Increased genetic risk or protection for canine autoimmune lymphocytic thyroiditis in Giant Schnauzers depends on DLA class II genotype.

Dogs represent an excellent comparative model for autoimmune thyroiditis as several dog breeds develop canine lymphocytic thyroiditis (CLT), which is clinically similar to Hashimoto's thyroiditis in human. We obtained evidence that dog leukocyte antigen (DLA) class II genotype function as either genetic risk factor that predisposes for CLT or as protective factor against the disease. Genetic diversity at their DLA-DRB1, -DQA1, and -DQB1 loci were defined and potential association to major histocompatibility complex II haplotypes and alleles was analyzed. Giant Schnauzers carrying the DLA-DRB1*01201/DQA1*00101/DQB1*00201 haplotype showed an increased risk (odds ratio of 6.5) for developing CLT. The same risk haplotype has, to date, been observed in three different breeds affected by this disease, Giant Schnauzer, Dobermann, and Labrador Retriever, indicating that it is a common genetic risk factor in a variety of breeds affected by this disease. Importantly, protection for development of the disease was found in dogs carrying the DLA-DRB1*01301/DQA1*00301/DQB1*00501 haplotype (odds ratio of 0.3).

Optimal testing for thyroid hormone concentration after treatment with methimazole in healthy and hyperthyroid cats.

BACKGROUND: Methimazole suppresses thyroid hormone synthesis and is commonly used to treat feline hyperthyroidism. The degree of variation in thyroid hormone concentrations 24 hours after administration of methimazole and optimal time for blood sampling to monitor therapeutic efficacy have not been determined. OBJECTIVE: To assess thyroid hormone concentration variation in serum of normal and hyperthyroid cats after administration of methimazole. ANIMALS: Four healthy cats and 889 retrospectively acquired feline thyroid hormone profiles. METHODS: Crossover and retrospective studies. In the crossover study, healthy cats were treated with increasing doses of oral methimazole until steady state of thyroid suppression was achieved. Thyroid hormones and thyroid stimulating hormone (TSH) were serially and randomly monitored after methimazole. Paired t-tests and a 3-factor analysis of variance were used to determine differences between thyroid hormone concentrations in treated and untreated cats in the crossover study. Thyroid profiles from methimazole-treated hyperthyroid cats were retrieved from the Diagnostic Center for Population and Animal Health database and reviewed. Linear regression analysis evaluated relationships of dosage (mg/kg), dosing interval (q24h versus q12h), and time after methimazole to all thyroid hormone concentrations. RESULTS: All serum concentrations of thyroid hormones were significantly suppressed and TSH was significantly increased for 24 hours after administration of oral methimazole in healthy cats (P < .005). In hyperthyroid cats, there were no significant relationships between thyroid hormone concentrations and time postpill or dosing interval. CONCLUSIONS: Timing of blood sampling after oral methimazole administration does not appear to be a significant factor when assessing response to methimazole treatment.

Prevalence of diagnostic characteristics indicating canine autoimmune lymphocytic thyroiditis in giant schnauzer and hovawart dogs.

OBJECTIVES: To investigate prevalence of autoantibodies to thyroglobulin (TgAA) and/or elevated levels of thyroid stimulating hormone (TSH), indicating canine autoimmune lymphocytic thyroiditis (CLT) and/or hypothyroidism, in two high-risk dog breeds. METHODS: A cohort study was conducted in two birth cohorts of giant schnauzer and hovawart dogs. The cohorts were three to four and six to seven years of age at the time of blood sampling and screening for TgAA and TSH levels. Blood sampling was accompanied by one initial and one follow-up questionnaire to the dog owners. A total number of 236 giant schnauzers and 95 hovawarts were included in the study. RESULTS: Seventeen (7.2 per cent) giant schnauzers and three (3.2 per cent) hovawarts had been diagnosed as hypothyroid at the time of sampling. Out of the remaining dogs, 22 giant schnauzers (10.0 per cent) and nine hovawarts (10.1 per cent) had elevated TgAA and/or TSH levels. Prevalence of elevated TgAA and TSH levels varied with age. CLINICAL SIGNIFICANCE: The high prevalence of diagnostic characteristics indicating CLT/hypothyroidism in these two breeds suggests a strong genetic predisposition. It would be advisable to screen potential breeding stock for TSH and TgAA as a basis for genetic health programmes to reduce prevalence of CLT in these breeds.

