Objective—To determine the pharmacokinetics of voriconazole following IV and PO administration and assess the distribution of voriconazole into body fluids following repeated PO administration in horses.
Animals—6 clinically normal adult horses.
Procedures—All horses received voriconazole (10 mg/kg) IV and PO (2-week interval between treatments). Plasma voriconazole concentrations were determined prior to and at intervals following administration. Subsequently, voriconazole was administered PO (3 mg/kg) twice daily for 10 days to all horses; plasma, synovial fluid, CSF, urine, and preocular tear film concentrations of voriconazole were then assessed.
Results—Mean ± SD volume of distribution at steady state was 1,604.9 ± 406.4 mL/kg. Systemic bioavailability of voriconazole following PO administration was 95 ± 19%; the highest plasma concentration of 6.1 ± 1.4 μg/mL was attained at 0.6 to 2.3 hours. Mean peak plasma concentration was 2.57 μg/mL, and mean trough plasma concentration was 1.32 μg/mL. Mean plasma, CSF, synovial fluid, urine, and preocular tear film concentrations of voriconazole after long-term PO administration were 5.163 ± 1.594 μg/mL, 2.508 ± 1.616 μg/mL, 3.073 ± 2.093 μg/mL, 4.422 ± 0.8095 μg/mL, and 3.376 ± 1.297 μg/mL, respectively.
Conclusions and Clinical Relevance—Results indicated that voriconazole distributed quickly and widely in the body; following a single IV dose, initial plasma concentrations were high with a steady and early decrease in plasma concentration. Absorption of voriconazole after PO administration was excellent, compared with absorption after IV administration. Voriconazole appears to be another option for the treatment of fungal infections in horses.
Objective—To determine the pharmacokinetics of
fluconazole in horses.
Animals—6 clinically normal adult horses.
Procedure—Fluconazole (10 mg/kg of body weight)
was administered intravenously or orally with 2
weeks between treatments. Plasma fluconazole concentrations
were determined prior to and 10, 20, 30,
40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48,
60, and 72 hours after administration. A long-term oral
dosing regimen was designed in which all horses
received a loading dose of fluconazole (14 mg/kg) followed
by 5 mg/kg every 24 hours for 10 days.
Fluconazole concentrations were determined in aqueous
humor, plasma, CSF, synovial fluid, and urine after
administration of the final dose.
Results—Mean (± SD) apparent volume of distribution
of fluconazole at steady state was 1.21 ± 0.01
L/kg. Systemic availability and time to maximum plasma
concentration following oral administration were
101.24 ± 27.50% and 1.97 ± 1.68 hours, respectively.
Maximum plasma concentrations and terminal halflives
after IV and oral administration were similar.
Plasma, CSF, synovial fluid, aqueous humor, and urine
concentrations of fluconazole after long-term oral
administration of fluconazole were 30.50 ± 23.88,
14.99 ± 1.86, 14.19 ± 5.07, 11.39 ± 2.83, and 56.99 ±
32.87 µg/ml, respectively.
Conclusion and Clinical Relevance—Bioavailability
of fluconazole was high after oral administration to
horses. Long-term oral administration maintained plasma
and body fluid concentrations of fluconazole above
the mean inhibitory concentration (8.0 mg/ml) reported
for fungal pathogens in horses. Fluconazole may be
an appropriate agent for treatment of fungal infections
in horses. (Am J Vet Res 2001;62:1606–1611).
Objective—To evaluate whether the effects of oxidative stress could be attenuated in cultures of canine lens epithelial cells (LECs) by incubation with grape seed proanthocyanidin extract (GSE), resveratrol (RES), or a combination of both (GSE+RES).
Sample Population—Primary cultures of canine LECs.
Procedures—LECs were exposed to 100MM tertiary butyl-hydroperoxide (TBHP) with or without GSE, RES, or GSE+RES. The dichlorofluorescein assay was used to detect production of reactive oxygen species (ROS), and immunoblot analysis was used to evaluate the expression of stress-induced cell-signaling markers (ie, the mitogen-activated protein kinase [MAPK] and phosphoinositide-3 kinase [PI3K] pathways).
