A review of the pharmacology of carbonic anhydrase inhibitors for the treatment of glaucoma in dogs and cats

Glaucoma is a heterogeneous group of disorders usually associated with elevated intraocular pressure (IOP), leading to optic nerve damage, retinal ganglion cell death and irreversible vision loss. Therefore, medications that lower IOP are the mainstay of glaucoma therapy. Carbonic anhydrase inhibitors (CAIs) are some of the principal drugs used in the management of canine and feline glaucoma. This paper summarises current knowledge of the mechanism of action of these agents and their effect on IOP in dogs and cats. It also discusses potential harmful side effects of CAIs and presents current opinions about their role and place in the medical management of glaucoma in small animals.     

Effects of twice daily application of 2% dorzolamide on intraocular pressure in normal cats

The effect of the topical carbonic anhydrase inhibitor, dorzolamide, on intraocular pressure in cats was studied. The intraocular pressure of both eyes of eight healthy cats was measured using applanation tonometery (Tono-Pen) during two phases: control and treatment. Both eyes were treated with 2% dorzolamide twice a day during the treatment phase. Application of dorzolamide resulted in a significant decrease of intraocular pressure over the treatment phase. By the fourth and fifth day of treatment, the mean intraocular pressure (+/- standard deviation) was 9.7 (+/- 1.5) mmHg, whereas the mean (+/- standard deviation) for the last 2 days of the control period was 12.2 (+/- 2.0) mmHg. Based on this study, dorzolamide is a potentially effective treatment for glaucoma in cats, significantly lowering intraocular pressure.     

Effects of topical 0.5% levobunolol alone or in association with 2% dorzolamide compared with a fixed combination of 0.5% timolol and 2% dorzolamide on intraocular pressure and heart rate in dogs without glaucoma

The goal of glaucoma management is to reduce intraocular pressure (IOP) and maintain it at a level compatible with the health of the optic nerve. New therapies are constantly being sought. Topical instillation of levobunolol 0.5%, alone or with dorzolamide 2%, has a hypotensive effect on the IOP in healthy dogs, and levobunolol combined with dorzolamide produces a stronger hypotensive effect than the combination of timolol and dorzolamide. All animals tolerate these topical medications well with no signs of discomfort, and no ocular side effects have been observed. Levobunolol, alone or in combination with dorzolamide, induces bradycardia, as does timolol with dorzolamide.     

Effects of 0.005% latanoprost solution on intraocular pressure in healthy dogs and cats

OBJECTIVE: To evaluate effects of daily topical ocular administration of latanoprost solution on intraocular pressure (IOP) in healthy cats and dogs. ANIMALS: 9 domestic shorthair cats and 14 dogs. PROCEDURE: Latanoprost solution (0.005%) was administered topically to 1 eye (treated) and vehicle to the other eye (control) of all animals once daily in the morning for 8 days. Intraocular pressure was measured twice daily for the 5 days preceding treatment, and IOP, pupillary diameter, conjunctival hyperemia, and blepharospasm were measured 0, 1, 6, and 12 hours after the first 4 treatments and 0 and 12 hours after the final 4 treatments. Measurements continued twice a day for 5 days after treatment was discontinued. Aqueous flare was measured once daily during and for 5 days after the treatment period. RESULTS: Intraocular pressure and pupillary diameter were significantly decreased in the treated eye of dogs, compared with the control eye. Mild conjunctival hyperemia was also detected, but severity did not differ significantly between eyes. Blepharospasm and aqueous flare were not detected in either eye. Intraocular pressure in cats was not significantly affected by treatment with latanoprost. However, pupillary diameter was significantly decreased in the treated eye, compared with the control eye. Conjunctival hyperemia, aqueous flare, and blepharospasm were not detected in either eye. CONCLUSIONS AND CLINICAL RELEVANCE: Once-daily topical ocular administration of latanoprost solution (0.005%) reduced IOP in healthy dogs without inducing adverse effects but did not affect IOP in healthy cats. Latanoprost may be useful for treating glaucoma in dogs.     