Primary hair growth in dogs depends on dietary selenium concentrations.

Selenium (Se) plays an important role in hair growth. The objective of this study was to investigate the effect of dietary selenium concentration on hair growth in dogs. Thirty-six beagles were stratified into six groups based on age, gender and body condition score. The dogs were fed a torula yeast-based canned food for 3 weeks. Then the dogs were fed varying amounts of selenium supplied as selenomethionine for an additional 24 weeks. Analysed selenium concentrations in the experimental foods for the six groups were 0.04, 0.09, 0.12, 0.54, 1.03 and 5.04 mg/kg dry matter respectively. Body weight and food intake were not affected by the selenium treatments. Serum selenium concentration was similar initially but was significantly different at the end of the study among groups. Dietary selenium concentration below 0.12 mg/kg diet may be marginal for an adult dog. Dietary treatment had no effect on serum total thyroxine (TT(4)), free thyroxine (FT(4)), and free 3,3',5-triiodothyronine (FT(3)). There was a significant diet and time interaction (p = 0.038) for total 3,3',5 triiodothyronine (TT(3)). Hair growth was similar among groups initially but significantly reduced in dogs fed diets containing 0.04, 0.09 or 5.04 mg Se/kg when compared with 0.12, 0.54 and 1.03 mg Se/kg at week 11 (p < 0.05) and week 22 (p = 0.061). These results demonstrated that both low and high selenium diets reduce hair growth in adult dogs.

Thyroid hormone responses to endurance exercise.

REASONS FOR PERFORMING STUDY: Limited information exists about changes in circulating thyroid hormone concentrations during prolonged endurance exercise in horses. OBJECTIVE: To examine the effects of prolonged exercise on serum iodothyronine concentrations in horses performing endurance exercise of varying distances. METHODS: Serum concentrations of iodothyronines were measured in horses before and after completion of 40, 56, 80 and 160 km endurance rides (Study 1); daily during a 5 day, 424 km endurance ride (Study 2); and before and for 72 h after completion of a treadmill exercise test simulating a 60 km endurance ride (Study 3). RESULTS: In Study 1, 40 and 56 km of endurance exercise had little effect on serum iodothyronine concentrations with the exception of a 10% decrease (P<0.05) in free thyroxine (FT4) concentration after the 56 km ride. In contrast, total thyroxine (T4), total triiodothyronine (T3), FT4 and free triiodothyronine (FT3) concentrations all decreased (P<0.05) after successful completion of 80 and 160 km rides, with decreases ranging from 13-31% and 47-54% for distances of 80 and 160 km, respectively. Further, pre-ride T4 concentration was lower (P<0.05) and FT3 concentration was higher (P<0.05) in horses competing 160 km as compared to horses competing over shorter distances. In Study 2, serum concentrations of T4, T3 and reverse triiodothyronine (rT3) progressively decreased (P<0.05) over the course of the multi-day ride. In Study 3, the greatest decrease (P<0.05) in all iodothyronines was observed at 12 h of recovery, ranging from 25% for FT4 to 53% for FT3, but all thyroid hormone concentrations had returned to the pre-exercise values by 24 h of recovery. CONCLUSION: Endurance exercise results in transient decreases in serum iodothyronine concentrations. POTENTIAL RELEVANCE: These data are important to consider when thyroid gland function is assessed by measurement of serum iodothyronine concentrations in endurance horses.

Tryptic peptides of canine thyroglobulin reactive with sera of patients with canine hypothyroidism caused by autoimmune thyroiditis.

Canine thyroglobulin (cTg) was treated with trypsin at a ratio of trypsin to cTg of 1:100 (w/w). Tryptic peptides of cTg were analysed by Western immunoblotting for their reactivity to serum thyroglobulin autoantibodies (TgAA) from patients with TgAA-positive hypothyroidism and normal individuals. The sera of patients with TgAA-positive hypothyroidism reacted with several peptides: 43, 32.5 and 31 kDa; the sera of normal individuals did not bind these tryptic peptides. Some of the TgAA-positive sera of patients reacted with 25 kDa peptide in addition to three tryptic peptides above. This experiment was the first report about antigenic epitopes of cTg. These small tryptic peptides recognized by TgAA may be related with the induction of TgAA and may be useful as markers for autoimmune thyroid diseases in dog.

