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- Author or Editor: Cynthia R. Ward x
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Abstract
Objective—To evaluate alterations in ligand-stimulated activity of G proteins in thyroid gland cells of hyperthyroid cats.
Sample Population—Membranes of thyroid gland cells isolated from 5 hyperthyroid cats and 3 age-matched euthyroid (control) cats immediately after the cats were euthanatized.
Procedures—Isolated thyroid cell membranes were treated with thyroid-stimulating hormone (TSH), and activation of G protein was quantified by measurement of the binding of guanosine triphosphate γ labeled with sulfur 35 (GTPγ35S). The separate effects of G-protein inhibitory (Gi) and G-protein stimulatory (Gs) proteins were determined by the use of pertussis toxin and cholera toxin, respectively.
Results—Thyroid cell membranes from hyperthyroid cats had higher basal GTPγ35S binding than did thyroid cell membranes from euthyroid cats. Thyroid cell membranes from hyperthyroid and euthyroid cats had a concentration-dependent increase in TSH-stimulated GTPγ35S binding over the TSH range of 0 to 100 mU/mL, with maximal activity at 1 to 100 mU/mL for both. The percentage increase in GTPγ35S binding stimulated by TSH was similar in magnitude between the membranes from hyperthyroid and euthyroid cats. The TSH-stimulated activation of Gs and Gi was not different between euthyroid and hyperthyroid cats.
Conclusions and Clinical Relevance—Ligand-stimulated activation of G proteins was the same in thyroid cell membranes obtained from hyperthyroid and euthyroid cats. Therefore, alterations in inherent Gs or Gi activities did not appear to be part of the pathogenesis of hyperthyroidism in cats.
Abstract
Objective—To determine whether expression of G proteins (Gi and Gs) is altered in thyroid gland adenomas obtained from hyperthyroid cats.
Sample Population—Adenomatous thyroid glands obtained from 8 hyperthyroid cats and thyroid glands obtained from 4 age-matched euthyroid cats.
Procedure—Expression of Gi and Gs was quantified in enriched membrane preparations of thyroid gland tissue, using immunoblotting with Gi and Gs antibodies and toxin-catalyzed ADP-ribosylation.
Results—Expression of Gi was significantly reduced in thyroid gland adenomas from hyperthyroid cats, compared with normal thyroid gland tissue from euthyroid cats. Expression of Gs was similar between the 2 groups.
Conclusions and Clinical Relevance—A decrease in expression of Gi in adenomatous thyroid glands of cats may reduce the negative inhibition of the cAMP cascade in thyroid cells, leading to autonomous growth and hypersecretion of thyroxine. Understanding the molecular mechanisms for hyperthyroidism in cats may lead to better treatment or, ultimately, prevention of the disease. (Am J Vet Res 2000;61:874–879)
Abstract
Objective—To evaluate glycemic response to insulin treatment in dogs with diabetes mellitus.
Design—Retrospective study.
Animals—221 dogs with diabetes mellitus.
Procedure—Type and dosage of insulin used, minimum and maximum blood glucose concentrations, time of blood glucose concentration nadir, and optimal duration of action of insulin were determined on the basis of data obtained prior to initial examination at the teaching hospital (127 dogs), at the time of initial examination (212 dogs), at the time a second follow- up blood glucose curve was performed (59 dogs), and at the time of clinical control of diabetes mellitus (83 dogs).
Results—Prior to examination, 69 of 127 dogs (54%) received 1 SC insulin injection daily. Thirty-one dogs (24%) received a high dose of insulin (ie, > 1.5 U/kg [0.7 U/lb] of body weight); 27 of these dogs (87%) received 1 injection/d. Eleven of 16 dogs (69%) that were hypoglycemic (blood glucose concentration < 80 mg/dl) also received 1 injection/d. However, optimal duration of action of insulin was > 12 hours in only 5 of 83 dogs (6%) evaluated at the time diabetes mellitus was clinically controlled. At that time, only 1 dog (1%) received a high dose of insulin, and the dog received 2 injections/d. Moreover, 8 of 10 dogs (80%) with hypoglycemia received 1 injection/d.
Conclusions and Clinical Relevance—Most dogs with diabetes mellitus are clinically regulated with 2 daily insulin injections. Administration of a high dose of insulin or development of hypoglycemia may be more common in diabetic dogs that receive insulin once daily, compared with dogs that receive insulin twice daily. ( J Am Vet Med Assoc 2000;216:217–221)
Abstract
Objective—To determine the effects of dexamethasone or synthetic ACTH administration on endogenous ACTH concentrations in healthy dogs.
