Myocilin protein levels in the aqueous humor of the glaucomas in selected canine breeds

Objective To compare aqueous humor myocilin protein levels in dogs with the primary glaucomas to those with the secondary glaucomas, primary cataracts, and diabetic cataracts. Materials and methods Four groups were selected, based on diagnosis by the attending veterinary ophthalmologists and included: primary glaucoma (primary open‐angle glaucoma (POAG) and primary closed angle glaucoma (PCAG); n = 155); secondary glaucoma (n = 94); primary (presumed inherited) cataract (n = 142), and diabetic cataract (n = 83). A total of 474 samples (187 males, 263 females, 24 unreported) with average ages of 117 months for the males and 101 months for the females were analyzed. Myocilin protein was measured using the Coomassie staining and Western blot methods relative to a myocilin control. Results Differences were seen between nonglaucomatous (cataractous) and glaucomatous dogs with myocilin levels in glaucomatous eyes being many times higher than those in the cataractous dogs. Primary glaucomatous dogs were found to have an aqueous humor myocilin protein level of 17.30 ± 1.03 units. Secondary glaucomas had the highest level of myocilin in the aqueous humor with 19.27 ± 1.41 units. Diabetic cataractous dogs had the lowest levels of myocilin reported with 6.60 ± 0.88 (mean ± SEM) units. Normal (cataractous) dogs had a myocilin level in the aqueous humor of 8.05 ± 0.86 units. Conclusion Aqueous humor protein levels were elevated, relative to the myocilin control, in both the primary and secondary glaucoma groups compared to the cataract and diabetic cataract groups. Like in the Beagle POAG, aqueous humor myocilin protein levels are increased. Further studies are indicated to investigate the exact role of the aqueous humor myocilin protein in the genesis in increased IOP in these primary glaucomatous breeds.     

Ascorbic acid levels of aqueous humor of dogs after experimental phacoemulsification

Phacoemulsification has been successfully employed in humans and animals for lens extraction. This ultrasonic extracapsular surgical technique induces hydroxyl radical formation in the anterior chamber, which accumulates despite irrigation and aspiration. In this paper we determined the total antioxidant status of aqueous humor after phacoemulsification by measuring aqueous humor ascorbic acid levels. Mixed-breed dogs (n = 11; weighing about 10 kg) with normal eyes as determined by slit-lamp biomicroscopy, applanation tonometry, and indirect ophthalmoscopy had phacoemulsification performed in one eye with the other eye used as a control. Samples of aqueous humor were obtained by anterior chamber paracentesis before surgery and at days 1, 2, 3, 7, and 15 after surgery. Total aqueous humor antioxidant status was inferred from the capacity of aqueous humor to inhibit free radical generation by 2,2-azobis (2-amidopropane) chlorine. Ascorbic acid concentrations were measured by high-pressure liquid chromatography with UV detection. Protein content was determined with the biuret reagent. Statistical analysis was performed by anova followed by the paired t-test. Total antioxidant capacity was reduced from 48 to 27 min during the first 24 h with a gradual increase thereafter, remaining statistically lower than the control eye until 7 days postoperatively. Reduced levels of ascorbic acid followed this reduction in antioxidant capacity (from 211 to 99 microm after 24 h), remaining lower than the control eye until 15 days postoperatively. Protein concentration in aqueous humor increased from 0.62 mg/mL to 30.8 mg/mL 24 h after surgery, remaining statistically lower than the control eye until 15 days postoperatively. Paracentesis alone did not significantly alter the parameters measured. These results indicate that after phacoemulsification, the aqueous humor ascorbic acid levels and antioxidant defenses in aqueous humor are reduced, indirectly corroborating free radical production in the anterior chamber as a result of phacoemulsification. The inflammatory process consequent to the surgical procedure demonstrated by increased protein content in aqueous humor can also contribute to free radical production and ascorbic acid consumption.     

