Salivary Cortisol Concentrations in Healthy Dogs and Dogs with Hypercortisolism

Background: Measurement of salivary cortisol is a useful diagnostic test for hypercortisolism (HC) in humans. Objectives: To determine whether measurement of salivary cortisol concentration is a practical alternative to plasma cortisol to diagnose HC, to validate the use of salivary cortisol, and to examine the effect of time of day and sampling location on salivary cortisol. Animals: Thirty healthy dogs and 6 dogs with HC. Methods: Prospective, observational clinical trial including healthy volunteer dogs and dogs newly diagnosed with HC. Salivary and plasma cortisol concentrations were measured with an immunoassay analyzer. Intra‐ and interassay variability, linearity, and correlation between salivary and plasma cortisol concentrations were determined. Results: The required 300 μL of saliva could not be obtained in 88/326 samples from healthy dogs and in 15/30 samples from dogs with HC. The intra‐assay variability for measurement of salivary cortisol was 5–17.7%, the interassay variability 8.5 and 17.3%, and the observed to expected ratio 89–125%. The correlation (r) between salivary and plasma cortisol was 0.98. The time of day and location of collection did not affect salivary cortisol concentrations. Dogs with HC had significantly higher salivary cortisol values than healthy dogs (10.2 ± 7.3 nmol/L versus 1.54 ± 0.97 nmol/L; P < .001). Conclusions and Clinical Importance: The ROCHE Elecsys immunoassay analyzer correctly measured salivary cortisol in dogs. However, a broad clinical application of the method seems limited, because of the large sample volume required.     

恩诺沙星混悬液在猪体内的药动学及生物利用度

本文比较了恩诺沙星混悬液和恩诺沙星溶液在猪体内的药动学特征和生物利用度。选用 7头健康猪按拉丁方设计进行静注、肌注恩诺沙星溶液和肌注恩诺沙星混悬液在猪体内的药物动力学研究。 3种给药方法的剂量均为 10mg/kg。猪静注给药的药时数据符合二室开放模型 ,主要药动学参数为 :t1/ 2α0 6 4± 0 15h ,t1/ 2 β9 0 6± 2 47h ,Vd(area) 4 40± 0 88L/kg ,ClB0 35± 0 0 6L·kg-1·h-1,AUC2 9 85± 4 11L·kg-1·h。猪肌注恩诺沙星溶液和恩诺沙星混悬液的药时数据符合一级吸收一室模型 ,其主要药动学参数分别为t1/ 2ka0 2 4± 0 10h和 1 2 5± 1 0 9h(P <0 0 5 ) ;t1/ 2ke8 90± 2 0 2h和 18 95± 4 5 5h(P <0 0 1) ;Tmax1 2 5± 0 41h和 5 14± 2 95h(P <0 0 1) ;Cmax1 5 4± 0 2 5 μg/ml和 0 87± 0 2 1μg/ml;AUC2 1 49± 4 94mg·L-1·h和 2 8 97± 10 80mg·L-1·h ;F72 0 %±17 4%和 97 7%± 35 0 %。比较肌注恩诺沙星混悬液和恩诺沙星溶液的主要药动学参数 ,二者有显著差异 ,前者的t1/ 2ka、Tmax、t1/ 2ke和Cmax分别为后者的 5 2、4 1、2 1和 0 6倍。这些差异说明恩诺沙星混悬液肌注后吸收缓慢 ,消除半衰期延长 ,临床应用 48h给药 1次仍能维持对常见病原菌的有效血药     

Infrared Thermography in Dogs with Mammary Tumors and Healthy Dogs

Background

Infrared thermography is a painless, noninvasive, nonionizing diagnostic imaging exam used in human medicine as an auxiliary tool for breast cancer diagnosis in women.

Hypothesis/Objectives

Define thermographic mean temperatures of healthy mammary glands and compare these temperatures with those of mammary glands with tumors in dogs.

Animals

Fifty client‐owned female dogs were evaluated, including 20 with histopathologically confirmed mammary tumor and 30 clinically healthy (control).

Methods

A randomized study using infrared thermography analyzed each mammary gland of the animals from the control group and mammary glands with tumors from the tumor group, then the thermographic temperatures obtained were compared. Thermographic exam was performed in a temperature‐controlled room with a cooled thermographic camera—Flir E‐40 (Flir Systems^®)

Results

There was significantly a higher temperature in the caudal abdominal and inguinal mammary glands than the other glands in the healthy group (P < .05). Dogs with mammary tumors had significantly higher thermographic temperature compared with unaffected glands regardless of the tumor size and the location (P < .05).

