Tiludronate as a new therapeutic agent in the treatment of navicular disease: a double-blind placebo-controlled clinical trial

REASONS FOR PERFORMING STUDY: Bisphosphonates, such as tiludronate, are used to normalise bone metabolism via inhibition of bone resorption. Areas of increased bone resorption and formation are typical lesions in a diseased navicular bone. OBJECTIVES: To determine if bone remodelling changes occurring in navicular disease may be corrected with therapies regulating bone metabolism. METHODS: We designed a double-blind, placebo-controlled clinical trial to compare 2 doses of tiludronate, 0.5 mg/kg and 1 mg/kg bwt administered via daily i.v. injections over 10 days for the treatment of navicular disease. Seventy-three horses, split into 2 subpopulations of recent and chronic cases, were enrolled to be followed-up over 6 months. Of these, 33 recent and 17 chronic cases meeting the selection criteria were maintained in the final efficacy analyses. Clinical examinations were videorecorded and reviewed blindly by an independent expert. RESULTS: Horses treated with the higher dose showed optimal improvement of lameness and return to normal level of activity 2-6 months post treatment. The more recent the onset of clinical signs at the time of treatment, the greater the efficacy. The treatment did not modify the response to extension and flexion tests. The lower dose failed to significantly improve the condition. CONCLUSIONS: Tiludronate efficacy is demonstrated in the treatment of navicular disease at the dose of 1 mg/kg bwt. POTENTIAL RELEVANCE: Our results support the clinical relevance of bone remodelling changes in the outcome of navicular disease.     

Succinylcholine chloride as a euthanatizing agent in dogs

In order to determine the efficacy of succinylcholine chloride as a euthanatizing agent, the possible situation encountered in mass euthanasia was recreated. While anesthetized or awake, sixteen 2-year-old Beagles of both sexes were subcutaneously injected with either 1.1 g or 11 mg of succinylcholine chloride/kg of body weight. Positive pressure respiration was given to 2 dogs, otherwise the treatment was allowed to run its course. Electrocardiogram, electroencephalogram, and impedance pneumogram recordings were obtained for time comparisons and for determination of the ultimate cause of death.     

Clinical evaluation of metrizamide as a myelographic agent in the dog.

Metrizamide, a new, water-soluble contrast agent, was clinically evaluated as a myelographic agent in 17 dogs. Nine dogs were given lumbar subarachnoid injections and six were given cisternal injections. Two dogs were given cisternal and lumbar injections; in one dog, both injections were given on the same day. The dosage ranged from 0.3 to 0.57 ml/kg of body weight, using an isotonic solution of metrizamide. Of eight dogs given cisternal injections, two experienced convulsive activity requiring diazepam treatment during the anesthetic recovery period. The lumbar injections did not cause convulsions. Satisfactory radiographic density persisted up to 45 minutes after injection, allowing time for several views to be obtained. In general, metrizamide appeared to be an adequate myelographic agent in the dog.     

Bioavailability of threonine in soybean meal for rats and chicks.

The bioavailability of threonine in soybean meal and the effects of the excess amino acids in soybean meal on the estimate were measured using rats and chicks in slope-ratio assays. In Exp. 1, a corn-based diet containing .23% threonine was supplemented with 0 to 45% L-threonine in .05% increments. The growth rate of weanling rats fed these diets increased quadratically (P less than .001) with L-threonine addition, the increase being essentially linear up to the .10% addition. In Exp. 2, the basal diet was supplemented with 0, .025, .050, .075, or 100% threonine from L-threonine, simulated soybean meal (a mixture of crystalline amino acids with a pattern designed to simulate soybean meal), or soybean meal. Regressions of partitioned weight gain and body N gain of rats vs supplemental threonine intake were calculated for each source using multiple regression. Slope ratios (soybean meal:L-threonine) were .91 for weight gain and .92 for body N gain. The additional amino acids in simulated soybean meal did not affect the estimate. For Exp. 3, a corn-soybean meal-based diet containing .48% threonine was supplemented with 0 to 60% L-threonine in .10% increments. The growth rate of broiler chicks fed the diets increased quadratically (P less than .001) with L-threonine addition. The increase was essentially linear up to the .10% addition. In Exp. 4, the basal diet was supplemented as in Exp. 2. Regressions of partitioned weight gain of chicks vs supplemental threonine intake were calculated for each source. The slope ratio for soybean meal:L-threonine was 1.03; however, the model exhibited fundamental invalidity and therefore the estimate should be interpreted with caution. The additional amino acids in the simulated soybean meal did not affect the value.     

Inositol as a lipotropic agent in dairy cattle diets

Fatty liver syndrome or hepatic lipidosis (HL) is a condition thought to contribute to an increased incidence of peripartum disease, reduced response to therapy and decreased fertility in dairy cows. This syndrome is characterized by excess triglyceride (TG) accumulation in the liver and apparent decreased hepatic lipoprotein output. In lactating rats, a similar condition results from feeding an inositol-deficient diet. It is also characterized by excess hepatic TG accumulation and decreased hepatic lipoprotein output. Myo-inositol is a necessary component of the phospholipid phosphatidyl-inositol, which is an important membrane constituent. Myo-inositol occurs in feed mainly as the inositol hexaphosphate phytic acid. Phytic acid is undigestible by the monogastric but rumen phytases are assumed to adequately hydrolyze it. In early lactation dairy cows, lipid mobilization is intense, and the myo-inositol requirement may exceed the dietary supply or availability. Myo-inositol is being tested in a field trial as a potential lipotropic agent for dairy cows. Preliminary results suggest no lipotropic benefit from added myo-inositol.     