Heparinised blood ionised calcium concentrations in horses with colic or diarrhoea compared to normal subjects.

Our objectives were to 1) establish ionised calcium (ICa), C-terminal PTH and biologically active PTH (intact molecule) concentrations in blood from normal horses, 2) examine the stability of ionised calcium and acid-base values in stored equine heparinised blood and serum and 3) check the applicability of the formulas based on these parameters in certain disease states. Mean +/- s.d. % ionised calcium in heparinised blood of normal Warmbloods was 51 +/- 2.7 (n = 20) of total calcium, range 1.45-1.75 mmol/l (n = 15) at Michigan State University and 1.43-1.69 mmol/l (n = 20) at Utrecht University. Mean +/- s.d. EDTA plasma concentration for intact +/PTH in normal horses measured 0.6 +/- 0.3 pmol/l (n = 11). Both mean serum and the heparinised blood ionised calcium concentrations changed (not significantly) after 102 h storage at room temperature. Six cycles of freezing and thawing did not affect serum ionised calcium concentration significantly. Ionised calcium concentration and pH in heparinised blood of 20 normal Warmbloods were used to calculate the regression equation for the prediction of the adjusted ionised calcium concentration to a pH of 7.4. The linear regression equation found was: adjusted plasma ICa at pH 7.4 mmol/l = -6.4570 + 0.8739 x (measured pH) + 0.9944 x (measured ICa mmol/l). By means of this formula, mean adjusted ionised calcium concentration in heparinised blood calculated was 100% of the actual value given by the analyser in the normal horses. When using this formula in horses with colic or diarrhoea, mean adjusted ionised calcium concentration was underestimated by 0.2 and 0.3%, respectively. Furthermore, to adjust the measured ionised calcium concentration in heparinised blood to a pH of 7.4 in healthy as well as in 2 groups of diseased horses 2 formulas with a good prediction are now available.

Update on the diagnosis and treatment of disorders of calcium regulation.

The availability of PTH, iCa, PTHrP, and 25OHD assays for evaluation of calcium abnormalities in companion animals has been well received [table: see text] by clinicians and diagnosticians. Use of these assays has heightened awareness that some of these disorders are more common than originally thought. Also, there is added insight of alterations of calcium homeostasis as a consequence of other illness or environmental factors such as diet. Animal counterparts of other disorders of calcium metabolism in people are likely to be identified, and use of these assays should play a significant role. As already emphasized, the foundation of using [table: see text] these assays is first assessing whether the calcium abnormality is of a parathyroid-dependent or parathyroid-independent classification.

Lymphocytic thyroiditis.

Lymphocytic thyroiditis is a common canine condition that can lead to functional hypothyroidism. It is associated with more than 50% of cases of canine hypothyroidism. Evidence in human beings and experimental situations suggests that it is a disease of defective immunoregulation, but specific investigation of the molecular pathogenesis of the naturally occurring disease in dogs has not yet been carried out. The condition is heritable in those breeds that have been studied, and progression to hypothyroidism, if it occurs, can be slow. Factors that influence the progression from subclinical thyroiditis to hypothyroidism in dogs are still to be identified, but excessive iodine intake is an important factor in other species.

Shear level influences resistance artery remodeling: wall dimensions, cell density, and eNOS expression.

