The aim of this article was to evaluate the influence and effects of chosen bioaccumulative substances i.e. heavy metals, pesticides, and polychlorinated biphenyls (PCBs) on fish, as well as provide information on time trends and potential threat to human health. Chemical substances which pollute water may affect living organisms in two ways. First of all, large amounts of chemical substances may cause sudden death of a significant part of the population of farmed fish, without symptoms (i.e. during breakdown of factories or industrial sewage leaks). However, more frequently, chemical substances accumulate in tissues of living organisms affecting them chronically. Heavy metals, pesticides, and polychlorinated biphenyls are persistent substances with a long-lasting biodegradation process. In a water environment they usually accumulate in sediments, which makes them resistant to biodegradation processes induced by, e.g., the UV light. These substances enter the fish through direct consumption of contaminated water or by contact with skin and gills. Symptoms of intoxication with heavy metals, pesticides, and PCBs may vary and depend on the concentration and bioavailability of these substances, physicochemical parameters of water, and the fish itself.

Objective--To describe the simple elimination kinetics of methyllycaconitine (MLA) and deltaline and evaluate the heart rate response in cattle following oral administration of larkspur. Animals--5 healthy Angus steers that were habituated to metabolism crates. Procedures--Tall larkspur (Delphinium barbeyi) in the early flowering stage was collected, dried, and ground. Each steer received a single dose of larkspur that was equivalent to 10.4 mg of MLA/kg and 11.0 mg of deltaline/kg via oral administration. Steers were housed in metabolism crates during a 96-hour period following larkspur administration; heart rate was monitored continuously, and blood samples were collected periodically for analysis of serum MLA and deltaline concentrations as well as assessment of pharmacokinetic parameters. Results--No overt clinical signs of poisoning developed in any steer during the experiment. Mean ± SE heart rate reached a maximum of 79.0 ± 5.0 beats/min at 17 hours after larkspur administration. Serum MLA concentration was correlated directly with heart rate. Mean times to maximal serum concentration of MLA and deltaline were 8.8 ± 1.2 hours and 5.0 ± 0.6 hours, respectively. Mean elimination half-life values for MLA and deltaline were 20.5 ± 4.1 hours and 8.2 ± 0.6 hours, respectively. Conclusions and Clinical Relevance--Following larkspur administration in 5 healthy steers, maximum serum concentrations of MLA and deltaline were detected within 10 hours, and changes in serum MLA concentration and heart rate were correlated. Results indicated that cattle that have consumed larkspur will eliminate 99% of MLA and deltaline from serum within 144 hours.

Objective--To determine whether larkspur-derived N-(methylsuccinimido) anthranoyllycoctonine (MSAL)-type alkaloids alter heart rate and electrically evoked electromyographic (eEMG) response of the external anal sphincter (EAS) in cattle and whether these effects can be reversed by acetylcholinesterase inhibitors. Animals--12 beef heifers and 4 cows. Procedures--3 or 4 heifers were used in 1 or 2 of 7 dose-response experiments; heart rate and EAS eEMG response were assessed before and 24 hours after oral treatment with larkspur (doses equivalent to 0.5 to 15 mg of MSAL-type alkaloids/kg). In 3 subsequent experiments, 3 heifers (1 of which was replaced with another heifer in the control experiment) each received 10 mg of MSAL-type alkaloids/kg and were injected IV with physostigmine (0.04 mg/kg), neostigmine (0.04 mg/kg), or saline (0.9% NaCl) solution 24 hours later, prior to assessment. Additionally, EAS eEMG response was measured in 4 cows before and after epidural administration of 2% lidocaine hydrochloride. Results--Larkspur-treated heifers developed dose-related increases in heart rate and decreases in EAS eEMG response. Twenty-four hours after administration of MSAL-type alkaloids, neostigmine decreased heart rate but did not affect eEMG response, whereas physostigmine did not affect heart rate but caused a 2-fold increase in eEMG response. In cows, epidural anesthesia did not alter eEMG response, suggesting that transdermal stimulation of the EAS pudendal innervation did not occur. Conclusions and Clinical Relevance--In cattle, cardiac effects and muscle weakness or loss of EAS eEMG response induced by larkspur-derived MSAL-type alkaloids were reversed by neostigmine or physostigmine, respectively. Treatment with anticholinesterase inhibitors may alter the clinical effects of larkspur poisoning in cattle.