Side effects of clenbuterol as a repartitioning agent

Clenbuterol, a synthetic beta-adrenergic agonist drug, can be used to increase the ratio of protein to fat in the carcase of meat animals. During the first one to three days of its administration to sheep or calves clenbuterol increased their heart rate, and in sheep it decreased blood pressure. Continued administration had no further effect on heart rate or blood pressure but in sheep dose levels above 1.5 mg/day depressed appetite for up to five days; at all dose levels clenbuterol brought about a long term increase in metabolic rate.     

Propofol as an induction agent in the goat: a pharmacokinetic study

Reid, J., Nolan, A.M., Welsh, E. Propofol as an induction agent in the goat: a pharmacokinetic study. J. vet. Pharmacol. Therap. 16, 488–493.
The pharmacokinetics of propofol, 4 mg/kg, administered as a bolus dose intravenously (i.v.) prior to the maintenance of anaesthesia with halothane in oxygen, were determined in five goats, and a clinical impression of its use as an induction agent was made. Induction of anaesthesia was rapid and smooth, providing satisfactory conditions for intubation in all animals. Post-induction apnoea occurred in one goat and minimal regurgitation of ruminal contents was recorded in two animals. Recovery times were rapid with a mean time to standing after halothane inhalation ceased of 13.7 min. The blood propofol concentration time profile was best described by a bi-exponential decline in all five goats. The mean elimination half-life was short (15.5 min), the volume of distribution at steady state large (2,56 1/kg) and the clearance rapid (275 ml/min.kg). Propofol was shown to be a very satisfactory induction agent in the goat.     

Bioavailability of a silybin-phosphatidylcholine complex in dogs

Liver dysfunction often is associated with an imbalance in the production and removal of free radicals derived from oxygen and nitrogen and has been managed clinically with antioxidant supplements, including silymarin extract derived from milk thistle. The potential for enhanced bioavailability of a phytosome complex containing phosphatidylcholine and silybin, the primary active flavonolignan in silymarin extract, was tested in dogs. A group of eight beagles (four males, four females) were dosed orally with a silybin-phosphatidylcholine complex (SPC) and a commercially available standardized silymarin extract containing equivalent levels of silybin. Dosing with the SPC resulted in Cmax, Tmax, and AUC0-24 h values (mean+/-SD) for total silybin of 1310+/-880 ng/mL, 2.87+/-2.23 h, and 11,200+/-6520 ng.h/mL, respectively; corresponding values for a standardized silymarin extract were 472+/-383 ng/mL, 4.75+/-2.82 h, and 3720+/-4970 ng.h/mL. A second, separate group of beagles were also dosed with the extract alone, yielding values of 449+/-402 ng/mL, 6.87+/-7.43 h, and 2520+/-2976 ng.h/mL. These data show that a phytosome complex of phosphatidylcholine and silybin markedly enhances bioavailability in dogs.     

Efficacy of atenolol as a single antihypertensive agent in hyperthyroid cats

beta-Adrenergic blockers, particularly atenolol, are often recommended for the tachycardia and hypertension that accompany hyperthyroidism; however, the effects of monotherapy with atenolol on both systolic blood pressure (SBP) and heart rate (HR) have not been reported. Twenty hyperthyroid cats with SBP > or = 160 mmHg were studied retrospectively to investigate the SBP and HR lowering effects of atenolol. Median pre-treatment SBP and HR for all cats were 186.5 mmHg and 231 beats/min, respectively. All cats were treated with atenolol at a dosage of 1-2 mg/kg PO q 12h for a minimum of 5 days prior to reassessment and treatment with radioactive iodine. SBP and HR both decreased following atenolol therapy in this group of cats to median values of 171.5 mmHg (P=0.0088) and 185/min (P=0.0003). However, when successful clinical control of hypertension was defined as a post-treatment SBP < 160 mmHg, atenolol monotherapy was ineffective in 70% of the cases. There was no statistically significant difference in baseline serum total thyroxine or atenolol dosage between clinical responders and non-responders. While atenolol effectively reduces HR in most cats with hyperthyroidism, elevated SBP is poorly controlled, and the addition of another vasodilator such as amlodipine or an angiotensin converting enzyme inhibitor is needed to treat associated hypertension.     

Use of hexadimethrine bromide as a heparin-neutralizing agent in canine plasma

Hexadimethrine bromide was evaluated as a heparin-neutralizing agent in a simple modification of the activated partial thromboplastin time test in canine plasma. Addition of various amounts of heparin in vitro to canine plasma indicated that heparin could be neutralized by adding 0.5 micrograms of hexadimethrine bromide 15 s before CaCl2 was added to the reaction mixture of the activated partial thromboplastin time test. In 8 dogs given (subcutaneous injection) 500 USP units of sodium heparin/kg, marked individual variations in clotting time prolongations were observed over the 12-hour period of study. The hexadimethrine bromide modification effectively neutralized the heparin-related clotting time prolongations to values that were not significantly different from base-line (preheparin) activated partial thromboplastin time values. The modification seems to be useful in confirming the presence of heparin and in monitoring heparin therapy in dogs.