Biomedical subjects
V R Beasley
Publications and source records attributed to V R Beasley.
The apparently minimal hazard posed to human consumers of products from animals fed trichothecene-contaminated grains.
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Blood lead values in dogs from a rural area (Champaign, IL in 1987).
We studied 87 healthy dogs to determine background levels of blood lead in dogs living in a presumably uncontaminated environment. We took blood samples from dogs and asked their owners for information regarding behavioral risk factors related to environmental lead exposure. The mean blood lead concentration was 5 (+/- 4.4) micrograms/dl (range 0-22 micrograms/dl).
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.
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.
Cottonseed meal (gossypol) toxicosis in a swine herd.
Cottonseed meal (CSM) that contained a high concentration of free gossypol was inadvertently used as a protein supplement, without appropriate iron supplementation, for a swine herd in Illinois. Fifty percent of 300 grower and finishing swine died, and an additional 20% became ill during a 4- to 6-week period. Clinical signs included respiratory distress and abdominal distention. At necropsy, the hearts were diffusely pale, flaccid, and rounded because of dilatation of all 4 chambers, the livers were large and congested, and hydropericardium, hydrothorax, and ascites were evident. Histologic changes consisted of diffuse myocardial fiber atropy with perinuclear vacuolation, and multifocal myocardial and skeletal muscle necrosis. Changes in the liver included marked centrilobular congestion, loss of hepatocytes, and fatty degeneration. Differential diagnoses included monensin, selenium, and gossypol toxicoses, and vitamin E/selenium deficiency. Analyzed feed samples did not contain monensin. Feed selenium concentrations ranged from 428 to 1,513 micrograms/kg, and iron concentrations from 160 to 180 mg/kg. Cottonseed meal (3 to 10%) was detected by feed microscopy. A sample of the 40% protein supplement contained 19% CSM and 1,300 mg of free gossypol/kg, whereas feed samples contained 200 to 400 mg of free gossypol/kg. The history, clinical signs, pathologic findings, and feed analyses were compatible with a diagnosis of gossypol toxicosis. Cottonseed meal, a high-protein supplement used widely in southern United States, may contain gossypol (a polyphenolic binaphthalene pigment), which in its free form is especially toxic to simple-stomached animals. If CSM is used, supplementation with ferrous sulfate is recommended at a 1:1 weight ratio with free gossypol, up to 400 mg of FeSO4/kg.
A new procedure for the analysis and purification of naturally occurring anatoxin-a from the blue-green alga Anabaena flos-aquae.
Anabaena flos-aquae produces at least two neurotoxins termed anatoxin-a (ANTX-a) and -a(s) [ANTX-a(s)]. ANTX-a is a potent postsynaptic depolarizing neuromuscular blocking agent. Its structure is the secondary amine, 2-acetyl-9-azabicyclo[4.2.1]non-2-ene. Known isolation and analysis methods have not always given satisfactory results. Therefore, an improved procedure was developed for both isolation and analysis of ANTX-a which involves four steps; extraction, clean-up, separation and determination. Extraction was efficiently done with 0.05 M acetic acid, and a reversed phase. ODS (octadecylsilanized) and a cation exchanger (COOH) organosilans bonded to silica gels were applied to a clean-up step. Separation and determination were then performed using two TLC and HPLC chromatographies.
Ecosystem health. IV. The National Animal Poison Information Network database as a tool for ecological risk assessment.
Toxicology is a unique discipline in human and veterinary medicine because there are orders of magnitude more toxicants available to man and animals than all known pathogenic microorganisms and parasites. The study of toxicologic responses of ecosystems to contaminants, ecoepidemiology, and the specific study of animal populations in this context, epizootiologic ecotoxicology, are concerned with identifying chemically induced causes and determining effects on and links among populations, communities, and ecosystems. Necessary activities implied by the term "epizootiologic ecotoxicology" are the systematic compilation and analysis of "health" data for ecosystem components. This concept paper describes the value and limitations of adapting methods used by the National Animal Poison Information Network (NAPINet) for epizootiologic ecotoxicology studies. It is concluded that NAPINet methodology, as part of an innovative use of population statistics and clinical measurements, could eventually be adapted into a valuable component of a standardized approach to epizootiologic ecotoxicology.