Ocular hypotensive effects of carbonic anhydrase inhibitors in normotensive and glaucomatous Beagles.

Four carbonic anhydrase inhibitors (acetazolamide, dichlorphenamide, ethoxzolamide, and methazolamide) cause ocular hypotony in normotensive and glaucomatous Beagles. Four dosages of acetazolamide and methazolamide and three dosages of dichlorphenamide and ethoxzolamide were evaluated. The extent of ocular hypotony after these carbonic anhydrase inhibitors was usually greater in glaucomatous Beagles than it was in normotensive Beagles.     

Safety of selamectin in dogs

Selamectin is a broad-spectrum avermectin endectocide for treatment and control of canine parasites. The objective of these studies was to evaluate the clinical safety of selamectin for topical use in dogs 6 weeks of age and older, including breeding animals, avermectin-sensitive Collies, and heartworm-positive animals. The margin of safety was evaluated in Beagles, which were 6 weeks old at study initiation. Reproductive, heartworm-positive, and oral safety studies were conducted in mature Beagles. Safety in Collies was evaluated in avermectin-sensitive, adult rough-coated Collies. Studies were designed to measure the safety of selamectin at the recommended dosage range of 6-12mgkg(-1) of body weight. Endpoints included clinical examinations, clinical pathology, gross and microscopic pathology, and reproductive indices. Selected variables in the margin of safety and reproductive safety studies were subjected to statistical analyses. Pups received large doses of selamectin at the beginning of the margin of safety study when they were 6 weeks of age and at their lowest body weight, yet displayed no clinical or pathologic evidence of toxicosis. Similarly, selamectin had no adverse effects on reproduction in adult male and female dogs. There were no adverse effects in avermectin-sensitive Collies or in heartworm-positive dogs. Oral administration of the topical formulation caused no adverse effects. Selamectin is safe for topical use on dogs at the recommended minimum dosage of 6mgkg(-1) (6-12mgkg(-1)) monthly starting at 6 weeks of age, and including dogs of reproducing age, avermectin-sensitive Collies, and heartworm-positive dogs.     

A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice

Medetomidine is a relatively new sedative analgesic drug that is approved for use in dogs in Canada. It is the most potent alpha2-adrenoreceptor available for clinical use in veterinary medicine and stimulates receptors centrally to produce dose-dependent sedation and analgesia. Significant dose sparing properties occur when medetomidine is combined with other anesthetic agents correlating with the high affinity of this drug to the alpha2-adrenoreceptor. Hypoventilation occurs with medetomidine sedation in dogs; however, respiratory depression becomes most significant when given in combination with other sedative or injectable agents. The typical negative cardiovascular effects produced with other alpha2-agonists (bradycardia, bradyarrhythmias, a reduction in cardiac output, hypertension +/- hypotension) are also produced with medetomidine, warranting precautions when it is used and necessitating appropriate patient selection (young, middle-aged healthy animals). While hypotension may occur, sedative doses of medetomidine typically raise the blood pressure, due to the effect on peripheral alpha2-adrenoreceptors. Anticholinergic premedication has been recommended with alpha2-agonists to prevent bradyarrhythmias and, potentially, the reduction in cardiac output produced by these agents; however, current research does not demonstrate a clear improvement in cardiovascular function. Negatively, the anticholinergic induced increase in heart rate potentiates the alpha2-agonist mediated hypertension and may increase myocardial oxygen tension, demand, and workload. Overall, reversal with the specific antagonist atipamezole is recommended when significant cardiorespiratory complications occur. Other physiological effects of medetomidine sedation include; vomiting, increased urine volumes, changes to endocrine function and uterine activity, decreased intestinal motility, decreased intraocular pressure and potentially hypothermia, muscle twitching, and cyanosis. Decreased doses of medetomidine, compared with the recommended label dose, should be considered in combination with other sedatives to enhance sedation and analgesia and lower the duration and potential severity of the negative cardiovascular side effects. The literature was searched in Pubmed, Medline, Agricola, CAB direct, and Biological Sciences.     

