Biomedical subjects

V R Beasley

Publications and source records attributed to V R Beasley.

At least 37 records · Page 2Linked to original sources

PubMed1991

Uptake and subcellular localization of tritiated dihydro-microcystin-LR in rat liver.

Microcystin-LR (MC-LR), a cyclic heptapeptide hepatotoxin (mol. wt = 994) produced by the blue-green alga (cyanobacterium), Microcystis aeruginosa, was reduced with tritium labeled sodium borohydride, converted to [3H]-dihydro-microcystin-LR ( [3H]-2HMC-LR), and purified to greater than 99% purity by C-18 reverse-phase high-performance liquid chromatography. The uptake and subcellular distribution of [3H]-2HMC-LR were determined in suspensions of hepatocytes at 0 degrees C and 37 degrees C, or following rifampicin pretreatment, and in perfused rat liver. The remaining cells were homogenized and subfractionated using sucrose gradient centrifugation. Suspensions of 7.5 x 10(6) hepatocytes also were incubated with 10 micrograms/ml of toxin, solubilized in Triton X-100, and ultracentrifuged to pellet the detergent insoluble fraction (containing actin). Isolated rat livers were perfused with media containing [3H]-2HMC-LR and the uptake of radiolabel was determined. Sequential biopsy samples were collected for histologic examination. The remaining liver was homogenized and subcellular fractions prepared. Uptake of radiolabel was rapid in both cell suspension at 37 degrees C and perfused liver; however, uptake in cell suspensions was reduced by about 50% at 0 degrees C and by rifampicin (50 micrograms/ml) pretreatment. Hepatocyte necrosis was observed in isolated perfused livers 45 min after initiation of perfusion with [3H]-2HMC-LR. In both hepatocyte suspensions and perfused livers 65 to 77% of the radiolabel was in the cytosolic fraction. In the hepatocyte suspensions, 13 to 18% of the radiolabel was present in the plasma membrane/nuclear fraction with lesser amounts in the other fractions. Trichloroacetic acid treatment of cytosolic fractions indicated that in hepatocyte suspensions, 50-60% of the radiolabel was bound to cytosolic protein. Studies using the perfused liver confirmed that the majority of the radiolabeled MCLR (78-88%) was bound to cytosolic protein. These data suggest that the uptake of [3H]-2HMC-LR occurs primarily by an energy-dependent transport process involving the rifampicin-sensitive hepatic bile acid carrier and that once inside the hepatocyte, the toxin binds to a cytosolic protein(s).

Animals↗

PubMed1991

Electromyographic assessment of the neuromuscular blockade produced in vivo by anatoxin-a in the rat.

The indirectly evoked compound action potentials (ECAP) of the plantar muscles of the rat were used to investigate the pharmacodynamics in vivo of the neuromuscular blockade produced by anatoxin-a. Onset time to maximum depression and the magnitude of maximum depression in amplitude of the ECAP were dose-dependent. The mean maximum percent depression (+/- S.D.) of the ECAP induced by single, supramaximal stimulations of the posterior tibial nerve after i.v. doses of (+)anatoxin-a hydrochloride at 0, 50, 100, 200 and 800 micrograms/kg were 3 (4), 53 (15), 82 (7), 95 (2), and 100 (1), respectively. The ED50 (95% confidence limits) for depression of the ECAP was 47 mg/kg (39-57 micrograms/kg). Rats administered 200 micrograms/kg or less of (+)anatoxin-a hydrochloride had 75% return of the pretoxin amplitude of the ECAP within 93 min. Animals dosed at 800 micrograms/kg did not have return of neuromuscular function and died despite mechanical ventilation, suggesting a lethal mechanism(s) of action in addition to respiratory paralysis. Percent decrements (+/- S.D.) in the amplitude of the fourth ECAP following repetitive stimulation at 10 Hz were 6 (5), 13 (22), 46 (18) and 59 (8) from (+)anatoxin-a hydrochloride given i.v. at 0, 50, 100 and 200 micrograms/kg, respectively. The decrement observed following repetitive stimulation was attributed to a presynaptic site of action. No change in maximal motor nerve conduction velocity or latency of the ECAP was observed after i.v. administration of (+)anatoxin-a hydrochloride at 100 micrograms/kg. LD50 values (95% confidence limits) for anatoxin-a administered i.v. to mice were 386 micrograms/kg (365-408 micrograms/kg, for (+)anatoxin-a hydrochloride and 913 micrograms/kg (846-985 micrograms/kg) for racemic anatoxin-a hydrochloride. No deaths were observed in mice after i.p. administration of (-)anatoxin-a hydrochloride at doses up to 73 mg/kg.

