargy and ataxia were not observed and may indicate that the utilization of CBD-rich hemp products for behavioral changes may require higher dosing to mitigate unwanted behaviors in normal, healthy dogs. Furthermore, serum chemistry and serum cortisol were evaluated after each treatment period showing only a mildly significant increase in serum alkaline phosphatase when dosing at 4 mg/kg every 12 h, which is consistent with previously reported CBD dosing at these higher concentrations. Adverse events associated with CBD/CBDA-rich hemp extract given at 2 and 4 mg/kg every 12 h for two weeks were not reported, suggesting that using CBD-rich hemp in young, healthy dogs was safe during two weeks of treatment.

2.
Front Vet Sci ; 11: 1356463, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38681854

RESUMEN

The pharmacokinetics and tolerability of cannabinoids and their metabolites were determined in eight horses after enteral administration of a commercial CBD/CBDA-rich hemp oil product. Each horse was administered 2 mg/kg or 8 mg/kg CBD/CBDA or no treatment in a randomized cross-over design. Serial serum samples collected over 48 h were analyzed by high performance liquid chromatography with tandem mass spectrometry. Plasma chemistry analysis was performed at 0 h and 24 h. Vital parameters, pedometry, and blinded mentation and gait evaluations were recorded at intervals up to 24 h. Manure production and gastrointestinal transit time were tracked for 48 h after oil administration. The median maximal concentration of CBD and CBDA were 5.2 and 36.95 ng/mL in the 2 mg/kg group, respectively; and 40.35 and 353.56 ng/mL in the 8 mg/kg group. The median half-life of elimination was not calculated for the 2 mg/kg CBD treatment due to lack of time points above the lower quantifiable limit beyond the Cmax while it was 7.75 h in the 8 mg/kg group. CBDA absorption was biphasic. Pharmacokinetic parameters for tetrahydrocannabinol, tetrahydrocannabinolic acid, cannabigerolic acid, and 7-carboxy cannabidiol are also reported. No significant differences in any of the measured tolerability parameters were demonstrated between treatment groups. Single-dose enteral administration of CBD/CBDA-rich hemp extract up to 8 mg/kg does not appear to produce neurologic, behavioral, or gastrointestinal effects in horses.

3.
J Vet Pharmacol Ther ; 47(1): 1-13, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37469115

RESUMEN

Phytocannabinoid-rich hemp extracts containing cannabidiol (CBD) and cannabidiolic acid (CBDA) are increasingly being used to treat various disorders in dogs. The objectives of this study were to obtain preliminary information regarding the in vitro metabolism of these compounds and their capacity to inhibit canine cytochrome P450 (CYP)-mediated drug metabolism and canine P-glycoprotein-mediated transport. Pure CBD and CBDA, and hemp extracts enriched for CBD and for CBDA were evaluated. Substrate depletion assays using pooled dog liver microsomes showed CYP cofactor-dependent depletion of CBD (but not CBDA) and UDP-glucuronosytransferase cofactor-dependent depletion of CBDA (but not CBD) indicating major roles for CYP and UDP-glucuronosytransferase in the metabolism of these phytocannabinoids, respectively. Further studies using recombinant canine CYPs demonstrated substantial CBD depletion by the major hepatic P450 enzymes CYP1A2 and CYP2C21. These results were confirmed by showing increased CBD depletion by liver microsomes from dogs treated with a known CYP1A2 inducer (ß-naphthoflavone) and with a known CYP2C21 inducer (phenobarbital). Cannabinoid-drug inhibition experiments showed inhibition (IC50 = 4.6-8.1 µM) of tramadol metabolism via CYP2B11-mediated N-demethylation (CBD and CBDA) and CYP2D15-mediated O-demethylation (CBDA only) by dog liver microsomes. CBD and CBDA did not inhibit CYP3A12-mediated midazolam 1'-hydroxylation (IC50 > 10 µM). CBD and CBDA were not substrates or competitive inhibitors of canine P-glycoprotein. Results for cannabinoid-enriched hemp extracts were identical to those for pure cannabinoids. These in vitro studies indicate the potential for cannabinoid-drug interactions involving certain CYPs (but not P-glycoprotein). Confirmatory in vivo studies are warranted.


Asunto(s)
Cannabidiol , Cannabinoides , Perros , Animales , Cannabidiol/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Glucuronosiltransferasa/metabolismo , Cannabinoides/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo , Microsomas Hepáticos/metabolismo , Interacciones Farmacológicas , Uridina Difosfato/metabolismo
4.
Front Vet Sci ; 10: 1286158, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38094499