The effects of increasing doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs

Different doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, with or without dexmedetomidine were compared in conscious dogs. Eight animals received either dexmedetomidine (10 μg/kg [D]), MK-467 (250 μg/kg [M250] or dexmedetomidine (10 μg/kg) with increasing doses of MK-467 (250 μg/kg [DM250], 500 μg/kg [DM500] and 750 μg/kg [DM750], respectively). Treatments were given intravenously (i.v.) in a randomized, crossover design with a 14-day washout period. Systemic hemodynamics and arterial blood gas analyses were recorded at baseline and at intervals up to 90 min after drugs administration. Dexmedetomidine alone decreased heart rate, cardiac index and tissue oxygen delivery and increased mean arterial pressure and systemic vascular resistance 5 min after administration. DM250 did not completely prevent these early effects, while DM750 induced a decrease in mean arterial pressure. With DM500, systemic hemodynamics remained stable throughout the observational period. MK-467 alone increased cardiac index and tissue oxygen delivery and had no deleterious adverse effects. No differences in arterial blood gases were observed between treatments that included dexmedetomidine. It was concluded that MK-467 attenuated or prevented dexmedetomidine's systemic hemodynamic effects in a dose-dependent manner when given simultaneously i.v. but had no effect on the pulmonary outcome in conscious dogs. A 50:1 dose ratio (MK-467:dexmedetomidine) induced the least alterations in cardiovascular function.     

Effect of topical anesthesia on evaluation of corneal sensitivity and intraocular pressure in rats and dogs

Objective To determine the effect of 0.5% proparacaine in tonometry by evaluating corneal touch threshold (CTT) and intraocular pressure (IOP). Animal studied Nine rats (18 eyes, Sprague–Dawley) and 10 dogs (20 eyes, Beagle) Procedures The IOP and CTT were measured in each eye before and after topical anesthesia with 0.5% proparacaine. The IOP was evaluated using Tonopen for dogs and Tonolab for rats. The corneal sensitivity was evaluated by CTT through a Cochet–Bonnet aesthesiometer. Results The mean IOP was not significantly changed in rats or dogs before and after topical anesthesia. However, after application of proparacaine, CTT was significantly increased in both animal groups compared with that before application of proparacaine. Conclusion From this study, topical anesthesia was found to significantly lower the corneal sensitivity but have little effect on IOP measurements. In ophthalmologic examination, topical anesthesia can be used to reduce corneal sensation without an effect on IOP.     

Effects of intracameral injection of preservative-free lidocaine on the anterior segment of the eyes in dogs

OBJECTIVE: To evaluate effects of intracameral injection of preservative-free 1% and 2% lidocaine hydrochloride solution on the anterior segment of the eyes in dogs. ANIMALS: 16 adult healthy dogs (8 male and 8 female) judged to be free of ocular disease. PROCEDURE: Dogs were randomly assigned to 2 groups of 8 dogs each. Group 1 dogs received an intracameral injection of 0.10 mL of preservative-free 1% lidocaine solution in the designated eye, and group 2 dogs received 0.10 mL of preservative-free 2% lidocaine solution in the designated eye. After injection, intraocular pressure was measured every 12 hours for 48 hours and then every 24 hours until 168 hours after injection. Slit-lamp biomicroscopy was performed preceding intracameral injection, 8 hours after injection, and then every 24 hours until 168 hours after injection. Ultrasonic pachymetry and specular microscopy were performed preceding intracameral injection and 72 and 168 hours after injection. Corneal thickness and endothelial cell density and morphology were compared with baseline measurements. RESULTS: No significant differences were found in intraocular pressure, corneal thickness, endothelial cell density, and morphologic features in either group, compared with baseline. A significant difference in aqueous flare was found for treated and control eyes 8, 24, and 48 hours after injection, compared with baseline. No significant difference in aqueous flare was found between treated and control eyes within either group. CONCLUSIONS AND CLINICAL RELEVANCE: No adverse ocular effects were detected after intracameral injection of preservative-free 1% or 2% lidocaine solution; thus, its use would be safe for intraocular pain management in dogs.     