Animals—10 healthy neutered dogs.
Procedures—Each dog received dexamethasone (0.01 mg/kg), synthetic ACTH (5 μg/kg), or saline (0.9% NaCl) solution (0.5 mL) IV at intervals of ≥ 30 days. Plasma endogenous ACTH concentrations were measured before (baseline; time 0) and 1, 8, 12, and 24 hours after drug administration; serum cortisol concentrations were measured before and 1 hour after synthetic ACTH and saline solution administration and 8 hours after dexamethasone administration.
Results—Analysis of serum cortisol concentrations confirmed effects of drug administration. Dexamethasone significantly decreased the endogenous ACTH concentration from the baseline value at both 8 and 12 hours. Synthetic ACTH administration significantly decreased the endogenous ACTH concentration from the baseline value at 8 hours. Saline solution administration had no significant effect on endogenous ACTH concentration.
Conclusions and Clinical Relevance—Dexamethasone and synthetic ACTH administered IV at doses used routinely during testing for hyperadrenocorticism caused significant but transient reductions of endogenous ACTH concentrations in healthy dogs. Thus, a 2-hour washout period following ACTH stimulation testing before collection of samples for measurement of the endogenous ACTH concentration may be insufficient. Although this effect has not been verified in dogs with hyperadrenocorticism, these data suggested that samples for measurement of endogenous ACTH concentrations should be obtained before or > 8 hours after initiation of an ACTH stimulation test or before or > 12 hours after the start of a low-dose dexamethasone suppression test.
Abstract
Objective—To determine which dog breeds are at low and high risk for developing diabetes mellitus (DM).
Design—Cohort study.
Animals—Hospital population of 221 dogs with DM and 42,882 dogs without DM during 5.5 years.
Procedure—165 breeds (including a mixed-breed category) were represented in the hospital population. Breed-specific expected numbers of dogs with DM were calculated by multiplying the proportion of all dogs admitted to the hospital that were determined to have DM during the study period by the breed-specific totals during the study period. Breeds or breed groups evaluated in the analysis (n = 20) were restricted to those that had a combined observed and expected count > 5 to document breeds at low and high risk for developing DM. Proportionate changes in the risk of developing DM by breed were calculated and presented using exact odds ratios, 95% confidence intervals, and P values. Mixed-breed dogs were chosen as the reference breed.
Results—Samoyeds, Miniature Schnauzers, Miniature Poodles, Pugs, and Toy Poodles were at high risk for developing DM. Dog breeds found to be at low risk for developing DM were German Shepherd Dog, Golden Retriever, and American Pit Bull Terrier.
Conclusion and Clinical Relevance—The finding that certain dog breeds are at low or high risk for developing DM suggests that some genetic defects may predispose dogs to development of DM, whereas other genetic factors may protect dogs from development of DM. (J Am Vet Med Assoc 2000;216: 1414–1417)
Objective
To determine, among dogs with urolithiasis, whether dogs that had hyperadrenocorticism would be more likely to have calcium-containing uroliths than would dogs that did not have clinical evidence of hyperadrenocorticism.
Design
Retrospective case-control study.
Animals
20 dogs that had urolithiasis and hyperadrenocorticism and 42 breed-matched dogs that had urolithiasis but did not have clinical evidence of hyperadrenocortiosm.
Procedure
Signalment, urolith composition, results of bacterial culture of urine, and results of adrenal axis tests were recorded. A multivariate logistic regression model was created, including terms for age, sex, and hyperadrenocorticism. The outcome variable was presence or absence of calcium-containing uroliths.
Results
Among dogs with urolithiasis, those that had hyperadrenocorticism were 10 times as likely to have calcium-containing uroliths as were dogs that did not have clinical evidence of hyperadrenocorticism (odds ratio, 10.5; 95% confidence interval, 1.5 to 23.4) Neutered and sexually intact females were less likely to have calcium-containing uroliths than were neutered males (odds ratios, 0.041 [95% confidence interval, 0.0057 to 0.29] and 0.024 [95% confidence interval, 0.0012 to 0.5], respectively).
Clinical Implications
Prompt diagnosis and treatment of hyperadrenocorticism may decrease prevalence of calcium-containing uroliths in dogs. (J Am Vet Med Assoc 1998:212:1889–1891)
Abstract
Objective—To identify within guanosine triphosphate–binding proteins (G proteins) the subset of inhibitory G proteins (Gi) that have decreased expression in adenomatous thyroid glands obtained from hyperthyroid cats.