Objective-To investigate the mechanisms by which corticosteroid administration may predispose cats to congestive heart failure (CHF). Animals-12 cats receiving methylprednisolone acetate (MPA) for the treatment of dermatologic disorders. Procedure-The study was conducted as a repeated-measures design. Various baseline variables were measured, after which MPA (5 mg/kg, IM) was administered. The same variables were then measured at 3 to 6 days and at 16 to 24 days after MPA administration. Evaluations included physical examination, systolic blood pressure measurement, hematologic analysis, serum biochemical analysis, thoracic radiography, echocardiography, and total body water and plasma volume determination. Results-MPA resulted in a substantial increase in serum glucose concentration at 3 to 6 days after administration. Concurrently, RBC count, Hct, and hemoglobin concentration as well as serum concentrations of the major extracellular electrolytes, sodium and chloride, decreased. Plasma volume increased by 13.4% (> 40% in 3 cats), whereas total body water and body weight slightly decreased. All variables returned to baseline by 16 to 24 days after MPA administration. Conclusions and Clinical Relevance-These data suggest that MPA administration in cats causes plasma volume expansion as a result of an intra- to extracellular fluid shift secondary to glucocorticoid-mediated extracellular hyperglycemia. This mechanism is analogous to the plasma volume expansion that accompanies uncontrolled diabetes mellitus in humans. Any cardiovascular disorders that impair the normal compensatory mechanisms for increased plasma volume may predispose cats to CHF following MPA administration.

Objective-To biomechanically and histologically compare single-layer continuous Cushing and simple continuous appositional cystotomy closure in rats with xylene-induced cystitis. Animals-40 female Sprague-Dawley rats. Procedure-Rats were anesthetized, their urinary bladders catheterized and evacuated, and xylene instilled in each bladder for 5 minutes and then aspirated. Forty-eight hours later, ventral midline celiotomy and cystotomy (8 mm) were performed. Cystotomies were closed with 6-0 poliglecaprone 25 by use of a single-layer continuous Cushing or simple continuous appositional pattern (20 rats/group), and cystotomy times were recorded. Rats were allocated to healing durations (5 rats/group) of 0, 3, 7, and 14 days. Celiotomies were closed in a routine manner. After the allotted healing interval, another celiotomy was performed, the urethra cannulated, and ureters ligated. The cannula was secured to the urethra, and the bladder infused at 0.1 mL/min. Leak pressure volume, leak pressure, peak pressure volume, and peak pressure were recorded via a pressure transducer. Bladders were harvested and histologically assessed. Results-Cystotomy time, biomechanical testing values, and overall inflammation scores did not differ between closure methods for any healing duration. Both methods had significantly greater leak pressures, with the appositional method also having significantly greater peak pressures on day 7, compared to day 0. Biomechanical testing values decreased from day 7 to 14 as a result of juxtaincisional weakening of the bladder and xylene-induced changes in collagen. Conclusions and Clinical Relevance-Simple continuous appositional was equal biomechanically and histologically to continuous Cushing for all comparison variables. Poliglecaprone 25 was acceptable for cystotomy closure.

Objective-To assess the biological response to recombinant feline interferon-omega (rFeIFN-omega) following ocular or oral administration in cats via estimation of Mx protein expression in conjunctival cells (CCs) and WBCs. Animals-10 specific pathogen-free cats. Procedures-In multiple single-dose drug experiments, each cat received various concentrations of rFeIFN-omega administered topically into both eyes (50 to 10,000 U/eye) and orally (200 to 20,000 units). The same cats received saline (0.9% NaCl) solution topically and orally as control treatments. The CCs and WBCs were collected prior to treatment (day 0), on day 1, and every third or seventh day thereafter until samples yielded negative results for Mx protein. Samples were examined for Mx protein expression via immunohistochemistry and immunoblotting procedures involving murine anti-Mx protein monoclonal antibody M143. Results-After topical application of 10,000 U of rFeIFN-omega/eye, CCs stained for Mx protein for a minimum of 7 days, whereas WBCs were positive for Mx protein for a minimum of 31 days. After topical application of lower concentrations, CCs did not express Mx protein, in contrast to WBCs, which stained for Mx protein at 1,000 units for at least 1 day. Following oral administration, Mx protein was expressed in WBCs at rFeIFN-omega concentrations as low as 200 units, whereas CCs did not stain for Mx protein at any concentration. Conclusions and Clinical Relevance-Results indicate that Mx protein expression (a marker of the biological response to rFeIFN-omega) in CCs and WBCs of rFeIFN-omega-treated cats depends on the dose of rFeIFN-omega, site of administration, and cell type.

Objective-To evaluate the efficacy and safety of intra-articular administration of ethyl alcohol for arthrodesis of tarsometatarsal joints in horses. Animals-8 healthy female horses without lameness or radiographic evidence of tarsal joint osteoarthritis. Procedure-In each horse, 1 tarsometatarsal joint was treated with 4 mL of 70% ethyl alcohol and the opposite joint was treated with 4 mL of 95% ethyl alcohol. Lameness examinations were performed daily for 2 weeks, followed by monthly evaluations for the duration of the 12-month study. Radiographic evaluations of both tarsi were performed 1 month after injection and every 3 months thereafter. Gross and histologic examinations of the tarsi were undertaken at completion of the study. Results-Horses had minimal to no lameness associated with the treatments. Radiography revealed that 8 of 16 joints were fused by 4 months after treatment, with significantly more joints fused in the 70% ethyl alcohol group. Fifteen of 16 joints were considered fused at postmortem examination at 12 months. Gross and histologic examinations revealed foci of dense mature osteonal bone spanning the joint spaces. Bony fusion appeared to be concentrated on the dorsolateral, centrolateral, and plantarolateral aspects of the joints. Significant differences were not detected between treatment groups for lameness or pathologic findings. Conclusions and Clinical Relevance-Administration of ethyl alcohol into the tarsometatarsal joint of healthy horses appeared to facilitate arthrodesis of the joint in a pain-free manner. Results warrant further investigation into the potential use of ethyl alcohol in horses clinically affected with osteoarthritis of the tarsometatarsal and distal intertarsal joints.

