Serum concentrations of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol in clinically normal dogs and dogs with acute and chronic renal failure

OBJECTIVE: To compare serum concentrations of 1,25-dihydroxycholecalciferol (1,25-[OH]2D3) and 25-hydroxycholecalciferol (25-[OH]D3) in healthy control dogs and dogs with naturally occurring acute renal failure (ARF) and chronic renal failure (CRF). ANIMALS: 24 control dogs, 10 dogs with ARF, and 40 dogs with CRF. PROCEDURE: Serum concentrations of 1,25-(OH)2D3 were measured by use of a quantitative radioimmunoassay, and serum concentrations of 25-(OH)D3 were measured by use of a protein-binding assay. RESULTS: Mean +/- SD serum concentration of 1,25-(OH)2D3 was 153 +/- 50 pmol/L in control dogs, 75 +/- 25 pmol/L in dogs with ARF, and 93 +/- 67 pmol/L in dogs with CRF. The concentration of 1,25-(OH)2D3 did not differ significantly between dogs with ARF and those with CRF and was in the reference range in most dogs; however, the concentration was significantly lower in dogs with ARF or CRF, compared with the concentration in control dogs. Mean +/- SD concentration of 25-(OH)D3 was 267 +/- 97 nmol/L in control dogs, 130 +/- 82 nmol/L in dogs with ARF, and 84 +/- 60 nmol/L in dogs with CRF. The concentration of 25-(OH)D3 was significantly lower in dogs with ARF or CRF, compared with the concentration in control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The concentration of 1,25-(OH)2D3 was within the reference range in most dogs with renal failure. Increased serum concentrations of parathyroid hormone indicated a relative deficiency of 1,25-(OH)2D3. A decrease in the serum concentration of 25-(OH)D3 in dogs with CRF appeared to be attributable to reduced intake and increased urinary loss.     

Comparison of serum-free thyroxine concentrations determined by standard equilibrium dialysis, modified equilibrium dialysis, and 5 radioimmunoassays in dogs

Measurement of serum-free thyroxine (fT4) concentration provides a more accurate assessment of thyroid gland function than serum thyroxine (T4) or 3,5,3'-triiodothyronine (T3). Techniques for measuring serum fT4 concentration include standard equilibrium dialysis (SED), radioimmunoassay (RIA), and a combination of both (modified equilibrium dialysis [MED]). This study compared results of serum fT4 measurements by means of SED, MED, and 5 RIAs in 30 healthy dogs, 10 dogs with hypothyroidism, and 31 euthyroid dogs with concurrent illness for which hypothyroidism was a diagnostic consideration. Serum fT4 concentrations were comparable when determined by the SED and MED techniques, and mean serum fT4 concentrations were significantly (P < .01) lower in dogs with hypothyroidism than in healthy dogs and euthyroid dogs with concurrent illness. Significant (P < .05) differences in fT4 concentrations were identified among the 5 RIAs and among the RIAs and MED and SED. Serum fT4 concentrations were consistently lower when fT4 was determined by the RIAs, compared with either equilibrium dialysis technique. Serum fT4 concentrations were significantly lower (P < .01) in dogs with hypothyroidism than in healthy dogs for all RIAs; were significantly lower (P < .05) in dogs with hypothyroidism than in euthyroid dogs with concurrent illness for 4 RIAs; and were significantly lower (P < .01) in euthyroid dogs with concurrent illness than in healthy dogs for 4 RIAs. RIAs had the highest number of low serum fT4 concentrations in euthyroid dogs with concurrent illness. This study documented differences in test results among fT4 assays, emphasizing the importance of maintaining consistency in the assay used to measure serum fT4 concentrations in the clinical or research setting.     