Conclusions and clinical importance

The technique seems to be able to assess for the presence of neoplasia within the mammary tissue in bitches. Further investigation is necessary to determine the impact of this technique when adopted clinically.     

Effects of Prednisone on Blood Lactate Concentrations in Healthy Dogs

Background: Glucocorticoids affect carbohydrate and lactate metabolism.
Hypothesis: Administration of prednisone to healthy dogs will result in clinically relevant hyperlactatemia.
Animals: Twelve healthy adult Beagle dogs.
Methods: Prospective, controlled experimental study. Twelve healthy adult Beagles were divided into 2 groups (3 of each sex per group). One group served as control. The other group received 2 treatments: low, 1 mg/kg prednisone PO q24h for 2 weeks; high, 4 mg/kg prednisone PO q24h for 2 weeks. A washout period of 6 weeks separated the treatments. Blood samples were drawn for whole blood lactate measurement on day (D) 0, D4, and D14 and measured in duplicate.
Results: Compared with the control group, low and high groups had significantly higher blood lactate concentrations at D4 and D14. There was no difference at D0. There was no effect of time within the control group. In the low and high groups, blood lactate concentration was increased at D4 and D14 versus D0. Blood lactate concentration was greater in the high group than the low group at D14 only.
Conclusions and Clinical Importance: Dogs treated with prednisone experience statistically significant increases in blood lactate concentrations, which can result in type B hyperlactatemia. In such cases, improving tissue perfusion, treatment for the commonest form of hyperlactatemia (type A) would be unnecessary.     

Effect of Chronic Administration of Phenobarbital,or Bromide,on Pharmacokinetics of Levetiracetam in Dogs with Epilepsy

Background

Levetiracetam (LEV) is a common add‐on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs.

Hypothesis/Objectives

To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs.

Animals

Eighteen client‐owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB–BR group, n = 6).

Methods

Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high‐pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area‐under‐the‐curve (AUC) calculated to the last measured time point.

Results

Compared to the PB and PB–BR groups, the BR group had significantly higher peak concentration (C _max) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*μg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028).

Conclusions and Clinical Importance

Concurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add‐on treatment with phenobarbital in dogs.     

Urinary Markers in Healthy Young and Aged Dogs and Dogs with Chronic Kidney Disease

Background: Blood urea nitrogen and serum creatinine concentrations only detect a decrease of >75% of renal functional mass. Therefore, there is a need for markers that allow early detection and localization of renal damage.
Hypothesis: Urinary albumin (uALB), C-reactive protein (uCRP), retinol binding protein (uRBP), and N -acetyl-β- d -glucosaminidase (uNAG) concentrations are increased in dogs with chronic kidney disease (CKD) compared with healthy controls and in healthy older dogs compared with young dogs.
Animals: Ten dogs with CKD, 10 healthy young dogs (age 1–3 years), and 10 healthy older dogs (age > 7 years) without clinically relevant abnormalities on physical examination, hematology, biochemistry, and urinalysis.
Methods: Urinary markers were determined using an ELISA (uALB, uCRP, and uRBP) or a colorimetric test (uNAG). Results were related to urinary creatinine (c). The fixed effects model or the Wilcoxon rank sum test were used to compare the different groups of dogs.
Results: uALB/c, uRBP/c, and uNAG/c were significantly higher in CKD dogs than in healthy dogs. No significant difference was found for uCRP, which was not detectable in the healthy dogs and only in 3 of the CKD dogs. Between the healthy young and older dogs, no significant difference was detected for any of the markers.
Conclusion: The urinary markers uALB/c, uRBP/c, and uNAG/c were significantly increased in dogs with CKD compared with healthy controls. Additional studies are needed to evaluate the ability of these markers to detect renal disease before the onset of azotemia.     

Microbiologic Evaluation of Gallbladder Bile of Healthy Dogs and Dogs with Iatrogenic Hypercortisolism: A Pilot Study