Detection of anti-lens crystallin antibody in dogs with and without cataracts

Objective To determine if antilens crystallin (ALC) serum and aqueous humor antibodies were present in normal dogs and dogs with cataracts, whether antibody incidence varied with stage of cataract, and whether antibody titer had a relationship to the presence of lens‐induced uveitis. Methods Serum and aqueous humor samples were obtained from normal dogs and dogs with cataracts. Lens crystallin was separated by SDS‐polyacrylamide gel electrophoresis (SDS‐PAGE), and antilens crystallin antibodies were detected by Western immunoblot analysis. An indirect ELISA using crystallin protein as antigen was also used to detect antilens crystallin antibodies in serum and aqueous humor. Test groups included normal, incipient, immature, mature, hypermature and diabetic cataract. Results SDS‐PAGE identified bands with molecular weights of lens crystallin subunits. Western immunoblotting demonstrated reaction between canine serum and these protein bands. The five canine serum samples that reacted with crystallin subunits on Western blots had corresponding reactivity on the ELISA. All aqueous humor samples (30) were negative. Serum ALC antibodies were detected in 59.3% (16/27) of controls, 66.7% (16/24) of incipients, 50.0% (10/20) of immatures, 37.9% (11/29) of matures, 28.6% (6/21) of hypermatures, and 26.7% (4/15) of diabetics. Serum ALC antibodies were detected in 43.1% (47/109) of all cataract samples. There was a statistically significant negative association between the presence (P = 0.004) and maturity (P = 0.004) of cataract and presence of ALC serum antibodies. In the immature and hypermature cataract groups, there was a statistically significant negative association between ALC serum antibody titer and severity of uveitis (95% confidence interval). Conclusions There is a negative association between the presence (P = 0.004) and maturity (P = 0.004) of cataract and presence of ALC serum antibodies.     

Glutathione, Cysteine, and Ascorbate Concentrations in Clinically Ill Dogs and Cats

Background: Oxidative stress plays a role in the pathogenesis of many systemic diseases. Hospitalized human patients are glutathione, cysteine, and ascorbate deficient, and antioxidant depletion has been correlated with poor clinical outcome. To date little is known about antioxidant concentrations in hospitalized veterinary patients. The purpose of this study was to determine whether ascorbate, cysteine, or glutathione depletion is present in ill dogs and cats compared with healthy controls.
Hypothesis: Clinically ill dogs and cats would be antioxidant depleted, and depletion would correlate with illness severity and clinical outcome.
Animals: Clinically ill client-owned dogs (n = 61) and cats (n = 37), healthy control dogs (n = 37) and cats (n = 33).
Methods: Prospective, observational, case control study. Erythrocyte reduced glutathione, plasma cysteine, and plasma ascorbate were quantified using high-performance liquid chromatography.
Results: Clinically ill dogs had significantly lower erythrocyte glutathione concentrations (1.22 mM, range 0.55–3.61) compared with controls (1.91 mM, range 0.87–3.51; P = .0004), and glutathione depletion correlated with both illness severity ( P = .038) and mortality ( P = .010). Cats had higher ascorbate concentrations when ill (10.65 μM, range 1.13–25.26) compared with controls (3.68 μM, range 0.36–13.57; P = .0009).
Conclusions and Clinical Importance: Clinically ill dogs had decreased erythrocyte glutathione concentrations, which could be a marker of illness severity and prognostic of a poor outcome. Clinically ill cats had an unexpectedly high plasma ascorbate, which could represent a unique species response to oxidative stress.     

Concentration of enrofloxacin and its active metabolite in alveolar macrophages and pulmonary epithelial lining fluid of dogs

The purpose of this study was to determine the concentration of enrofloxacin and its active metabolite, ciprofloxacin, in alveolar macrophages (AM) and epithelial lining fluid (ELF) of the lungs in comparison to plasma concentrations in healthy dogs. Eleven dogs were given a single oral dose (5 mg/kg) of enrofloxacin. Four hours later, plasma and bronchoalveolar lavage (BAL) fluid were collected. Cells were separated from the BAL fluid and lysed for determination of drug concentrations within AM. Supernatant was used to determine concentrations of drugs in ELF. Drug assays were performed by high-performance liquid chromatography.
  The concentration of enrofloxacin (mean ± SD) was 0.33 ± 0.14 μg/mL in plasma, 3.34 ± 2.4 μg/mL in AM and 4.79 ± 5.0 μg/mL in ELF. The concentration of ciprofloxacin was 0.42 ± 0.26 μg/mL in plasma, 1.15 ± 1.03 μg/mL in AM and 0.26 ± 0.26 μg/mL in ELF. Mean concentrations of both drugs in AM were greater than in plasma (AM to plasma ratio, 10.3 for enrofloxacin and 4.7 for ciprofloxacin). Mean concentrations of enrofloxacin, but not ciprofloxacin, in ELF were greater than in plasma (ELF to plasma ratio, 13.5 for enrofloxacin and 0.52 for ciprofloxacin). Enrofloxacin concentrations in AM and ELF largely exceeded the MICs of the major bacterial pathogens and surpassed by about two times the breakpoint MIC of that drug, and ciprofloxacin concentrations in AM surpassed the MIC of many susceptible organisms. These results suggest that sufficient antimicrobial activity is present in AM and ELF of dogs following oral administration of enrofloxacin to be effective in the treatment of lower respiratory tract infections involving susceptible organisms.     