RESUMEN

Introduction: Cannabinoids are increasingly popular in human and veterinary medicine and have been studied as an alternative treatment for a wide range of disorders. The goal of this study was to perform a pharmacokinetic analysis of oral cannabidiol (CBD)-/cannabidiolic acid (CBDA)-rich hemp oil (CBD/ArHO) in juvenile cynomolgus macaques (Macaca fascicularis). Methods: After a 2 mg/kg CBD/ArHO pilot study, 4 and 8 mg/kg direct-to-mouth CBD/ArHO were administered (n = 4 per dose) once daily for 14 days and blood was collected at 0-, 0.5-, 1-, 2-, 4-, 8-, 12-, and 24-h, and on Days 7 and 14, to quantify serum cannabinoid concentrations by high-performance liquid chromatography-tandem mass spectrometry. Serum biochemistries and complete blood counts were performed on Days 0, 1, and 14. Results: The maximum mean serum concentration (Cmax) of CBDA was 28.6-36.2 times that of CBD at 4 and 8 mg/kg. At 8 mg/kg, the Cmax of CBD was 1.4 times higher (p = 0.0721), and CBDA was significantly 1.8 times higher (p = 0.0361), than at 4 mg/kg. The maximum mean serum concentration of ∆9-tetrahydrocannabinol (THC) was 4.80 ng/mL at 8 mg/kg. Changes in serum biochemistries and complete blood counts over time were not clinically significant. Discussion: Given the low serum CBD concentrations, the doses and frequency used in this study may be insufficient for a therapeutic effect of CBD in particular; therefore, clinical studies are needed to determine the therapeutic dose of CBD and CBDA for macaques, which may differ based on the disorder targeted.

5.
J Vet Intern Med ; 37(6): 2334-2343, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37680008

RESUMEN

BACKGROUND: The role of diet in the pathogenesis and treatment of chronic enteropathies (CE) in dogs is unresolved. OBJECTIVES: To compare the ability of diets composed of hydrolyzed fish, rice starch, and fish oil without (HF) or with prebiotics, turmeric, and high cobalamin (HF+) against a limited ingredient diet containing mixed nonhydrolyzed antigens and oils (control) to resolve clinical signs and maintain serum cobalamin and folate concentrations in dogs with nonprotein losing CE (non-PLE). To determine the ability of hydrolyzed fish diets to support recovery and remission in dogs with PLE. ANIMALS: Thirty-one client-owned dogs with CE: 23 non-PLE, 8 PLE. METHODS: Randomized, blinded, controlled trial. Diets were fed for 2 weeks; responders continued for 12 weeks. Nonresponders were crossed over to another diet for 12 weeks. Response was determined by standardized clinical evaluation with long-term follow-up at 26 weeks. Concurrent medications were allowed in PLE. RESULTS: Nineteen of 23 (83%; 95% confidence interval [CI], 60%-94%) non-PLE CE responded clinically to their initial diet, with no difference between diets (P > .05). Four nonresponders responded to another diet, with sustained remission of 18/18 (100%; 95%CI, 78%-100%) at 26 weeks. Serum cobalamin concentration was increased (P < .05) and maintained by diet. Serum folate concentration decreased posttreatment (P < .05) but was restored by dietary supplementation. Hydrolyzed fish diets supported weight gain, serum albumin concentration, and recovery (P < .05) in dogs with PLE. CONCLUSIONS AND CLINICAL IMPORTANCE: Changing diet, independent of antigen restriction or supplemental ingredients, induced long-term remission in dogs with non-PLE CE. Serum cobalamin and folate concentrations were maintained by diet. Hydrolyzed fish diets supported clinical recovery and remission in PLE.


Asunto(s)
Enfermedades de los Perros , Productos Pesqueros , Enfermedades Inflamatorias del Intestino , Enteropatías Perdedoras de Proteínas , Animales , Perros , Dieta/veterinaria , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/dietoterapia , Ácido Fólico , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/dietoterapia , Enfermedades Inflamatorias del Intestino/veterinaria , Enteropatías Perdedoras de Proteínas/patología , Enteropatías Perdedoras de Proteínas/veterinaria , Estudios Retrospectivos , Vitamina B 12
6.
J Zoo Wildl Med ; 54(2): 219-230, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37428684

RESUMEN

Vitamin D supplementation may pose a significant health risk in species where levels of deficiency, sufficiency, and toxicity have not been clearly established, and species-specific research on vitamin D supplementation should be performed. This study documented the effect of vitamin D supplementation on serum vitamin D metabolites and other analytes of Ca homeostasis in Asian elephants (Elephas maximus). Six adult Asian elephants received PO supplementation with cholecalciferol at 300 IU/kg of body weight (BW) once a week for 24 wk. Serum was analyzed every 4 wk for 25-hydroxyvitamin D2/D3 [25(OH)D]; 24,25-dihydroxyvitamin D2/D3 [24,25(OH)2D]; 1,25-dihydroxyvitamin D [1,25(OH)2D]; parathyroid hormone (PTH); total Ca; ionized Ca (iCa); P; and Mg. After the supplement was discontinued, serum 25(OH)D2/D3 was measured every 4 wk until levels returned to baseline. At the start of the study, the average serum 25(OH)D3 was nondetectable (<1.5 ng/ml). With cholecalciferol supplementation, 25(OH)D3 increased at an average rate of 2.26 ng/ml per month and reached an average concentration of 12.9 ± 3.46 ng/ml at 24 wk. Both 24,25(OH)2D3 and 1,25(OH)2D increased over time with supplementation from an average of <1.5 to 12.9 ng/ml and from 9.67 to 36.4 pg/ml, respectively. PTH, iCa, Ca, P, and Mg remained within reported normal ranges throughout supplementation. After the supplement was discontinued, serum 25(OH)D3 demonstrated a slow decline to baseline, taking an average of 48 wk. Elephants demonstrated significant individual variation in response to supplementation and subsequent return to baseline. Supplementation of Asian elephants with a weekly dose of 300 IU/kg BW cholecalciferol for 24 wk appears to be effective and safe. Additional clinical studies would be necessary to investigate the safety of other routes of administration, dosages, and duration of vitamin D supplementation, as well as associated health benefits.


