Comparison of two heavy metal chelators for treatment of lead toxicosis in cockatiels.

OBJECTIVE: To compare efficacy and safety of meso-2,3-dimercaptosuccinic acid (DMSA) and Ca EDTA for treatment of experimentally induced lead toxicosis in cockatiels (Nymphicus hollandicus). ANIMALS: 137 (69 females, 68 males) healthy cockatiels between 6 months and 8 years old. PROCEDURE: Lead toxicosis was induced by placing lead shot in the gastrointestinal tract. Treatment with Ca EDTA (40 mg/kg of body weight, IM, q 12 h), DMSA (40 or 80 mg/kg, PO, q 12 h), and sodium sulfate salts (SSS; 0.5 mg/kg, PO, q 48 h) was initiated 4 days after induction of lead toxicosis. Blood lead concentrations were determined, using atomic absorption spectrophotometry. Number of birds surviving and blood lead concentrations were compared among groups. RESULTS: In Phase II of the study, administration of DMSA and Ca EDTA significantly decreased blood lead concentrations when used alone or in combination in birds with lead toxicosis. Addition of SSS did not result in further decreases in lead concentrations. Eight of 12 (66.7%) birds without lead toxicosis given 80 mg of DMSA/kg did not survive to the end of the study. Lesions related to treatment with chelating agents were not detected during necropsy. CONCLUSIONS AND CLINICAL RELEVANCE: DMSA and Ca EDTA are effective chelating agents in cockatiels. Because DMSA is administered orally, it may be easier than other chelating agents for bird owners to administer at home. However, the narrow margin of safety of DMSA indicates that this agent should be used with caution.

Selenium elimination in pigs after an outbreak of selenium toxicosis.

In May 1996, 150 grower pigs in 5 California counties were exposed to selenium-contaminated feed distributed by a single feed company. Feed samples from 20 herds had a mean selenium concentration of 121.7 ppm dry weight (range, 22.1-531 ppm). In San Luis Obispo County, 52 pigs in 24 herds were exposed to the feed, and 8 pigs died with signs of paralysis. Bilateral symmetrical poliomyelomalacia involving the ventral horns of the cervical and lumbar intumescence was evident on histologic examination of spinal cord from affected pigs. Of 44 surviving exposed pigs, 33 (75%) exhibited signs of selenosis, including anorexia, alopecia, and hoof lesions. Thirty-nine of 44 pigs (88.6%) had elevated (>1 ppm) blood selenium concentrations. Surviving exposed pigs were changed to a standard commercial ration containing approximately 0.5 ppm (dry weight) selenium. Blood selenium concentrations were determined weekly for 46 days following removal of the contaminated feed and were compared with values of 20 control pigs fed a standard commercial ration. Mean (+/-SD) blood selenium concentrations of exposed pigs were 3.2 +/- 2.6 ppm at the initial sampling and 0.4 +/- 0.1 ppm after 46 days. Mean blood selenium concentrations of < or = 0.3 ppm for control pigs at all samplings were significantly lower (P < 0.001) than concentrations for exposed pigs. Muscle and liver samples of 22 of the 44 exposed pigs were collected at slaughter approximately 72 days after withdrawal of the selenium-contaminated feed. Muscle samples had a mean selenium concentration of 0.36 ppm (wet weight). Liver samples had a mean selenium concentration of 1.26 ppm (wet weight). One liver sample had a selenium value in the toxic range for pigs (3.3 ppm wet weight; reference range, 0.4-1.2 ppm). A 1-compartment pharmacokinetic model of selenium elimination in exposed pigs was generated, and the geometric mean blood selenium elimination half-life was estimated to be 12 days. The 60-day withdrawal time recommended by the Food Animal Residue Avoidance Database was considered sufficient to allow safe human consumption of tissues from exposed pigs.

Sweet clover poisoning in dairy cattle in California.

Eight of 600 Holstein heifers and cows died after ingestion of sweet clover silage (Melilotus sp) that contained excessive concentrations of dicumarol caused by mold infestation. The cattle developed subcutaneous hemorrhages and bled from the vagina, became weak, were unable to move, and died. To the best of our knowledge, this is the first report of sweet clover poisoning in cattle from California and is discussed in light of previous findings in the Midwest and Canada. Sweet clover poisoning is caused by dicumarol, a fungal metabolite produced from substrates in sweet clover, and is a common livestock problem in the Northern Plains and Canada. Sweet clover poisoning should be considered in livestock animals with clinical evidence of hemostatic dysfunction, prolonged coagulation times, subcutaneous hemorrhages, and hemorrhagic abortions. Definite diagnosis of moldy sweet clover poisoning can be accomplished by analysis of serum and feed samples for dicumarol concentrations.

Intramuscular selenium administration in selenium-deficient cattle.

