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Abstract
OBJECTIVE
To determine the safety and pharmacokinetics of various doses of plant-derived cannabidiol (CBD) versus placebo following repeated oral administration.
ANIMALS
20 healthy adult Beagles.
PROCEDURES
In a randomized, blinded, placebo-controlled trial, dogs were randomized to 5 groups balanced in body weight and sex (n = 4 dogs/group) and received a CBD (1, 2, 4, or 12 mg/kg; from cannabis extract) or placebo oil formulation PO once daily for 28 days. Outcome variables were assessed through daily health observations, veterinary examinations, CBC, and serum biochemical analysis. Blood samples were collected at various time points to estimate 24-hour pharmacokinetic profiles of CBD and selected metabolites (7-carboxy-CBD and 7-hydroxy-CBD).
RESULTS
Repeated CBD administration was well tolerated by dogs, with no clinically important changes in measured safety outcomes. Veterinary examinations revealed no clinically important abnormal findings. Adverse events were mild in severity. Relative to placebo administration, CBD administration at 12 mg/kg/d resulted in more gastrointestinal adverse events (mainly hypersalivation) and significantly higher serum alkaline phosphatase activity. Total systemic exposure to CBD increased on a dose-dependent basis following both acute (first dose) and chronic (28 days) administration. Within each CBD dose group, repeated administration increased total systemic exposure to CBD 1.6- to 3.3-fold. The 24-hour trough plasma CBD concentrations were also dose dependent, with a steady state reached following 2 weeks of administration.
CONCLUSIONS AND CLINICAL RELEVANCE
Repeated, daily oral administration of the CBD formulation led to dose-dependent increases in total systemic exposure to CBD and 24-hour trough plasma concentrations in healthy dogs. These findings could help guide dose selection.
Objective—
To measure and compare blood values in sled dogs before and after long-distance racing.
Design—
Prospective study.
Animals—
17 adult sled dogs in the 1991 Iditarod Trail Sled Dog Race and 21 in a simulated sled dog race.
Procedure—
Blood samples were obtained from 17 dogs 7 days before they began and after they finished (finisher group) or were eliminated from (nonfinisher group) the Iditarod Trail Sled Dog Race. Blood samples were also obtained from 21 dogs before and after a simulated sled dog race.
Results—
In finisher-group dogs, BUN and uric acid (UA) concentrations were increased after racing; nonfinisher-group dogs had significantly lower postrace BUN and UA concentrations. Significant increases in creatine kinase (CK) and aspartate transferase (AST) activities were detected in all dogs after racing, and postrace values were higher in nonfinisher-group dogs, compared with finisher-group dogs. Mean alkaline phosphate activities were significantly increased after racing in nonfinisher-group dogs only. In dogs that ran the simulated race, postrace values for serum albumin, total protein, calcium, and potassium concentrations, as well as Hct, hemoglobin concentration, and RBC count, were significantly lower than prerace values. Postrace values for alkaline phosphate, alanine transaminase, AST, lactate dehydrogenase, CK, BUN, and UA were significantly higher than prerace values.
Clinical Implications—
High CK activities are indicative of severe muscle degeneration and, in sled dogs, may represent a degree of muscle breakdown beyond which a dog cannot continue to work. Markedly high CK, and possibly AST, serum activities may be indicators of performance failure in sled dogs competing in long-distance races. (J Am Vet Med Assoc 1997; 211:175–179)
Summary
Three configurations of cast padding and no cast padding were evaluated for their effects on skin in dogs. Padding was placed over bony prominences, between bony prominences, and over both areas for full-length padding under short-limb walking casts applied to 1 pelvic limb of Greyhounds. Evaluations were performed by pressure measurement over the calcaneal tuberosity, measurement of skin thromboxane B2 (TxB2) concentrations in skin over bony prominences, and measurement of plasma TXB2 concentrations.
Pressure studies were performed to evaluate cutaneous pressures related to no cast padding and various configurations of cast padding. Concentrations of TxB2 in the skin were determined to evaluate the skin inflammatory effects of no padding and the padding configurations, and TXB2 concentrations in the plasma were analyzed to ascertain whether they could be used to predict impending dermal pressure lesions.
Flexion of casted limbs revealed the greatest pressure over the calcaneal tuberosity with full-length cast padding. This was followed in decreasing order by no cast padding, padding over the prominences, and padding between the prominences.