Asunto(s)
Colecalciferol , Elefantes , Animales , Elefantes/metabolismo , Vitamina D , Ergocalciferoles , Hormona Paratiroidea , Suplementos Dietéticos
7.
Vet Clin North Am Small Anim Pract ; 53(5): 1083-1098, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37353417

RESUMEN

Feeding during normal reproduction is often not thought of until there is a problem with conception or gestational losses. Energy demands of lactation and early puppy/kitten are of concern, particularly in large and giant breed dogs where mineral balance is crucial to normal development. There is a paucity of information around optimizing feeding during conception and gestation with many myths around ingredients which will be explored in this article along with supplements that may be able to support spermatogenesis and conception which primarily comes from the human literature and may have validity in times of difficult conception.


Asunto(s)
Enfermedades de los Gatos , Enfermedades de los Perros , Masculino , Gatos , Embarazo , Perros , Animales , Femenino , Humanos , Destete , Dieta/veterinaria , Lactancia , Suplementos Dietéticos , Cruzamiento , Alimentación Animal/análisis
8.
J Am Vet Med Assoc ; 261(7): 1054-1060, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-37072120

RESUMEN

There is considerable confusion in the veterinary profession surrounding the rise in hemp cannabidiol-based animal products and what veterinarians should know before discussing these products with clients. There is emerging evidence for the potential use in case management across many veterinary indications; however, the cannabinoid concentrations and whether these are isolated cannabinoids or whole hemp extracts is difficult to elucidate, even from the published papers. Much like any extract from a plant, there are multiple considerations including quality control, pharmacokinetics in the intended species, microbiological and chemical contamination, and product consistency-all aspects that should be considered before a conversation can begin with a client. The aim of this review is to help practitioners make informed decisions and better facilitate discussions with clients for companion animals kept as pets. This review will not address food animal issues, as established withholding times have yet to be fully researched.


Asunto(s)
Cannabinoides , Cannabis , Veterinarios , Animales , Humanos , Mascotas , Control de Calidad
9.
J Am Vet Med Assoc ; 261(5): 623-631, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36965472

RESUMEN

The endocannabinoid system (ECS) is an integral neuromodulatory system involved in neuronal development, synaptic plasticity, and homeostasis regarding immunity, as well as brain and other physiological functions such as anxiety, pain, metabolic regulation, and bone growth. Cannabis is a plant that contains exogenous cannabinoids, which have the potential for profound interplay within the ECS as enzymatic inhibitors or receptor-mediated interactions. Activation of cannabinoid receptors leads to various intracellular signaling processes that are involved in cellular functions, but those interactions are diverse due to different affinities of each cannabinoid with relevant receptors. Among the exogenous cannabinoids, cannabidiol (CBD) has drawn attention due to its potential anticancer, antiangiogenic, anti-inflammatory, and antiseizure properties using in vitro and in vivo models. Although scientific evidence is limited in dogs, there appears to be cautious optimism regarding the utilization of CBD in conjunction with other therapeutics for a range of disorders. This review will primarily focus on current scientific research on the efficacy of CBD on seizure, anxiety, osteoarthritis, and atopic dermatitis, following a brief discussion of endo- and exogenous cannabinoids, ECS, their molecular mechanism, and potential side effects in veterinary medicine. Cannabinoid pharmacology and pharmacokinetics will be addressed in the companion Currents in One Health by Schwark and Wakshlag, AJVR, May 2023.


Asunto(s)
Cannabidiol , Cannabinoides , Cannabis , Enfermedades de los Perros , Humanos , Animales , Perros , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , Cannabinoides/farmacología , Cannabinoides/uso terapéutico , Convulsiones/tratamiento farmacológico , Convulsiones/veterinaria , Enfermedades de los Perros/tratamiento farmacológico
10.
Am J Vet Res ; 84(5)2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36972696

RESUMEN

The goal of pharmacokinetic (PK) studies is to provide a basis for appropriate dosing regimens with novel therapeutic agents. With a knowledge of the desired serum concentration for optimum pharmacological effect, the amount and rate of drug administration can be tailored to maintain that concentration based on the 24-hour PK modeling (eg, every 24 hours, every 12 hours) to achieve therapeutic ranges. This dosing and PK information are tailored to maintain that concentration. Typically, these optimum serum concentrations pertain across species. Single-dose PK modeling provides fundamental parameters to suggest dosing regimes. Multiple-dose PK studies provide information on steady-state serum levels to assure that desired therapeutic levels are maintained during chronic administration. Clinical trials using dosing suggested by these PK determinations provide proof that the compound is producing the desired therapeutic effect. A number of PK studies with cannabinoids in humans and domestic animals have been conducted with the goal of determining appropriate clinical use with these plant-derived products. The following review will focus on the PK of cannabidiol (CBD) and the lesser-known precursor of CBD, cannabidiolic acid (CBDA). Although Δ9-tetrahydrocannabinol (THC) has profound pharmacological effects and may be present at variable and potentially violative concentrations in hemp products, PK studies with THC will not be a major consideration. Because, in domestic animals, hemp-CBD products are usually administered orally, that route will be a focus. When available, PK results with CBD administered by other routes will be summarized. In addition, the metabolism of CBD across species appears to be different in carnivorous species compared with omnivorous/herbivorous species (including humans) based on current information, and the preliminary information related to this will be explained with the therapeutic implication being addressed in Currents in One Health by Ukai et al, JAVMA, May 2023.