Vascular endothelial growth factor in diabetic and nondiabetic canine cataract patients

Objective To measure vascular endothelial growth factor (VEGF) levels in aqueous humor, serum, and plasma in diabetic and nondiabetic cataractous dogs. Methods Canine VEGF was assayed in the plasma and serum of 32 dogs (20 diabetics; 12 nondiabetics) and aqueous humor in 57 eyes of those dogs (39 diabetic; 18 nondiabetic) undergoing phacoemulsification, using a commercial canine VEGF assay. Statistical analysis was performed using Fisher’s PLSD, t‐test, and regression analysis to compare values by diabetic status, duration of diabetes, age, weight, gender, left vs. right eye, and blood clarity. Results Plasma, but not serum or aqueous humor VEGF values of diabetics were significantly greater than nondiabetics (P = 0.019). Older nondiabetics (10–15 years) had higher plasma VEGF values than younger (0–5 and 5–10 years) dogs (P = 0.0002 and 0.0001, respectively). There was no significant difference in aqueous humor VEGF between left and right eyes in all patients. Serum and plasma, but not aqueous humor, VEGF values in females were significantly higher than males in both groups. Conclusion Similar to human diabetic patients, VEGF aqueous humor values in all dogs are significantly higher than blood values. Aqueous humor VEGF values in human diabetics are elevated and correlate with the severity of diabetic retinopathy. However, aqueous humor values of VEGF in diabetic dogs are not greater than nondiabetics and may serve to protect the dog against development of diabetic retinopathy.     

Assessment of degree of oxidative stress and antioxidant concentrations in dogs with idiopathic dilated cardiomyopathy.

OBJECTIVE: To assess degree of oxidative stress and antioxidant concentrations in dogs with idiopathic dilated cardiomyopathy (IDCM). DESIGN: Prospective study. ANIMALS: 18 dogs with IDCM and 16 healthy control dogs. PROCEDURE: Concentrations of malondialdehyde (an indicator of oxidative stress); vitamins A, C, and E; glutathione peroxidase; and superoxide dismutase were measured. RESULTS: Glutathione peroxidase concentration was significantly increased in dogs with IDCM, compared with control dogs. Vitamin A and superoxide dismutase concentrations were not significantly different between groups. A negative correlation was found between disease severity and plasma vitamin E concentration. Disease severity was not correlated with concentrations of other antioxidants. Medications did not significantly affect oxidant or antioxidant concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: The change in glutathione peroxidase concentration and the correlation between vitamin E concentration and disease severity suggest that the oxidant-antioxidant system may play a role in development of IDCM.     

Distribution of voriconazole in seven body fluids of adult horses after repeated oral dosing

Passler, N. H., Chan, H.-M., Stewart, A. J., Duran, S. H., Welles, E. G., Lin, H.-C., Ravis, W. R. Distribution of voriconazole in seven body fluids of adult horses after repeated oral dosing. J. vet. Pharmacol. Therap . 33 , 35–41.
The purpose of this study was to assess safety and alterations in body fluid concentrations of voriconazole in normal horses on days 7 and 14 following once daily dose of 4 mg/kg of voriconazole orally for 14 days. Body fluid drug concentrations were determined by the use of high performance liquid chromatography (HPLC). On day 7, mean voriconazole concentrations of plasma, peritoneal, synovial and cerebrospinal fluids, aqueous humor, epithelial lining fluid (ELF), and urine were 1.47 ± 0.63, 0.61 ± 0.22, 0.70 ± 0.20, 0.62 ± 0.26, 0.55 ± 0.32, 79.45 ± 69.4, and 1.83 ± 0.44 μg/mL respectively. Mean voriconazole concentrations in the plasma, peritoneal, synovial and cerebrospinal fluids, aqueous humor, ELF and urine on day 14 were 1.60 ± 0.37, 1.02 ± 0.27, 0.86 ± 0.25, 0.64 ± 0.21, 0.68 ± 0.13, 47.76 ± 45.4 and 3.34 ± 2.17 respectively. Voriconazole concentrations in the bronchoalveolar cell pellet were below the limit of detection. There was no statistically significant difference between voriconazole concentrations of body fluids when comparing days 7 and 14. Results indicated that voriconazole distributes widely into body fluids.     