Ecosystem health. II. Quantifying and predicting ecosystem effects of toxic chemicals: can mammalian testing be used for lab-to-field and field-to-lab extrapolations?
An understanding of the "health" of an ecosystem after exposure to toxic chemicals can be achieved through studies which concentrate on the description of effects on ecosystem homeostasis, identification of disruption, and determination of pathways between these. Studies using native mammals to determine effects of toxicants on terrestrial ecosystems must be designed so that they identify the populations at risk, select appropriate biological effect endpoints, and obtain appropriate numbers and types of samples and contextual ecological data. Accompanying laboratory studies are often needed to complement or confirm observations from the field. Although aquatic biologists routinely use about 10 selected native species for toxicological work, terrestrial biologists seem to prefer using laboratory mammals in "ecotoxicological" studies. Some have advocated using only laboratory rodents in a field setting, while others have suggested using both laboratory mammals and native species. We take the position that there are considerable limitations in the use of laboratory rodents in toxicological studies which purport to be meaningful with regard to prediction of toxicant-induced effects on ecological systems. Nevertheless, we are able to suggest an integrated plan that includes the systematic monitoring of native species in conjunction with laboratory animals exposed in the laboratory and in the field.
Regional brain cholinesterase activity in rats injected intraperitoneally with anatoxin-a(s) or paraoxon.
Adult male Long-Evans rats were injected intraperitoneally with 1.5, 3.0 or 9.0 micrograms/kg of anatoxin-a(s) that had been extracted from laboratory-grown Anabaena flos-aquae NRC-525-17, 800 micrograms/kg of paraoxon, or a control solution. Blood, anterior spinal cord, and brain cerebellar, cortical, medullary, midbrain, hippocampal, hypothalamic, olfactory and striatal cholinesterase activity was determined in rats that died prior to 2 hours or were anesthetized and killed at 2 hours. Unlike paraoxon, anatoxin-a(s) did not cause detectable inhibition of cholinesterase in the central nervous system, but did cause inhibition of cholinesterase in blood, suggesting that anatoxin-a(s) is strictly a peripheral cholinesterase inhibitor.
Algae intoxication in livestock and waterfowl.
Blue-green algae toxins include (1) hepatotoxic peptides that are known to be toxic to cattle, dogs, swine, waterfowl, and sometimes other species; (2) a nicotinic agonist neurotoxin that appears to be toxic to a wide range of animal species; (3) a peripheral-acting cholinesterase inhibitor that is very toxic to swine, birds, and dogs; (4) toxins that impair nervous transmission by blocking sodium channels in nerve cells; and (5) lipopolysaccharide endotoxins. This article provides current information on the mechanisms of action of the primary toxins recognized to date as well as on procedures important in the diagnosis and management of some of the more common cyanobacterial toxicoses in livestock and waterfowl.
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.
A model system for studying the bioavailability of intestinally administered microcystin-LR, a hepatotoxic peptide from the cyanobacterium Microcystis aeruginosa.
Sprague-Dawley rats were used to evaluate a model system for studying the hepatotoxicity caused by microcystin-LR (MCYST-LR), a toxin produced by the cyanobacterium (blue-green alga) Microcystis aeruginosa, and for evaluating the in vivo therapeutic potential of cholestyramine resin (CTR) which was found to bind the toxin in vitro. Female rats were treated with either toxin or an equivalent volume of the saline vehicle by direct administration into the lumen of an in situ isolated ileal loop. Male rats were dosed with toxin as described above, and then animals were dosed in the ileal loop with either cholestyramine resin (CTR, 50 mg/rat) or an equivalent vehicle. The survivors in both studies were killed six hours after dosing and hepatotoxicity was assessed by change in relative liver weights. In all groups given toxin alone, there was a significant increase in liver weight and males and females were equally susceptible. Liver weights of the toxin plus CTR treated rats were similar to those in vehicle-treated rats. When the toxin was administered into a similarly isolated jejunal loop, liver weight was significantly less than that found when an equivalent dose was administered into the ileal loop suggesting an intestinal site specificity for toxin absorption.