Nine recently weaned Hereford heifers were randomly assigned to a control group (n = 3) or a treatment group (n = 6). The animals were selenium (Se) deficient (mean +/- SD blood Se concentration = 0.024 +/- 0.012 microgram/mL). They were maintained on a selenium-deficient diet, and on day 0 of the study the treatment group was given 0.05 mg Se/kg body weight intramuscularly, while the control group received a placebo. The Se concentration of blood, serum, and urine as well as the glutathione peroxidase (GSH-Px) activity of blood and serum was measured over an 84-day period. Peak blood Se and serum Se concentrations (mean +/- SD) in the treatment group occurred at 5 hours postinjection and were 0.131 +/- 0.028 microgram/mL and 0.154 +/- 0.027 microgram/mL, respectively. The mean blood Se concentration of the treatment group was greater (P < .05) than that of the control group for the first 28 days after injection. The mean serum Se concentration of the treatment group was greater (P < .05) than that of the control group for all times after injection, except for day 56. The mean (+/- SD) blood GSH-Px activity of the treatment group (12.0 +/- 2.3 mU/min/mg hemoglobin) was increased (P < .05) over the control group (2.0 +/- 1.4 mU/min/mg hemoglobin) by day 28 and continued to be greater (P < .05) throughout the 84 day postinjection period.(ABSTRACT TRUNCATED AT 250 WORDS)

The correlation between serum selenium and blood selenium in cattle.

The selenium (Se) concentration of paired blood and serum samples from cattle was determined by 2 methods: 1) atomic absorption spectroscopy using hydride generation (HG-AAS), and 2) inductively coupled argon plasma emission spectroscopy using hydride generation (ICP). Samples from 327 cattle were analyzed by HG-AAS, and samples from 344 cattle were analyzed by ICP. The data were examined by linear regression analysis, and the technique of inverse prediction was utilized to determine prediction intervals for estimating blood Se concentration from known serum Se concentration. The correlation coefficients, by simple linear regression of serum Se on blood Se, were 0.79 (r2 = 0.62) and 0.88 (r2 = 0.77) for the HG-AAS data and the ICP data, respectively. For the HG-AAS data, the inverse prediction formula for estimating blood Se when serum Se is known, at the 95% prediction interval, was [formula; see text]. For the ICP data, the inverse prediction formula for estimating blood Se when serum Se is known, at the 95% prediction interval, was [formula; see text]. The prediction intervals were quite wide, and the accuracy of estimating blood Se from a known serum Se was not useful for diagnostic purposes. The use of serum Se concentration to assess nutritional status of cattle with respect to Se does not appear to be appropriate.

Black walnut (Juglans nigra) toxicosis: a model for equine laminitis.

Twelve light horse geldings developed laminitis within 8 to 12 h of being dosed by nasogastric tube with an aqueous extract of black walnut (Juglans nigra). Four of the 12 horses developed the severe signs of grade 3 laminitis (lame at a walk, refused to lift feet). Laminitis was accompanied by mild depression and limb oedema. There was no evidence of shock or colic. The horses developed neutropenia by 4 h after dosing with the extract, which shifted to a relative neutrophilia by 8 to 12 h. Minimal increases in plasma epinephrine and cortisol concentrations were suggested in severely affected horses. Severe laminitis was characterized by necrosis of dermal tips of dorsal primary epidermal laminae. A proliferative epithelial response in these laminae was distinguished by numerous mitotic figures and clusters of epithelial cells. This evidence suggests that black walnut toxicosis is not only a consistent clinical model, but is also a reliable clinico-pathological and pathological model for study of the pathogenesis and treatment of laminitis.

Forage-related nitrate toxicoses possibly confounded by nonprotein nitrogen and monensin in the diet used at a commercial dairy heifer replacement operation.

Two clinically different episodes of nitrate toxicosis in heifers at the same dairy were evaluated to determine whether dietary supplements could have contributed to the confounding signs of illness. The first episode followed a 24-hour period of feeding mismanagement and resultant overconsumption of both a protein/nonprotein nitrogen supplement and a monensin supplement. This episode was characterized by ataxia, bloating, and death, without the classic clinical signs of dyspnea, salivation, cyanosis, and dark-colored blood, or the cardinal histologic changes of cyanosis, tissue staining, petechiations, or congestion. Approximately 5 weeks later, another episode developed, without the feeding mismanagement or the presence of supplements, and was characterized by classic signs of nitrate toxicosis along with response to methylene blue treatment. In both episodes, the feed source was the same, with high concentrations of nitrate. Heifers of both episodes had high ocular nitrate values, confirming the toxicoses. The difference was the availability of supplements. Calculation of exposure makes it unlikely that either the nonprotein moiety or the monensin moiety could have reached toxic values. However, the cell-level effects of monensin may have caused the animals to not display classic signs of nitrate toxicosis, confusing the diagnosis and treatment. This report demonstrates how field toxicosis can differ from reports of toxicoses caused by single etiologic agents. Practitioners must be aware of the potential for interactions between (and confounding by) commercially used feed components.

