Forelimb skeletal scintigraphy responses in previously untrained Thoroughbreds undergoing initial treadmill training.

Scintigraphy has been used in numerous clinical settings to examine horses to determine the origin of lameness problems, but it has not been used previously to monitor prospectively the skeletal responses of a group of similarly-trained racehorses. Our hypothesis was that in naïve Thoroughbred (TB) racehorses, initial treadmill training induces increased radiopharmaceutical uptake in high-motion joints and in the dorsal third metacarpal bone (MC3). Eight previously-untrained TB racehorses underwent sequential skeletal scintigraphic examinations as they exercised daily for 9 weeks on an inclined treadmill. At the end of Weeks 0 (pre-training), 3 (trotting at 4.2 m/s and initial galloping), 6 (galloping at 7.5 m/s), and 9 (sprinting 600 m at 12.5 m/s), horses received 140 mCi 99m Technetium-methylene diphosphonate i.v. followed by a standard skeletal scintigraphic forelimb examination 2 h later. Views were graded for increased radiopharmaceutical uptake by 3 co-investigators who were blinded to horse identification, breed, sex, date, and clinical findings. Results were compared before and after training for each skeletal location using the Mann-Whitney Rank Sum Test with the level of significance set at P<0.05. Initial treadmill training resulted in increased radiopharmaceutical uptake in the carpus (P = 0.031), metacarpophalangeal joint (P = 0.021), proximal phalanx (P = 0.035), and distal phalanx (P = 0.003). Training did not affect dorsal MC3 radiopharmaceutical uptake (P>0.05).

The effect of Ginkgo biloba extract (EGb 761) on gliotic reactions in the hippocampal formation after unilateral entorhinal cortex lesions.

PURPOSE: Ginkgo biloba extract (EGb 761) has been shown to facilitate behavioral and neuro-morphological recovery from brain injury, but less is known about its effects on glia. Since gliosis may be an important component of the recovery process, we tested the hypothesis that EGb 761 alters the time course and development of microglial activation and astrocytosis after brain injury. METHODS: Rats were treated with either saline or EGb 761 and killed at 2 hrs, 1, 3, 7, and 14 days following unilateral entorhinal cortex (EC) lesions. Microglia and their precursors were visualized with a silver impregnation method, and astrocytes with GFAP. RESULTS: Blood-borne monocytes/macrophages were seen as early as 2 hrs after injury in all animals. The side contralateral to the injury showed minimal microglial activation and there were no significant effects of drug treatment. On the side ipsilateral to the lesion EGb 761 enhanced microglial activation at 3, 7, and 14 days in the molecular layer and the hilus of the dentate gyrus; the areas of most profound deaf-ferentation after EC injury. Regions of the corpus callosum also showed enhanced microglial activation over the same time course. Reactive astrocytes were stained with GFAP and were found to be more numerous than activated microglia, particularly in the ipsilateral corpus callo-sum. EGb 761 treatment enhanced astrocytosis at 3 days in the molecular layer, the hilus, and the corpus callosum on the ipsilateral side. CONCLUSIONS: Taken together our results show that EGb 761 enhances, accelerates and prolongs the activation of microglia and astrocytosis at the site of injury.

Valproate reduces intake of alcoholic beverage among rats.

A series of experiments was carried out to assess the effects of valproate (VAL) on the intake of ethanol by rats. In Experiment 1, the effects of VAL (150 and 200 mg/kg, i.p.) were assessed across 10 days. Compared with controls, the 200 mg/kg dose reliably reduced intake of ethanol while also reliably increasing intake of water. The 150 mg/kg dose did not reliably reduce the intake of ethanol across the initial days, but it did across later days. Neither dose affected the total intake of fluids. Similarly, 5 days of oral dosing with VAL (400 and 600 mg/kg) reliably reduced the intake of ethanol without affecting the intake of water. However, body weights were reduced by the oral doses across the procedure. In another procedure, VAL (200 mg/kg, i.p.) produced a mild conditioned taste aversion to a saccharin solution, suggesting that VAL may reduce intake of ethanol because it produces a general malaise. However, this dose of VAL enhanced the intoxicating effects of ethanol (2.0 g/kg). Overall, the results are equivocal with respect to VAL as a potential medicine for treating alcohol misuse and alcoholism.

