Pharmacokinetics of tildipirosin in beagle dogs

The objective of this study was to investigate the pharmacokinetic profile of tildipirosin (TD) in 24 beagle dogs following intravenous (i.v.) and intramuscular (i.m.) administration, respectively, at 2, 4, and 6 mg/kg. Plasma samples at certain time points (0–14 days) were collected, and the concentrations of drug were quantified by UPLC‐MS/MS. Plasma concentration–time data and relevant parameters were described by noncompartmental through WinNonlin 6.4 software. After single i.m. injection at 2, 4, and 6 mg/kg body weight, mean maximum concentration (C_max) was 412.73 ± 76.01, 1,051 ± 323, and 1,061 ± 352 ng/ml, respectively. Mean time to reach C_max was 0.36 ± 0.2, 0.08 ± 0.00, and 0.13 ± 0.07 hr after i.m. injection at 2, 4, and 6 mg/kg, respectively. The mean value of T_1/2λz for i.m. administration at doses of 2, 4, and 6 mg/kg was 71.39 ± 28.42, 91 .33 ± 50.02, and 96.43 ± 45.02 hr, respectively. The mean residence times were 63.81 ± 10.96, 35.83 ± 15.13, and 38.18 ± 16.77 hr for doses of 2, 4, and 6 mg/kg, respectively. These pharmacokinetic characteristics after i.m. administration indicated that TD could be rapidly distributed into tissues on account of the high lipid solubility and then released into plasma. In addition, the absolute bioavailability of 2 mg/kg after i.m. injection was 112%. No adverse effects were observed after i.v. and i.m. administration.     

Mineralisation in kidney and stomach of beagle dogs

Histological examination of 753 Beagle dogs showed renal foci of calcification in 27.9% of males and 21.5% of females. In contrast, stomach calcification was observed in 6.2% of males and 5.2% of females examined. It is suggested that the focal calcification seen in both organs was possibly of dietary origin and may have been related to the phosphate content.     

Salivary secretory IgA concentrations in beagle dogs

The normal concentrations of salivary secretory IgA (sIgA) were examined, and the response of sIgA to acute stress was evaluated in dogs. Ten clinically healthy beagle dogs familiarized with the method of saliva sampling were used. During the non-stress period, saliva samples were collected between 0800 hr and 1700 hr at 1-hr intervals for 7 consecutive days and analyzed for sIgA concentration. After a 1-day control period, a noise stressor was presented for 15 min between 0845 hr and 0900 hr on 2 consecutive days. Saliva was collected at pre-stress, immediately after, 30 min after and 60 min after the stress. The average sIgA concentration over the 2-day period was compared with the control value. Environmental stimuli were restricted. During the non-stress period, significant variations were observed during the diurnal pattern, in which sIgA increased in the morning and then decreased; and the day-to-day variations were significant except at 0800 hr and 0900 hr. During the stress experiments, the sIgA concentration decreased significantly, immediately after and 30 min after the noise stress, and then increased to the same level as the control value by 60 min after the stress. When estimating the effectiveness of salivary sIgA as a marker of stress in dogs, the appropriate time for saliva sampling appears to be in the morning. Salivary sIgA was deemed potentially useful as a marker of stress in dogs.     

Effect of skin graft preparation and graft survival on the secondary contraction of full-thickness skin grafts in dogs

The effects of 4 skin grafting techniques and graft survival on the secondary contraction of full-thickness skin grafts were evaluated. A total of 48 skin grafts were done on 12 dogs, with 2 skin grafts placed on both sides of the thorax of each dog. The grafting techniques included the sheet graft, sheet graft with continuous low-level suction provided by a butterfly catheter and evacuated glass tube, pie-crust graft, and nonexpanded mesh graft. Graft viability was assessed by visual inspection 10 days after surgical operation. Thirty skin grafts (64%) had a viability of 90% or greater. The final area of these grafts ranged from 73% to 119% of the original area. The secondary graft contraction followed a similar pattern for all graft types. During the first 10 days after surgical operation, the grafts contracted to 83% of their original area. Enlargement of the grafts began between 10 and 21 days after surgical operation. By 12 weeks, the grafts had attained a mean value of 96% of the original area. A significant difference in final area was not observed among graft types. Grafts with a high percentage of viability generally contracted less than those with larger areas of necrosis, but statistical relationship between viability and degree of contraction could not be proven. The results of the present study indicate that full-thickness skin grafts may be successfully done in dogs and that the grafts can be expected to undergo minimal postoperative contraction when graft survival is nearly complete.     