Cataracts in the Bichon Frise

Purpose To determine the clinical characteristics of possible inherited cataract in the Bichon Frise breed. These characteristics include the relative frequency, gender effects, site of first cataract formation, age of onset, relationship of age to cataract maturity, and other concurrent pre‐ and postoperative ophthalmic diseases. Methods Four different populations of Bichon Frise were examined. They included: (1) referred patients of the University of Florida (VMTH; 1990–2000); (2) patients from other universities and large institutions (VMDB; 1970–2000); (3) patients from the Canine Eye Registry Foundation (CERF; 1970–2000); and (4) special patients recruited from eye clinics and ACVO specialty practices (1995–2001). Blood samples were obtained from many patients for future DNA analyzes. Statistical comparisons between groups were by general linear and anova analyzes, and P < 0.05 was considered significant. Results The four populations of cataractous and total Bichon Frise dogs included: (1) UF‐VMTH: 57 cataractous dogs; (2) VMDB: 406 dogs (28%) with cataracts; total dogs ? 1407; (3) CERF: 505 cataractous dogs (6%); total dogs ? 8222; and (4) ACVO: 223 cataractous dogs (57%); total dogs ? 391. In each population group, gender did not affect cataract distribution. Dogs between 2 and 8 years of age were most frequently affected, and initial cataract involvement affected equally the anterior and posterior cortices. Immature cataracts occurred more often in younger dogs, and hypermature cataracts were more frequently diagnosed in older dogs. Dogs with early cataracts were encountered more frequently in the CERF population. Pre‐ and postoperative retinal detachments (RD) were not infrequently diagnosed in the UF‐VMTH and VMDB groups. RD in the UF‐VMTH and VMDB groups occurred in 33% and 13% of the patients, respectively. Conclusions Cataracts were first encountered in CERF and VMDB data between 1975 and 1979 and have increased since this time. As expected, both similarities and differences between the four different populations of Bichon Frise were encountered. Both sexes of dogs are equally affected. The anterior and posterior cortical areas of the lens were first involved and dogs 2–8 years of age are most frequently affected. Cataracts affected younger dogs in the CERF group and older cataractous dogs in the other populations. Cataract formation appears to be inherited in the Bichon Frise dog. The frequency of pre‐ and postoperative retinal detachments present higher risks for cataract surgery in this breed.     

The relationship of cataract maturity to intraocular pressure in dogs

Objective To determine the distribution of intraocular pressure, as measured by applanation tonometry, in dogs with cataracts, and compare these tonometric results to the different stages of cataract formation (incipient, immature, mature, and hypermature). Animals studied Retrospection study of canine clinical patients (86 dogs). Procedures All records of dogs presented from 1991 to 1996 to the university veterinary medical teaching hospital for diagnosis of cataracts and evaluation for cataract surgery were reviewed. The tonometric measurements from the initial ophthalmic examination were selected in cataractous and nonglaucomatous eyes either receiving no topical or no systemic medications. The stage of cataracts was based on the degree of opacification, tapetal reflection, clinical vision, and visibility of the ocular fundus by indirect ophthalmoscopy. The distribution of tonometric results were grouped by the cataract maturity, and compared by anova and Tukey’s general linear tests. Results Intraocular pressure with incipient cataracts ranged from 9 to 17 mmHg (mean 12.7 ± 1.2 mmHg). Intraocular pressure with immature cataracts ranged from 3 to 27 mmHg (mean 13.6 ± 0.6 mmHg). For the mature cataracts, IOP ranged from 5 to 22 mmHg (mean 11.9 ± 0.7 mmHg). For the hypermature cataract group, IOP ranged from 4 to 23 mmHg (mean 10.8 ± 0.6 mmHg). Comparison of the tonometric results among the different stages of cataract formation indicated a significant difference (P = 0.0086) between only the immature and hypermature groups. Conclusions Intraocular pressure in lens‐induced uveitis (LIU) is lowered but the relationship to the stage of cataract maturity is less clear. Significant tonometric differences were present between the immature and hypermature cataract groups, but these differences are too small to be clinically useful. Decreased intraocular pressure of dogs with all stages of cataract formation suggests concurrent LIU during all stages of cataract formation, especially with the mature and hypermature stages. The average tonometric measurements in dogs with these cataracts were about two standard deviations below the mean IOP reported in normal dogs.     