Asunto(s)
Cannabidiol , Cannabinoides , Salud Única , Humanos , Animales , Cannabidiol/farmacocinética , Dronabinol/farmacocinética , Animales Domésticos , Cannabinoides/farmacocinética , Biotransformación
11.
Equine Vet J ; 55(2): 182-193, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35491961

RESUMEN

BACKGROUND: High serum γ-glutamyl-transferase (GGT) activity syndrome in racehorses has been associated with maladaption to exercise. Investigation of affected horses before and immediately after standard exercise may provide critical insight into the syndrome's pathophysiology. OBJECTIVES: To investigate blood biomarker changes in actively competing racehorses with high GGT activity associated with an exercise challenge. STUDY DESIGN: Case-control study. METHODS: High GGT case (age: 2-3 years) and normal GGT control (age: 2-7 years) pairs (3 Thoroughbred, 4 Standardbred pairs) at least 3 months into their training/racing season were included. Horses with a recent history of high GGT activity (≥50 IU/L) without additional biochemical evidence of liver disease were identified by veterinarians. Horses were tested again in the week prior to a planned exercise challenge to confirm persistent increases in GGT activity. Controls from the same stable with similar training/racing intensity and serum GGT activity ≤36 IU/L were matched with each case. Blood samples were obtained immediately before, 15 and 120 min after exercise. Pre-exercise serum samples were analysed for baseline select serum chemistries, selenium and vitamin E concentrations. Cortisol concentration and markers of oxidative status were measured in serum or plasma for all time points. Individual serum bile acid and coenzyme Q10 concentrations, plasma lipid mediator (fatty acids, oxylipids, isoprostanes) concentrations and targeted metabolomics analyses were performed using liquid chromatography-mass spectrometry. Serum viral PCR for equine hepaci- and parvovirus was performed in each animal. RESULTS: Cases had higher baseline concentrations of total glutathione, taurocholic acid, cortisol and cholesterol concentrations and higher or lower concentrations of specific oxylipid and isoprostane mediators, but there were no case-dependent changes after exercise. MAIN LIMITATIONS: Small sample size. CONCLUSIONS: Results indicated that glutathione metabolism was altered in high GGT horses. Enhanced glutathione recycling and mild cholestasis are possible explanations for the observed differences.


Asunto(s)
Hidrocortisona , Condicionamiento Físico Animal , Caballos , Animales , Estudios de Casos y Controles , gamma-Glutamiltransferasa , Condicionamiento Físico Animal/fisiología
12.
J Am Vet Med Assoc ; 260(S3): S77-S82, 2022 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-36173760

RESUMEN

OBJECTIVES: To evaluate the serum concentrations of myostatin and growth and differentiation factor 15 (GDF-15) in Alaskan Husky sled dogs participating in a 350-mile (560-km) race and in an older population, and to examine correlations between changes in serum concentrations and body condition scores (BCSs). ANIMALS: Dogs were recruited from 3 teams of Alaskan Huskies participating in the Alaskan-Yukon Quest sled-dog race and retirees from a research sled-dog colony. PROCEDURES: Serum samples and BCSs were collected prior to racing, midway, and postrace; and in an older cohort (13 to 14 years). Myostatin and GDF-15 concentrations were assessed using commercially available ELISA kits. RESULTS: The median myostatin prerace concentration (9,519 pg/mL) was significantly greater than the mid- and postrace concentrations (7,709 pg/mL and 3,247 pg/mL, respectively). The prerace concentration was also significantly greater than that of the retired sled group dogs at 6,134 pg/mL. GDF-15 median serum concentrations did not change significantly across any racing time point (approx 350 pg/mL) or in the older cohort. No significant correlations were observed between changes in BCS and myostatin or GDF-15 concentrations. CLINICAL RELEVANCE: Serum myostatin decreases dramatically, yet no correlations to loss of BCS could be found. Myostatin signaling may be involved in maintaining hypertrophic signaling during intense exercise. Neither racing distance nor geriatric/retirement status appears to have an effect on serum GDF-15 concentration. Myostatin was less in the older, retired sled dogs compared to the younger racing cohort. Such differences highlight the roles that fitness level and age play regarding myostatin levels.