The use of semiconductor diode laser for deflation and coagulation of anterior uveal cysts in dogs, cats and horses: a report of 20 cases

OBJECTIVE: To describe semiconductor diode laser use for anterior uveal cyst deflation and coagulation in dogs, horses and cats. ANIMALS STUDIED: The presenting clinical signs, surgical technique and postoperative results for four dogs, nine horses and seven cats with anterior uveal cysts treated with diode laser are described. Treated cysts were of sufficient size and/or number to potentially impair vision, damage the corneal endothelium, or increase intraocular pressure (IOP). One dog with free-floating cysts exhibited 'fly biting' behavior. Cysts were suspected of causing shying on the affected side and/or head-shaking behavior in seven horses. Cysts were free floating within the anterior chamber in dogs, occurred in the corpora nigrum in horses and were attached to the posterior iris surface in cats. In cats, shallowing of the anterior chamber and dyscoria were observed. In all cats prior to cyst deflation, IOP increased after pharmacologic pupil dilation. Cats were more likely than dogs and horses to have bilateral and multiple cysts. PROCEDURE: Two dogs and all horses were treated without general anesthesia and two dogs and all cats were treated under general anesthesia. Diode laser was used to perforate, deflate and coagulate the cysts. RESULTS: Postoperatively, all eyes were free of discomfort or significant inflammation and minimal or no topical or systemic anti-inflammatory therapy was required. Abnormal behavior improved or resolved in all cases. In all cats, IOP 24 h after photocoagulation was lower than the postdilation IOP. Cysts did not recur, but new cysts were discovered in several cases. CONCLUSION: Semiconductor diode laser coagulation of anterior uveal cysts is safe, effective and noninvasive.     

Role of carbon dioxide and ion transport in the formation of sub-embryonic fluid by the blastoderm of the Japanese quail

1. The explanted blastoderm of the Japanese quail was used to explore the role of ions and carbon dioxide in determining the rate of sub-embryonic fluid (SEF) production between 54 and 72 h of incubation. 2. Amiloride, an inhibitor of Na+/H+ exchange, at concentrations of 10(-3) to 10(-6) M substantially decreased the rate of SEF production when added to the albumen culture medium. N-ethylmaleimide, an inhibitor of V type H+ ATPase, also decreased this rate but only to a small extent at the highest dose applied, 10(-3) M. Both inhibitors had no effect on SEF production when added to the SEF. 3. The inhibitors of cellular bicarbonate and chloride exchange, 4-acetamido-4'-isothiocyano-2,2'-disulphonic acid (SITS) and 4,4' diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), had no effect upon SEF production. 4. Ouabain, an inhibitor of Na+/K+ ATPase, decreased SEF production substantially at all concentrations added to the SEF (10(-3) to 10(-6) M). Three sulphonamide inhibitors of carbonic anhydrase, acetazolamide, ethoxzolamide and benzolamide, decreased SEF production when added to the SEF at concentrations of 10(-3) to 10(-6) M. Benzolamide was by far the most potent. Neither ouabain nor the sulphonamides altered SEF production when added to the albumen culture medium. 5. Using a cobalt precipitation method, carbonic anhydrase activity was localised to the endodermal cells of the area vasculosa. The carbonic anhydrase activity was primarily associated with the lateral plasma membranes, which together with the potent inhibitory effect of benzolamide, suggests the carbonic anhydrase of these cells is the membrane-associated form, CA IV. 6. The changes in SEF composition produced by inhibitors were consistent with the production of SEF by local osmotic gradients. 7. It is concluded that a Na+/K+ ATPase is located on the basolateral membranes of the endodermal cells of the area vasculosa, and that a sodium ion/hydrogen ion exchanger is located on their apical surfaces. Protons for this exchanger would be provided by the hydration of CO2 catalysed by the membrane-associated carbonic anhydrase. Furthermore, it is proposed that the prime function of the endodermal cells of the area vasculosa is the production of SEF.     