Altered Oxidant–Antioxidant Profile in Canine Mammary Tumours

Mammary tumours are the most common neoplasms in female dogs. Oxidative stress arising due to overproduction of reactive oxygen species, coupled with altered antioxidant capacities has been implicated in the pathogenesis of all types of cancers. However, the extent of lipid peroxidation and the status of antioxidants in canine mammary tumours have not been investigated. The present study was designed to evaluate the oxidant-antioxidant profile in canine mammary tumours. Lipid peroxidation as evidenced by the formation of thiobarbituric acid-reactive substances, lipid hydroperoxides, and conjugated dienes, as well as the status of the antioxidants superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase, glutathione S-transferase and vitamin C, in tumour tissues of 25 bitches was estimated. Lipid peroxidation in tumour tissues was enhanced compared to the corresponding adjacent uninvolved tissues. This was accompanied by significant elevation in both enzymatic and non-enzymatic antioxidants. This study suggests that upregulation of antioxidants induced by lipid peroxidation confers a selective growth advantage to tumour cells over their adjacent normal counterparts.     

Effect of three treatment protocols on acute ocular hypertension after phacoemulsification and aspiration of cataracts in dogs

Objective  To compare the effect of topical latanoprost, intracameral carbachol, or no adjunctive medical therapy on the development of acute postoperative hypertension (POH) and inflammation after routine phacoemulsification and aspiration (PA) of cataracts in dogs.
Design  Retrospective study.
Procedures  Dogs received either one drop of topical 0.005% latanoprost (21 dogs, 39 eyes), an intracameral injection of 0.3 mL of 0.01% carbachol (15 dogs, 30 eyes), or no adjunctive therapy (46 dogs, 90 eyes) immediately following PA of cataract(s). Intraocular pressure (IOP) was measured in all dogs 2 and 4 h after surgery. IOP was measured and aqueous flare assessed at 8 am the day after surgery.
Results  Carbachol-treated dogs had significantly higher mean IOP (33.2 ± SD 20.8 mmHg) 2 h after surgery than dogs receiving no adjunctive therapy (22.0 ± SD 14.1 mmHg) ( P  =  0 .049). There were no significant differences in IOP among groups at any other time point. There were no significant differences in number of POH episodes between dogs treated with carbachol (47%), latanoprost (29%), or dogs that received no adjunctive therapy (33%). There were no significant differences in mean aqueous flare grade between eyes treated with latanoprost (1.7 ± SD 0.4) or carbachol (1.4 ± SD 0.6), and eyes that received no adjunctive therapy (1.7 ± SD 0.4).
Conclusions  Topical 0.005% latanoprost or intracameral injection of 0.3 mL of 0.01% carbachol after PA in dogs did not reduce POH or increase intraocular inflammation compared to dogs not receiving adjunctive therapy after PA of cataracts.     

Concentrations of acute-phase proteins in dogs with steroid responsive meningitis-arteritis

Background: Measurement of concentrations of acute-phase proteins (APPs) is used as an aid in the diagnosis of a variety of diseases in animals.
Objective: To determine the concentration of APPs in dogs with steroid responsive meningitis-arteritis (SRMA) and other neurologic diseases.
Animals: One hundred and thirty-three dogs with neurologic diseases, 6 dogs with sepsis, and 8 healthy dogs were included in the study. Thirty-six dogs had SRMA (31 of which had monitoring), 14 dogs had other meningoencephalitides (ME), 32 had disk disease (IVDD/DLSS), 26 had tumors affecting the central nervous system (TCNS), and 25 had idiopathic epilepsy (IE).
Methods: Prospective, observational study: C-reactive protein (CRP), α₂-macroglobulin (AMG), and albumin concentrations were determined in the serum or plasma. CRP was also measured in the cerebrospinal fluid.
Results: Serum CRP was significantly higher in dogs with SRMA (     = 142 μg/mL ± 75) and sepsis (     = 114 μg/mL ± 67) in comparison with dogs with other neurologic diseases (     = 2.3–21 μg/mL; P < .001). There was no significant difference detected in AMG between groups. Serum albumin concentration was significantly lower ( P < .01) in dogs with SRMA (     = 3.2 g/dL ± 0.41) than in other groups (     = 3.6–3.9 g/dL). Serum CRP concentration of SRMA dogs correlated with alkaline phosphatase levels ( r = 0.515, P = .003).
Conclusions and Clinical Importance: CRP concentrations in serum are useful in diagnosis of dogs with SRMA. Serum CRP could be used as a monitoring parameter in treatment management of these dogs.     