The magnitude of shear stimulus has been shown to determine the level of growth factor expression in cell culture. However, little is known regarding what effect shear level has on specific arterial wall remodeling events in vivo. We have hypothesized that the rate of luminal diameter change and specific remodeling events within the arterial wall layers are dependent on shear level. Selective ligations were made to alter the number of microvascular perfusion units of mesenteric arteries within the same animal to approximately 50%, 200%, and 400% of control. Arterial blood flow and wall shear rate were correlated with the degree of alteration in perfusion units. Luminal diameters were decreased in 50% arteries by day 2 and increased approximately 17% and 33% respectively, in 200% and 400% arteries at day 7. The rate of diameter change was greatest in 50% and 400% arteries. Wall areas (medial +37%; intimal +18% at day 2) and cell densities (intimal +26%; adventitial +44% at day 2) were altered only in the 400% arteries. A positive correlation existed by day 2 between endothelial staining for endothelial nitric oxide synthase and shear level. The results demonstrate that shear level influences the rate of luminal expansion, specific remodeling events within each wall layer, and the degree of endothelial gene expression. A greater understanding of how shear level influences specific remodeling events within each wall layer should aid in the development of targeted therapies to manipulate the remodeling process in health and disease.

The effects of thyroid hormones on the skin of beagle dogs.

The effects of hypothyroidism on canine skin were determined by comparing morphologic, morphometric, and hair cycle differences in skin biopsy samples from 3 groups of age- and gender-matched Beagle dogs: (1) euthyroid dogs; (2) dogs made hypothyroid by administration of 131I; and (3) dogs made hypothyroid and maintained in a euthyroid state by treatment with synthetic thyroxine. After 10 months of observation, there was slower regrowth of hair 2 months after clipping in the untreated-hypothyroid dogs. Untreated-hypothyroid dogs had a greater number of follicles in telogen and fewer hair shafts (ie, a greater number of hairless telogen follicles) than did the control group. The control dogs had a greater number of telogen follicles but the same number of hair shafts as the treated-hypothyroid group. Treated-hypothyroid dogs had the greatest number of follicles in the growing stage of the hair cycle (anagen). This study suggests that, at least in Beagles, induced hypothyroidism does not affect the pelage as dramatically as has been described in naturally occurring disease. This is because normal Beagles retain hair shafts in follicles for long periods, and the alopecia of hypothyroidism appears to evolve slowly because of the prolongation of this haired telogen stage. The evaluation of thyroxine-treated hypothyroid dogs demonstrates that thyroid hormone supplementation of Beagle dogs with induced hypothyroidism stimulates hair growth.

Effects of acetylpromazine or morphine on urine production in halothane-anesthetized dogs.

OBJECTIVE: To assess the influence of preanesthetic administration of acetylpromazine or morphine and fluids on urine production, arginine vasopressin (AVP; previously known as antidiuretic hormone) concentrations, mean arterial blood pressure (MAP), plasma osmolality (Osm), PCV, and concentration of total solids (TS) during anesthesia and surgery in dogs. ANIMALS: 19 adult dogs. PROCEDURE: Concentration of AVP, indirect MAP, Osm, PCV, and concentration of TS were measured at 5 time points (before administration of acetylpromazine or morphine, after administration of those drugs, after induction of anesthesia, 1 hour after the start of surgery, and 2 hours after the start of surgery). Urine output and end-tidal halothane concentrations were measured 1 and 2 hours after the start of surgery. All dogs were administered lactated Ringer's solution (20 ml/kg of body weight/h, i.v.) during surgery. RESULTS: Compared with values for acetylpromazine, preoperative administration of morphine resulted in significantly lower urine output during the surgical period. Groups did not differ significantly for AVP concentration, Osm, MAP, and end-tidal halothane concentration; however, PCV and concentration of TS decreased over time in both groups and were lower in dogs given acetylpromazine. CONCLUSIONS AND CLINICAL RELEVANCE: Preanesthetic administration of morphine resulted in significantly lower urine output, compared with values after administration of acetylpromazine, which cannot be explained by differences in AVP concentration or MAP When urine output is used as a guide for determining rate for i.v. administration of fluids in the perioperative period, the type of preanesthetic agent used must be considered.

Effects of racing and training on serum thyroid hormone concentrations in racing Greyhounds.