Comparison of bronchoalveolar lavage fluid obtained from Mannheimia haemolytica-inoculated calves with and without prior treatment with the selectin inhibitor TBC1269

OBJECTIVES: To determine effects of selectin inhibitor TBC1269 on neutrophil infiltration, and neutrophil-associated injury during pneumonia induced by Mannheimia haemolytica and concentration of antimicrobial anionic peptide (AAP) in bronchoalveolar lavage fluid (BALF) as well as antimicrobial activity of BALF from healthy (control) neonatal calves, neonatal calves with M haemolytica-induced pneumonia, neonatal calves with prior treatment with TBC1269, and adult cattle. ANIMALS: Eighteen 1- to 3-day-old calves and 9 adult cattle. PROCEDURE: Calves were inoculated with M haemolytica or pyrogen-free saline (0.14M NaCl) solution into the right cranial lung lobe, and BALF was collected 2 or 6 hours after inoculation. Thirty minutes before and 2 hours after inoculation, 4 calves received TBC1269. The BALF collected from 9 adult cattle was used for comparison of BALF AAP concentration and antimicrobial activity. Protein concentration and neutrophil differential percentage and degeneration in BALF were determined. An ELISA and killing assay were used to determine BALF AAP concentration and antimicrobial activity, respectively. RESULTS: Total protein concentration was significantly decreased in BALF from calves receiving TBC1269. Similar concentrations of AAP were detected in BALF from all calves, which were 3-fold higher than those in BALF from adult cattle. However, BALF from neonates had little or no anti-M haemolytica activity. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that TBC1269 decreases pulmonary tissue injury in neonatal calves infected with M haemolytica. Although AAP is detectable in neonatal BALF at 3 times the concentration detected in adult BALF, neonatal BALF lacks antimicrobial activity for M haemolytica.     

Serum and bronchoalveolar lavage fluid endothelin-1 concentrations as diagnostic biomarkers of canine idiopathic pulmonary fibrosis

Background: Diagnosis of canine idiopathic pulmonary fibrosis (IPF) is challenging. Endothelin‐1 (ET1) is a biomarker of IPF in humans, but whether ET1 can detect and differentiate IPF from other canine respiratory diseases is unknown. Objective: To evaluate whether measurement of the concentration of ET1 in serum and bronchoalveolar lavage fluid (BALF) can be used to distinguish canine IPF from chronic bronchitis (CB) and eosinophilic bronchopneumopathy (EBP). Animals: Twelve dogs with IPF, 10 dogs with CB, 6 dogs with EBP, 13 privately owned healthy West Highland White Terriers (WHWT), and 9 healthy Beagle dogs. Methods: Prospective, case control study. ET1 concentration was determined by ELISA in serum and in BALF. Results: No significant difference in serum ET1 concentration was detected between healthy Beagle dogs and WHWT. Serum ET1 concentration was higher in dogs with IPF (median interquartile range; 2.32 pg/mL, 2.05–3.38) than healthy Beagle dogs (1.28, 1.07–1.53; P < .001), healthy WHWT (1.56, 1.25–1.85; P < .001), dogs with EBP (0.94 0.68–1.01; P = .001), and dogs with CB (1.54 0.74–1.82; P = .005). BALF ET1 concentration was below the detection limit in healthy WHWT and in dogs with CB, whereas it was measurable in all dogs with IPF. A cut‐off serum concentration of 1.8 pg/mL had a sensitivity of 100% and a specificity of 81.2% for detection of IPF, with an area under the receiver operating characteristic curve of 0.818. Conclusions and Clinical Importance: Serum ET1 can differentiate dogs with IPF from dogs with EBP or CB. ET1 can be detected in BALF of dogs with IPF.     

Serum-free thyroxine concentrations, measured by chemiluminescence assay before and after thyrotropin administration in healthy dogs, hypothyroid dogs, and euthyroid dogs with dermathopathies.