Lens morphometry determined by B-mode ultrasonography of the normal and cataractous canine lens

Purpose To determine axial lens thickness, anterior chamber depth and axial globe length in canine eyes with normal lenses and in eyes with immature, mature, congenital, posterior polar and diabetic cataract. Methods B‐mode ultrasonography was performed in 50 normal dogs and, as a prephacoemulsification screening procedure, in 100 dogs with cataract. Axial B‐mode ultrasonograms were used to determine lens thickness, anterior chamber depth and globe diameter. Statistical comparisons between groups were made by analysis of variance and multivariate analysis, with a significance level of P < 0.05. Results Axial globe lengths were not statistically significantly different between groups apart from the smaller globes in younger dogs with congenital cataract. Axial lens thickness in diabetics (8.4 ± 0.9 mm) was statistically significantly different from the lens thickness in normal eyes (6.7 ± 1.0 mm), eyes with immature cataract (6.4 ± 0.8 mm) and eyes with mature cataract (7.4 ± 0.9 mm) although these groups, while varying in thickness, were not statistically significantly different from each other. Anterior chamber depth was statistically significantly reduced in eyes with diabetic cataract (2.9 ± 0.1 mm) from that in normal eyes (3.8 ± 0.1 mm), eyes with immature cataract (3.5 ± 0.1 mm) and eyes with mature cataract (3.2 ± 0.6 mm) although these groups, while varying in chamber depth, were not statistically significantly different from each other. Conclusions Lenses with diabetic cataracts were significantly increased in axial thickness compared to lenses in other eyes, although lenses with mature cataracts showed a trend towards increased axial thickness and immature cataracts demonstrated a trend towards reduced thickness. While previous studies on cataract pathobiology have suggested a reduction in lens thickness in immature cataract through lens protein loss and an increase in thickness in mature cataracts through intumescence, this study is the first to document these changes in the canine lens.     

Effect of lidocaine on the minimum alveolar concentration of sevoflurane in dogs

Objective  To investigate the effects of a low-dose constant rate infusion (LCRI; 50 μg kg⁻¹ minute⁻¹) and high-dose CRI (HCRI; 200 μg kg⁻¹ minute⁻¹) lidocaine on arterial blood pressure and on the minimum alveolar concentration (MAC) of sevoflurane (Sevo), in dogs.
Study design  Prospective, randomized experimental design.
Animals  Eight healthy adult spayed female dogs, weighing 16.0 ± 2.1 kg.
Methods  Each dog was anesthetized with sevoflurane in oxygen and mechanically ventilated, on three separate occasions 7 days apart. Following a 40-minute equilibration period, a 0.1-mL kg⁻¹ saline loading dose or lidocaine (2 mg kg⁻¹ intravenously) was administered over 3 minutes, followed by saline CRI or lidocaine LCRI or HCRI. The sevoflurane MAC was determined using a tail clamp. Heart rate (HR), blood pressure and plasma concentration of lidocaine were measured. All values are expressed as mean ± SD.
Results  The MAC of Sevo was 2.30 ± 0.19%. The LCRI reduced MAC by 15% to 1.95 ± 0.23% and HCRI by 37% to 1.45 ± 0.21%. Diastolic and mean pressure increased with HCRI. Lidocaine plasma concentration was 0.84 ± 0.18 for LCRI and 1.89 ± 0.37 μg mL⁻¹ for HCRI. Seventy-five percent of HCRI dogs vomited during recovery.
Conclusion and clinical relevance  Lidocaine infusions dose dependently decreased the MAC of Sevo, did not induce clinically significant changes in HR or arterial blood pressure, but vomiting was common during recovery in HCRI.     