OBJECTIVES: To determine the effects of racing and training on serum thyroxine (T4), triiodothyronine (T3), and thyroid stimulating hormone (TSH) concentrations in Greyhounds. ANIMALS: 9 adult racing Greyhounds. PROCEDURE: Serum thyroid hormone concentrations were measured before and 5 minutes after a race in dogs trained to race 500 m twice weekly for 6 months. Resting concentrations were measured again when these dogs had been neutered and had not raced for 3 months. Postrace concentrations were adjusted relative to albumin concentration to allow for effects of hemoconcentration. Thyroid hormone concentrations were then compared with those of clinically normal dogs of non-Greyhound breeds. RESULTS: When adjusted for hemoconcentration, total T4 concentrations increased significantly after racing and TSH concentrations decreased; however, there was no evidence of a change in free T4 or total or free T3 concentrations. Resting total T4 concentrations increased significantly when dogs had been neutered and were not in training. There was no evidence that training and neutering affected resting TSH, total or free T3, or free T4 concentrations. Resting concentrations of T3, TSH, and autoantibodies against T4, T3, and thyroglobulin were similar to those found in other breeds; however, resting free and total T4 concentrations were lower than those found in other breeds. CONCLUSIONS AND CLINICAL RELEVANCE: Except for total T4, thyroid hormone concentrations in Greyhounds are affected little by sprint racing and training. Greyhounds with low resting total and free T4 concentrations may not be hypothyroid.

The postmortem diagnosis of cholecalciferol toxicosis: a novel approach and differentiation from ethylene glycol toxicosis.

The objectives of this study were to develop a novel approach to postmortem diagnosis of cholecalciferol (CCF) toxicosis in dogs using kidney, bile, and urine samples, and to differentiate CCF from ethylene glycol (EG) toxicosis. To achieve these objectives, specimens collected from 2 previous laboratory studies in which dogs were given a single oral toxic dose of CCF (8.0 mg/kg) were used. For EG toxicosis, historical data from the previous 13 years (1985-1998) were reviewed and confirmed cases of EG toxicosis were selected. The historical data were used to compare trace mineral concentrations, specifically of calcium and phosphorus to differentiate between intoxications caused by CCF from that caused by EG in dogs. Kidneys, bile, and urine from dogs that died of CCF toxicosis were analyzed for 25 monohydroxy vitamin D3 (25(OH)D3) and 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) and compared to known control unexposed dogs. Results of this study show that biliary and renal 25(OH)D3 concentrations and renal calcium to phosphorus ratio are of diagnostic value in dogs exposed to toxic concentrations of CCF. The renal calcium to phosphorus ratio was <0.1 in normal dogs, 0.4-0.9 in dogs that died of CCF toxicosis, and >2.5 in dogs that died of EG toxicosis.

Proliferation of maxillary and mandibular periodontal squamous cells in mink fed 3,3',4,4',5-pentachlorobiphenyl (PCB 126).

This report characterizes squamous cell proliferation in young farm mink (Mustela vison) fed a diet supplemented with 0.024 ppm 3,3',4,4',5-pentachlorobiphenyl (polychlorinated biphenyl [PCB] congener 126). One to 2 months of dietary exposure to PCB 126 resulted in gross lesions of the upper and lower jaws consisting of mandibular and maxillary nodular proliferation of the gingiva and loose teeth. The maxilla and mandible of the PCB-treated mink were markedly porous because of loss of alveolar bone. Histologically, this osteoporosis was caused by proliferation of squamous cells that formed infiltrating cords. This report clearly documents the fact that the environmental contaminant PCB 126 can cause osteoinvasive squamous proliferation in young mink, although the dose used in the present study was 7 and 36 times higher than what is typically encountered in contaminated bird eggs and fish, respectively.

Effects of anesthesia, surgery, and intravenous administration of fluids on plasma antidiuretic hormone concentrations in healthy dogs.

OBJECTIVE: To evaluate effects of anesthesia, surgery, and intravenous administration of fluids on plasma concentrations of antidiuretic hormone (ADH), concentration of total solids (TS), PCV, arterial blood pressure (BP), plasma osmolality, and urine output in healthy dogs. ANIMALS: 22 healthy Beagles. PROCEDURE: 11 dogs did not receive fluids, and 11 received 20 ml of lactated Ringer's solution/kg of body weight/h. Plasma ADH adn TS concentrations, PCV, osmolality, and arterial BP were measured before anesthesia (T0) and after administration of preanesthetic agents (T1), induction of anesthesia (T2), and 1 and 2 hours of surgery (T3 and T4, respectively). Urine output was measured at T3 and T4. RESULTS: ADH concentrations increased at T1, T3, and T4, compared with concentrations at T0. Concentration of TS and PCV decreased at all times after administration of preanesthetic drugs. Plasma ADH concentration was less at T3 in dogs that received fluids, compared with those that did not. Blood pressure did not differ between groups, and osmolality did not increase > 1% from To value at any time. At T4, rate of urine production was less in dogs that did not receive fluids, compared with those that did. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma ADH concentration increased and PCV and TS concentration decreased in response to anesthesia and surgery. Intravenous administration of fluids resulted in increased urine output but had no effect on ADH concentration or arterial BP. The causes and effects of increased plasma ADH concentrations may affect efficacious administration of fluids during the perioperative period in dogs.

