Adrenocortical suppression in dogs on daily and alternate-day prednisone administration

Three groups of eight normal dogs each were orally given prednisone at doses of 0.22 mg/kg of body weight/day, 0.55 mg/kg/day, or 1.1 mg/kg on alternate mornings. Four dogs served as nontreated controls. Samples were obtained from members of each group to determine baseline serum cortisol and ACTH-stimulated cortisol values and histologic features in the lateral thoracic skin before prednisone administration, and after 1, 2, 3, and 4 weeks of administration. Some animals from each group were necropsied after 1, 2, 3, and 4 weeks of prednisone administration. Each course of prednisone administration resulted in adrenocortical atrophy and hypofunction, but adrenocortical suppression was less severe and slower in onset in the group given prednisone on alternate days. Extra-adrenal effects observed were atrophy of the skin and focal, fatty change of the liver. These changes were most evident in dogs given daily pharmacologic doses of prednisone (0.55 mg/kg/day). Fewer extra-adrenal effects were observed in dogs given alternate-day therapy. There were no extra-adrenal lesions in the dogs given equivalent glucocorticoid replacement doses (0.22 mg/kg/day).     

The effect of supplementing layer diets with shark cartilage or chitosan on egg components and yolk lipids

1. An experiment was designed to evaluate the effects of the addition of shark cartilage (SC) or chitosan (CH) to layer diets on egg component weights, yolk lipids and hen plasma lipids. 2. Hy-Line laying hens (80) were used during a 56 d feeding trial. Treatments were: basal diet (BD), BD + 20 g/kg SC, BD + 30 g/kg SC, BD + 20 g/kg CH and BD + 30 g/kg CH. Eggs were analysed on d 14, 28, 42 and 56. 3. Egg weight and egg component weights were not affected by these treatments throughout the experimental period. 4. After 14d of experimental feeding, cholesterol levels were higher in eggs from birds given BD + 20 g/kg CH and BD + 30 g/kg CH than in those from birds given BD. 5. Furthermore, eggs from hens given BD + 20 g/kg SC or BD + 20 g/kg CH were higher in palmitic and stearic acids and lower in oleic acid than those from birds fed on BD. After 56 d feeding, however, palmitic and stearic acid contents in eggs from hens given any of the supplemented diets were lower than in those from hens given BD, and oleic acid in eggs from hens given BD + 20 g/kg SC, BD + 30 g/kg SC and BD + 30 g/kg CH was higher than in those from birds fed on BD. 6. Plasma cholesterol and triacylglycerol levels were not significantly affected by dietary treatment. 7. Shark cartilage or chitosan at up to 30 g/kg in layer diets did not affect egg component weights (yolk, white and shell) and total lipid contents. During the period from 42 to 56d of experimental feeding, diets containing up to 30 g/kg chitosan reduced egg yolk contents of cholesterol, palmitic and stearic acids and increased the content of oleic acid.     

Efficacy of albendazole for prevention of fascioliasis in sheep

Daily doses of albendazole administered as a premix in the feed for 35 days were effective in preventing Fasciola hepatica infections in 17 sheep in three groups: 5 mg/kg/day (6 sheep) was 100% effective; 3 mg/kg/day (5 sheep) was 98% effective; and 1 mg/kg/day (6 sheep) was 42% effective. Infective cysts were given daily for 5 days during the first week of treatment, treatment was continued an additional 28 days, and sheep were necropsied 14 weeks after final cyst inoculation. There were no visible lesions in any livers of sheep given albendazole at the rate of 5 mg/kg/day or in three of five livers of sheep dosed at the rate of 3 mg/kg/day. Sheep treated with albendazole had a mean weight gain of 2.7 kg, 4.0 kg, and 4.0 kg greater than the controls for the dosages of 1, 3, and 5 mg/kg/day, respectively. Determination of bile duct damage by measurement of serum gamma-glutamyl transpeptidase activity at 9 weeks after final cyst inoculation revealed increases of 3.0X, 1.0X, and 1.1X for the dosages of 1, 3, and 5 mg/kg/day, respectively, and 2.3X for the control, as compared with 7 weeks after final cyst inoculation.     

