Activities of enzymes in some types of peripheral leucocytes may reflect the differences in nutrient metabolism between dogs and cats

Plasma metabolites and immunoreactive insulin (IRI) concentrations and enzyme activities of some types of peripheral leucocytes were measured to clarify one aspect of the differences in nutrient metabolism between dogs and cats. There were no significant differences in plasma concentrations of glucose, triglyceride, free fatty acids and IRI between dogs and cats. Higher total cholesterol and lower HDL cholesterol concentrations were observed in feline plasma, and H/T ratio (HDL/total cholesterol concentrations) was significantly lower than that in canine plasma. The cytosolic activities of fructokinase (FK), pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) were significantly higher and the activities of cytosolic malate dehydrogenase (MDH) and mitochondrial glutamate dehydrogenase (GLDH) were significantly lower in feline leucocytes than those in canine leucocytes. Higher activities of FK, PK and G6PD, which regulate the rate of biosynthesis of fatty acids, may reflect the different characteristics in nutrient metabolism in feline tissues from canine tissues.     

Gentamicin pharmacokinetics and nephrotoxicity in naturally acquired and experimentally induced disease in dogs

Pharmacokinetic disposition of gentamicin was studied in 69 dogs--12 control and 33 subtotally nephrectomized dogs representing combined data from previous experimental studies, and 24 dogs with a variety of diseases and degrees of renal dysfunction. Drug disposition varied considerably within and between diseases, and dosages had to be altered to achieve therapeutic drug concentrations and to minimize drug toxicosis. Decreased drug clearance when serum creatinine and urea nitrogen concentrations are normal may be indicative of subclinical renal disease and therefore may indicate a predisposition for development of nephrotoxicosis. Results of the study indicated the need to individualize aminoglycoside dosage regimens on the basis of pharmacokinetic disposition of drug, especially in dogs with preexisting subclinical renal dysfunction. Because of the large variability normally encountered in dogs with various diseases, monitoring of renal function alone is not sufficient to accurately predict gentamicin clearance, volume of distribution, or half-life.     

Use of Body Surface Area (BSA)-Based Dosages to Calculate Chemotherapeutic Drug Dose in Dogs: I. Potential Problems with Current BSA Formulae

The dose of most cancer chemotherapeutic drugs administered to dogs is calculated on the basis of estimated body surface area (BSA); however, results of some chemotherapy trials have revealed that this dosing method increases toxicosis in small dogs. The current formula used to estimate BSA in dogs may be inaccurate or the assumption that BSA correlates with chemotherapeutic drug exposure may be unfounded. Results presented in this review suggest that canine BSA estimates may be inaccurate because the values for the constant (K) and exponent (a) in the formulae (BSA = K.W^a) are incorrect or because a linear parameter such as body length is lacking from the formulae. Results that suggest the relationship between BSA and the physiologic/pharmacologic factors that influence drug exposure may not be closely correlated are also presented. Studies are warranted to determine whether there are dosing methods that normalize chemotherapeutic drug toxicity in dogs.     

Effects of a mock ultrasonographic procedure on cortisol concentrations during low-dose dexamethasone suppression testing in clinically normal adult dogs

OBJECTIVE: To determine whether the stress of an ultrasonographic procedure would interfere with the suppressive effect of dexamethasone during a low-dose dexamethasone suppression test (LDDST) in healthy dogs. ANIMALS: 6 clinically normal adult dogs. PROCEDURE: In phase 1, an LDDST was performed 5 times at weekly intervals in each dog. Serum samples were obtained 0, 2, 4, 6, and 8 hours after dexamethasone injection. A mock 20-minute abdominal ultrasonographic examination was performed on all dogs at each time point during the LDDST on weeks 2 through 5. In phase 2, serum cortisol concentrations were measured before and immediately after a 20-minute mock abdominal ultrasonographic examination, as described for phase 1. RESULTS: We did not detect significant differences after dexamethasone injection when comparing median cortisol concentrations for weeks 2 to 5 (mock ultrasonographic procedure) with median concentration for week 1 (no mock ultrasonographic procedure). For 5 of the 6 dogs, cortisol concentrations after dexamethasone injection decreased to < 35.9 nmol/L after each mock ultrasonographic procedure and remained low for the duration of the LDDST. In phase 2, all dogs had significant increases in cortisol concentrations immediately after the mock ultrasonographic procedure. CONCLUSIONS AND CLINICAL RELEVANCE: A 20-minute mock abdominal ultrasonographic examination performed during LDDST did not alter results of the LDDST in most dogs. Cortisol concentrations measured immediately after a mock ultrasonographic examination were significantly increased. Ultrasonographic procedures should be performed a minimum of 2 hours before collection of samples that will be used to measure cortisol concentrations.     