Effects of methimazole on renal function in cats with hyperthyroidism.

The purpose of this study was to investigate the effects of methimazole on renal function in cats with hyperthyroidism. Twelve cats with naturally occurring hyperthyroidism and 10 clinically normal (i.e., control) cats were included in this study. All cats initially were evaluated with a history, physical examination, complete blood count, serum biochemistry profile, basal serum total thyroxine concentration, complete urinalysis, and urine bacterial culture. Glomerular filtration rate (GFR) was estimated by a plasma iohexol clearance (PIC) test. After initial evaluation, hyperthyroid cats were treated with methimazole until euthyroidism was achieved. Both groups of cats were then reevaluated by repeating the initial tests four to six weeks later. The mean (+/-standard deviation) pretreatment estimated GFR for the hyperthyroid cats was significantly higher (3.83+/-1.82 ml/kg per min) than that of the control cats (1.83+/-0.56 ml/kg per min). Control of the hyperthyroidism resulted in a significantly decreased mean GFR of 2.02+/-0.81 ml/kg per minute when compared to pretreatment values. In the hyperthyroid group, the mean increases in serum urea nitrogen (SUN) and creatinine concentrations and the mean decrease in the urine specific gravity after treatment were not statistically significant when compared to pretreatment values. Two of the 12 hyperthyroid cats developed abnormally high serum creatinine concentrations following treatment. These results provide evidence that cats with hyperthyroidism have increased GFR compared to normal cats, and that treatment of feline hyperthyroidism with methimazole results in decreased GFR.

Use of pamidronate disodium to reduce cholecalciferol-induced toxicosis in dogs.

OBJECTIVE: To determine whether pamidronate disodium can reduce cholecalciferol-induced toxicosis in a dose-related manner. ANIMALS: 20 clinically normal, 8- to 12-month-old male Beagles. PROCEDURE: All dogs were given 8 mg of cholecalciferol (CCF)/kg of body weight once orally, then were randomly assigned to 4 groups of 5 dogs each. Dogs were treated with IV administration of 0.9% NaCl solution (SC group), 0.65 mg of pamidronate/kg in 0.9% NaCl solution (LP group), 1.3 mg of pamidronate/kg in 0.9% NaCl solution (MP group), or 2.0 mg of pamidronate/kg in 0.9% NaCl solution (HP group) on days 1 and 4 after administration of CCF. Dogs were observed for 14 days, and serial blood samples were collected for serum biochemical, electrolyte, and 25-hydroxyvitamin D3 analyses. Urine samples were collected for determination of specific gravity. Glomerular filtration rate (GFR) was determined by plasma iohexol clearance. Histologic examination of renal tissue was performed. RESULTS: One dog in the SC group was euthanatized 3 days after administration of CCF because of severe clinical signs of toxicosis. Dogs in the HP group had significantly higher mean GFR (day 3), serum potassium concentrations (day 14), and urine specific gravity (days 7 and 14) and significantly lower mean serum creatinine concentrations and total calcium X phosphorus concentration product (days 4 and 7) than dogs in the SC group. Dogs in the HP group had no abnormal findings on histologic examination of renal tissue, dogs in the LP and MP groups had trace to mild mineralization of renal tissue, and dogs in the SC group had moderate mineralization and cellular necrosis of proximal renal tubules. CONCLUSIONS AND CLINICAL RELEVANCE: Pamidronate disodium is a potentially useful drug to reduce CCF-induced toxicosis and other causes of hypercalcemia associated with increased bone resorption in dogs.