Background: In people, hypercortisolism (HC) has been associated with acalculous cholecystitis and biliary dyskinesia, which may potentiate ascending biliary infections. In dogs, an association between HC and gallbladder disease recently has been documented, although the role of bacteria remains controversial. Furthermore, there is no information on the gallbladder bile microbial flora in healthy dogs.
Objectives: To investigate the microbial flora in gallbladder bile in healthy dogs, the relationship between iatrogenic hyperadrenocorticism and bactibilia and possible changes in biliary microbial flora after cortisol withdrawal in dogs.
Animals: Six control dogs and 6 dogs treated with hydrocortisone.
Methods: Gallbladder bile obtained by percutaneous ultrasound-guided cholecystocentesis was cultured aerobically and anaerobically and examined cytologically before (d0), during (d28, d56, d84), and after (d28p, d56p, d84p) administration of hydrocortisone (8 mg/kg PO q12h).
Results: In the control group, 2/42 bile cultures yielded bacterial growth ( Enterococcus sp.; Escherichia coli on d0) and 1/42 bile smears had cytological evidence of bacteria (d28). In the HC group, 2/42 bile cultures yielded bacterial growth ( Enterococcus sp. on d28; Bacillus sp. on d28p) and 3/42 bile smears had cytological evidence of bacteria (d84, d84, d28p). All dogs remained healthy throughout the study period (168d).
Conclusions and Clinical Importance: Based on the results of conventional bacterial culture techniques, gallbladder bile of healthy dogs periodically may harbor bacteria, which do not appear to be clinically relevant. A 3-month period of iatrogenic HC was not associated with bactibilia. A higher prevalence of bactibilia may be detected with micromolecular techniques.     

Urinary and Plasma Catecholamines and Metanephrines in Dogs with Pheochromocytoma,Hypercortisolism, Nonadrenal Disease and in Healthy Dogs

Background

Diagnosis of pheochromocytoma (PC) is based on a combination of clinical suspicion, finding an adrenal mass, increased plasma, and urine concentrations of catecholamine metabolites and is finally confirmed with histopathology. In human medicine, it is controversial whether biochemically testing plasma is superior to testing urine.

Objectives

To measure urinary and plasma catecholamines and metanephrines in healthy dogs, dogs with PC, hypercortisolism (HC), and nonadrenal diseases (NAD) and to determine the test with the best diagnostic performance for dogs with PC.

Animals

Seven PC dogs, 10 dogs with HC, 14 dogs with NAD, 10 healthy dogs.

Methods

Prospective diagnostic clinical study. Urine and heparin plasma samples were collected and stored at −80°C before analysis using high‐pressure liquid chromatography (HPLC) coupled to electrochemical detection or tandem mass spectrometry were performed. Urinary variables were expressed as ratios to urinary creatinine concentration.

Results

Dogs with PC had significantly higher urinary normetanephrine and metanephrine : creatinine ratios and significantly higher plasma‐total and free normetanephrine and plasma‐free metanephrine concentrations compared to the 3 other groups. There were no overlapping results of urinary normetanephrine concentrations between PC and all other groups, and only one PC dog with a plasma normetanephrine concentration in the range of the dogs with HC and NAD disease. Performances of total and free plasma variables were similar. Overlap of epinephrine and norepinephrine results between the groups was large with both urine and plasma.

Conclusion and clinical importance

Measurement of normetanephrine is the preferred biochemical test for PC and urine was superior to plasma.     

The Gastroduodenal Effects of Buffered Aspirin, Carprofen, and Etodolac in Healthy Dogs

Twenty-four healthy mixed-breed dogs were divided into 4 groups. Group 1 received a placebo p.o. q12h, group 2 received an average of 16.5 (15.1-17.8) mg/kg buffered aspirin p.o. q12h, group 3 received an average of 2.2 (2.0-2.4) mg/kg carprofen p.o. q12h, and group 4 received an average of 12.8 (11.7-13.8) mg/kg etodolac p.o. q24h (with a placebo in the PM). All treatments continued for 28 consecutive days. Gastroduodenal endoscopy was performed on days -9, 0, 5, 14, and 28. Multiple gastric biopsies were obtained endoscopically on day -9 to determine each dog's Helicobacter infection status. Four regions in the stomach and 1 region in the proximal duodenum were evaluated endoscopically, and each was assigned a score from 1 to 11. Scores for each region then were summed to give a total score for each endoscopic evaluation. Erosions and submucosal hemorrhages were seen in all dogs receiving aspirin. Only minor gastric lesions were observed in the carprofen, etodolac, and control groups. No adverse clinical signs were noted in any dog given any treatment. Median total score on days 0, 5, 14, and 28, respectively, were as follows: group 1: 5.0, 5.0, 5.0, 5.0; group 2: 5.0, 27.0, 26.0, 27.5; group 3: 5.0, 5.0, 6.0, 5.0, group 4: 5.0, 7.0, 5.0, 5.0. There was no significant difference among dogs receiving carprofen, etodolac, or placebo. The administration of carprofen, etodolac, or placebo to healthy dogs resulted in significantly less gastroduodenal lesion development than in dogs receiving buffered aspirin.     