Pharmacokinetic disposition and arthropathic potential of oral ofloxacin in dogs

We examined the relation between the pharmacokinetic disposition and arthropathic potential of ofloxacin, a new quinolone antibacterial agent, using both male immature (3-month-old) and mature (18-month-old) beagles. Ofloxacin was orally administered to these dogs at 20 mg/kg once daily for 8 consecutive days, and the animals were killed 2 h after the last treatment. Serum ofloxacin concentrations were repeatedly measured on days 1 and 7 by use of high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were calculated. In addition, on day 8, the drug concentrations in the joint synovial fluid and humeral and femoral condyles were measured. Clinico-pathological tests of blood and serum or histopathological examination of bone specimens were also performed. Arthropathy was macroscopically observed in the cartilage surface of all immature dogs, but not in mature dogs. There were, however, no noticeable differences in pharmacokinetic parameters between the two age groups of dogs or between single and 7-day treatments. In contrast to the occurrence of arthropathic lesions, the synovial fluid and condylar drug concentrations in immature dogs was equal to or lower than those in mature dogs, suggesting that the pharmacokinetic disposition of ofloxacin may not be essential for cartilage lesions.     

Fructosamine

Fructosamines are glycated serum proteins that, depending on their life span, reflect glycemic control over the previous 2 to 3 weeks. The nitroblue tetrazolium reduction method adapted to autoanalysis appeared to be a practical means to assay fructosamine quickly, economically, and accurately. The upper limit of the reference range is 374 μmol/L in dogs (95% percentile) and 340 μmol/L in cats (95% percentile). Newly diagnosed diabetic dogs and cats that had not undergone previous insulin therapy had significantly higher fructosamine concentrations than nondiabetic animals. In diabetic dogs that were receiving insulin therapy, the fructosamine test reflected the glycemic state far more accurately than did individual blood glucose measurements. Animals with satisfactory metabolic control revealed fructosamine concentrations within the reference range, whereas fructosamine concentrations above 400 μmol/L indicated insufficient metabolic control. On the basis of fructosamine concentrations, cats with a transitory hyperglycemia and cats with diabetes mellitus were differentiated. The fructosamine test is a valuable parameter for the diagnosis and metabolic control of diabetes mellitus in dogs and cats.     

Ciprofloxacin and norfloxacin pharmacokinetics and prostatic fluid penetration in dogs after multiple oral dosing

The aims of this study were to assess the pharmacokinetics and pharmacokinetic/pharmacodynamic (PK/PD) indices predictive of clinical outcome of ciprofloxacin (CIP) and norfloxacin (NOR) after multiple oral dosing, and to investigate their penetration into prostatic fluid in dogs. Eight dogs received seven oral doses b.i.d. of NOR (20 mg/kg) and CIP (15 mg/kg). Drug concentrations were determined in blood and in two prostatic fluid samples. Prostatic fluid concentrations were lower than plasma concentrations for both drugs. No statistically significant differences were determined between the pharmacokinetic parameters calculated after the first and seventh doses for either CIP or NOR. The PK/PD indices were found to be useful for predicting bacteriological outcome for fluoroquinolones (area under the disposition curve/minimum inhibitory concentration [MIC] and peak plasma concentration/MIC) and indicate that with this dose regimen CIP presents a more favourable disposition than NOR for successful clinical outcome.     

Drug choice and therapeutic drug monitoring in the management of canine primary epilepsy

Therapeutic drug monitoring is an underutilised resource in the management of canine primary epilepsy. Many of the anti-epileptic drugs, including phenobarbitone, have variable pharmacokinetic profiles in different dogs, with each individual animal showing variable rates of absorption, distribution, metabolism and excretion. This results in variable serum drug concentrations with the same oral dose. Many clinicians interpret this situation as therapeutic failure and classify these patients as refractory to treatment. By measuring blood concentrations of drugs at appropriate times, it is possible to explain the efficacy or failure of treatment, and also to prevent serum concentrations from reaching toxic levels. By analysing paired samples, key pharmacokinetic parameters may be calculated for each patient and a profile for the disposition of the drug obtained. Individual optimal drug dosage can be calculated for each patient at little cost to the pet owner.     