Asunto(s)
Condicionamiento Físico Animal , Carrera , Perros , Animales , Miostatina , Factor 15 de Diferenciación de Crecimiento , Envejecimiento
13.
Front Vet Sci ; 9: 895368, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35937287

RESUMEN

Hemp based cannabinoids have gained popularity in veterinary medicine due to the potential to treat pain, seizure disorders and dermatological maladies in dogs. Cat owners are also using hemp-based products for arthritis, anxiety and neoplastic disorders with no studies assessing hemp cannabinoids, namely cannabidiol efficacy, for such disorders. Initial twenty-four pharmacokinetic and chronic dosing serum concentration in cats are sparse. The aim of our study was to assess 8 cats physiological and 24 h and 1-week steady state pharmacokinetic response to a cannabidiol (CBD) and cannabidiolic acid (CBDA) rich hemp in a palatable oral paste. Using a standard dose of paste (6.4 mg/CBD + CBDA 5.3 mg/gram) across 8 cats weighing between 4.2 and 5.4 kg showed an average maximal concentration of CBD at 282.0 ± 149.4 ng/mL with a half-life of ~2.1 ± 1.1 h, and CBDA concentrations of 1,011.3 ± 495.4 ng/mL with a half-life of ~2.7 ± 1.4 h, showing superior absorption of CBDA. After twice daily dosing for 1 week the serum concentrations 6 h after a morning dosing showed that the acidic forms of the cannabinoids were approximately double the concentration of the non-acidic forms like CBD and Δ9- tetrahydrocannabinol (THC). The results of this study compared to two other recent studies suggest that the absorption in this specific paste product may be superior to oil bases used previously, and show that the acidic forms of cannabinoids appear to be absorbed better than the non-acidic forms. More importantly, physical and behavioral examinations every morning after dosing showed no adverse events related to neurological function or behavioral alterations. In addition, bloodwork after 1 week of treatment showed no clinically significant serum biochemical alterations as a reflection of hepatic and renal function all remaining within the reference ranges set by the diagnostic laboratory suggesting that short-term treatment was safe.

14.
J Dairy Sci ; 105(10): 8497-8508, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35965128

RESUMEN

The 3 branched-chain AA (BCAA), Val, Leu, and Ile, are essential AA used by tissues as substrates for protein synthesis and energy generation. In addition, BCAA are also involved in modulating cell signaling pathways, such as nutrient sensing and insulin signaling. In our previous study, dietary BCAA supplementation was shown to improve protein synthesis and glucose homeostasis in transition cows. However, a more detailed understanding of the changes in metabolic pathways associated with an increased BCAA availability is desired to fine-tune nutritional supplementation strategies. Multiparous Holstein cows (n = 20) were enrolled 28 d before expected calving and assigned to either the BCAA treatment (n = 10) or the control group (n = 10). Cows assigned to BCAA were fed 550 g/d of rumen-protected BCAA mixed with 200 g/d of dry molasses from calving until 35 DIM, whereas the cows assigned to the control were fed only 200 g/d of dry molasses. Serum samples were collected on d 10 before expected calving, as well as on d 4 and d 21 postpartum. Milk samples were collected on d 14 postpartum. From a larger cohort, we selected 20 BCAA-supplemented cows with the greatest plasma urea nitrogen concentration, as an indicator for greater BCAA availability, for the metabolomics analysis herein. Serum and milk samples were subjected to a liquid chromatography-mass spectrometry-based assay, detecting and measuring the abundance of 241 serum and 211 milk metabolic features, respectively. Multivariable statistical analyses revealed that BCAA supplementation altered the metabolome profiles of both serum and milk samples. Increased abundance of serum phosphocholine and glutathione and of milk Val, Ile, and Leu, and decreased abundance of milk acyl-carnitines were associated with BCAA supplementation. Altered phosphocholine and glutathione abundances point to altered hepatic choline metabolism and antioxidant balance, respectively. Altered milk acyl-carnitine abundances suggest changes in mammary fatty acid metabolism. Dietary BCAA supplementation was associated with a range of alterations in serum and milk metabolome profiles, adding to our understanding of the role of BCAA availability in modulating dairy cow protein, lipid, and energy metabolism on a whole-body level and how it affects milk composition.


Asunto(s)
Insulinas , Leche , Aminoácidos de Cadena Ramificada/metabolismo , Animales , Antioxidantes/metabolismo , Carnitina/análogos & derivados , Carnitina/análisis , Bovinos , Colina/metabolismo , Dieta/veterinaria , Suplementos Dietéticos , Ácidos Grasos/metabolismo , Femenino , Glucosa/metabolismo , Glutatión/metabolismo , Humanos , Lactancia , Lípidos/análisis , Metaboloma , Leche/química , Nitrógeno/metabolismo , Fosforilcolina/análisis , Fosforilcolina/metabolismo , Fosforilcolina/farmacología , Urea/metabolismo
15.
Front Vet Sci ; 9: 939966, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35967998