Action Potentials↗

PubMed1991

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.

Animals↗

PubMed1991

Actin filament alterations in rat hepatocytes induced in vivo and in vitro by microcystin-LR, a hepatotoxin from the blue-green alga, Microcystis aeruginosa.

The morphologic effects of microcystin-LR (MCLR) were examined in vitro and in vivo to identify the specific cell type(s) affected and to characterize the actin filament changes occurring in hepatocytes. Male Sprague Dawley rats were used for all studies. For in vitro studies, hepatic cells were isolated by collagenase perfusion of liver, while parenchymal cells (hepatocytes) and nonparenchymal cells were prepared by pronase digestion and metrimazide gradient centrifugation. Cell suspensions and and primary hepatocyte monolayer cultures were treated with MCLR at doses up to 10 micrograms/ml; cultured hepatocytes were also treated with phalloidin or cytochalasin B at a dose of 10 micrograms/ml; and rats were treated intraperitoneally with MCLR at 180 mg/kg. Cultured hepatocyte preparations and frozen liver sections were stained with rhodamine-labeled phalloidin for filamentous actin. In cell suspensions, MCLR did not affect nonparenchymal cells but caused rapid, progressive, blebbing of the plasma membrane in hepatocytes. In cultured hepatocytes, MCLR caused plasma membrane blebbing as well as marked reorganization of actin microfilaments. These alterations were dose and time dependent. Cultured hepatocytes treated with phalloidin or cytochalasin B also showed extensive plasma membrane blebbing and actin filament alterations; however, actin filament changes were morphologically distinct from those induced by MCLR. In vivo, MCLR-induced hepatocyte actin alterations occurred at the same time as, or slightly preceded, histologic changes that began 30 minutes after dosing. These studies suggest that early MCLR-induced morphologic changes occurring both in vivo and in vitro are due to alterations in hepatocyte actin filaments.

Actins↗

PubMed1991

Neurotoxicology of pyrethrin and the pyrethroid insecticides.

Natural pyrethrin and synthetic pyrethroid insecticides have been considered among the safest classes of insecticides available. Pyrethrins and pyrethroids are classified on the basis of their chemical structures and their toxicologic, neurophysiologic and pharmacologic effects. Cellular effects of pyrethrin and pyrethroid insecticides have been postulated to involve interactions with sodium channels, receptor-ionophore complexes, neurotransmitters, and ATPases. Toxicity is a function of chemical structure, metabolism, route of exposure, and the presence or absence of synergists. Pyrethroid insecticides are neurotoxic, and the development and severity of clinical signs is proportional to the nervous tissue pyrethroid concentration. Type I pyrethroid poisoning in mice and rats produces a syndrome characterized by tremors, prostration and altered startle reflexes. Type II pyrethroid poisoning in mice and rats causes ataxia, convulsions, hyperactivity, choreoathetosis and profuse salivation. A presumptive diagnosis of pyrethrin/pyrethroid poisoning is based upon history of exposure, development of appropriate clinical signs, and chemical analysis for insecticide residues. Treatment of pyrethrin and pyrethroid toxicosis involves basic life support, seizure control when needed, and the prevention of further insecticide absorption.