Dosing regimen and hematologic effects of pentoxifylline and its active metabolites in normal dogs

The disposition of pentoxifylline and two of its active metabolites (metabolite 1 [M1] and metabolite 5 [M5]) were studied following i.v. (8 mg/kg) and p.o. (30 mg/kg) administration to eight normal dogs using a randomized crossover design. Blood samples were collected at fixed time intervals after drug administration for determination of drug concentrations, platelet aggregation, and plasma fibrinogen. Complete blood counts, serum chemistry profiles, fibrinogen, and urinalysis were monitored at the beginning and end of each phase of the study (p.o. versus i.v. administration). Pentoxifylline was readily metabolized and bioavailable (50% +/- 26%). Both M1 and M5 were present throughout the study, with M5 predominating. Human drug therapeutic concentrations (1,000 ng/ml) were present for 170 +/- 24 minutes following i.v. administration and 510 +/- 85 minutes after p.o. dosing. These findings suggest that a 12-hour dosing regimen is appropriate. None of the dogs experienced any adverse effects after pentoxifylline administration. The lack of hematologic effects suggests that the immunologic effects of pentoxifylline may be of more importance in dogs.     

Pharmacokinetics of selamectin following intravenous,oral and topical administration in cats and dogs

The pharmacokinetics of selamectin were evaluated in cats and dogs, following intravenous (0.05, 0.1 and 0.2 mg/kg), topical (24 mg/kg) and oral (24 mg/kg) administration. Following selamectin administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). After intravenous administration of selamectin to cats and dogs, the mean maximum plasma concentrations and area under the concentration-time curve (AUC) were linearly related to the dose, and mean systemic clearance (Clb) and steady-state volume of distribution (Vd(ss)) were independent of dose. Plasma concentrations after intravenous administration declined polyexponentially in cats and biphasically in dogs, with mean terminal phase half-lives (t(1/2)) of approximately 69 h in cats and 14 h in dogs. In cats, overall Clb was 0.470 +/- 0.039 mL/min/kg (+/-SD) and overall Vd(ss) was 2.19 +/- 0.05 L/kg, compared with values of 1.18 +/- 0.31 mL/min/kg and 1.24 +/- 0.26 L/kg, respectively, in dogs. After topical administration, the mean C(max) in cats was 5513 +/- 2173 ng/mL reached at a time (T(max)) of 15 +/- 12 h postadministration; in dogs, C(max) was 86.5 +/- 34.0 ng/mL at T(max) of 72 +/- 48 h. Bioavailability was 74% in cats and 4.4% in dogs. Following oral administration to cats, mean C(max) was 11,929 +/- 5922 ng/mL at T(max) of 7 +/- 6 h and bioavailability was 109%. In dogs, mean C(max) was 7630 +/- 3140 ng/mL at T(max) of 8 +/- 5 h and bioavailability was 62%. There were no selamectin-related adverse effects and no sex differences in pharmacokinetic parameters. Linearity was established in cats and dogs for plasma concentrations up to 874 and 636 ng/mL, respectively. Pharmacokinetic evaluations for selamectin following intravenous administration indicated a slower elimination from the central compartment in cats than in dogs. This was reflected in slower clearance and longer t(1/2) in cats, probably as a result of species-related differences in metabolism and excretion. Inter-species differences in pharmacokinetic profiles were also observed following topical administration where differences in transdermal flux rates may have contributed to the overall differences in systemic bioavailability.     

Effect of enrofloxacin on digoxin clearance and steady-state serum concentrations in dogs.

The effect of enrofloxacin on the oral clearance and steady-state concentrations of digoxin in serum was evaluated in dogs. Digoxin was administered orally to six healthy adult Beagle dogs following a multiple-dose regimen of 0.0625 mg every 12 h for 23 days. From days 14 to 23 enrofloxacin was administered orally at a dosage of 2.5 mg/kg every 12 h, with subjects receiving enrofloxacin 2 h prior to digoxin. Trough serum concentrations of digoxin were measured using an immunoassay technique. On days 13 and 22, dogs were catheterized for multiple blood sample collection during the 12 h digoxin dosing interval and serum samples were analyzed for digoxin concentrations. In general, steady-state digoxin concentrations in trough serum were not significantly different during enrofloxacin treatment than before enrofloxacin administration. Similarly, digoxin oral clearance was not significantly different between pre-enrofloxacin and digoxin + enrofloxacin periods. We conclude that enrofloxacin is unlikely to have a significant impact on digoxin disposition in dogs.     