RESUMEN

The use of cannabidiol (CBD) in childhood refractory seizures has become a common therapeutic approach for specific seizure disorders in human medicine. Similarly, there is an interest in using CBD, cannabidiolic acid (CBDA) or cannabinoid-rich hemp products in the treatment of idiopathic epilepsy in dogs. We aimed to examine a small cohort in a pilot investigation using a CBD and CBDA-rich hemp product for the treatment of refractory epileptic seizures in dogs. Fourteen dogs were examined in a 24-week randomized cross-over study being provided placebo or CBD/CBDA-rich hemp extract treatment at 2 mg/kg orally every 12 h for each 12-week arm of the study. Serum chemistry, complete blood counts, serum anti-seizure medication (ASM) concentrations and epileptic seizure frequency were followed over both arms of the cross-over trial. Results demonstrated that besides a mild increase in alkaline phosphatase, there were no alterations observed on routine bloodwork at 2, 6, and 12 weeks during either arm of the study. Epileptic seizure frequency decreased across the population from a mean of 8.0 ± 4.8 during placebo treatment to 5.0 ± 3.6 with CBD/CBDA-rich hemp extract (P = 0.02). In addition, epileptic seizure event days over the 12 weeks of CBD/CBDA-rich hemp treatment were 4.1 ± 3.4, which was significantly different than during the 12 weeks of placebo treatment (5.8 ± 3.1; P =0.02). The number of dogs with a 50% reduction in epileptic activity while on treatment were 6/14, whereas 0/14 had reductions of 50% or greater while on the placebo (P = 0.02). No differences were observed in serum zonisamide, phenobarbital or bromide concentrations while on the treatment across groups. Adverse events were minimal, but included somnolence (3/14) and transient increases in ataxia (4/14) during CBD/CBDA-rich hemp extract treatment; this was not significantly different from placebo. This further indicates that providing CBD/CBDA-rich hemp extract during refractory epilepsy (only partially responsive to ASM), in conjunction with other ASM appears safe. Based on this information, the use of 2 mg/kg every 12 h of a CBD/CBDA-rich hemp extract can have benefits in reducing the incidence of epileptic seizures, when used concurrently with other ASMs.

16.
Front Vet Sci ; 9: 859066, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35774974

RESUMEN

Sled dogs are purpose-bred dogs selected for endurance work. Prior studies in racing dogs showed that serum thyroid parameters (total T4, free T4, and T3) are lower than the reference range in approximately 25% of dogs. Whether this is related to training, breeding, or body condition remains unclear. We hypothesized that retired sled dogs of normal body condition (9-13 years old) would have predominantly normal serum thyroid parameters and that serum thyroid status would be correlated to energy consumption based on metabolic body weight. Eighty-six sled dogs who were deemed healthy on physical exam, not on confounding medications, and without a prior diagnosis of hypothyroidism were included. All dogs' mean body condition scores were 5.1 ± 0.4 and body weight 24.5 ± 4.2 kg at fasting blood collection with stable dietary intake for 3 months before sampling. The total T4, free T4, and T3 serum concentrations were 23.4 ± 9.1 nmol/L, 9.53 ± 4.3 pmol/L, and 0.93 ± 0.39 nmol/L, respectively, with 38% lower than the reference range for total T4, 45% for free T4, and 37% for T3. All dogs were negative for thyroglobulin antibody, and TSH results were within normal ranges. Pearson's correlates based on kilocalories consumed on a metabolic body weight basis for total T4 (R = 0.14), free T4 (R = 0.01) and T3 (R = 0.23) showed poor correlation. No differences were observed between thyroid hormones and age, breed, or sex. Inactive, retired sled dogs can be misdiagnosed with hypothyroidism; therefore, our data suggests that misdiagnosis of hypothyroidism can occur and that the racing Alaskan sled dog has a unique reference range that should be considered when assessing serum thyroid status.

17.
Vet Dermatol ; 33(4): 329-e77, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35644533

RESUMEN

BACKGROUND: Cannabidiol (CBD) and cannabidiolic acid (CBDA) are reported to have antinociceptive, immunomodulatory and anti-inflammatory actions. OBJECTIVES: To determine if CBD/CBDA is an effective therapy for canine atopic dermatitis (cAD). ANIMALS: Thirty-two privately owned dogs with cAD. MATERIALS AND METHODS: Prospective, randomised, double-blinded, placebo-controlled study. Concurrent therapies were allowed if remained unchanged. Dogs were randomly assigned to receive either 2 mg/kg of an equal mix of CBD/CBDA (n = 17) or placebo for 4 weeks. On Day (D)0, D14 and D28, Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) and pruritus Visual Analog Scale (pVAS) scores were determined by investigators and owners, respectively. Complete blood count, serum biochemistry profiles and cytokine bioassays were performed on serum collected on D0 and D28. RESULTS: There was no significant difference in CADESI-04 from D0 to D14 (p  = 0.42) or D28 (p  = 0.51) in either group. pVAS scores were significantly lower for the treatment group at D14 (p  = 0.04) and D28 (p  = 0.01) and a significant change in pVAS from baseline was seen at D14 (p  = 0.04) and not D28 (p  = 0.054) between groups. There was no significant difference in serum levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein - 1, IL-31 or IL-34 between groups at D0 or D28. Elevated alkaline phosphatase was observed in four of 17 treatment group dogs. CONCLUSIONS AND CLINICAL RELEVANCE: CBD/CBDA as an adjunct therapy decreased pruritus, and not skin lesions associated with cAD in dogs.