The purpose of this study was to determine the usefulness of free thyroxine (FT4) measured by chemiluminescence in evaluating thyroid function in dogs. Total thyroxine (TT4) concentration measured by radioimmunoassay (RIA) and FT4 measured by chemiluminescence were evaluated in 30 healthy dogs, 60 euthyroid dogs with concurrent dermatopathies, and 30 hypothyroid dogs before and after intravenous stimulation with 1 or 2 IU of thyrotropin (TSH). Median basal TT4 and median TT4 concentrations at 4 h post-TSH administration were not significantly different (P < 0.0001) between healthy dogs and euthyroid dogs with dermatopathies, but were significantly higher than those in hypothyroid dogs. In healthy dogs, the median TT4 concentrations at 4 and 6 h post-TSH administration were not significantly different. Median basal FT4 and median FT4 concentrations at 4 h post-TSH administration in healthy dogs were significantly lower (P < 0.0001) than those in euthyroid dogs with dermatopathies, but significantly higher than the same parameters in hypothyroid dogs. There was a significant difference between the median FT4 concentrations at 4 h post-TSH administration and median basal FT4 concentrations for healthy dogs and euthyroid dogs with dermatopathies, but not for hypothyroid dogs. Lastly, in healthy dogs, median FT4 concentrations at 4 and 6 h post-TSH administration were not significantly different. Free thyroxine measured by chemiluminescence was highly correlated (P < 0.0001; Spearman r = 0.91) with FT4 measured by the reference method for free hormone analysis, namely, equilibrium dialysis, when sera from 56 dogs were used.     

Associations between N-terminal procollagen type III,fibrosis and echocardiographic indices in dogs that died due to myxomatous mitral valve disease

ObjectivesTo evaluate associations between N-terminal procollagen type III (PIIINP), a serum biomarker of collagen biosynthesis, and myocardial fibrosis in dogs with naturally-occurring myxomatous mitral valve disease (MMVD).AnimalsTwenty-two dogs with echocardiographically-confirmed MMVD were prospectively recruited from a hospital population. All died as a result of MMVD and their hearts were available for post mortem examination.MethodsEchocardiographic measurements and serum PIIINP concentrations were obtained from all dogs prior to death or euthanasia. Serum PIIINP concentrations (μg/mL) were measured using a validated commercially available radioimmunoassay. Myocardial tissue samples were collected post mortem and myocardial fibrosis was scored. The average fibrosis score for all cardiac sites in the heart was designated the global fibrosis score (GFS). The average fibrosis score for all papillary muscle sites was designated the papillary fibrosis score (PFS). Univariate and multivariate linear regression analyses were used separately to evaluate associations between GFS and PFS, respectively, and PIIINP and echocardiographic variables.ResultsLeft ventricular end-diastolic diameter normalized for body weight (LVEDDN) and PIIINP were weakly independently positively associated with both GFS and PFS. LVEDDN and PIIINP were weakly negatively correlated.ConclusionsBoth LVEDDN and serum PIIINP increase with increasing fibrosis score, although these relationships were not strong enough to be clinically useful. Although LVEDDN and PIIINP were positively correlated with fibrosis, PIIINP decreased with increasing LVEDDN, suggesting a complex interplay between fibrosis and remodeling in MMVD.     

Rhinitis/Bronchopneumonia syndrome in Irish Wolfhounds

This study describes the clinical, immunologic, genetic, and pathologic features of Irish Wolfhounds with rhinitis/bronchopneumonia syndrome. The dogs examined were from Belgium, The Netherlands, UK, Canada, Germany, and Switzerland. Signs included transient to persistent mucoid or mucopurulent rhinorrhea, cough, and respiratory dyspnea. Radiographic, rhinoscopic, and bronchoscopic findings were variable. Analysis of ciliary ultrastructure was performed in 5 affected dogs, but no characteristic primary ciliary defects (primary ciliary dyskinesia) were detected. Serum and bronchoalveolar lavage fluid (BALF) concentrations of IgA, IgG, and IgM were determined in some affected dogs and clinically normal Irish Wolfhounds. Serum IgA concentration was below the reference range in 5 of 8 affected dogs tested, whereas BALF IgA concentration was above the normal range in 2 affected adult dogs. The CD4 to CD8 lymphocyte subset ratio (CD4:CD8) in peripheral blood was tested in 3 affected dogs and was within the normal range. BALF CD4:CD8 was tested in 1 affected dog and was higher than the normal range. Decreased neutrophil phagocytosis was observed in 1 of the 4 dogs tested. Analysis of pedigrees of the Belgian, Canadian, German, and Swiss dogs revealed common ancestry, suggesting a heritable syndrome.     