Effects of short courses of different doses of prednisone and dexamethasone on serum third component of complement (C3) levels in dogs.

The effect of different doses of prednisone and dexamethasone on serum C3 levels was determined in 35 dogs. Dogs in Group A (n = 15) were administered prednisone (1.1 mg/kg/day) for 14 days; dogs in Group B (n = 10) were given prednisone at 2.2 mg/kg/day for 7 days; dogs in group C (n = 10) were administered dexamethasone (0.25 g/kg/day) for 7 days. Serum C3 concentrations were determined using a sandwich ELISA in samples obtained before and after glucocorticoid administration. Concentrations were expressed as a percentage of a reference standard. No statistically significant differences were found after glucocorticoid administration in all groups. Thus, short-term administration of prednisone and dexamethasone at commonly used doses did not result in significantly lower serum C3 levels.     

Yttrium oxide (Y2O3) as an inert marker in digestibility studies with dogs, blue foxes and mink fed diets containing different protein sources

The study evaluated the use of yttrium oxide (Y(2)O(3)) as an inert marker in studies of apparent total tract digestibility in dogs, blue foxes and mink. Comparison was made with total faecal collection, and use of chromic oxide (Cr(2)O(3)) as marker respectively. Four experimental diets were added 0.1 g/kg yttrium oxide and 10 g/kg chromic oxide and fed to four animals of each species. Faecal recovery of yttrium oxide was 94.4% (SEM +/- 1.0), and of chromic oxide 105.8% (SEM +/- 1.5). The digestibilities of dry matter, crude protein, crude fat, starch and total carbohydrates obtained by total collection and yttrium oxide as marker showed close similarity, and in most cases not significant differences, independent of species and diets. In dogs, overall digestibilities of main nutrients with chromic oxide as marker were not significantly different from overall means obtained with yttrium oxide (p > 0.05). Overall digestibility of dry matter, crude protein and total carbohydrates in blue foxes and mink was significantly higher with chromic oxide than with yttrium oxide (p < 0.05). In dogs and blue foxes, digestibilities of individual amino acids determined by use of yttrium oxide were not different from values obtained using total collection of faeces, both within diets and for overall mean (p > 0.05). Overall amino acid digestibilities in dogs determined with chromic oxide as marker were similar to corresponding figures for yttrium oxide, whereas use of chromic oxide resulted in significantly higher digestibilites for a number of amino acids compared with yttrium oxide in foxes and mink (p < 0.05). The digestibilities of most main nutrients and amino acids revealed no interaction between diet and method (p > 0.05). The study showed that yttrium oxide can be used in low concentration in the feed, and allows high accuracy of analyses and thereby precise digestibility determination. It is concluded that yttrium oxide is an alternative inert marker to chromic oxide in the studied species.     

Effects of flunixin meglumine in dogs following experimentally induced endotoxemia

Twelve dogs were randomly divided into three groups. Group 1 dogs were given Escherichia coli endotoxin and then treated with flunixin meglumine. Group 2 dogs were given endotoxin as group 1, but untreated. Group 3 dogs were given flunixin meglumine alone. The dogs were monitored clinically and urine and serum samples were collected at regular intervals for 72 hours. All surviving dogs were humanely killed after 72 hours and examined for gross and histologic lesions. Group 1 dogs all survived 72 hours, but showed prerenal azotemia, hepatocellular damage, hemorrhagic enteritis, and numerous gastric ulcerations. Three of the four dogs in group 2 died before 72 hours. Group 2 dogs showed many of the same chemical and hemodynamic changes as group 1. They had severe hemorrhage into the intestinal lumen; however, there were no gastric ulcerations. Group 3 dogs all survived and showed little physical or hematologic change. The study suggested the following: 1) flunixin meglumine was an effective drug in ameliorating the fatal effects of canine endotoxemia, 2) the effects of endotoxin in combination with flunixin meglumine, at 1.1 mg/kg body weight, caused gastric ulcerations, and 3) in normal dogs flunixin meglumine at 1.1 mg/kg body weight did not cause severe side effects or gross lesions.     