Procollagen type-III aminoterminal peptide in serum and synovial fluid of dogs with hip dysplasia and coxarthrosis

Hip dysplasia is an affection of the coxofemoral joint that progresses until stabilization is caused by fibrosis and osteoarthritic changes. This stabilization process can be examined by clinical and radiographic methods. The capability of evaluating the procollagen concentrations in liquids, such as serum and synovial fluid, has further offered the basis for an objective biochemical evaluation of the stabilization process. Our study was performed to evaluate whether determination of procollagen concentrations was suitable for the use in practice. The procollagen type-III aminoterminal peptide (P-III-NP) concentration was measured in serum and in synovial fluid from coxofemoral joints in 20 dogs. Dogs were grouped on the basis of evidence of dysplasia and osteoarthritic changes of the hip: (1) a control group of 6 dogs without clinical or radiographic signs of hip dysplasia, and (2) dysplastic group of 14 dogs, which was further grouped with respect to the coxofemoral joint laxity, as determined by the Ortolani test. Synovial fluid concentration of P-III-NP was significantly (P less than 0.05) higher in fluid from dysplastic joints than in fluid from normal joints. Serum concentrations of P-III-NP were significantly (P less than 0.05) higher in dogs in which results of the Ortolani test were positive.     

Cardiac troponins in canine babesiosis

This study compared the sensitivity of ECG and cardiac troponins to predict cardiac histopathological changes, clinical severity, and survival in canine babesiosis. One control group (n = 9) and 4 groups of dogs with mild uncomplicated babesiosis (n = 8), severe uncomplicated babesiosis (n = 9), complicated babesiosis (n = 8), and babesiosis and concurrent immune-mediated hemolytic anemia (IMHA) (n = 9) were studied. A 1-minute lead II ECG was recorded, and cardiac troponin I (cTnI) and T (cTnT) concentrations in plasma were measured. cTnI concentrations were significantly higher in the complicated (mean, 9.9; SE, +/-5.76) and concurrent IMHA (mean, 6.53; SE, +/-4.32) groups and in the 3 dogs that died of the disease (mean, 22.17; SE, +/-12.85) than in the control dogs (concentration below detection limit of test, -0.3 ng/mL). The 3 nonsurvivors had the most severe cardiac histopathological changes, but no arrhythmia and minimal other ECG changes. Dogs with babesiosis developed a variety of ECG abnormalities, but the abnormalities were not associated with disease severity, outcome, or plasma cardiac troponin concentrations. The exception was the presence of ventricular premature complexes (VPCs), which were associated with high cardiac troponin concentrations. This study showed an association between cTnI concentration and histological changes, clinical severity, and survival and no correlation between ECG abnormalities and histological changes or biochemical evidence of myocardial damage as reflected by cTnI concentrations. From this study, it was concluded that the analysis of plasma cTnI is a feasible and sensitive test and is superior to cTnT in diagnosing cardiac involvement in dogs with babesiosis.     

QUANTITATIVE THYROID SCINTIGRAPHY IN GREYHOUNDS SUSPECTED OF PRIMARY HYPOTHYROIDISM

The existence of hypothyroidism in greyhounds remains controversial and its investigation is complicated by the low circulating thyroid hormone concentrations typically found in healthy dogs of this breed. Quantitative measurement of thyroidal technetium-99m pertechnetate (^99mTcO₄⁻) uptake is known to be useful in assessing thyroid function in other breeds. The aim of this study was to evaluate thyroid scintigraphy as a method of assessing thyroid function in greyhounds suspected of primary hypothyroidism. Twenty greyhounds (eight females, 12 males) were studied. Thirteen had bald thigh syndrome and seven poor performance and low total T4. Total T4 concentrations were decreased in 18 (90%), and free T4 in two (10%) dogs. All canine thyroid stimulating hormone concentrations were within the reference interval. Thyroidal ^99mTcO₄⁻ uptake values (mean ± SD, 0.76 ± 0.26%) were within the reference limits published for euthyroid dogs (0.39–1.86%) making hypothyroidism highly unlikely. There were no significant differences ( P <0.05) when comparing data between dogs with bald thigh syndrome (13 dogs) and the remaining dogs (seven dogs). Seventeen (85%) dogs had higher uptake in the left thyroid gland than in the right that might reflect an anatomic feature of the greyhound breed. Calculation of percent thyroidal uptake of ^99mTcO₄⁻ is more accurate than thyroid:salivary gland ratios because of high variability in salivary gland uptake. Percent thyroidal uptake of ^99mTcO₄⁻ should be used when assessing thyroid function scintigraphically in the greyhound breed.     