Basal and Glucagon-Stimulated Plasma C-PeDtide Concentrations in Healthy Dogs, Dogs With Diabetes Millitus, and Dogs With Hyperadrenocorticism

Serum glucose and plasma C-peptide response to IV glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5,10,20,30, and (for healthy dogs) 60 minutes after IV administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after IV glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after IV glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sarnplkg times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .001) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .011 in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, >0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired β-cell function (ie, diabetes mellitusl, and dogs with increased β-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of β-cell loss in dogs with type-1 diabetes. J Vet Intern Med 1996;10:116–122. Copyright © 1996 by the American College of Veterinary Internal Medicine.     

Effects of age, sex, and body size on serum concentrations of thyroid and adrenocortical hormones in dogs

Thyroxine (T4), 3,5,3'-triiodothyronine (T3), and cortisol frequently are quantified in canine serum or plasma samples to aid in the diagnosis of hypothyroidism, hypoadrenocorticism, and hyperadrenocorticism. Many laboratories have established reliable references values for concentrations of these hormones in blood of clinically normal animals. However, nonpathologic factors that affect thyroidal and adrenocortical secretion may lead to misinterpretation of test results when values for individual animals are compared with reference values. The objective of the study reported here was to identify effects of age, sex, and body size (ie, breed) on serum concentrations of T3, T4, and cortisol in dogs. Blood samples were collected from 1,074 healthy dogs, and serum concentrations of the iodothyronines and cortisol were evaluated for effects of breed/size, sex, and age. Mean (+/- SEM) serum concentration of T4 was greater in small (2.45 +/- 0.06 micrograms/dl)- than in medium (1.94 +/- 0.04 micrograms/dl)- or large (2.03 +/- 0.03 micrograms/dl)-breed dogs, the same in females (2.11 +/- 0.04 micrograms/dl) and males (2.08 +/- 0.04 micrograms/dl), and greater in nursing pups (3.04 +/- 0.05 micrograms/dl) than in weanling pups (1.94 +/- 0.05 micrograms/dl), rapidly growing dogs (1.95 +/- 0.04 micrograms/dl), and young adult (1.90 +/- 0.06 micrograms/dl), middle-aged adult (1.72 +/- 0.05 micrograms/dl), or old adult (1.50 +/- 0.05 micrograms/dl) dogs. Dogs greater than 6 years old had lower mean serum T4 concentration than did dogs of all other ages, except middle-aged adults. Mean serum T3 concentration in medium-sized dogs (1.00 +/- 0.01 ng/ml) was greater than that in small (0.90 +/- 0.01 ng/ml)- and large (0.88 +/- 0.01 ng/ml)-breed dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Additive effects of a sodium chloride restricted diet and furosemide administration in healthy dogs.

OBJECTIVE: To determine the effects of a low or high sodium (Na) diet with or without furosemide administration on plasma electrolyte concentrations and the renin-angiotensin-aldosterone system in healthy dogs. ANIMALS: 20 healthy adult dogs. PROCEDURE: Dogs were randomly allotted to 4 groups of 5 dogs each as follows: dogs fed a low Na diet (0.08% Na and 0.8% chloride [CI] on a dry matter [DM] basis); dogs fed a low Na diet with added NaCl (1.0% Na and 2.2% Cl on a DM basis); dogs fed a low Na diet and treated with furosemide (2 mg/kg of body weight, PO, q 12 h); and dogs fed a low Na diet with added NaCl and treated with furosemide. Plasma electrolyte concentrations were measured on days 0, 21, and 35. Plasma renin activity and aldosterone concentration were analyzed by use of radioimmunoassays on days 0, 21, 35, and 53. RESULTS: Furosemide treatment significantly decreased plasma Cl concentration and significantly increased plasma renin activity and aldosterone concentration. Dogs fed a low Na diet had significantly higher plasma renin activities and plasma aldosterone concentrations. A significant interaction between a low Na diet and furosemide administration resulted in the lowest plasma Cl concentrations, highest plasma renin activities, and highest plasma aldosterone concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs, feeding a low Na diet and administering furosemide resulted in an additive effect on plasma Cl concentration, renin activity, and aldosterone concentration, which may be an important consideration for treating dogs with cardiac disease.     