Animals↗

PubMed1991

2,4-D toxicosis. I: A pilot study of 2,4-dichlorophenoxyacetic acid- and dicamba-induced myotonia in experimental dogs.

English Pointer dogs dosed po with encapsulated 2,4-dichlorophenoxyacetic acid (2,4-D) or 2-methoxy-3,6-dichlorobenzoic acid (dicamba) developed varying degrees of myotonia. Dogs given 175 or 220 mg of 2,4-D/kg body weight rapidly developed clinical and electromyographic (EMG) manifestations consistent with a diagnosis of myotonia or pseudomyotonia. Dogs given 2,4-D at 86.7, 43.7 or 8.8 mg/kg body weight developed subclinical manifestations of myotonia detectable only with an electromyograph. The administration of 2,4-D at 1.3 or 1.0 mg/kg body weight failed to produce detectable EMG changes. One dog given dicamba at 86.7 mg/kg body weight developed clinical and EMG manifestations of myotonia similar to those induced by the highest doses of 2,4-D.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1991

2,4-D toxicosis.II: A pilot study of clinical pathologic and electroencephalographic effects and residues of 2,4-D in orally dosed dogs.

English pointer dogs dosed po with encapsulated 2,4-dichlorophenoxyacetic acid (2,4-D) at 1.3, 8.8, 43.7, 175 or 220 mg/kg body weight failed to exhibit abnormalities in hematologic, serum biochemical, urinalysis, or electrocardiographic parameters. At the 3 lowest doses, no changes were noted in electro-encephalograms (EEGs). In the dog given 175 mg/kg, at 24 h postdosing mild sedation was accompanied by excessive slowing in the EEG with loss of low voltage fast activity. In the dog given 220 mg/kg, nonspecific alterations in the EEG suggestive of irritation and mild seizure activity was detected 7 h, but the EEG returned to normal by 24 h. A maximum 2,4-D concentration in serum of 1075 ppm was detected 5 h after a po dose of 220 mg/kg. A maximum 2,4-D, concentration in urine of 1792 ppm was detected 2 h after a po dose of 175 mg/kg, while 25 h after that dose kidney issue contained 271 ppm.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1991

2,4-D toxicosis.III: An attempt to produce 2,4-D toxicosis in dogs on treated grass plots.

Eighteen English pointer dogs were randomly assigned to 3 outdoor grass-plot enclosures (6/enclosure) uniformly sprayed once with either the 2,4-dichlorophenoxyacetic acid (2,4-D) dimethylamine formulation (DMA-4) at the maximum recommended application rate, DMA-4 at 4 times the maximum recommended application rate, or the DMA-4 vehicle alone at 4 times the maximum recommended application rate. A heavy rain shower occurred 24 h after application. The dogs were observed for clinical signs and evaluated using an electroencephalograph, electrocardiograph (lead I), and electromyograph prior to exposure, and either 1 or 7 d after continuous exposure. Clinical examination, hematologic and serum biochemical data were obtained, and serum, urine and kidney 2,4-D were quantified. Half of the dogs from each group were killed after 1 d of continuous exposure, while the other half were killed after 7 d. Gross postmortem and histologic examinations were conducted on each dog. No obvious 2,4-D effects were detected in any of the dogs.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1991

Regional brain blood flow in swine following T-2 toxin administration.

Three groups of swine (6/group) were used to assess alterations in regional brain blood flow induced by T-2 toxin. One group served as vehicle (70% ethanol) control, and groups were dosed intravascularly with T-2 toxin at 0.6 or 2.4 mg/kg body weight. Cerebral, cerebellar, and brain stem blood flows were evaluated at 0 h (predosing) and at 90-min intervals for 6 h postdosing. Fifteen-micron diameter radionuclide labeled microspheres were used to determine blood flow. Hemodynamic variables were determined at the same time points. The infusion of T-2 toxin resulted in dose-dependent reductions in both cardiac index and mean arterial pressure, accompanied by significant increases in heart rate. In animals given the lower dose of T-2 toxin, significant reductions in blood flow were evident in the cerebrums and cerebellum but not in the brain stem. Reductions in blood flow to all regions of the brain were evident in those animals given 2.4 mg T-2 toxin/kg. Brain blood flow was less severely compromised than was cardiac output, suggesting intact local autoregulation.