In vitro efficacy of chemotherapeutics as determined by 50% inhibitory concentrations in cell cultures of mammary gland tumors obtained from dogs.

OBJECTIVE: To determine the 50% inhibitory concentration (IC-50) of carboplatin, cisplatin, and doxorubicin in cell cultures of mammary gland tumors obtained from dogs and to assess whether in vitro efficacy was within the range of clinically relevant concentrations, SAMPLE POPULATION: 30 mammary gland tumors excised from dogs. PROCEDURE: Cell cultures were established from the 30 tumors. Cultures then were treated with carboplatin, cisplatin, or doxorubicin. Growth inhibition of cultures was assessed via DNA measurement 24, 48, and 72 hours after treatment. The IC-50 values were calculated by use of linear interpolation. RESULTS: Cultures varied in their pattern of susceptibility. Doxorubicin induced significantly lower IC-50 values than the platinum derivatives. Cisplatin and carboplatin had comparable effects. The IC-50 values for carboplatin and doxorubicin were in the range of clinically relevant concentrations, but only part of the cisplatin cultures had IC-50 values within clinically relevant concentrations. We did not detect differences in the in vitro susceptibility among subtypes of tumors (ie, adenocarcinoma, solid carcinoma, malignant mixed tumor). CONCLUSION AND CLINICAL RELEVANCE: The IC-50 values determined in this study allowed assessment of in vitro drug efficacy of chemotherapeutics in cultures of mammary gland tumors obtained from dogs. Variations in susceptibility were evident and emphasize the importance of assessing susceptibility and resistance patterns for each tumor. Prospective studies to assess direct correlations between in vitro and in vivo efficacy must be performed to determine the clinical predictive value of this in vitro chemosensitivity assay for treatment of dogs with mammary gland tumors.     

Pharmacology and therapeutics in donkeys

Therapeutics are often administered to donkeys based on dosage and intervals recommended for horses because very few drugs have donkey‐specific label indications. Yet differences between donkeys and horses in drug distribution, metabolism and elimination have been noted for most therapeutic agents studied. These differences can be partially explained by the donkey's unique physiology. Since their ancestors evolved in a desert environment, the modern donkey exhibits qualities that allow them to tolerate dehydration better than the horse and recover more quickly from its effects. Fluid balance and body water compartment partitioning differ from the horse and may have implications regarding drug distribution. Since donkeys are preferential browsers, differences in diet may have influenced evolutionary differences in metabolic disposition of drugs. It is important to acknowledge these differences when designing dose regimes for donkeys based on horse protocols in order to avoid either lack of efficacy or toxicity.     

Penicillins and beta-lactamase inhibitor combinations.

beta-Lactamase production by bacteria continues to be one of the main mechanisms of bacterial resistance to beta-lactam antibiotics, and it seems likely to remain so. beta-Lactamase inhibitors provide 1 strategy to overcome this mechanism of bacterial resistance. Although 3 beta-lactamase inhibitor/antibiotic combinations are currently available, only 1 is approved for veterinary use. Because the beta-lactamase inhibitor must be present concurrently with the antibiotic for synergistic activity, it is important to consider the pharmacokinetic profile of these drugs in combination. These combinations were developed and optimized for human patients, so it is unlikely that they would achieve the ideal plasma and tissue concentrations and ratios in veterinary patients. Indeed, several differences in pharmacokinetic variables of beta-lactam antibiotic/beta-lactamase inhibitor agents have been described in dogs, compared with people. Such pharmacokinetic differences should be considered when interpreting in vitro susceptibility results in veterinary species, because these tests use ratios of drug that were established for humans. The beta-lactamase inhibitors represent a successful example of targeted drug development. However, the currently available inhibitors are active primarily against class-A beta-lactamases. Because the frequency with which class-C beta-lactamases are recognized is rapidly increasing in human isolates, and because beta-lactamase enzymes continue to evolve, new beta-lactamase inhibitors will need to be developed to target these enzymes.     