Results—GSE and GSE+RES significantly reduced ROS production after a 30-minute exposure to TBHP. Only GSE significantly reduced ROS production after a 120-minute exposure to TBHP. Incubation with GSE reduced TBHP-induced activity of the MAPK and PI3K pathways.
Conclusions and Clinical Relevance—GSE inhibited key components associated with cataractogenesis, ROS production, and stress-induced cell signaling. On the basis of the data reported here, there is strong evidence that GSE could potentially protect LECs from the damaging effects of oxidative stress.
Objective—To determine histologic and immunohistochemical
characteristics of the multifocal adherent
plaques that commonly develop on the internal surfaces
of the anterior and posterior lens capsules in
dogs with cataracts.
Sample Population—31 anterior and 4 posterior capsular
specimens collected during lens extraction
surgery in dogs with cataracts.
Procedure—Specimens were evaluated, using light
and transmission electron microscopy. Immunohistochemical
techniques were used to localize cytokeratin,
vimentin, α-smooth muscle-specific actin,
fibronectin, tenascin, and transforming growth factor-
β (TGF-β) within plaques.
Results—Histologically, plaques comprised elongated
spindle-shaped cells that formed a placoid mass. Cells
were embedded in an extracellular matrix containing
collagen fibrils, often with duplicated or split basement
membranes. Immunohistochemically, normal lens
epithelial cells and cells within plaques stained for
vimentin. Most cells and some areas of the extracellular
matrix within plaques stained for TGF-β and
α-smooth muscle-specific actin. Fibronectin and
tenascin were also detected in the extracellular matrix.
Conclusions and Clinical Relevance—Canine lens
capsular plaques are histologically and immunohistochemically
similar to posterior capsule opacification
and subcapsular cataracts in humans, which suggests
that the canine condition, like the human conditions,
is associated with fibrous metaplasia of lens epithelial
cells. Transforming growth factor-β may play a role in
the genesis of capsular plaques. Because severity of
plaques was correlated with stage of cataract development,
earlier surgical removal of cataracts may be
useful to avoid complications associated with plaque
formation. (Am J Vet Res 2000;61:139–143)
OBJECTIVE To identify factors associated with keratopathy in captive pinnipeds and to provide guidance for preventive measures.
ANIMALS 319 captive pinnipeds (229 otariids [sea lions and fur seals], 74 phocids [true seals], and 16 odobenids [walrus]) from 25 facilities.
PROCEDURES Descriptive data collected from questionnaires completed by facilities and from medical records and physical examinations of pinnipeds were compiled and evaluated. Variables were assessed with χ2 tests of homogeneity to determine potential association with keratopathy, and variables with values of P ≤ 0.25 were inserted into the multivariable logistic regression model.
RESULTS Results indicated that variables associated with significantly increased odds of keratopathy in captive pinnipeds included lighter or reflective pool color (OR, 2.11; 95% confidence interval [CI], 1.20 to 3.97), pool water salinity < 29 g/L (OR, 3.48; 95% CI, 1.89 to 6.56), and history of eye disease (OR, 3.30; 95% CI, 1.85 to 5.98), trauma (OR, 3.80; 95% CI, 1.72 to 8.89), and having been tested for leptospirosis (OR, 3.83; 95% CI, 1.54 to 10.26). However, odds of keratopathy decreased with UV index ≤ 6 (OR, 0.39; 95% CI, 0.2 to 0.72) and age < 20 years (OR, 0.32; 95% CI, 0.15 to 0.66).
CONCLUSIONS AND CLINICAL RELEVANCE Findings indicated that odds of keratopathy in pinnipeds could be reduced by maintenance of pool water salinity ≥ 29 g/L and reduction of UV radiation exposure (eg, with adequate shade structures and use of darker, natural colors). Because UV radiation exposure is cumulative, even small attempts to reduce lifetime exposure to it could help control keratopathy in pinnipeds.
Objective—To determine the role of intraocular bacteria in the pathogenesis of equine recurrent uveitis (ERU) in horses from the southeastern United States by evaluating affected eyes of horses with ERU for bacterial DNA and intraocular production of antibodies against Leptospira spp.