Determination of calcium fractionation in dogs with chronic renal failure

OBJECTIVE: To determine concentrations of calcium (total [tCa], ionized [iCa], protein-bound [pCa], and complexed [cCa]) in dogs with chronic renal failure (CRF). ANIMALS: 23 dogs with CRF. PROCEDURE: Serum calcium was fractionated by use of a micropartition system. Total calcium and iCa concentrations and pH were measured in unfractionated serum, and tCa concentration was measured in the ultrafiltrate. The pCa fraction was calculated by subtracting tCa of the ultrafiltrate from tCa concentration of unfractionated serum. The iCa concentration in unfractionated serum was subtracted from tCa concentration in the ultrafiltrate to determine the concentration of cCa. RESULTS: Concentrations of tCa, iCa, pCa, and cCa had wide ranges among dogs with CRF Dogs with significantly low tCa concentration (770 +/- 1.73 mg/dL) had cCa concentration (0.76 +/- 0.38 mg/dL) within reference range, whereas dogs with reference range to high tCa concentration (10.85 +/- 1.13 mg/dL) had significantly high cCa concentration (2.62 +/- 1.04 mg/dL). There was no significant difference in iCa or pCa concentrations between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Concentrations of tCa, iCa, cCa, and pCa varied widely in dogs with CRF Overall, cCa concentration was high, although subpopulations differed in cCa and tCa concentrations. Differences in tCa concentration were primarily attributable to differences in cCa fraction.     

Serial plasma lactate concentrations in 68 puppies aged 4 to 80 days

Objective: To determine a reference range for venous blood lactate concentrations in healthy neonatal dogs. Design: A prospective cohort study. Setting: All work was conducted at the College of Veterinary Medicine, Texas A&M University. Animals: Clinically healthy dogs: 68 puppies and 30 adults. Measurements and main results: A blood sample was collected from each puppy into lithium heparin via jugular venipuncture at 4, 10, 16, 28, 70, and 80 days of age. A single venous sample was collected from each adult dog. Lactate concentration in each sample was measured immediately using an automated analyzer. Two hundred seventy‐seven blood samples were analyzed. Blood lactate concentrations of adult dogs were 1.80±0.84 mmol/L (mean±SD). Mean blood lactate concentrations of puppies were significantly higher at 4, 10, 16, and 28 days of age compared with those of adult dogs. The reference range for lactate concentration for puppies at 4 days of age was 1.07–6.59, and for the puppies from 10 to 28 days of age was 0.80–4.60. Conclusions: Assessment of perfusion can be challenging in neonates due to normal physiologic variation and small size. Measurement of lactate is rapid, minimally invasive, and has potential to be a useful marker of perfusion in neonatal dogs. However, lactate concentrations of neonatal dogs in this study were significantly higher than those of adult dogs. Reference ranges for venous lactate concentrations in adult dogs should not be used for puppies younger than 70 days of age.     

Serum triglyceride concentration in dogs with epilepsy treated with phenobarbital or with phenobarbital and bromide

OBJECTIVE: To compare serum triglyceride concentrations obtained after food had been withheld (i.e., fasting concentrations) in dogs with epilepsy that had been treated long term (> or = 3 months) with phenobarbital or with phenobarbital and potassium bromide with concentrations in healthy control dogs. DESIGN: Cross-sectional study. ANIMALS: 57 epileptic dogs that had been treated with phenobarbital (n=28) or with phenobarbital and bromide (29) and 57 healthy, untreated control dogs matched on the basis of age, breed, sex, neuter status, and body condition score. PROCEDURES: Blood samples were collected after food had been withheld for at least 12 hours, and serum biochemical and lipid concentrations were determined. Oral fat tolerance tests were performed in 15 control dogs and 9 dogs with epilepsy treated with phenobarbital alone. RESULTS: 19 of the 57 (33%) epileptic dogs had fasting serum triglyceride concentrations greater than the upper reference limit. Nine (16%) dogs had a history of pancreatitis, and 5 of the 9 had high fasting serum triglyceride concentrations at the time of the study. A significant relationship was found between body condition score and fasting serum triglyceride concentration in all dogs, but serum triglyceride concentration was not significantly associated with phenobarbital dosage or serum phenobarbital concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that dogs treated long term with phenobarbital or with phenobarbital and bromide may develop hypertriglyceridemia. Fasting serum triglyceride concentration should be periodically monitored in dogs treated with phenobarbital because hypertriglyceridemia is a risk factor for pancreatitis.     