Effects of preoperative administration of ketoprofen on whole blood platelet aggregation,buccal mucosal bleeding time,and hematologic indices in dogs undergoing elective ovariohysterectomy

OBJECTIVE: To determine effects of preoperative administration of ketoprofen on whole blood platelet aggregation, buccal mucosal bleeding time, and hematologic indices in dogs after elective ovariohysterectomy. DESIGN: Randomized, masked clinical trial. ANIMALS: 22 healthy dogs. PROCEDURE: 60 minutes before induction of anesthesia, 11 dogs were given 0.9% NaCl solution (control), and 11 dogs were given ketoprofen (2 mg/kg [0.9 mg/lb], IM). Thirty minutes before induction of anesthesia, glycopyrrolate (0.01mg/kg [0.005 mg/lb]), acepromazine (0.05 mg/kg [0.02 mg/lb]), and butorphanol (0.2 mg/kg 10.09 mg/lb]) were given IM to all dogs. Anesthesia was induced with thiopental (5 to 10 mg/kg [2.3 to 4.5 mg/lb], IV) and maintained with isoflurane (1 to 3%). Ovariohysterectomy was performed and butorphanol (0.1 mg/kg [0.05 mg/lb], IV) was given 15 minutes before completion of surgery. Blood samples for measurement of variables were collected at intervals before and after surgery. RESULTS: In dogs given ketoprofen, platelet aggregation was decreased 95 +/- 10% and 80 +/- 35% (mean +/- SD) immediately after surgery and 24 hours after surgery, respectively, compared with preoperative values. At both times, mean values in dogs given ketoprofen differed significantly from those in control dogs. Significant differences between groups were not observed for mucosal bleeding time or hematologic indices. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative administration of ketoprofen inhibited platelet aggre gation but did not alter bleeding time. Ketoprofen can be given before surgery to healthy dogs undergoing elective ovariohysterectomy, provided that dogs are screened for potential bleeding problems before surgery and monitored closely after surgery.     

The effect of nitroscanate tablets of Echinococcus granulosus and Taenia hydatigena infections in dogs

Tablets of micronised nitroscanate (nominal particle size 2--3 microns) were given to a total of 190 dogs that had been experimentally infected with either Echinococcus granulosus or Taenia hydatigena. The efficiency of the drug in tablet form in freeing dogs from tapeworms, was investigated. The dose rate at which 50 per cent of normally fed dogs can be expected to be freed from E granulosus was found to be 89 mg/kg (95 per cent confidence limits 55 mg/kg to 140 mg/kg). The 90 per cent effective dose rate was not determined within the range 32 mg/kg to 250 mg/kg. The dose rate at which 90 per cent of normally fed dogs can be expected to be freed from T hydatigena was 37 mg/kg (95 per cent confidence limits 23 mg/kg to 60 mg/kg).     

Uredofos: anthelmintic activity against nematodes and cestodes in dogs with naturally occurring infections.

A new broad-spectrum anthelmintic, uredofos, was tested in 146 dogs by single and multiple oral dosing. Single doses of 100 and 50 (but not 25) mg/kg were totally effective in removing Dipylidium caninum and Taenia spp from 46 dogs with infections of tapeworms. Among groups of 15 to 20 dogs, the average percentage efficacies against Toxocara canis for single soese of 100, 50, and 25 mg/kg were 98, 96, and 81%, respectively. The average percentage of efficacies against hookworm (Ancylostoma caninum) were greater than 96% in dogs treated with single doses of 100, 50, or 25 mg/kg and were 100% in the 35 dogs given 2 or 3 treatments (24-hour intervals) at dose levels of either 25 or 50 mg/kg. The whipworm, Trichuris vulpis, was not efficaciously eliminated by single doses of 25, 50, and 100 mg/kg (av percentage of efficacies of 30, 35, and 71%, respectively). Efficacy against T vulpis markedly improved when 2 doses were given at a 24-hour interval (av percentage of efficacies were 89% at dose level of 25 mg/kg and 99% at dose level of 50 mg/kg). At either dose (25 or 50 mg/kg), 3 daily treatments were no more efficacious against whipworms than were 2 doses. There was no evidence of drug toxicosis in any dogs tested. It was concluded that uredofos is highly effective against canine tapeworms, ascarids, and hookworms when given as a single dose of 50 mg/kg and against whipworm when given at dose level of 50 mg/kg/day for 2 days.     