CCK-8 infusion increases plasma LMW alkaline phosphatase coincident with enterohepatic circulation of bile acids.

Bile acids may facilitate the release of liver alkaline phosphatase (ALP) from its hydrophobic membrane anchor. The purpose of this study was to determine whether such a facilitatory role could be observed during the enterohepatic circulation of bile acids in dogs. Increased hepatic ALP activity was induced in four dogs by daily injections of 4 mg.kg-1.day-1 of prednisone for 10 days. Intravenous infusions of cholecystokinin octapeptide (CCK-8) were given before treatment and on treatment days 3, 5, 7, and 10 to induce gallbladder emptying and the enterohepatic circulation of bile acids. Blood samples were taken hourly for 4 h before and for 4 h after CCK-8 infusion. These showed that plasma ALP activity increased significantly only after CCK-8 infusion. Gel exclusion chromatography, polyacrylamide gel electrophoresis, and octyl Sepharose phase separation showed that the increased ALP activity was a hydrophilic, low-molecular-weight (LMW) isoform, which is consistent with phospholipase release. Histochemical staining of endogenous ALP activity showed increased ALP activity over sinusoidal surfaces of prednisone-treated dogs. There was also an increased serum-to-tissue ratio of ALP activity in the prednisone-treated dogs, suggestive of increased release of ALP into blood. It was concluded that bile acids probably play a facilitatory role in the enzymatic release of ALP from the sinusoidal surface of hepatocytes, which may be accentuated by the presence of increased amounts of ALP on the sinusoidal surface in some disease states.

Hepatic total 3 alpha-hydroxy bile acids concentration and enzyme activities in prednisone-treated dogs.

High serum alkaline phosphatase (ALP) activity is considered a sensitive marker of cholestasis in most mammalian species, including dogs. Induction of high serum ALP activity in association with cholestasis is dependent on high hepatic bile acids concentrations. Treatment of dogs with glucocorticoids also results in high serum ALP activity. The possible causal relation between serum ALP activity and bile acids concentration was investigated in dogs treated with glucocorticoids. The relation of glucocorticoid treatment to changes in the activity of individual ALP isoenzymes, alanine transaminase (ALT) and gamma-glutamyltransferase (GGT) also was investigated. Eight conditioned dogs were given 4 mg of prednisone/kg of body weight, i.m., daily for 10 days. Blood samples were taken prior to treatment and on treatment days 3, 5, 7, and 10. Liver tissue was then taken from each dog. Serum total ALP activity was significantly (P < 0.05) high at day 3 in prednisone-treated dogs. Isoenzyme analysis indicated that this increase was attributable to an increase in the liver ALP isoenzyme (LALP). Significant increases in serum corticosteroid-induced ALP (CALP) and bone ALP were first observed on days 7 and 10, respectively. Serum ALT and GGT activities were significantly increased by day 5. Increased serum or hepatic tissue bile acids concentrations were not observed in prednisone-treated dogs, compared with values in 8 clinically normal (control) dogs, but were high in 3 dogs with complete bile duct ligation. Hepatic activities of LALP, CALP, and GGT were higher in prednisone-treated dogs than values in controls, indicating probable increased hepatic synthesis of these enzymes. Hepatic ALT activity was not increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of trimethoprim/sulfamethoxazole on thyroid function in dogs with pyoderma.

The effect of trimethoprim/sulfamethoxazole (T/SMX, 30 mg/kg, PO, q 12 h for 6 weeks) on thyroid function was evaluated in 21 dogs with pyoderma and normal baseline serum thyroxine concentrations. The population mean serum thyroxine concentration, but not the population mean serum triiodothyronine concentration, was significantly decreased at the end of treatment. After 6 weeks of treatment, the response in 3 dogs to thyrotropin administration was substantially reduced. Radionuclide thyroid imaging of 2 dogs after T/SMX treatment revealed higher-than-normal thyroid technetium 99m pertechnetate uptake, suggestive of an interference with iodide metabolism. Use of T/SMX may cause hypothyroidism, and inadequate thyroid function may be incorrectly diagnosed in dogs treated with this antimicrobial.