Serum α‐1‐acid glycoprotein concentration in clinically healthy puppies and adult dogs and in dogs with various diseases

Background: α‐1‐acid glycoprotein (AGP) is an acute‐phase protein and a serum marker of inflammation and neoplasia in humans. AGP concentrations in diseased dogs and the potential effects of age, breed, and sex have not been elucidated. Objective: The purpose of this study was to examine differences in AGP concentration based on age, sex, and breed in a large population of clinically healthy dogs and to compare AGP concentrations in dogs with various diseases. Methods: Serum was obtained from clinically healthy puppies (n=74) and adults (n=172) of both sexes, and included mongrels (n=205) and Beagles (n=41). Serum also was obtained from 192 dogs with various diseases, including 8 with pyometra that were sampled before, and 1, 2, 3, and 10 days after surgery. AGP concentration was measured by single radial immunodiffusion. Statistical comparisons were made among age, sex, breed, and disease groups. Results: Serum AGP in healthy adult mongrels was 364±106 mg/L (reference interval, 152–576 mg/L). AGP was lowest in newborns (n=11, 122±54 mg/L) and gradually increased to adult levels by 3 months of age. Median AGP concentration was highest in dogs with parvovirus (n=17, 2100 mg/L), distemper (n=7, 1250 mg/L), and pyometra (n=18, 2480 mg/L) and was also significantly higher in dogs with acute filariasis, renal failure, urolithiasis, pancreatitis, hepatitis, trauma, hyperadrenocorticism, and immune‐mediated hemolytic anemia. Dogs with acute filariasis and acute hepatopathy had significantly higher AGP concentrations than dogs with chronic filariasis and chronic hepatopathy. Serum AGP concentration decreased gradually following surgery for pyometra but remained increased after 10 days (896±175 mg/L). Conclusions: Because of significantly lower AGP in puppies, the age of dogs should be considered when using AGP as a marker of disease. Serum AGP may be a useful marker of inflammatory disease in dogs and may help differentiate acute and chronic stages of disease.     

Serum 17-alpha-hydroxyprogesterone and corticosterone concentrations in dogs with nonadrenal neoplasia and dogs with suspected hyperadrenocorticism

OBJECTIVE: To assess serum 17-alpha-hydroxyprogesterone (17OHP) and corticosterone concentrations in dogs with nonadrenal neoplasia and dogs being screened for hyperadrenocorticism. DESIGN: Prospective study. ANIMALS: 16 clinically normal dogs, 35 dogs with nonadrenal neoplasia, and 127 dogs with suspected hyperadrenocorticism. PROCEDURE: ACTH stimulation tests were performed in all dogs. Baseline serum cortisol and corticosterone concentrations were measured in the healthy dogs; baseline serum cortisol concentration and ACTH-stimulated cortisol, corticosterone, and 17OHP concentrations were measured in all dogs. Endogenous plasma ACTH concentration was also measured before administration of ACTH in dogs with neoplasia. RESULTS: In 35 dogs with neoplasia, 31.4% had high serum 17OHP concentration and 22.9% had high serum corticosterone concentration. Of the 127 dogs with suspected hyperadrenocorticism, 59 (46.5%) had high ACTH-stimulated cortisol concentrations; of those, 42 of 59 (71.2%) and 32 of 53 (60.4%) had high serum 17OHP and corticosterone concentrations, respectively. Of dogs with serum cortisol concentration within reference range after ACTH administration, 9 of 68 (13.2%) and 7 of 67 (10.4%) had high serum 17OHP and corticosterone concentrations, respectively. In the dogs with neoplasia and dogs suspected of having hyperadrenocorticism, post-ACTH serum hormone concentrations were significantly correlated. CONCLUSIONS AND CLINICAL RELEVANCE: Serum concentrations of 17OHP or corticosterone after administration of ACTH may be high in dogs with nonadrenal neoplasia and no evidence of hyperadrenocorticism. Changes in serum 17OHP or corticosterone concentrations after administration of ACTH are proportionate with changes in cortisol concentration.     