Non-linear relationship between bioavailability and dose after oral administration of four single doses of acepromazine in dogs and cats

Acepromazine maleate is used in veterinary medicine as a pre-anaesthetic agent. The pharmacokinetics of this drug administered orally in dogs and cats are poorly documented. In an open, single dose, randomised cross-over study, the disposition of acepromazine and the dose-concentration time relationships were studied following single oral administration of 1.25, 2.5, 5 and 10 mgkg bwt, respectively, in 5 dogs and 5 cats. Treatments were allocated randomly to the animals at 10 day intervals. Using high performance liquid chromatography, ACP was determined in blood samples at 0, 5, 20, 40, 60, 90, 120 and 240 min and 8, 12, 18 and 24 h in dogs; and at 0, 30 min and then the same intervals in cats. ACP was detected in 4 of the 5 dogs and in all 5 cats at a dose of 1.25 mgkg bwt. However, in cats, estimation of the apparent elimination half-life at the lowest dose was imprecise due to some very low detectable concentrations during the elimination phase. In dogs, the area under the curve (AUC) increased with the dose but not simply as a linear relationship as indicated by significantly different normalised AUC (AUCD) among the doses. In cats, the concentration curve was higher than in dogs at the same dose per kg bwt. Dose-normalised AUC did not differ significantly between the 4 doses. The apparent elimination half-life remained similar over the tested dose range in both species and was about 2.5 h in dogs and 3 h in cats. The relationship between oral absorption of acepromazine and the dose (range 1.25 to 10 mgkg bwt) was consistent with pre-systemic metabolism becoming saturated at the higher dose (10 mgkg bwt) in dogs and at a lower dose in cats (between 2.5 and 5 mgkg bwt) or with a saturable absorption.     

Pharmacokinetic estimation for therapeutic dosage regimens (PETDR) – a software program designed to determine intravenous drug dosage regimens for veterinary applications

Pharmacokinetic estimation for therapeutic dosage regimens (PETDR) is a soft-ware program used to design individualized intravenous dosage regimens, determine concentration-time profiles, predict serum concentrations at a specific time after intravenous dosing and predict the time after the last dose to achieve a specified concentration of drug. The reference pharmacokinetic parameters may be based on an individual animal's pharmacokinetic disposition of drug or on FARAD (Food Animal Residue Avoidance Databank) mean population kinetic parameters. An individual animal's kinetic parameters may be input for predetermined analysis or the program can calculate these values by input of raw serum concentration-time data. The program allows the user to specify certain parameters of the dosage regimen, then calculates the other parameters (given desired maximum and minimum serum concentrations, dose and interval are calculated; given desired maximum serum concentration and interval, dose is calculated, etc.). Given the kinetic parameters, the dose and dosing interval, the program calculates and plots the serum concentration-time profile of the drug for that animal. The time and the number of doses to reach steady state can be calculated as well as the determination of loading dose. The percentage of the time of a dosing interval at steady state that the serum concentration is above a specific minimum inhibitory concentration (MIC) allows evaluation of efficacy of an antimicrobial regimen. Similarly, the time to reach a specific concentration (e.g. residue tolerance) or the MIC of a drug can be calculated. Legal tissue tolerances can be accessed from FARAD to aid in predicting for what period of time illegal residues will remain in the animal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the usefulness of sensitization to aeroallergens as a model for canine atopic dermatitis in genetically predisposed Beagles

OBJECTIVE: To evaluate a model for atopic dermatitis (AD) and to measure the effect of sensitization in Beagles genetically predisposed to produce high serum concentrations of allergen specific IgE. ANIMALS: 22 laboratory Beagles. PROCEDURE: Seventeen dogs were sensitized from birth to 3 allergens (recombinant birch pollen, Dermatophagoides pteronyssinus, and D farinae). Five nonsensitized dogs from the same litters served as controls. Clinical scoring, regular intradermal testing, measurement of serum concentrations of allergen-specific IgE, and collection of biopsy specimens of skin at 23, 32, and 43 weeks of age were performed. Serial tissue sections were stained for identification of IgE+ cells, mast cells and their subtypes, T-cells, Langerhans cells, and major histocompatibility complex class-II+ cells. At the age of 15 months, dogs were continuously exposed to 2 microg of mite allergen/g of dust. RESULTS: Sensitized dogs had positive intradermal test reactions and significantly higher serum concentrations of allergen specific IgE, compared with nonsensitized dogs. In sensitized and nonsensitized dogs, a significantly higher number of mast cells was found at predilection sites, compared with the control biopsy site. The number of mast cells at predilection sites increased with age. Sensitization significantly increased the number of epidermal Langerhans cells by 23 weeks of age. The number of epidermal Langerhans cells significantly increased in nonsensitized dogs by 32 weeks of age. Clinical scoring only revealed mild transient erythema in some dogs. CONCLUSIONS: increases in concentrations of serum allergen-specific IgE and exposure to allergens is not sufficient to induce clinical signs of AD in genetically predisposed dogs.