Plasma lactate measurements in healthy beagle dogs

Plasma lactate concentrations were determined in venous blood samples collected from 60 healthy Beagles aged 5 to 9 months. The range of values (0.42 to 3.58 mmol/L) obtained with an enzymatic method in the present study was similar to values reported in smaller studies with the colorimetric procedures.     

美洛昔康片剂在比格犬内的药代动力学及生物利用度研究

本研究以0.1 mg/kg体重的剂量研究美洛昔康片在比格犬中的药代动力学和生物利用度。HPLC分析血浆中的药物浓度,WinNonlin 6.4非房室模型计算药动学参数。比格犬内服美洛昔康片后测得0~48 h美洛昔康的T1/2、Cmax、Tmax和AUC0-t分别为14.55 ± 2.18 h、296.16 ± 74.15 ng·mL-1、6.0 ± 0.00 h和6356.79 ± 1089.78 ng·h·mL-1;比格犬静脉注射美洛昔康溶液后,测得0~48 h美洛昔康的T1/2和AUC0-t分别为11.54 ± 4.18 h和5510.68 ± 1075.29 ng·h·mL-1。内服美洛昔康片剂的绝对生物利用度为115.35%。美洛昔康片在比格犬体内消除速率较慢,消除半衰期较长,在体内滞留时间较长,绝对生物利用度高,药物在体内作用时间较长等药动学特征。     

Idiopathic extramural coronary arteritis in beagle and mongrel dogs

Hearts obtained from 119 toxicological experiments on dogs during a 21-year period (1965-1986) were evaluated histologically to determine the incidence and characteristics of focal microscopic inflammatory lesions of the extramural coronary arteries. Lesions were encountered in 23% of 119 experiments. The average overall incidence was 2.3% of 1,905 control and chemically treated male and female beagle hearts (3.1% of male and 1.3% of female control beagles, and 1.8% of male and 2.8% of female treated beagles). Lesions were seen in 4.7% of 127 random-source mongrel dogs. Histologically, lesions were characterized by adventitial infiltrates of mononuclear cells, areas of mural necrosis, and inflammatory cell infiltrates in both mural and subendothelial regions. In the latter region, fibrosis developed separating the intima from the internal elastic membrane. Lesions occurred in the right and left coronary arteries and in the dorsal, circumflex, and ventral descending branches of the left coronary artery. Vascular lesions were not present in the intramural coronary vessels or in vessels of other organs in affected animals. More extensive sampling of the extramural coronary arteries revealed an incidence of 5-9%. The lesion of focal extramural coronary arteritis was idiopathic, and not a manifestation of the polyarteritis syndrome of dogs.     

Oleic acid-associated bronchiolitis obliterans-organizing pneumonia in beagle dogs

Accidental intra-airway exposure of dogs with pure oleic acid produced bronchiolitis obliterans and bronchopneumonia. Pulmonary changes included multifocal to coalescing necrosis of bronchioles and adjacent alveoli, hemorrhage, inflammation, and exudation of fibrin. Hyperplasia of bronchiolar and alveolar epithelial cells and proliferation of loose fibrovascular connective tissue formed polyps or plugs of variable size and shape. Polyps in the airways primarily consisted of fibroblasts with loose or myxoid stroma and were variably covered with attenuated epithelial cells. Some polyps had prominent vasculature, mixed inflammatory cell infiltration, and/or necrosis. Polyps or plugs variably effaced bronchioles and adjacent alveoli. The changes closely resembled human bronchiolitis obliterans-organizing pneumonia (BOOP). Controlled intra-airway delivery of oleic acid in dogs may be a potential animal model of obstructive pulmonary diseases such as BOOP or bronchiolitis obliterans.     