Effects of flunixin and flunixin plus prednisone on the gastrointestinal tract of dogs

Flunixin meglumine has been reported to induce gastrointestinal lesions in dogs when administered at therapeutic dosages. We administered flunixin meglumine to dogs daily for 10 days to assess the effect of this drug on the gastrointestinal tract. We also evaluated the possibility of corticosteroid potentiation of gastrointestinal toxicosis by concurrent administration of prednisone to 1 group of dogs. Dogs were monitored for gastrointestinal toxicosis by means of serial endoscopic evaluation, measurement of fecal occult blood, PCV, and total solid concentration, and by physical examination. There were 3 treatment groups of 5 dogs each. Group-1 dogs were given 2.2 mg of flunixin meglumine/kg daily, in 2 divided doses IM; group-2 dogs were given 4.4 mg of flunixin meglumine/kg daily, in 2 divided doses IM; and group-3 dogs were given 2.2 mg of flunixin meglumine/kg daily, in 2 divided doses IM plus 1.1 mg of prednisone/kg/d orally, in 2 divided doses. A fourth group of 5 dogs served as a control group. Endoscopically visible gastric mucosal lesions developed in all treated dogs within 4 days of initiating treatment. Lesions first developed in the gastric pylorus and antrum and lesions at these sites were more severe than those observed elsewhere. Dogs treated with flunixin meglumine plus prednisone developed the earliest and most severe lesions; lesion scores in group-2 dogs were higher than those in group-1 dogs. All dogs treated had occult blood in their feces by day 5 and its presence appeared to correlate more closely with endoscopic findings than did physical examination findings or changes in values for PCV or total solids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of Three Midazolam-Xylazine Mixtures Preliminary Trials in Dogs

The depressant effects of midazolam and xylazine on the central nervous system (CNS) were evaluated in 12 dogs. Xylazine was administered to six dogs (1.1 mg/kg intravenously [IV]) followed in 5 minutes by midazolam (1.0 mg/kg intramuscularly [IM]). In a second group of six dogs, xylazine (2.2 mg/kg IM) was followed in 5 minutes by midazolam (1.0 mg/kg IV). Both drug regimens induced rapid and profound sedation or anesthesia. Duration of action varied with the doses and routes of administration. Dogs given the high dose of xylazine IM had an arousal time of 95.4 +/- 8.9 minutes and a walking time of 155.4 +/- 8.8 minutes. These values exceeded the IV xylazine values threefold. Partial reversal of CNS depression was accomplished with either a benzodiazepine antagonist (flumazenil) or an alpha-2 antagonist (yohimbine). In a separate trial, a mixture of xylazine (0.55 mg/kg), midazolam (1.0 mg/kg), and butorphanol (0.1 mg/kg) with and without glycopyrrolate was evaluated in eight dogs. As with the xylazine-midazolam combinations, the CNS depressant effect of this mixture was clinically indistinguishable from anesthesia achieved with other rapid-acting injectable agents. Clinical signs of CNS depression were readily and completely antagonized by the simultaneous injection of flumazenil and yohimbine.     

Role of platelet activating factor in development of thrombocytopenia and neutropenia in dogs with endotoxemia

OBJECTIVE: To determine the role of platelet activating factor (PAF) in lipopolysaccharide (LPS)-induced thrombocytopenia and neutropenia in dogs. ANIMALS: 42 dogs. PROCEDURES: Blood samples were obtained from dogs given LPS (40 microg/kg of body weight; n = 16), PAF (1 microg/kg; 6), PAF (5 microg/kg/h for 90 minutes; 4), or physiologic saline (0.9% NaCl) solution (0.1 ml/kg/h for 90 minutes; 3) IV to monitor changes in blood cell counts, using automated counters and blood smears stained with Giemsa. Blood samples were also obtained from dogs given LPS (40 microg/kg) that had (n = 5) or had not (6) been treated beforehand with TCV-309, a potent PAF antagonist. Concentration of PAF in blood was determined by use of 125I-radioimmunoassay in dogs given LPS at 1 mg/kg (n = 3) and 40 microg/kg (9). RESULTS: Thrombocytopenia and neutropenia were found in all dogs except those given saline solution. The LPS-induced thrombocytopenia was significantly suppressed by prior treatment with TCV-309. The PAF concentrations increased markedly 1 hour after injection of 1 mg/kg of LPS and increased slightly but significantly 10 minutes after injection of 40 microg/kg of LPS. CONCLUSION AND CLINICAL RELEVANCE: PAF plays an important role in the development of LPS-induced thrombocytopenia and neutropenia in dogs. Control of PAF production, PAF-induced effects, or both may be important in the treatment of dogs with gram-negative bacterial infections and associated thrombocytopenia and neutropenia.     