Contexte - Le cannabidiol (CBD) et l'acide cannabidiolique (CBDA) auraient des actions antinociceptives, immunomodulatrices et anti-inflammatoires. Objectifs - Déterminer si le CBD/CBDA est une thérapie efficace pour la dermatite atopique canine (cAD). Animaux - Trente-deux chiens de propriétaires privés atteints de cAD Matériels et méthodes - Étude prospective, randomisée, en double aveugle, contrôlée versus placebo. Les thérapies concomitantes étaient autorisées si elles restaient inchangées. Les chiens ont été répartis au hasard pour recevoir soit 2 mg/kg d'un mélange égal de CBD/CBDA (n = 17) soit un placebo pendant quatre semaines. Aux jours (J)0, J14 et J28, les scores Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) et prurit Visual Analog Scale (pVAS) ont été déterminés respectivement par les investigateurs et les propriétaires. Une formule sanguine complète, des profils biochimiques sériques et des dosages biologiques des cytokines ont été réalisés sur le sérum prélevé à J0 et J28. Résultats - Il n'y avait pas de différence significative au CADESI-04 de J0 à J14 (P = 0,42) ou J28 (P = 0,51) dans les deux groupes. Les scores pVAS étaient significativement inférieurs pour le groupe de traitement à J14 (P = 0,04) et J28 (P = 0,01) et un changement significatif de la pVAS par rapport à l'inclusion a été observé à J14 (P = 0,04) et non à J28 (P = 0,054) entre les groupes. Il n'y avait pas de différence significative dans les taux sériques d'interleukine (IL)-6, IL-8, protéine chimiotactique des monocytes-1, IL-31 ou IL-34 entre les groupes à J0 ou J28. Une phosphatase alcaline élevée a été observée chez quatre des 17 chiens du groupe de traitement. Conclusions et pertinence clinique - Le CBD/CBDA en tant que traitement d'appoint a diminué le prurit, et non les lésions cutanées associées à la DAC chez les chiens.


Introducción- se ha descrito que el cannabidiol (CBD) y el ácido cannabidiólico (CBDA) tienen acciones antinociceptivas, inmunomoduladoras y antiinflamatorias. Objetivos- determinar si el CBD/CBDA es una terapia eficaz para la dermatitis atópica canina (CAD). Animales - Treinta y dos perros de propietarios privados con cAD Materiales y métodos - Estudio prospectivo, aleatorio, doble ciego, controlado con placebo. Se permitieron terapias concurrentes si permanecían sin cambios. Los perros fueron asignados al azar para recibir 2 mg/kg de una mezcla igual de CBD/CBDA (n = 17) o placebo durante cuatro semanas. En el día (D)0, D14 y D28, los investigadores y los propietarios determinaron las puntuaciones del índice de extensión y gravedad de la dermatitis atópica canina, cuarta revisión (CADESI-04) y la escala análoga visual de prurito (pVAS), respectivamente. Se realizaron hemogramas completos, perfiles bioquímicos séricos y bioensayos de citoquinas en suero obtenido en D0 y D28. Resultados- no hubo diferencias significativas en CADESI-04 de D0 a D14 (P = 0,42) o D28 (P = 0,51) en ninguno de los grupos. Las puntuaciones de pVAS fueron significativamente más bajas para el grupo de tratamiento en D14 (P = 0.04) y D28 (P = 0.01) y se observó un cambio significativo en pVAS desde el inicio en D14 (P = 0.04) y no en D28 (P = 0.054) entre grupos . No hubo diferencias significativas en los niveles séricos de interleuquina (IL)-6, IL-8, proteína quimioatrayente de monocitos-1, IL-31 o IL-34 entre los grupos en D0 o D28. Se observó fosfatasa alcalina elevada en cuatro de los 17 perros del grupo de tratamiento. Conclusiones y relevancia clínica- CBD/CBDA como terapia adjunta disminuyó el prurito y no las lesiones cutáneas asociadas con la CAD en perros.


Contexto - O canabidiol (CBD) e ácido canabidiólico (CBDA) são relatados como tendo ações antinociceptivas, imunomoduladoras e anti-inflamatórias. Objetivos - Determinar se CBD/CBDA é eficaz no tratamento da dermatite atópica canina (CAD) Animais - Trinta e dois cães de propriedade privada com DAC. Materiais e métodos - Estudo prospectivo, randomizado, duplo-cego, placebo-controle. As terapias concomitantes foram permitidas se permanecessem inalteradas. Os cães foram divididos aleatoriamente em dois grupos, o que receberia 2 mg/kg de uma mistura igual de CBD/CBDA (n = 17) ou placebo durante quatro semanas. No Dia (D) 0, D14 e D28, o Índice de Extensão e Gravidade da Dermatite Atópica Canina, 4ª iteração (CADESI-04) e os escores da Escala Visual Analógica de Prurido (pVAS) foram determinados pelos investigadores e proprietários, respectivamente. Hemograma completo, perfis bioquímicos séricos e ensaios de citocinas foram realizados no soro coletado em D0 e D28. Resultados - Não houve diferença significativa no CADESI-04 de D0 a D14 (P = 0,42) ou D28 (P = 0,51) em nenhum dos grupos. Os escores de pVAS foram significativamente menores para o grupo de tratamento no D14 (P = 0,04) e D28 (P = 0,01) e observou-se uma alteração significativa no pVAS do D0 comparado ao D14 (P = 0,04) e não ao D28 (P = 0,054) entre os grupos. Não houve diferença significativa nos níveis séricos de interleucina (IL)-6, IL-8, proteína quimiotática de monócitos-1, IL-31 ou IL-34 entre os grupos em D0 ou D28. Elevação na fosfatase alcalina foi observada em quatro dos 17 cães do grupo de tratamento. Conclusões e relevância clínica - CBD e CBDA como uma terapia adjuvante é capaz de reduzir prurido, mas não lesões cutâneas associadas à DAC em cães.