Gamma scintigraphic analysis of the distribution of perfusion of blood in the equine foot during black walnut (Juglans nigra)-induced laminitis.

Twelve horses, with acute laminitis (primarily in the forefeet) at 12 hours after intragastric dosing with an aqueous extract of black walnut (Juglans nigra) heart-wood, were studied. The distribution of perfusion of blood to the foot and to outlined regions within the foot was quantified, using gamma scintigraphy of regionally infused 99mTc-labeled macroaggregated albumin, before and 12 hours after extract administration. Horses 1 to 3 were not studied further. Perfusion was quantified again for horses 4 to 12 at 84 hours after extract administration. At the onset of acute laminitis, horses 7 to 12 were administered a single dose of prazosin (0.025 mg/kg of body weight, IV) immediately after scintigraphy of the right forelimb and before scintigraphy of the left forelimb. When compared with baseline images, perfusion to the forefoot of horses after the development of acute laminitis was quantitatively decreased vs perfusion to the entire distal portion of the forelimb. Also with the onset of laminitis, perfusion also decreased to the dorsal laminar and coronary corium regions vs the distal portion of the forelimb. The acute laminitis-associated deficit in perfusion to the dorsal laminitis-associated deficit in perfusion deficit in perfusion to either the coronary corium or the entire forefoot. Equivalent deficits in the distribution of perfusion were not detected in forelimbs from horses with acute laminitis and which had been treated with prazosin. When compared with baseline images, perfusion to the dorsal lamina was increased in relation to perfusion to the distal portion of the limb at postdosing hour 84. Prazosin treatment did not influence that increase in perfusion to the dorsal lamina.

Effect of an aqueous extract of black walnut (Juglans nigra) on isolated equine digital vessels.

An aqueous extract was made from black walnut (Juglans nigra) heartwood obtained in the fall of the year. Ten hours after nasogastric administration of 5 L of the extract, a 550-kg, 13-yr-old Quarter Horse gelding experienced Obel grade-3 laminitis. The effect of aqueous extract of black walnut on vascular contractility was then tested, using isolated equine digital arteries and veins. The vessels were maintained in Krebs bicarbonate buffer with 95% oxygen at 37 C. The extract did not induce a direct contractile effect. It did, however, reversibly enhance the vasoconstriction induced in the isolated vessels by administration of epinephrine potentiated with hydrocortisone. In contrast, aqueous extracts made, using the same techniques, from the shavings of eastern white pine (Pinus strobus), eastern red cedar (Juniperus virginiana), and pin oak (Quercus palustrus) had no effect on epinephrine-induced digital vessel contractions.

Antagonism in isolated equine digital vessels of contraction induced by epinephrine in the presence of hydrocortisone and an aqueous extract of black walnut (Juglans nigra).

Prazosin, isoxsuprine, and nifedipine were screened for ability to reverse contraction of isolated equine digital vascular strips produced by epinephrine (Epi) in the presence of hydrocortisone (Hc) and an aqueous extract of black walnut (Juglans nigra) (BW). Two arteries and two veins from each of three horses for each drug (n = 9) were maintained in isolated tissue baths in Krebs' bicarbonate buffer with 95% oxygen at 37 degrees C. Six-point Epi concentration-response (C-R) curves were obtained for each vessel in the presence of Hc, BW, and the appropriate vehicle. This was repeated for each vessel using one of two concentrations of one of the three test drugs. Each drug and concentration combination was tested on a total of three arteries and three veins. Prazosin produced a concentration-dependent shift of the Epi C-R curve to the right but the curve maintained the same maximum height and slope, which is consistent with competitive alpha 1 adrenergic blockade. Isoxsuprine exhibited similar behavior, although the precise mechanism of action for isoxsuprine is unknown. Conversely, nifedipine did not shift the curve but did depress maximum contraction, suggesting a non-competitive interaction consistent with its mechanism of calcium-channel blockade.

Therapeutic efficacy of superactive charcoal in rats exposed to oral lethal doses of T-2 toxin.

Superactive charcoal, a compound known to complex with many toxins, was evaluated in this study for its effectiveness in preventing death in rats given an oral lethal dose of 8 mg/kg body weight of T-2 toxin. The median effective dose of oral superactive charcoal in preventing deaths in rats was 0.175 g/kg body weight. Concurrent use of cathartics, such as sorbitol, magnesium sulfate and sodium sulfate, to facilitate removal of the superactive charcoal:T-2 toxin complex formed in vivo did not enhance the survival rates of rats. One gram per kilogram body weight oral superactive charcoal enhanced survival times and survival rates in rats given 8 mg/kg of T-2 toxin as late as 3 hr after the T-2 toxin was administered. Some benefit in survival rate may be derived from giving the superactive charcoal as late as 5 hr after the T-2 toxin.