Mammary tumors in a colony of beagle dogs

In a lifetime study, female beagle dogs in a closed colony were administered 226radium and 90strontium. An unirradiated control group was included in the study. A total of 223 of 356 dogs at risk developed 1,112 mammary proliferative growths (hyperplastic nodules and neoplasms). There was no correlation between occurrence and types of lesions in radiation and control groups. The age range for first occurrence of lesions was 10.4 to 13.9 years; hyperplastic nodule and benign mixed tumor occurred 1 to 2 years earlier than other lesions. A multiplicity of growths of similar or different morphological type were common throughout the lifetime of the dog. The female beagles, collectively, developed 244 hyperplastic nodules, 78 adenomas, 694 benign mixed tumors, 78 carcinomas, 14 malignant mixed tumors, and four myoepitheliomas. Proliferations occurred with increasing frequency from the cranial to caudal mammary glands. Metastasis was found in 77% of the dogs with carcinoma. The median time from diagnosis to metastasis was 10 months, but was shorter in dogs with infiltrative carcinoma.     

Thyroid neoplasms in a colony of beagle dogs

The histologic, clinicopathologic, and epidemiologic features of spontaneous thyroid neoplasms were evaluated in a control population of Beagle dogs. The mean age of thyroid tumor-bearing dogs (16.2 years) as significantly higher than non-tumor-bearing dogs (13.6 years). Thirteen benign and 18 malignant tumors were identified, with the incidence of both tumors increasing rapidly near the mean age of 16.2 years for tumor-bearing dogs. The age-specific incidence of tumors was 1.1% per year at 8 to 12 years, increasing to 4.0% per year by 12 to 15 years and 67% over 17 years of age. Numbers of malignant tumors were greater than benign tumors at an earlier age. Approximately 44% of the malignant tumors metastasized but only 22% resulted in death of the dog. There was no difference in tumor incidence when compared according to sex, if total tumor numbers were considered or if tumors were separated into benign and malignant categories. The age at death of tumor-bearing dogs was not increased significantly by the surgical resection of the thyroid tumors. Of dogs with thyroid tumors, 15% had clinical diagnoses of hypothyroidism, and no dogs with thyroid tumors had diagnoses of hyperthyroidism.     

Intradermal and serological testing for mites in healthy beagle dogs

Background – Intradermal testing (IDT) is widely used in veterinary medicine to select allergens for immunotherapy. The recommended concentration for mites is 250 protein nitrogen units (PNU)/mL. It is not known whether healthy dogs responding to this concentration have asymptomatic sensitization or irritation. Furthermore, interbatch and intersupplier variability of allergens has not been fully addressed. Hypothesis/Objectives – The incidence of positive IDTs in healthy beagles was recorded and the value of combining these results with serology to differentiate between asymptomatic sensitization and irritancy evaluated. Additionally, the interbatch and intersupplier variability of allergens was assessed. Animals – Seventeen healthy laboratory beagles with no history or clinical signs of canine atopic dermatitis were used. Methods – Intradermal tests were performed with four mite allergens from two suppliers (varying batches). An initial IDT at 250 PNU/mL was used to determine whether decreasing or increasing test concentrations were used in the subsequent titration IDTs. Additionally, two IgE ELISA tests from different manufacturers were performed. Results – Seven of 17 dogs showed IDT reactions at 250 PNU/mL. There were highly significant allergen interbatch and significant intersupplier correlations and agreement. The associations between the IDT reactions and the IgE serologies statistically identified two groups of dogs: one with positive serology and IDT reactions at 250 PNU/mL; and another with negative serology and IDT reactions. Conclusions and clinical importance – Our results suggest that dogs that have IDT reactions and positive serology are asymptomatically sensitized, while dogs that react at higher allergen concentrations, but have negative serology, do so as a result of irritant reactions.     