Effects of topical nipradilol and timolol maleate on intraocular pressure, facility of outflow, arterial blood pressure and pulse rate in dogs

Nipradilol is an alpha(1), beta-blocker with milder side effects than other beta-blockers used in humans. In this study the effects of nipradilol were compared with those of timolol maleate in dogs. Twelve clinically normal dogs (nine mongrels, two beagles, and one Akita) were used. We applied 0.25% nipradilol or 0.5% timolol maleate drops for a period of 28 days. Intraocular pressure (IOP) was measured before and after administration on the 2nd, 4th, 7th, 14th, 21st and 28th day. Blood pressure, pulse rate and coefficient of aqueous outflow (C-value) were also measured before and after administration on the 7th, 14th, 21st and 28th day. Both nipradilol and timolol maleate significantly lowered IOP from the 2nd day to the end of the study period. Nipradilol lowered IOP to an equivalent degree to timolol maleate. There was no significant change in blood pressure and pulse rate throughout the study period with administration of nipradilol. C-value showed a significant rise from the 14th day with administration of nipradilol, while it did not show any significant change during the study period with administration of timolol maleate. The reduction of IOP by nipradilol was similar to that by an existing beta-adrenergic antagonist, timolol maleate, but nipradilol was associated with fewer systemic side effects in dogs. Nipradilol appears to be a useful drug for treatment of glaucoma in dogs.     

Carbonic anhydrase localization in normal and osteochondrotic joint cartilage of growing pigs.

The histochemical localization of carbonic anhydrase in the normal and osteochondrotic epiphyseal growth cartilage from 15 growing pigs (6 to 18 weeks old) was studied. All animals were clinically normal. The entire thickness of the articular-epiphyseal cartilage complex from the femoral condyles was fixed in 2% glutaraldehyde and embedded in a water-soluble glycolmethacrylate. Sections (1-2 microns) were incubated on the surface of a medium containing cobalt, phosphate, and bicarbonate. A black precipitate formed at sites of enzymatic activity. This method shows the activity of all different isoenzymes of carbonic anhydrase. The specificity was checked by adding the carbonic anhydrase inhibitor acetazolamide to the incubation medium. Osteochondrosis in the epiphyseal growth cartilage was characterized by chondronecrotic areas in resting, proliferative, hypertrophic, and calcifying regions. When the hypertrophic and calcifying regions were involved, insufficient cartilage calcification and focally impaired ossification were seen. The chondronecrotic areas were surrounded by groups of morphologically viable cells, or so-called "clusters." Carbonic anhydrase was present in chondrocytes of hypertrophic and calcifying regions of the normal growth cartilage and in osteoclasts and erythrocytes. No evidence of carbonic anhydrase activity was found in the articular cartilage or in the resting region of normal growth cartilage in any of the pigs. No enzyme activity was found in the osteochondrotic cartilage, either in clusters or dead cells. The lack of carbonic anhydrase in the osteochondrotic cartilage demonstrated in this study may result in an inability to produce the alkaline matrix necessary for calcification and could be one reason for the insufficient calcification typical of this cartilage.     