The Gross and Micro Anatomy of the Accessory Sex Glands of the Male Agouti (Dasyprocta leporina)

This study was a follow up to the study on the gross anatomy of the male agouti ( Dasyprocta leporina ) reproductive system. The seminal vesicles of the agouti are lobulated structures. The mean diameter of the large lumen is 883.6 ± 76.83 μm. The mucosa (24.1 ± 0.92 μm), which is lined by pseudo-stratified columnar epithelium is thrown into folds, which often branch. The lamina muscularis mucosa is thin and is made of loose connective tissue containing blood vessels. The mucosa of the leaf-like coagulating glands of the agouti is folded. The mean diameter of the lumen is 488.3 ± 41.96 μm. The mucosa contains tubuloalveolar glands, which have a mean length of 199.5 ± 28.83 μm. The thin epithelium, 15.0 ± 1.25-μm wide, consists mostly of pseudo-stratified columnar cells. The epithelium also has surface modifications in the form of apical blebs and cilia. The epithelium of the agouti's lobulated prostate gland is also folded creating a large lumen with a mean diameter of 995.5 ± 55.70 μm. The mucosa contains tubular and tubuloalveolar glands, each having a mean length of 134.4 ± 13.59 μm. The epithelium (13.9 ± 1.16 μm) consists of pseudo-stratified columnar cells. The pea-shaped bulbourethral gland (BG) of the agouti consists of convoluted tubular, mucous secretory units, which are irregularly shaped each with a mean length of 177.9 ± 7.10 μm and a mean width of 63.5 ± 3.97 μm. The BG of the agouti are ventro-lateral to the rectum and dorsally positioned to the pubic symphysis, and connected to the urethra by short ducts.     

Pharmacokinetics of indomethacin in sheep after intravenous and intramuscular administration

The pharmacokinetics of indomethacin (1mg/kg) was determined in six adult sheep after intravenous (i.v.) and intramuscular (i.m.) injection. Plasma concentrations were maintained within the therapeutic range (0.3–3.0 μg/mL) from 5 to 50 min after i.v. and from 5 to 60–90 min after i.m. administration. After two trials, indomethacin best fitted an open two-compartment model. The mean (±SD) volumes of distribution at steady state ( V d_ss) were 4.10 ± 1.40 and 4.21 ± 1.93 L/kg and the mean clearance values ( C l_B) were 0.17 ± 0.06 and 0.22 ± 0.12 L/h.kg for i.v. and i.m. routes, respectively. The elimination phase half-lives did not show any significant difference between routes of injection ( t _½β = 17.4 ± 4.6 and 21.25 ± 4.44 h, i.v. and i.m. respectively). After i.m. administration, plasma maximum concentration ( C _max =  1.10 ± 0.68 μg/mL) was reached 10 min after dosing; the absorption phase was fast ( K _ab = 26 ± 18 h-1) and short ( t _½ab = 2.33 ± 1.51 min) and the mean bioavailability was 91.0 ± 32.8%, although there was considerable interanimal variation. In some individuals, bioavailability was higher than 100%. This fact combined with the slower elimination phase after i.m. than after i.v. administration, could be related with enterohepatic recycling.     

Antioxidant status in hyperthyroid cats before and after radioiodine treatment

Background

Reversible antioxidant depletion is found in hyperthyroid humans, and antioxidant depletion increases the risk of methimazole toxicosis in rats.

Objectives

To determine whether abnormalities in concentrations of blood antioxidants or urinary isoprostanes were present in hyperthyroid cats, and were reversible after radioiodine treatment. To determine whether or not antioxidant abnormalities were associated with idiosyncratic methimazole toxicosis.

Animals

Hyperthyroid cats presented for radioiodine treatment (n = 44) and healthy mature adult control cats (n = 37).

Methods

Prospective, controlled, observational study. Red blood cell glutathione (GSH), plasma ascorbate (AA), plasma free retinol (vitamin A), α‐tocopherol (vitamin E), and urinary free 8‐isoprostanes in hyperthyroid cats were compared to healthy cats and to hyperthyroid cats 2 months after treatment.