Sample Population—Aqueous humor, vitreous humor, and serum samples of 24 clinically normal horses, 52 horses with ERU, and 17 horses with ocular inflammation not associated with ERU (ie, non-ERU inflammation).
Procedures—Ribosomal RNA quantitative PCR (real-time PCR) assay was used to detect bacterial DNA in aqueous humor and vitreous humor from clinically normal horses (n = 12) and horses with chronic (> 3-month) ERU (28). Aqueous humor and serum were also evaluated for anti-Leptospira antibody titers from clinically normal horses (n = 12), horses with non-ERU inflammation (17), and horses with confirmed chronic ERU (24).
Results—Bacterial DNA was not detected in aqueous humor or vitreous humor of horses with ERU or clinically normal horses. No significant difference was found in titers of anti-Leptospira antibodies in serum or aqueous humor among these 3 groups. Only 2 horses, 1 horse with ERU and 1 horse with non-ERU inflammation, had definitive intraocular production of antibodies against Leptospira organisms.
Conclusions and Clinical Relevance—In horses from the southeastern United States, Leptospira organisms may have helped initiate ERU in some, but the continued presence of the organisms did not play a direct role in the pathogenesis of this recurrent disease.
Objective—To evaluate effect of adjunctive treatment with tetracycline analogues on time to complete corneal reepithelialization in dogs with nonhealing (ie, refractory) corneal ulcers.
Design—Randomized controlled clinical trial.
Animals—89 dogs with refractory corneal ulcers.
Procedures—Corneal ulcers were treated via debridement and grid keratotomy. Dogs were assigned to receive 1 of 3 treatment regimens for up to 6 weeks: doxycycline (5 mg/kg [2.27 mg/lb], PO, q 12 h) with topically applied ophthalmic ointment containing neomycin, polymyxin B, and bacitracin (ie, triple antibiotic ointment; q 8 h); cephalexin (22 mg/kg [10 mg/lb], PO, q 12 h) with topically applied oxytetracycline ophthalmic ointment (q 8 h); or a control treatment of cephalexin (22 mg/kg, PO, q 12 h) with topically applied triple antibiotic ointment (q 8 h). Healing was monitored via measurements of the wound with calipers and evaluation of photographs obtained every 2 weeks. Treatment effectiveness was evaluated by wound healing and decreased signs of pain.
Results—The Boxer breed was overrepresented in all groups. At the 2-week time point, wound healing was significantly more common in small-breed dogs, compared with large-breed dogs. Dogs treated with oxytetracycline ophthalmic ointment had a significantly shorter healing time than did dogs receiving the control treatment. Corneal ulcers in dogs that received doxycycline PO healed more rapidly than did ulcers in dogs in the control treatment group; however, this difference was not significant.
Conclusions and Clinical Relevance—Topical tetracycline ophthalmic ointment was a safe, inexpensive, and effective adjunctive treatment for refractory corneal ulcers in dogs.
Objective—To determine risk factors for lens luxation and cataracts in captive pinnipeds in the United States and the Bahamas.
Animals—111 pinnipeds (99 California sea lions [Zalophus californianus], 10 harbor seals [Phoca vitulina], and 2 walruses [Odobenus rosmarus]) from 9 facilities.
Procedures—Eyes of each pinniped were examined by a veterinary ophthalmologist for the presence of cataracts or lens luxations and photographed. Information detailing husbandry practices, history, and facilities was collected with a questionnaire, and descriptive statistical analyses were performed for continuous and categorical variables. Odds ratios and associated 95% confidence intervals were estimated from the final model.
Results—Risk factors for lens luxation, cataracts, or both included age ≥ 15 years, history of fighting, history of ocular disease, and insufficient access to shade.
Conclusions and Clinical Relevance—Diseases of the lens commonly affect captive pinnipeds. Access to UV-protective shade, early identification and medical management of ocular diseases, and prevention of fighting can limit the frequency or severity of lens-related disease in this population. An extended life span may result from captivity, but this also allows development of pathological changes associated with aging, including cataracts.