Evaluation of the Cortisol‐to‐ACTH Ratio in Dogs with Hypoadrenocorticism,Dogs with Diseases Mimicking Hypoadrenocorticism and in Healthy Dogs

Background

The adrenocorticotropic hormone (ACTH) stimulation test is the gold standard for diagnosing hypoadrenocorticism (HA) in dogs. However, problems with the availability of synthetic ACTH (tetracosactrin/cosyntropin) and increased costs have prompted the need for alternative methods.

Objectives

To prospectively evaluate the cortisol‐to‐ACTH ratio (CAR) as a screening test for diagnosing canine HA.

Animals

Twenty three dogs with newly diagnosed HA; 79 dogs with diseases mimicking HA; 30 healthy dogs.

Methods

Plasma ACTH and baseline cortisol concentrations were measured before IV administration of 5 μg/kg ACTH in all dogs. CAR was calculated and the diagnostic performance of ACTH, baseline cortisol, CAR and sodium‐to‐potassium ratios (SPRs) was assessed based on receiver operating characteristics (ROC) curves calculating the area under the ROC curve.

Results

The CAR was significantly lower in dogs with HA compared to that in healthy dogs and in those with diseases mimicking HA (P < .0001). There was an overlap between HA dogs and those with HA mimicking diseases, but CAR still was the best parameter for diagnosing HA (ROC AUC 0.998), followed by the ACTH concentration (ROC AUC 0.97), baseline cortisol concentration (ROC AUC 0.96), and SPR (ROC AUC 0.86). With a CAR of >0.01 the diagnostic sensitivity and specificity were 100% and 99%, respectively.

Conclusion and Clinical Importance

Calculation of the CAR is a useful screening test for diagnosing primary HA. As a consequence of the observed overlap between the groups, however, misdiagnosis cannot be completely excluded. Moreover, additional studies are needed to evaluate the diagnostic reliability of CAR in more dogs with secondary HA.     

Comparison of Serum Zinc Levels in Healthy, Systemically Ill and Dermatologically Diseased Dogs

Abstract— Decreased levels of total body zinc can lead to profound effects on both the immune and integumentary systems. Unfortunately, accurate measurements of total body zinc are difficult because the mineral is ubiquitous in the environment and many endogenous and exogenous factors can falsely elevate or depress measurements. In man, various dermatologic and non-dermatologic diseases have been associated with low serum zinc levels. The objective of this study was to analyse by atomic absorption and compare the serum zinc levels of healthy dogs, dogs with non-dermatologic diseases, dogs with allergic skin diseases and dogs with other dermatologic diseases. Using the Student-Newman-Keuls test, no significant differences in the mean serum zinc levels were demonstrated among any of the four groups (P > 0.05). Résumé— Une diminution des taux zinc total dans le corps peut avoir de profondes répercussions sur la réponse immunitaire et les systèmes tégumentaires. Malheureusement, La mesure du taux global de zinc corporel ets difficile car ce miniral est ubiquitaire dans l'environnement et de nombreux facteurs endogènes ou exogènes peuvent élever ou diminuer de façon erronnée les dosages. Chez l'homme, quelques maladies, dermatologiques ou non, ont été associées à des zincémies faibles, objectif de cette étude était d'analyser par absorptio atomique et comparer les zincémies plasmatiques de chiens sains, atteints de maladies générales et de maladies cutanées. En utilisant le test de Student-Newman-Keuls, aucune difference significative n'a été retrouvée entre les 4 groupes (P > 0.05). Resumen Niveles bajos de zinc pueden conducir a profundos efectos en tanto el sistema inmunitario, como en el integumentario. Desafortunadamente la medida de la cantidad total de zinc en el organismo es compleja debido a la ubicuidad del mineral en el medio ambiente, y a la gran cantidad de factores endógenos y exógenos que pueden producir medidas falsas del mismo. En medicina humana se han asociado varias enfermedades dermatólogicas y sistémicas con bajos niveles de zinc. El objetivo de éste estudio es el análisis por medio del método de absorción atómica y la comparación de los niveles de zinc en el suero de perros sanos, perros con enfermedades de tipo general, perros con enfermedades de piel de tipo alérgico, y perros que presentaban enfermedades cutáneas de tipo no alérgico. Utilizando el test de Student-Newman-Keuls no se encontraron diferencias significativas en la cantidad media de zinc en suero delos cuatro grupos (P > 0.05).     