Control of ocular inflammation

Although both topical and systemic anti-inflammatory agents have a place in veterinary ophthalmology, they play only a small role in overall patient management. They must be used appropriately to prevent ocular damage and loss of vision from inflammation and are not a replacement for a complete ophthalmic examination and specific treatment directed at the etiology of the problem. If used indiscriminately, they can result in local or systemic side effects or toxicities, many of which are worse than the initial problem for which they were selected. Just as topical corticosteroids are contraindicated with infectious keratitis, so are systemic corticosteroids contraindicated in patients with ocular inflammation resulting from a systemic infectious process. Anti-inflammatories must be used at the appropriate dosage and frequency. Use of corticosteroids that have low intraocular penetration for intraocular disease or corticosteroids with low potency is a waste of time and money. The most expensive medication is one that does not work. Avoid combination therapies when only a single medication is required. These do not save time or money and have the potential to result in the development of drug-related diseases. Diseases for which anti-inflammatory therapy has little or no indication include corneal scars, corneal edema, corneal pigmentation, corneal dystrophy, cataracts without inflammation, glaucoma, and retinal atrophy and degeneration. Last, remember that all commercially available ophthalmic medications are specifically formulated for use in the eye. Their pH, concentration, osmolality, and melting temperature all are designed to facilitate penetration. The use of dermal and otic preparations to treat ophthalmic problems is contraindicated.     

Plasmapheresis in five dogs with systemic immune-mediated disease

Five dogs with signs referable to systemic immune-mediated disease, four with systemic lupus erythematosus, and one with probable lupus myopathy were treated with plasmapheresis in combination with low-dose immunosuppressive drug therapy. Previous treatment with conventional dosages of prednisone was not satisfactory and was associated with adverse side effects. Two dogs had short-term responses to combined therapy, and 3 dogs had sustained responses. Clinical remission was associated with normalization of serum complement levels and decreases in antinuclear antibody titers. Toxicosis potentially related to plasma component depletion was observed in 2 dogs. Acute clinical illness and disease states refractory to conventional immunosuppressive therapy should be considered indications for plasmapheresis.     

Lack of effects on lymphocyte function from chronic topical ocular cyclosporine medication: a prospective study

Aim Topical cyclosporine has been widely used in the treatment of canine keratoconjunctivitis sicca without apparent documented clinical side effects. Thus the finding of reduced lymphocyte proliferation in animals treated with the drug at a concentration of 2% was both surprising and concerning. This study aimed to repeat the previous study and to compare the systemic effects of 2% cyclosporine in corn oil and 0.2% topical cyclosporine ointment (Optimmune, Intervet‐Schering Plough, Welwyn, UK). Methods Twenty dogs treated with Optimmune or with topical 2% cyclosporine in corn oil where previous treatment with Optimmune had failed were included in this study. Blood samples were taken at the time of first evaluation and at 1, 3 and 6 months of treatment to provide a biochemical and hematological health evaluation of the dogs and at each examination to measure circulating levels of cyclosporine and to obtain a lymphocyte population with which to determine a mitogen stimulation index (MSI) on treatment with phytohaemagglutinin‐P (PHA) and conconavlin A (con‐A). Levels of circulating cyclosporine were measured with an enzyme‐multiplied immunoassay method and also the more sensitive quantification technique of mass spectroscopy (MS). Results No blood samples contained over 15 ng/ml cyclosporine, the lower limit of detection using the radioimmunoassay or the enzyme‐multiplied immunoassay technique. Positive control samples taken from dogs treated with oral cyclosporine for anal furunculosis showed measurable levels in blood, demonstrating that the technique worked. Mean MSI values at 0, 1, 3 and 6 months of treatment were 10.2, 11.4, 11.6, and 10.5 for dogs treated with 0.2% cyclosporine and 10.4, 11.9, 11.7, and 12.9 for dogs treated with 2% cyclosporine. Mitogen stimulation index values were not statistically different between the first examination and any subsequent examination time‐point. Conclusions The findings of the study contradict those of the previous studies. No change in lymphocyte stimulation index was noted, neither were significant blood levels of cyclosporine documented after topical administration of either 0.2% or 2% cyclosporine. This study shows that topical cyclosporine is safe to use in the canine eye in line with the drug’s safety record in this therapeutic regime over the past 20 years since its first use.     