Compared with all other bony prominences and padding configurations, TXB2 skin concentrations were significantly higher over the calcaneal tuberosity when no padding was used and over the lateral base of metatarsal V when padding was placed between the prominences. Over the calcaneal tuberosity, this was attributed to the sharpness of the prominence and its potential for movement. This high TxB2 concentration corresponded to the high pressure found in the pressure studies. Over the lateral base of metatarsal V, the increase in TxB2 concentration was related to the mass of the prominence and the tendency for localized padding to settle around the area.
Although the fully padded cast produced the highest pressure over the calcaneal tuberosity in the pressure measurement studies, this form of padding had the lowest TXB2 skin concentrations over this prominence in the 7- day TXB2 measurement studies. This was attributed to compacting of cast padding over time with resultant decrease in pressure over the bony prominence. There were no significant differences in plasma TxB2 concentrations before and after casting.
On the basis of cutaneous pressure measurements and or dermal or plasma TxB2 measurements after short-limb casts had been in place for 7 days, we concluded that absence of cast padding can cause dermal pressure injury over sharp prominences; in some areas, localized cast padding may settle around larger prominences, increase pressure, and potentiate dermal pressure injury; although pressure may be high after applying full-length cast padding, some compacting of the padding occurs, and this provides the best form of padding to prevent dermal pressure injury; and plasma TxB2 concentrations cannot be used to predict impending dermal pressure injury in a coaptation cast.
SUMMARY
Objectives
To ascertain the effects of dietary omega-3 (n-3) fatty acids on biochemical and histopathologic components of the inflammatory stage of wound healing.
Animals
30 purpose-bred Beagles.
Procedure
Dogs were allotted to 5 groups of 6. Each group was fed a unique dietary fatty acid ratio of omega-6 to n-3—diet A, 5.3:1; diet B, 10.4:1; diet C, 24.1:1; diet D, 51.6:1; and diet E, 95.8:1. Dogs were fed once daily for 12 weeks, then biopsy specimens were taken from 4-day-old wounds of each dog and analyzed by gas chromatography-mass spectrometry for: prostaglandin E2 (PGE2) metabolites, and ratios of omega-6 to n-3 fatty acids, arachidonic acid (AA) to eicosapentaenoic acid (EPA), adrenic acid to docosahexaenoic acid, and PGE2 to prostaglandin E3 (PGE3) metabolites.
Results
Qualitative analysis was carried out on AA, EPA, adrenic acid, docosahexaenoic acid, and the major metabolite from the PGE2 and PGE3 pathway. These molecules were further quantified with respect to diet to determine significant differences. By analysis of the AA-to-EPA ratio, diet A was different from diets D and E and diets B and C were different from diet E (P < 0.05). By analysis of the PGE2-to-PGE3 metabolite ratio, diet A was different from diet E (P < 0.05). Though biochemical analysis indicated dietary dependence, histopathologic data indicated no significant difference with respect to diet groups.
Conclusion
The biochemical component of the inflammatory stage of wound healing can be manipulated by diet.
Clinical Relevance
Omega-3 fatty acid-enriched diets can be used to control inflammation associated with dermatologic conditions. (Am J Vet Res 1998;59:859–863)
Abstract
Objective
To ascertain the effects of locally injected immunostimulant and tripeptide-copper complex (TCC) on improving healing of pad wounds.
Design
Wounds in pads of large dogs were injected with either medication or physiologic saline solution (controls). Healing was evaluated.
Animals
12 mature English Pointers.
Procedure
Full-thickness 6 × 8-mm wounds in metatarsal and third and fourth digital pads were injected with immunostimulant or TCC at 0, 3, and 6 days after wounding. Wounds on control dogs were injected with physiologic saline solution. Using planimetric measurements at 0, 3, 6, 14, and 21 days, rates of healing were evaluated. Biopsy of the digital pad wounds at 3, 6, and 14 days was used to evaluate collagen content by hydroxyproline analysis. Biopsy specimens were also evaluated for type-I and type-III collagen, using Sirius red differential staining.
Results
Effect on healing rate and hydroxyproline content was best during the first week for immunostimulant. Immunostimulant- and TCC-injected wounds had more type-I collagen than did controls at 6 days; TCC-injected wounds had the most type-I collagen. At 14 days, the amount of type-I collagen in TCC-injected wounds was significantly greater than that in other wounds.
Conclusions
Tested medications had positive effects on healing of pad wounds.
Clinical Relevance
Intralesional injection of medications helps ensure their presence for enhancement of wound healing. The benefit could be lost with topical use in a bandage if the bandage is lost or becomes wet.(Am J Vet Res 1996;57:394-399)