Diagnostic and prognostic value of endothelin-1 plasma concentrations in dogs with heart and respiratory disorders

The endothelin-1 (ET-1) plasma concentration was measured in dogs with spontaneous cardiac or respiratory diseases. Plasma samples were obtained from 76 healthy control dogs and 73 dogs, of which 58 were suffering from heart disease and 15 were suffering from respiratory disease. Dogs were evaluated using echocardiography, thoracic radiography, biochemical evaluation and a radioimmunoassay for ET-1. ET-1 plasma concentrations were significantly higher in dogs with spontaneous cardiac or respiratory diseases (mean [se] 5.3 [0.3] and 5.3 [0.6] pg/ml, respectively) than in healthy dogs (1.9 [0.1] pg/ml) (P<0.0001). ET-1 plasma concentrations increased with the class of heart failure (International Small Animal Cardiac Health Council classification) (P<0.0001) and with the severity of pulmonary disorders. ET-1 plasma concentrations were positively correlated with the extent of systolic pulmonary hypertension measured by Doppler echocardiography (P<0.05; r=0.75) and with the clinical outcome of dogs with respiratory disease. Evaluation of the ET-1 plasma concentration allowed differentiation between heart and respiratory disorders in dogs exhibiting clinical signs at exercise, but not in patients exhibiting clinical signs at rest.     

Nitric oxide metabolite production in the cranial cruciate ligament, synovial membrane, and articular cartilage of dogs with cranial cruciate ligament rupture

OBJECTIVE: To measure concentrations of nitric oxide metabolites (nitrite-nitrate [NOt]) in cartilage, synovial membrane, and cranial cruciate ligament (CCL) in dogs and evaluate associations with osteoarthritis in dogs with CCL rupture. ANIMALS: 46 dogs with CCL rupture and 54 control dogs without joint disease. PROCEDURE: Tissue specimens for histologic examination and explant culture were harvested during surgery in the CCL group or immediately after euthanasia in the control group; NOt concentrations were measured in supernatant of explant cultures and compared among dogs with various degrees of osteoarthritis and between dogs with and without CCL rupture. RESULTS: Osteoarthritic cartilage had significantly higher NOt concentration (1,171.6 nmol/g) than did healthy cartilage (491.0 nmol/g); NOt concentration was associated with severity of macroscopic and microscopic lesions. Synovial membrane NOt concentration did not differ between dogs with and without CCL rupture. Ruptured CCL produced less NOt than did intact ligaments. In control dogs, NOt concentrations were similar for intact ligaments (568.1 nmol/g) and articular cartilage (491.0 nmol/g). Synthesis of NOt was inhibited substantially by coincubation with inhibitors. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that NOt in canine joint tissues originates from the inducible nitric oxide synthase pathway. Nitric oxide metabolite production in cartilage was greater in dogs with osteoarthritis than in healthy dogs and was associated with lesion severity, suggesting that nitric oxide inhibitors may be considered as a treatment for osteoarthritis. The CCL produces substantial concentrations of NOt; the importance of this finding is unknown.     