Comparison of the rebound tonometer (ICare) to the applanation tonometer (Tonopen XL) in normotensive dogs

OBJECTIVE: To compare intraocular pressure (IOP) measurements obtained by recently introduced rebound tonometer (ICare) and the well-known applanation tonometer Tonopen XL in normal canine eyes. METHODS: In a prospective, randomized, single-center study, IOP measurements by ICare and Tonopen XL tonometers were compared in 160 nonpathologic canine eyes (80 dogs). Complete slit-lamp biomicroscopy and indirect ophthalmoscopy were performed on each dog. Rebound tonometry was performed first and immediately after topical anesthetic drops were instilled in both eyes. One minute after the application of the topical anesthetic, applanation tonometry was performed in both eyes. The intraocular pressures obtained by use of both techniques were compared by statistical analysis. RESULTS: The mean IOP readings were 9.158 mmHg (SD 3.471 mmHg) for the ICare tonometer (x) and 11.053 mmHg (SD 3.451 mmHg) for the Tonopen XL readings (y). The mean difference in intraocular pressures (-1.905 mmHg) was within clinically acceptable limits. The correlation coefficient (r2) of the relationship within both tonometers was r2=0.7477. The corresponding linear regression between the tonometers readings was y=0.6662x+4.942. CONCLUSIONS: Intraocular pressures obtained with the ICare rebound tonometer were concordant with the IOP readings obtained by applanation Tonopen XL, but ICare values were significantly (P<0.0001) lower. Rebound tonometry could be an appropriate tonometry method for routine clinical use after its calibration for canine eyes.     

Multiple-center study of reduced-concentration triamcinolone topical solution for the treatment of dogs with known or suspected allergic pruritus

OBJECTIVE: To determine the efficacy of triamcinolone acetonide topical solution (TTS) in dogs for use in reduction of clinical signs of pruritic inflammatory skin diseases of a known or suspected allergic basis and to evaluate adverse effects associated with TTS administration. ANIMALS: 103 pruritic adult dogs with known or suspected allergic skin disease. PROCEDURE: Dogs were treated for 4 weeks with TTS or with vehicle solution (control dogs) in a multiple-center study. Clinical signs were scored by owners and by examining veterinarians before and after treatment. Blood samples obtained before and after treatment were subjected to routine hematologic and serum biochemical analyses. RESULTS: Treatment success, as defined by an improvement of at least 2 of 6 grades in overall clinical score, was evident in 35 of 52 (67%) TTS-treated dogs (mean improvement, 1.98) and 12 of 51 (24%) control dogs (mean improvement, 0.29). For several criteria, TTS was significantly more effective than vehicle in reducing clinical signs. Minor alterations in hematologic determinations in TTS-treated dogs were limited to slightly lower total leukocyte, lymphocyte, and eosinophil counts after treatment. Minor adverse effects were reported by owners in 6 of 52 (12%) TTS-treated and 9 of 51 (18%) control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Triamcinolone used as a spray solution at a concentration approximately one-sixth the concentration of triamcinolone topical preparations currently available for veterinary use is effective for short-term alleviation of allergic pruritus in dogs. Adverse effects are few and mild and, thus, do not preclude prolonged treatment with the solution.     

Carbonic anhydrase and its isozymes in heat stressed white Leghorn hens

Experiments were conducted to study the effect of heat stress on uterine tissue carbonic anhydrase levels and their isozyme patterns in relation to production of no- and thin-shelled eggs. Birds exposed to naturally occurring heat stress had lower enzyme levels in their uteri than birds kept in an air-conditioned pen. 4 isozyme bands of carbonic anhydrase were visible in uterine tissue homogenate from both groups of birds. Isozymes were suppressed in heat-stressed birds, as was evident from staining intensities of the bands. This provided evidence to the effect that heat stress not only decreased the total quantity of carbonic anhydrase in the uteri of the hens but also suppressed its isozyme fractions, leading to greater production of no-shell and thin-shelled eggs.