Hepatotoxicity to dogs of horse meat contaminated with indospicine

SUMMARY: An outbreak of liver disease which killed more than 30 dogs at Alice Springs was associated with feeding meat from horses, some of which had developed Indigofera linnaei poisoning (Birdsville horse disease). Affected livers were small, nodular and yellow. There was associated jaundice, ascites, elevation of alanine aminotransferase levels in serum, a tendency to bleed, and signs of hepatic encephalopathy. Histologically, livers showed periacinar necrosis, collapse and haemorrhage, with severe swelling, vacuolation and cholestasis in remaining hepatocytes. Indospicine, a toxic amino acid found in the genus Indigofera, was detected in samples of suspect horsemeat. Experimental feeding of horsemeat containing 16 mg indospicine/kg for 32 days produced periacinar necrosis and hepatocellular swelling in 2 dogs, although neither died nor showed clinical illness. In another experiment, intakes of as little as 0.13 mg indospicine/kg bodyweightlday for 70 days produced periacinar liver lesions, and indospicine concentrations in serum, muscle and liver rose during this period to 3.9, 7.9 and 17.5 mg/kg, respectively. It was concluded that meat from horses grazing l. linnael can be hepatotoxic for dogs, and that this toxicity may be related to its indospicine content.     

Serum salicylate concentrations and endoscopic evaluation of the gastric mucosa in dogs after oral administration of aspirin-containing products

The serum salicylate concentration produced by oral administration of plain aspirin and several aspirin-containing products given at 8-hour intervals for 7 treatments was measured in 36 laboratory-conditioned adult dogs. The dogs were randomly allotted to 6 groups of 6 dogs each: group 1 was given plain aspirin at a dosage of 25 mg/kg of body weight: group 2 was given plain aspirin at a dosage of 10 mg/kg; group 3 was given buffered aspirin at a dosage of 25 mg/kg; group 4 was given enteric-coated aspirin at a dosage of 25 mg/kg; group 5 was given buffered aspirin at a dosage of 25 mg/kg; and, group 6 was given a placebo. Serum salicylate concentration was measured at 2-hour intervals for the first 8 hours, and then at 8-hour intervals for the next 40 hours. Following the last dosing, serum salicylate concentration was measured at 2-hour intervals until 56 hours; the final 2 samples were measured at 64 and 72 hours. The effect of aspirin on the gastric mucosa was studied in 12 dogs, 3 each randomly selected from groups 1, 3, 4, and 5. The gastric mucosa of each dog was examined with a fiberoptic gastroscope 3 days before the beginning of treatment; lesions were not seen. The drugs were administered as described and the gastric mucosa of each dog was reexamined at 72 hours. Administration of the aspirin-containing products at 8-hour intervals resulted in sustained therapeutic serum salicylate concentrations (greater than 5 mg/dl) in all dogs, except those of group 2. The greatest fluctuation in serum salicylate concentration was found in dogs of group 4. Gastric lesions were seen only in the 3 dogs of group 1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Promotion of liver and kidney carcinogenesis by ethyl tertiary-butyl ether (ETBE) in male Wistar rats