Effect of trilostane on serum concentrations of aldosterone, cortisol, and potassium in dogs with pituitary-dependent hyperadrenocorticism

OBJECTIVE: To evaluate the effect of trilostane on serum concentrations of aldosterone, cortisol, and potassium in dogs with pituitary-dependent hyperadrenocorticism (PDH), compare the degree of reduction of aldosterone with that of cortisol, and compare aldosterone concentrations of healthy dogs with those of dogs with PDH. ANIMALS: 17 dogs with PDH and 12 healthy dogs. PROCEDURE: For dogs with PDH, the initial dose of trilostane was selected in accordance with body weight. A CBC count, serum biochemical analyses, and ACTH stimulation tests were performed in each dog. Dogs were evaluated 1, 3 to 4, 6 to 8, and 10 to 12 weeks after initiation of treatment. Healthy dogs were evaluated only once. RESULTS: Serum aldosterone concentrations before ACTH stimulation did not change significantly after initiation of treatment with trilostane. At each evaluation after initiation of treatment, serum aldosterone concentrations after ACTH stimulation were significantly lower than corresponding concentrations before initiation of treatment. The overall effect of trilostane on serum aldosterone concentration was less pronounced than the effect on serum cortisol concentration. Median potassium concentrations increased slightly after initiation of treatment with trilostane. Dogs with PDH had significantly higher serum aldo sterone concentrations before and after ACTH stimulation than healthy dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with trilostane resulted in a reduction in serum cortisol and aldosterone concentrations in dogs with PDH, although the decrease for serum aldosterone concentration was smaller than that for serum cortisol concentration. There was no correlation between serum concentrations of aldosterone and potassium during treatment.     

D-dimer concentrations in healthy dogs and dogs with disseminated intravascular coagulation

OBJECTIVE: To determine sensitivity and specificity of assays of D-dimer concentrations in dogs with disseminated intravascular coagulation (DIC) and healthy dogs and to compare these results with those of serum and plasma fibrin-fibrinogen degradation product (FDP) assays. ANIMALS: 20 dogs with DIC and 30 healthy dogs. PROCEDURE: Semi-quantitative and quantitative D-dimer concentrations were determined by use of latex-agglutination and immunoturbidometry, respectively. Fibrin-fibrinogen degradation products were measured by use of latex-agglutination. A reference range for the immunoturbidometric D-dimer concentration assay was established; sensitivity and specificity of the assay were determined at 2 cutoff concentrations (0.30 microg/ml and 0.39 microg/ml). RESULTS: Reference range for the immunoturbidometric D-dimer concentration assay was 0.08 to 0.39 microg/ml; median concentrations were significantly higher in dogs with DIC than in healthy dogs. Latex-agglutination D-dimer and serum and plasma FDP assays had similar sensitivity (85 to 100%) and specificity (90 to 100%); the immunoturbidometric assay had lower specificity (77%) at the 0.30 microg/ml cutoff and lower sensitivity (65%) at the 0.39 microg/ml cutoff. Sensitivity or specificity of the latex-agglutination D-dimer assay was not significantly improved when interpreted in series or parallel with FDP assays. CONCLUSIONS AND CLINICAL RELEVANCE: Measurement of D-dimer concentrations by latex-agglutination appears to be a sensitive and specific ancillary test for DIC in dogs. Specificity of D-dimer concentrations in dogs with systemic disease other than DIC has not been determined, therefore FDP and D-dimer assays should be performed concurrently as supportive tests for the diagnosis of DIC in dogs.     

Methylation of free-floating deoxyribonucleic acid fragments in the bronchoalveolar lavage fluid of dogs with chronic bronchitis exposed to environmental tobacco smoke

Background

The etiology of canine chronic bronchitis (CB) is not completely understood, although exposure to environmental tobacco smoke (ETS) affects the airway inflammatory responses in some dogs with CB. The mechanism by which this occurs is unknown.

Findings

We investigated the concentrations and methylation rates of free-floating DNA fragments in bronchoalveolar lavage fluid (BALF) from dogs with chronic bronchitis. Based on serum cotinine levels, dogs with CB were divided into 2 groups: dogs that either had or had not been exposed to ETS. Our results demonstrated that the total nucleated cell and macrophage numbers increased in BALF of ETS-exposed dogs with CB. There were no significant differences in DNA concentrations and methylation rates in BALF between the 2 groups. However, 3 out of 8 dogs exposed to ETS had high DNA methylation rates in their BALF samples.

Conclusion

Our results suggest that ETS exposure leads to epigenetic modifications of cellular components in BALF in dogs diagnosed with CB.