Objective-To determine the pharmacokinetics of marbofloxacin after single IV and orally administered doses in blue and gold macaws. Animals-10 healthy blue and gold macaws. Procedures-In a crossover study, marbofloxacin (2.5 mg/kg) was administered orally (via crop gavage) to 5 birds and IV to 5 birds. Blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after marbofloxacin administration. After a 4-week washout period, the study was repeated, with the first 5 birds receiving the dose IV and the second 5 birds receiving the dose orally. Serum marbofloxacin concentrations were quantitated by use of a validated liquid chromatography-mass spectrometry assay. Results-After oral administration, mean +/- SD area under the curve was 7.94 +/- 2.08 microgram.h/mL, maximum plasma concentration was 1.08 +/- 0.316 microgram/mL, and bioavailability was 90.0 +/- 31%. After IV administration of marbofloxacin, the apparent volume of distribution was 1.3 +/- 0.32 L/kg, plasma clearance was 0.29 +/- 0.078 L/h/kg, area under the curve was 9.41 +/- 2.84 microgram.h/mL, and the harmonic mean terminal half-life was 4.3 hours. Conclusions and Clinical Relevance-Single IV and orally administered doses of marbofloxacin were well tolerated by blue and gold macaws. The orally administered dose was well absorbed. Administration of marbofloxacin at a dosage of 2.5 mg/kg, PO, every 24 hours may be appropriate to control bacterial infections susceptible to marbofloxacin in this species.

Objective-To investigate the effects of IV administration of ergotamine and ergovaline and intraruminal administration of ergotamine on electromyographic (EMG) activity of reticuloruminal smooth muscle in conscious sheep. Animals-3 sheep with indwelling electrodes in the musculature of the reticulum and rumen. Procedure-In a crossover design study, reticuloruminal motility before and after IV administration of ergotamine (5, 10, 20, and 40 nmol/kg) or ergovaline (2.5, 5, and 10 nmol/kg) was evaluated; EMG effects were compared with those of corresponding control treatments (IV administration of saline 0.9% NaCl solution or acetone, respectively) in sheep. Ergotamine (800 nmol/kg) or water was also administered intraruminally and their effects compared. Results-After IV administration of ergopeptides, vagally dependent cyclical A and B sequences of contraction of the reticulorumen were immediately inhibited, preceding increases in baseline EMG activity (tonus). The return of cyclical contractions was associated with an increase in contraction amplitude. The effects were dose dependent; administration of 40 nmol of ergotamine/kg resulted in responses that continued for 3 to 4 hours. The effects of intraruminal administration of ergotamine were variable; after 8 hours, EMG activity was increased from baseline for < 2 hours in 1 sheep, 10 hours in another, and > 15 hours in the third. Conclusions and Clinical Relevance-In sheep, the effects of ergotamine and ergovaline on reticuloruminal motility after IV administration and the duration of responses following intraruminal administration suggest that disruption of digestion may occur in animals grazing endophyte-infected pasture that has a high ergopeptide content.

Objective-To evaluate the effects of deracoxib and aspirin on serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) in healthy dogs. Animals-24 dogs. Procedure-Dogs were allocated to 1 of 3 groups of 8 dogs each. Dogs received the vehicle used for deracoxib tablets (PO, q 8 h; placebo), aspirin (23 to 25 mg/kg, PO, q 8 h), or deracoxib (1.25 to 1.8 mg/kg, PO, q 24 h) and placebo (PO, q 8 h) for 28 days. Measurement of serum concentrations of T4, T3, fT4, and TSH were performed 7 days before treatment (day -7), on days 14 and 28 of treatment, and 14 days after treatment was discontinued. Plasma total protein, albumin, and globulin concentrations were measured on days -7 and 28. Results-Mean serum T4, fT4, and T3 concentrations decreased significantly from baseline on days 14 and 28 of treatment in dogs receiving aspirin, compared with those receiving placebo. Mean plasma total protein, albumin, and globulin concentrations on day 28 decreased significantly in dogs receiving aspirin, compared with those receiving placebo. Fourteen days after administration of aspirin was stopped, differences in hormone concentrations were no longer significant. Differences in serum TSH or the free fraction of T4 were not detected at any time. No significant difference in any of the analytes was detected at any time in dogs treated with deracoxib. Conclusions and Clinical Relevance-Aspirin had substantial suppressive effects on thyroid hormone concentrations in dogs. Treatment with high dosages of aspirin, but not deracoxib, should be discontinued prior to evaluation of thyroid function.