Tumor-promoting effects of ethyl tertiary-butyl ether (ETBE) were investigated in a 2-stage carcinogenesis bioassay with regard to hepatic and renal carcinogenesis in rats. Male 6-week-old Wistar rats were given drinking water containing N-ethyl-N-(2-hydroxyethyl)nitrosamine (EHEN), as an initiator, at a dose of 500 ppm for 2 weeks. Starting one week thereafter, the animals were administered ETBE at dose levels of 0 (control), 100, 300, 500 or 1,000 mg/kg/day by gavage for 19 weeks from week 4 to 22. Necropsy of all rats was performed at week 23, and livers and kidneys were examined histopathologically. Incidences of hepatocellular adenomas, and those of combined hepatocellular adenomas and carcinomas were significantly elevated in rats given 1,000 mg/kg/day ETBE, but not 100‒500 mg/kg/day ETBE, and there was a significant increase in the average numbers of lesions. No significant differences in incidences and average numbers of renal tubule neoplasms were found in rats administered 100‒1,000 mg/kg/day ETBE. However, the average numbers of atypical tubule hyperplasias, considered to be preneoplastic lesions, were significantly increased in rats given ETBE at 1,000 mg/kg/day, but not in rats given 500 mg/kg/day or lower doses. Thus, these results imply that ETBE has hepatic and renal tumor-promoting activities that affect EHEN-induced carcinogenesis in male rats, and the no-observed-effect level is 500 mg/kg/day under the present experimental conditions.     

Preclinical evaluation of L-asparaginase and methotrexate administered at intermediate doses in dogs.

The role of L-asparaginase (L-ASP) in limiting signs of methotrexate (MTX) toxicosis was studied. Eight dogs were randomly allotted to 2 groups of 4 dogs. All dogs were given 400 IU of L-ASP/kg of body weight IM, on day 1. On day 10, group-1 dogs were given 3 mg of MTX/kg, IV, and group-2 dogs were given 6 mg of MTX/kg, IV. All dogs were given 400 IU of L-ASP/kg, IM, 24 hours later (on day 11). One group-2 dog was euthanatized on day 16 because of severe gastrointestinal signs that were unresponsive to treatment. A second dose of MTX, identical to that given on day 10, was given on day 20 to each surviving dog, followed by L-ASP on day 21. On day 67, the 7 surviving dogs were given 3 mg of MTX/kg, IV. Adverse reactions observed were vomiting, diarrhea, and weight loss. Gastrointestinal side effects of MTX were not attenuated with L-ASP and would be a serious limitation to use of MTX administered at an intermediate dose in the treatment of lymphoma in dogs.     

Effects of isoprothiolane and phytosterol on lipogenesis and lipolysis in adipocytes from rats of dietary fat necrosis

To study effects of isoprothiolane and phytosterol on dietary fat necrosis, 3 groups of rats were fed hardened-tallow (HT) diet. Two groups of rats received either isoprothiolane (50 mg/kg) or phytosterol (20 mg/kg) orally once a day consecutively for 10 weeks. One group of rats received standard diet (CE-2) as a control. Fat necrotic lesions were observed in epididymal and perirenal adipose tissues from all rats in the 3 groups fed HT diet. Rats with fat necrosis were characterized by visceral type obesity and saturation in fatty acid composition of triglyceride in adipose tissue. The highest glucose conversion to total lipids was seen in adipocytes from the rats given phytosterol. There was no lipolytic response to epinephrine stimulation (1-100 microM) in adipocytes from the rats given only HT diet, while similar response of adipocytes from the 2 groups treated with either drug to those from the rats fed standard diet was observed. The levels of total saturated fatty acids of phospholipid in adipose tissue from the rats given either drug were lower than that of the rats given only HT diet. These data suggest that either drug alters fatty acid composition of phospholipid in fat cell membrane and enhances lipolysis of the cells.     

Effects of single intravenous doses of dexamethasone on baseline plasma cortisol concentrations and responses to synthetic ACTH in healthy dogs