Asunto(s)
Cannabidiol , Dermatitis Atópica , Enfermedades de los Perros , Animales , Cannabidiol/uso terapéutico , Cannabinoides , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Dermatitis Atópica/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/patología , Perros , Estudios Prospectivos , Prurito/tratamiento farmacológico , Prurito/veterinaria
18.
Vet Clin North Am Small Anim Pract ; 52(4): 939-958, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35562213

RESUMEN

The typical canine rehabilitation patient with orthopedic disease may differ in its nutritional needs, with the assumption that most patients will be on a complete and balanced commercial dog food that is not enriched with agents for ameliorating their condition. For a significant number of rehabilitation patients, obesity is a major issue where hypocaloric diet plans are often implemented and are covered extensively elsewhere (VCNA Small Animal Practice May 2021). The focus of this article will be implementation of physical activity or structured physical exercise protocols and how they might be used in combination with a typical hypocaloric diet plan, a diet low in calories. Considering the limited information regarding physical activity or structured exercise programs in dogs, a human comparative assessment of efficacy is fundamental as a baseline of information regarding typical interventions. In addition, many of these long-term rehabilitation cases typically exhibit osteoarthritis (OA) and as part of case management, there is a need to implement nutrient or nutraceutical intervention to either diminish the progression of OA or help with pain control measures, particularly for the nonsteroidal anti-inflammatory intolerant patient. Nutraceutical intervention comes in many forms from botanicals to nutritional enhancement; botanicals will be covered elsewhere in this issue. This overview of nutraceuticals will cover nonbotanical interventions including fish oil, glucosamine/chondroitin, avocado/soybean unsaponifiables, undenatured collagen, green lipped mussel, and egg shell membrane supplementation.


Asunto(s)
Suplementos Dietéticos/clasificación , Enfermedades de los Perros/terapia , Obesidad/veterinaria , Osteoartritis/veterinaria , Animales , Dieta Reductora/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Perros , Humanos , Obesidad/tratamiento farmacológico , Obesidad/terapia , Osteoartritis/tratamiento farmacológico , Osteoartritis/terapia
19.
Front Vet Sci ; 9: 838481, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35464390

RESUMEN

Objective: The purpose of this study was 2-fold: to evaluate whether the timing of collection influences the platelet counts and leukocyte counts of PRP samples, and to evaluate growth factor concentrations in canine PRP after freezing and storage without a preservation agent for 6 months of time. Materials and Methods: Whole blood collection was performed three times over the course of 4 weeks. All PRP samples were evaluated with a CBC analysis. The PRP samples were frozen and stored without a preservation agent for the duration of the 4-week study. Results: The platelet and leukocyte counts were not statistically significant between the timing of blood draws over the course of 4 weeks. All three growth factors were present in measurable quantities after freezing and storage for 6 months without a preservation agent. Clinical Relevance: PDGF, TGF-ß1, and VEGF were all present in measurable quantities. Furthermore, PDGF and TGF-ß1 were correlated with platelet count of the final PRP. VEGF concentrations were able to be quantified. We correctly hypothesized growth factor concentrations would be present and measurable in canine PRP frozen and stored without a preservation agent for 6 months.

20.
J Vet Pharmacol Ther ; 45(3): 245-254, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35246858

RESUMEN

The use of cannabinoids in veterinary medicine has been increasing exponentially recently and there is little information regarding the pharmacokinetics of cannabinoids except for cannabidiol (CBD) and tetrahydrocannabinol (THC), with even more sparse information related to their native acid forms found in cannabis. Cannabigerol (CBG) is the precursor molecule to cannabinoid formation in the cannabis plant which may have medicinal properties as well, yet there are no publications related to CBG or the native cannabigerolic acid (CBGA) in companion animal species. The aim of this study was to investigate similar dosing of CBG and CBGA from hemp plants that have been used for cannabidiol pharmacokinetic studies. Administration in the fed and fasted state was performed to better understand absorption and retention of these unique hemp-derived cannabinoids in dogs. Results suggest that when providing a hemp-derived CBG/CBGA formulation in equal quantities, CBGA is absorbed approximately 40-fold better than CBG regardless of being given to fed or fasted dogs. After twice daily dosing for two weeks at 2 mg/kg in the fasted and then fed state, no differences in the mean serum CBG (5 ng/ml) or CBGA (250 ng/ml) serum concentrations were observed between states. Importantly, physical examination, complete blood counts, and serum chemistry evaluations over the two weeks suggest no adverse events during this short-term dosing trial.


Asunto(s)
Cannabidiol , Cannabinoides , Cannabis , Animales , Perros , Administración Oral , Benzoatos , Cannabinoides/química , Cannabis/química , Extractos Vegetales/química
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