Sample Population—Adenomatous thyroid glands obtained from 5 hyperthyroid cats and normal thyroid glands obtained from 3 age-matched euthyroid cats.
Procedure—Expression of Gi1, Gi2, and Gi3 in enriched membrane preparations from thyroid glands was quantified by use of immunoblotting with Gi subtype-specific antibodies.
Results—Expression of Gi2 was significantly decreased in tissues of hyperthyroid glands, compared with expression in normal thyroid tissue. Expression of Gi1 and Gi3 was not significantly different between normal thyroid tissues and tissues from hyperthyroid glands.
Conclusions and Clinical Relevance—A decrease in Gi2 expression decreases inhibition of adenylyl cyclase and allows a relative increase in stimulatory G protein expression. This results in increased amounts of cAMP and subsequent unregulated mitogenesis and hormone production in hyperthyroid cells. Decreased Gi2 expression may explain excessive growth and function of the thyroid gland in cats with hyperthyroidism. (Am J Vet Res 2005;66:1478–1482)
Abstract
Objective—To evaluate the effects of diets differing in type and quantity of fiber on glycemic control in dogs with naturally occurring insulin-dependent diabetes mellitus.
Design—Prospective randomized crossover controlled trial.
Animals—7 dogs with well-regulated naturally occurring insulin-dependent diabetes mellitus.
Procedure—Dogs were fed 1 of 3 diets for 1 month each in 1 of 6 randomized diet sequences. Diets included a low-fiber diet (LF) and 2 high-fiber diets; 1 contained only insoluble fiber (HIF), and 1 contained soluble fiber in addition to insoluble fiber (HSF). Caloric intake was unchanged throughout the study. Glycemic control was assessed after each feeding trial by measuring serum fructosamine concentration and performing 5 serial measurements of blood glucose concentration every 2 hours after the morning feeding and insulin injection.
Results—Significant differences were not detected in body weight, required insulin dosage, or albumin concentration among dogs fed the HIF, HSF, and LF diets. Mean and maximum blood glucose concentrations and area under the blood glucose curve were significantly lower in dogs fed the HIF diet, compared with values in the same dogs fed the HSF or LF diet. Fructosamine concentration was significantly lower in dogs fed the HIF or HSF diet, compared with values in the same dogs fed the LF diet.
Conclusions and Clinical Relevance—In dogs with naturally occurring insulin-dependent diabetes mellitus, a dry, high insoluble-fiber diet may aid in glycemic control. (J Am Vet Med Assoc 2000;216:1076–1081)
Abstract
Objective—To characterize concurrent disorders in dogs with diabetes mellitus (DM).
Design—Retrospective study.
Animals—221 dogs with DM.
Procedure—Medical records were reviewed, and clinical signs, physical examination findings, and results of clinicopathologic testing, urinalysis, aerobic bacterial culture of urine samples, coagulation testing, endocrine testing, histologic evaluation, diagnostic imaging, and necropsy were recorded.
Results—For most dogs, CBC results were normal. Common serum biochemical abnormalities included hypochloremia (127 dogs, 60%) and high alanine aminotransferase (163, 78%), aspartate aminotransferase (78, 71%), and alkaline phosphatase (188, 90%) activities. Venous pH and serum ionized calcium concentration were measured in 121 and 87 dogs, respectively, and were low in 56 (46%) and 41 (47%) dogs. Lipemia was observed in 92 (42%) dogs. Urine samples from 159 (72%) dogs were submitted for aerobic bacterial culture, and 34 (21%) yielded bacterial growth. Escherichia coli was the most commonly isolated organism. Thirty-six (16%) dogs had dermatitis or otitis. Hyperadrenocorticism was diagnosed in 51 (23%) dogs on the basis of clinical signs and results of a low-dose dexamethasone suppression test (41 dogs), an adrenocorticotropic hormone stimulation test (5), both tests (4), or histologic evaluation of necropsy specimens (1). Acute pancreatitis was diagnosed in 28 (13%) dogs. Eleven (5%) dogs had tumors for which a histologic diagnosis was obtained. Eight (4%) dogs were hypothyroid.
Conclusions and Clinical Relevance—Results suggest that dogs with diabetes mellitus may have many concurrent disorders. The most commonly identified concurrent disorders included hyperadrenocorticism, urinary tract infection, dermatitis, otitis, acute pancreatitis, neoplasia, and hypothyroidism. (J Am Vet Med Assoc 2000;217:1166–1173)