The duration of adrenocortical suppression resulting from a single IV dose of dexamethasone or dexamethasone sodium phosphate was determined in dogs. At 0800 hours, 5 groups of dogs (n = 4/group) were treated with 0.01 or 0.1 mg of either agent/kg of body weight or saline solution (controls). Plasma cortisol concentrations were significantly (P less than 0.01) depressed in dogs given either dose of dexamethasone or dexamethasone sodium phosphate by posttreatment hour (PTH) 2 and concentrations remained suppressed for at least 16 hours. However, by PTH 24, plasma cortisol concentrations in all dogs, except those given 0.1 mg of dexamethasone/kg, returned to control values. Adrenocortical suppression was evident in dogs given 0.1 mg of dexamethasone/kg for up to 32 hours. The effect of dexamethasone pretreatment on the adrenocortical response to ACTH was studied in the same dogs 2 weeks later. Two groups of dogs (n = 10/group) were tested with 1 microgram of synthetic ACTH/kg given at 1000 hours or 1400 hours. One week later, half of the dogs in each group were given 0.01 mg of dexamethasone/kg at 0600 hours, whereas the remaining dogs were given 0.1 mg of dexamethasone/kg. The ACTH response test was then repeated so that the interval between dexamethasone treatment and ACTH injection was 4 hours (ACTH given at 1000 hours) or 8 hours (ACTH given at 1400 hours). Base-line plasma cortisol concentrations were reduced in all dogs given dexamethasone 4 or 8 hours previously.(ABSTRACT TRUNCATED AT 250 WORDS)     

Xylazine and tiletamine-zolazepam anesthesia in horses

The cardiopulmonary and anesthetic effects of xylazine in combination with a 1:1 mixture of tiletamine and zolazepam were determined in 6 horses. Each horse was given xylazine IV or IM, as well as tiletamine-zolazepam IV on 4 randomized occasions. Anesthetics were administered at the rate of 1.1 mg of xylazine/kg of body weight, IV, 1.1 mg of tiletamine-zolazepam/kg, IV (treatment 1); 1.1 mg of xylazine/kg, IV, 1.65 mg of tiletamine-zolazepam/kg, IV (treatment 2); 1.1 mg of xylazine/kg, IV, 2.2 mg of tiletamine-zolazepam/kg, IV (treatment 3); and 2.2 mg of xylazine/kg, IM, 1.65 mg of tiletamine-zolazepam/kg, IV (treatment 4). Tiletamine-zolazepam doses were the sum of tiletamine plus zolazepam. Xylazine, when given IV, was given 5 minutes before tiletamine-zolazepam. Xylazine, when given IM, was given 10 minutes before tiletamine-zolazepam. Tiletamine-zolazepam induced recumbency in all horses. Duration of recumbency in group 1 was 31.9 +/- 7.2 (mean +/- 1 SD) minutes. Increasing the dosage of tiletamine-zolazepam (treatments 2 and 3) significantly (P less than 0.05) increased the duration of recumbency. Xylazine caused significant (P less than 0.05) decreases in heart rate and cardiac output and significant (P less than 0.05) increases in central venous pressure and mean pulmonary artery pressure 5 minutes after administration. Respiratory rate was decreased. Arterial blood pressures increased significantly (P less than 0.05) after xylazine was administered IV in treatments 1 and 3, but the increases were not significant in treatment 2. Xylazine administered IM caused significant (P less than 0.05) increases in central venous pressure and significant (P less than 0.05) decreases in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intramuscular, intravenous and oral levetiracetam in dogs: safety and pharmacokinetics

Intravenous (IV) levetiracetam (LEV) is available for humans for bridge therapy when the oral route is unavailable. We investigated the safety and pharmacokinetics of LEV administered intramuscularly (IM), IV, and orally to dogs.
Six Hound dogs received 19.5–22.6 mg/kg of LEV IM, IV and orally with a wash-out period in between. All dogs received 500 mg LEV orally and 5 mL of 100 mg/mL LEV IM. Three dogs received 500 mg of LEV IV and three dogs received 250 mg LEV IV with 250 mg given perivascularly to approximate extravasation. Safety was assessed using a pain scale at time of IM administration and histopathological examination 24 h to 5 days after injection.
Intravenous LEV half-life was 180 ± 18 min. Bioavailability of IM LEV was 100%. Mean time to T_max after IM was 40 ± 16 min. The mean C_max IM was 30.3 ± 3 μg/mL compared to the C₀ of 37 ± 5 μg/mL for IV. Mean inflammation score (0–4 scale) for IM LEV was 0.28 and for saline 0.62. Extravasation did not cause tissue damage.
Parenteral LEV is well tolerated and appears safe following IM and IV injections in dogs. Parenteral LEV should be evaluated for use in dogs with epilepsy.