Disposition of propofol after medetomidine premedication in beagle dogs

Propofol by infusion was administered to 6 adult beagle dogs on 2 separate occasions. The dogs received either no premedication or 20 μg/kg im medetomidine 15 min before induction of anaesthesia, with propofol given at 7 mg/kg/min to permit tracheal intubation. After tracheal intubation the infusion rate was maintained for 120 min at 0.4 mg/kg/min in the non-premedicated, and 0.2 mg/kg/min in the premedicated dogs. The latter group received atipamezole 50 μg/kg im immediately at the end of the infusion. After induction of anaesthesia, a 7F balloon catheter designed for thermal dilution measurement of cardiac output was inserted via the right jugular vein. Blood propofol concentrations were measured by HPLC with fluorescence detection and kinetic variables calculated using non-compartmental moment analysis. The induction dose of propofol was 7.00 (sem 0.55) mg/kg in non-premedicated compared with 3.09 (0.25) mg/kg in premedicated dogs. There were differences in systemic clearance and mean residence time (MRT_iv); 47.5 (6.2) ml/kg/min vs 29.0 (4.4) ml/kg/min (non-premedicated vs premedicated) and 132.3 (5.2) min vs 152.4 (3.1) min (P < 0.02 and P < 0.001, respectively). Cardiorespiratory effects were similar in the 2 groups although heart rate was lower in the premedicated dogs. Venous admixture was high (20–45%) but similar in the 2 groups.     

Artificial insemination of frozen epididymal sperm in beagle dogs

Freeze-storage of epididymal sperm is an important technique for the preservation of gametes in animals, including those becoming extinct. We froze canine sperm recovered from the cauda epididymis and investigated the fertility. The qualities of sperm from the cauda epididymis before freezing were: mean sperm motility, 89.4 +/- 1.6 (SE) %; sperm viability, 89.1 +/- 1.1%; and these were significantly higher than those of sperm from the caput-corpus epididymis (P<0.01, P<0.05). The number of sperm recovered from both cauda epididymides varied among animals: 6.3-122.3 x 10(7), mean 61.5 +/- 10.0 x 10(7). Freezing was used only for sperm recovered from the cauda epididymis. The sperm motility and viability after thawing were 19.5 +/- 2.5% and 53.1 +/- 3.3%, respectively. These were slightly lower than those of frozen-thawed ejaculated sperm, but the differences were not significant. When 2 x 10(8), 3 x 10(8), or 4 x 10 (8) sperm were inseminated in the unilateral uterus, only one animal inseminated with 3 x 10(8) sperm was fertilized (1/16, 6.3%). When 1 x 10(8) sperm were inseminated in the bilateral uterine tubes, one of six animals (16.7%) was fertilized. Therefore, although the qualities of epididymal sperm after thawing were similar to those of ejaculated sperm, the conception rate obtained with frozen-thawed epididymal sperm was low in beagle dogs. It is necessary to investigate the differences in damage between epididymal sperm after thawing and ejaculated sperm and to develop a method for improving the conception rate.     

Effects of orchidectomy on bone metabolism in beagle dogs

The effects of orchidectomy on bone metabolism in male beagle dogs were examined using twelve 2-year-old dogs that were orchidectomized. The dogs' bilateral iliac bones, double-labeled with tetracycline and calcein for the histomorphometry, were obtained from three dogs prior to orchidectomy and at 3, 6, 9, and 12 months afterwards. The serum biochemical constituents related to bone metabolism were examined before and every month after orchidectomy. Between 1 and 6 months after orchidectomy, the value of serum testosterone decreased (1 month), while the levels of parathyroid hormone, calcitonin, total calcium, osteocalcin, and alkaline phosphatase activity increased significantly, indicating a high bone turnover. The mean trabecular thickness and the fraction of labeled osteoid surface decreased significantly 3 months after orchidectomy, but other histomorphometric parameters were unchanged. In the period 7-12 months after orchidectomy, the parathyroid hormone level increased ever and above that of the first 6-month period, while the levels of calcitonin, osteocalcin, alkaline phosphatase activity, and phosphorus decreased. The bone volume, mean trabecular thickness, and the fraction of labeled trabecular surface decreased significantly compared with the pre-orchidectomy values. These findings indicate an imbalance in bone metabolism (i.e. bone resorption > bone formation). These results indicate that a loss of bone volume accompanied the fall in sex hormone levels following orchidectomy and suggest that the orchidectomized dog is available as an animal model for studying osteoporosis caused by hypogonadism and the decline of sex functions in men.