Phalaris arundinacea (reed canarygrass) grass staggers in beef cattle.

Four adult mixed-breed beef cows from a cow-calf operation in West Virginia were referred to the Virginia-Maryland Regional College of Veterinary Medicine in March 2009 with weakness, ataxia, hind limb paresis progressing to lateral recumbency, and death within 2-3 days. Histologically, there was accumulation of light brown, granular pigment in neurons of the ventral gray horns of the spinal cord (more severe in thoracic and lumbar sections), brain stem, and pons, resulting in distortion and bulging of the cell body and displacement of the Nissl substance, suggestive of Phalaris sp. grass toxicosis. The most severely affected cow had accumulation of dark green-brown pigment in renal tubular epithelial cells. Reed canarygrass (Phalaris arundinacea) was identified in pastures, and the concentration of tryptamine alkaloids in new leaf blades was approximately 0.2% on a wet weight basis. These alkaloids are serotonergic receptor agonists, resulting in neurologic "staggers" in ruminants. Delayed onset times of up to 4-5 months have been reported in sheep after removal from Phalaris sp. pastures. Distribution of pigment in serotonergic tracts of the midbrain, brain stem, and spinal cord with Phalaris sp. toxicoses is distinct and differs from lipofuscin. Electron microscopy confirmed that the pigment was not lipofuscin. From these findings, a diagnosis of delayed P. arundinacea toxicosis was made. Over a 2-month period, 18 cows died with similar clinical signs.

Examination of concurrent exposure to repeated stress and chlorpyrifos on cholinergic, glutamatergic, and monoamine neurotransmitter systems in rat forebrain regions.

Repeated stress has been reported to cause reversible impairment in the central nervous system (CNS). It was proposed that alterations in glutamatergic, cholinergic, and monoamine neurotransmitter systems after exposure to stress are initial CNS events contributing to this impairment and that exacerbation could occur with concurrent exposure to cholinesterase inhibitors. Effects of concurrent exposure to repeated stress and chlorpyrifos on activities of acetylcholinesterase (AChE), carboxylesterase, and choline acetyltransferase (ChAT); concentrations of excitatory amino acids, monoamines, and their metabolites; and maximum binding densities (B(max)) and equilibrium dissociation rate constants (K(d)) of glutamatergic N-methyl-d-aspartate (NMDA) and total muscarinic cholinergic receptors were studied in the blood, hippocampus, cerebral cortex, or hypothalamus of adult Long-Evans rats. Stress treatments extended over 28 days included (1) control rats handled 5 days/week; (2) rats restrained 1 h/day for 5 days/week; (3) rats swum 30 min for 1 day/week; or (4) rats restrained 4 days/week and swum for 1 day/week. On day 24, each stress treatment group was randomly divided and injected either with corn oil or chlorpyrifos, 160 mg/kg subcutaneously (sc) (60% of the maximum tolerated dose), 4 h after restraint. Blood and brain tisssues were collected on day 28. Rats restrained and swum had a statistical trend toward increasing concentrations of glutamate in the hippocampus when compared to rats only swum (p = .064). Chlorpyrifos administration decreased restraint-induced elevated aspartate in the hippocampus, and decreased B(max) of total muscarinic receptors in the cerebral cortex. In addition, chlorpyrifos decreased B(max) and K(d) of total muscarinic receptors in the cerebral cortex of swum rats. Results demonstrated that chlorpyrifos inhibited AChE activity in blood, cerebral cortex, and hippocampus, but stress did not affect AChE activity. Carboxylesterase activity was inhibited by chlorpyrifos and by repeated restraint with swim. Swim stress decreased concentrations of norepinephrine in the hippocampus and hypothalamus, and increased concentrations of dopamine and its metabolite, DOPAC, in the hypothalamus. Both stress and chlorpyrifos altered serotonin concentrations, and the interactions of repeated stress and chlorpyrifos on serotonin approached significance in the hippocampus (p = .06) and hypothalamus (p = .08). Therefore, stress models were demonstrated to alter glutamatergic and monoamine responses, whereas chlorpyrifos alone had effects on cholinergic and monoamine systems in the rat CNS. However, the interactions between stress and chlorpyrifos significant at p < 0.05 were restricted to attenuation of elevated aspartate in the hippocampus of restrained with swim rats and decreased K(d) of acetylcholine receptors in the cerebral cortex of swum rats and restrained rats.

Elution of metronidazole and gentamicin from polymethylmethacrylate beads.

OBJECTIVE: To characterize the elution and bioactivity of metronidazole and gentamicin sulfate polymerized, individually and in combination, with polymethylmethacrylate (PMMA). STUDY DESIGN: In vitro experimental study. METHODS: PMMA beads containing metronidazole (3 concentrations), gentamicin sulfate, or metronidazole and gentamicin sulfate were immersed in 5 mL of phosphate-buffered saline in triplicate. Eluent was replaced at specified time intervals for 1 or 21 days, and antibiotic concentrations were measured by high-performance liquid chromatography. Changes in antibiotic bioactivity attributable to polymerization or copolymerization of the antibiotics with PMMA, ethylene oxide sterilization, and storage of AIPMMA beads containing metronidazole were evaluated. RESULTS: Antibiotic elution patterns were similar for all groups. Day 1 elution for groups containing metronidazole or gentamicin individually represented a mean 63%-66% and 79%, respectively, of the 21-day total. Approximately 50% of the day 1 elution occurred during the first hour. The elution of metronidazole was dose dependent. The elution of metronidazole (day 3-21) and gentamicin (all days) was significantly greater when metronidazole and gentamicin were combined (P <.05). The addition of metronidazole delayed polymerization of PMMA. Neither polymerization nor copolymerization of metronidazole and gentamicin with PMMA, gas sterilization, or 2-month storage of beads containing metronidazole significantly affected antimicrobial bioactivity. CONCLUSIONS: Metronidazole elution from PMMA was dose dependent. Copolymerization of metronidazole and gentamicin sulfate in PMMA resulted in increased rates of elution. Intraoperative preparation of metronidazole-impregnated PMMA beads is not practical, but sterilization and storage for 2 months should not affect efficacy. CLINICAL RELEVANCE: The local delivery of biologically active metronidazole and gentamicin by elution from PMMA is feasible.

How to evaluate toxicant exposures.

Susceptibility of individual animals to any specific toxicant is influenced by many factors, including genetics, environment, age, gender, and preexisting disease. Because the relative influence of these factors on a specific toxicosis is often unknown and unmeasured, it is difficult to predict how an individual animal is likely to respond to a toxic challenge compared with the "average" animal in the population. Safety or uncertainty factors of 10 have been proposed to deal with intraspecies and interspecies variability in regard to LD50 values. These safety factors may be too conservative for many situations. Toxicant exposure is assessed in animals to determine if preventive treatment is warranted or for differential diagnosis purposes. Calculation techniques require converting English and apothecary units to metric units by either of several methods.

Cretinism in a North American black bear (Ursus americanus).

Congenital hyperplastic goiter and cretinism were documented in a 16 month-old male North American black bear (Ursus americanus). The cub was captured at approximately 8 months of age and maintained for an additional 8 months in captivity. Clinical signs included growth retardation, clumsiness, and facial dysmorphism. Hypothyroidism was documented by determining serum triiodothyronine (T3) and thyroxine (T4) levels. Lysosomal storage disease was ruled out by measuring various lysosomal enzyme activities. Serologic, radiographic, computed tomographic, necropsy, and histopathologic findings were consistent with congenital hypothyroidism and cretinism.