Toxicity of microcystin LR, a cyclic heptapeptide hepatotoxin from Microcystis aeruginosa, to rats and mice.
Rats (Sprague-Dawley) and mice (Balb/c) were given microcystin LR intraperitoneally and were killed at intervals up to 24 hr (rats) or 90 min (mice) and necropsied. The lowest consistently lethal dose was 160 micrograms/kg in rats and 100 micrograms/kg in mice. Rats that were clinically unaffected had no lesion. All clinically affected rats in all dose groups died (from 20 to 32 hr after toxin) and had similar hepatic lesions. Livers were enlarged and dark red beginning 40 to 60 min after toxin. Mild disassociation and rounding of centrilobular hepatocytes developed within 20 min. By 60 min after toxin, degeneration and necrosis of hepatocytes involved most of the lobules except for small periportal zones. Weights of livers and kidneys were significantly increased. Eosinophilic fibrillar material filled renal glomerular capillaries as early as 9 hr after toxin. At 18 to 24 hr there was moderate vacuolation of proximal tubular epithelium with mild tubular dilatation. Beginning at 1 hr, intact hepatocytes and hepatic debris were present in pulmonary vessels. Analysis of serum revealed an increase in alanine aminotransferase 40 min after toxin; at 6 to 12 hr there were significant increases in alkaline phosphatase, total bilirubin, blood urea nitrogen, and creatinine. Mice survived only 60 to 90 min after toxin. Hepatic lesions were similar to those in rats, but renal and pulmonary lesions were not seen.
Preliminary studies with bovine retina cholinesterase determinations in organophosphorus insecticide poisoning.
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Diagnostic and clinically important aspects of cyanobacterial (blue-green algae) toxicoses.
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Effect of anatoxin-a(s) from Anabaena flos-aquae NRC-525-17 on blood pressure, heart rate, respiratory rate, tidal volume, minute volume, and phrenic nerve activity in rats.
The effects of anatoxin-a(s) [antx-a(s)] from the cyanobacterium Anabaena flos-aquae NRC-525-17 on mean arterial blood pressure, heart rate, respiratory rate, tidal volume, minute volume, and phrenic nerve activity were evaluated in anesthetized Sprague-Dawley rats. Anatoxin-a(s) was administered by continuous intravenous infusion. The initial effect of the toxin was to slow the heart rate and reduce arterial blood pressure, followed by much more pronounced reductions in these parameters. The marked decline in heart rate and blood pressure frequently occurred before there was a large decrease in respiratory minute volume [reduced by only 15.4 +/- 3% (mean +/- S.E.) compared to the predose period], suggesting that antx-a(s) has an important muscarinic action on the cardiovascular system in vivo. Phrenic nerve amplitude increased, but, nevertheless, tidal and minute volumes decreased progressively, indicating that antx-a(s), unlike most low-molecular-weight organophosphorus cholinesterase inhibitors, does not have any remarkable inhibitory action on central mediation of respiration.
The pharmacokinetics of chlorinated phenoxy acid herbicides: a literature review.
The chlorinated phenoxy acid herbicides (CPAHs) appear to have similar pharmacokinetics. They are rapidly and almost completely absorbed from an oral dose. They distribute to other tissues and are highly protein-bound in the plasma. The CPAHs are rapidly eliminated unchanged in the urine by an active process in the kidneys. Increasing doses apparently influence absorption, metabolism, distribution and elimination of the CPAHs so that biological effects are increased. Combinations of CPAHs are likely to result in additive or potentiated biological effects. Data suggest that CPAH toxicosis may be alleviated by treatment with fluids and bicarbonate to increase urinary pH and volume, thereby increasing excretion.