Cortisol Response in Healthy and Diseased Dogs after Stimulation with a Depot Formulation of Synthetic ACTH

Background

The ACTH stimulation test is used to evaluate the adrenocortical reserve. Recently, the availability of the synthetic ACTH formulation was limited, causing major problems in clinical practice.

Objectives

The objective of this study was to evaluate poststimulation peak cortisol concentrations and the duration of the stimulatory effect of a depot ACTH preparation in dogs.

Animals

Twenty‐two healthy dogs, 10 dogs with suspected hypoadrenocorticism (HA) and 15 dogs with suspected hyperadrenocorticism (HC).

Methods

Prospective study. An ACTH stimulation test using a synthetic depot tetracosactide, administered intramuscularly (5 μg/kg or at least 0.1 mL) was performed. Blood samples for determination of cortisol were taken immediately before and 1, 2, 3, 4, 6, and 24 hours after stimulation.

Results

Peak cortisol concentrations were reached after 2–4 hours in all dogs. Cortisol concentrations 1 hour after stimulation were >9 μg/dL in all healthy dogs and >5 μg/dL in all dogs in which HA was excluded. None of the dogs with HA showed a cortisol‐increase above the detection‐limit of the assay. After 6 hours, cortisol concentrations had decreased in the healthy and HC group and were back to baseline after 24 hours.

Conclusions and Clinical Importance

The depot formulation can be used in place of the short‐acting ACTH to evaluate the adrenocortical reserve. Blood for peak cortisol concentrations should be drawn 3 hours after stimulation in cases in which HC is suspected; in HA‐suspected cases, blood sampling can take place after 1 hour. As the stimulatory effect is gone after 24 hours, interference with other hormonal tests is unlikely after that time.     

恩诺沙星和环丙沙星对金葡菌的抗菌后效应及抗菌后亚抑菌浓度效应

报告了抗菌后效应 (postantibiotic effect,PAE)、抗菌后亚抑菌浓度效应 (postantibiotic sub- MIC effect,PASME)、亚抑菌浓度效应 (sub- MIC effect,SME)研究的方法学和恩诺沙星、环丙沙星对金葡菌抗菌后效应及抗菌后亚抑菌浓度效应的研究结果。试验表明 :2、4MIC的恩诺沙星对金葡菌的 PAE为 1.0 3、1.5 0 h,1/2、1、2、4MIC的环丙沙星的 PAE为 0 .5 1、0 .88、1.47、1.92 h;1/8、1/4、1/2 MIC的恩诺沙星对经 4MIC药物诱导 1h的金葡菌可产生0 .38、1.15、>12 .31h的 PASME,1/8、1/4、1/2 MIC的环丙沙星的 PASME为 2 .6 9、>10 .17、>13.17h;1/8、1/4、1/2 MIC的恩诺沙星和环丙沙星对金葡菌产生的 SME分别为 0 .40、0 .91、>9.44 h和 0 .42、1.14、>9.0 2 h。上述结果说明 ,PAE、PASME和 SME的大小与药物浓度呈正相关 ,且环丙沙星比恩诺沙星对金葡菌有更长的效应     

恩诺沙星在猪体内的生物利用度及药物动力学研究

选用２１头健康杂种猪，随机分为３组，对静注、肌注及内服恩诺沙星（２．５ｍｇ／ｋｇ）的生物利用度和药物动力学进行了研究。用乙腈提取血浆中的药物，反相高效液相色谱法测定血浆中恩诺沙星及其主要代谢产物环丙沙星的浓度。所得血药浓药－时间数据用ＭＣＰＫＰ计算机程序处理。静注给药的药时数据适合二室开放模型，主要药物动力学参数：ｔ１／２ａ０．４８±０．２４ｈ；ｔ１／２ａ３．４５±０．８５ｈ；ｔ１／２Ｋ１０２．０     

Bioavailability and Tolerability of Topical and Oral Diclofenac Sodium Administration in Healthy Ponies

Aiming to characterize the bioavailability and assess the safety of topical and oral treatment of diclofenac sodium in healthy ponies, 18 animals were divided in three groups: one treated with topical (group I, n = 6), the second with oral diclofenac (group II, n = 6) at 2.5 mg/kg for 3 days, and the third group received 2.2 mg/kg oral phenylbutazone (group III, n = 6) also for 3 days to serve as positive control. To evaluate bioavailability, blood samples were collected before and at 0, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 60, 72, 96, 120, and 144 hours after starting treatment. To evaluate diclofenac sodium concentration in the synovial fluid, samples of six ponies (group I, n = 3; group II, n = 3) were collected at 6, 12, and 24 hours after starting the treatment.