Results

Blood antioxidants were not significantly different in hyperthyroid cats (mean GSH 1.6 ± 0.3 mM; AA 12.8 ± 4.9 μM, and vitamin E, 25 ± 14 μg/mL) compared to controls (GSH 1.4 ± 0.4 mM; AA 15.0 ± 6.6 μM, and vitamin E, 25 ± 17 μg/mL). Urinary isoprostanes were increased in hyperthyroid cats (292 ± 211 pg/mg creatinine) compared to controls (169 ± 82 pg/mg; P = .006), particularly in hyperthyroid cats with a USG < 1.035. Plasma free vitamin A was higher in hyperthyroid cats (0.54 ± 0.28 μg/mL versus 0.38 ± 0.21 in controls; P = .007). Both abnormalities normalized after radioiodine treatment. No association was found between oxidative status and prior idiosyncratic methimazole toxicosis.

Conclusion and Clinical Importance

Increased urinary isoprostane could reflect reversible renal oxidative stress induced by hyperthyroidism, and this requires additional evaluation.     

α-Luminol prevents decreases in glutamate, glutathione, and glutamine synthetase in the retinas of glaucomatous DBA/2J mice

Objective  To test the hypothesis that in DBA/2J mice, oxidative stress decreases glutamine synthetase (GS) levels resulting in a loss of neuronal glutamate and that the antioxidant α-luminol (GVT®) decreases this stress and glutamate loss in some types of glaucoma.
Animals  DBA/2J mice were separated into two groups, of which one was not treated, and the other treated with GVT in the drinking water. At 7 months of age, retinas were examined from five untreated DBA/2J mice, seven GVT-treated mice, and five C57BL/6 mice (negative controls).
Methods  Serial 0.5 μm plastic sections were immunogold stained for glutamate, GS, and total glutathione, followed by image analysis for staining patterns and density.
Results  Focal decreases in glutamate immunostaining were common in the inner nuclear layer (INL) of DBA/2J retinas, but not in C57BL/6 or GVT-treated DBA/2J retinas. Decreases in glutathione and GS immunostaining were found in DBA/2J retinal regions where neuronal glutamate immunostaining was reduced. Retinas from GVT-treated DBA/2J had no significant decreases in INL levels of glutamate, glutathione, or GS.
Conclusions  Retinas of dogs with primary glaucoma are reported to have focal depletion of neuronal glutamate. In DBA/2J mice, similar changes occur prior to the development of clinical disease. In these focal glutamate-depleted regions, levels of glutathione and GS are also reduced, consistent with the hypothesis that oxidative stress contributes to retinal changes in glaucoma. The ability of GVT, an antioxidant, to inhibit retinal abnormalities in DBA/2J mice provides further support for this hypothesis.     

Effect of Catalase and Superoxide Dismutase on Motility, Viability and Acrosomal Integrity of Frozen-Thawed Cat Spermatozoa

The aim of this study was to evaluate the effect of antioxidant catalase (CAT) and superoxide dismutase (SOD) in semen extender on motility, viability and acrosomal integrity of frozen-thawed cat spermatozoa. Semen was collected by using an artificial vagina from five domestic cats (two ejaculates/cat). Spermatozoa were diluted in egg yolk Ttris-fructose citrate solution (EYT-FC) without glycerol and cooled at 4°C for 1 h, then diluted further with EYT-FC with glycerol (7% final concentration) and 400 IU/ml of CAT (treatment 1) or SOD (treatment 2) or without antioxidants (control). Before freezing using a styrofoam box, diluted spermatozoa filled in 0.25-ml straws were equilibrated for 1 h at 4°C. After thawing, spermatozoa were assessed for motility, viability and acrosomal integrity. Cryopreservation significantly impaired sperm motility, viability and acrosomal integrity (p   <   0.05). However, motility, viability and acrosomal integrity of frozen-thawed cat spermatozoa in the EYT-FC with CAT, SOD and without the antioxidants were not significantly different. The average percentages of spermatozoa motility after thawing compared between control, treatment 1 and treatment 2 group were 43.5 ± 3.2, 42 ± 4.1 and 38 ± 4.5; for viability: 44.8 ± 3.5, 50.6 ± 5.7 and 47.1 ± 4.1 and for acrosomal integrity: 45 ± 3.5, 44.9 ± 3.4 and 44.4 ± 3.3, respectively. In conclusion, adding CAT and SOD to EYT-FC did not improve motility, viability and acrosomal integrity in cryopreserved cat spermatozoa.