Animals↗

PubMed1991

Reversal of cholinesterase inhibition and clinical signs and the postmortem findings in mice after intraperitoneal administration of anatoxin-a(s), paraoxon or pyridostigmine.

The reversibility of inhibition of plasma, red blood cell (RBC), and diaphragm cholinesterase (ChE) and clinical signs in mice given anatoxin-a(s) [antx-a(s)], a ChE inhibitor from Anabaena flos-aquae NRC-525-17, were characterized and compared with the effects of 2 known ChE inhibitors, the organophosphorus compound paraoxon and the carbamate pyridostigmine bromide. To follow recovery of ChE activity, mice were given either a control solution or an LD40 dose of one of the toxicants ip and killed at time points up to 8 d postdosing. After dosing, mice were monitored for diarrhea, fasciculations, respiratory difficulty, salivation, and tremors. In general, clinical signs in mice given antx-a(s) persisted longer than in mice given pyridostigmine and were more similar in duration to the clinical signs in mice given paraoxon. Histologic lesions were not detected in tissues of mice killed after administration of antx-a(s). Anatoxin-a(s) inhibited lesions were diaphragm ChE for greater than 1 but less than 2 d and RBC ChE for 8 d. The time required for recovery from Antx-a(s)-induced inhibition of ChE in plasma, RBC, and diaphragm was similar to or longer than that with paraoxon and longer than that with pyridostigmine. Based on the duration of antx-a(s) induced clinical signs and ChE inhibition in mice, antx-a(s) appears to be an in vivo irreversible inhibitor of ChE.

Animals↗

PubMed1990

Algal poisoning.

Explore the source record for details and available documents.

Animal Diseases↗

PubMed1990

Emergency treatments for police dogs used for illicit drug detection.

The key to saving police dogs that have been exposed to large quantities of illicit substances is rapid action. Removal from the gastrointestinal tract, adsorption, and catharsis are the first steps. Some of these measures can be instituted on site by the attending officer. In case of accidental drug exposures of a dog during a search, police officers should have on hand apomorphine, syringes for administration of the drug and rinsing of the conjunctival sac, activated charcoal, a saline cathartic such as sodium sulfate (not needed if the activated charcoal product contains sorbitol), a resuscitator bag, and a well-fitting canine face mask. If bags of drugs are ingested intact, immediate surgery by a veterinarian may be required to remove the bag and prevent an obstruction or rapid absorption of a lethal dose. Injectible medications to antagonize the effects of the drugs should be reserved for administration by a readily available veterinarian upon arrival of the dog at the veterinary hospital. Pharmacologic antagonistic agents may have adverse side effects, especially if used in the treatment of a drug exposure against which they are not specifically indicated. Proper dosage and route of administration are additional important factors with such treatment. The veterinarian must instruct the police officers on the proper use, dosages, and methods of administration of the detoxifying agents as well as the proper procedures for using the face mask and resuscitator bag before an emergency arises. The officer should also be aware of the clinical signs likely to be produced following exposure to the agents for which these dogs search.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamines↗

PubMed1990

Fenvalerate/N,N-diethyl-m-toluamide (Deet) toxicosis in two cats.

Toxicosis attributable to fenvalerate and N,N-diethyl-m-toluamide (Deet) exposure was suspected in 2 cats. Clinical signs of toxicosis developed within 4 to 6 hours of dermal application of the pesticide. Clinical signs of toxicosis seen in both cats included hypersalivation, ataxia, and depression. In addition, seizures were seen in 1 cat. Both cats died. Analysis of skin, kidney/urine, liver, and brain tissues confirmed the presence of fenvalerate and Deet. The pyrethroid fenvalerate and the insect repellent Deet are used for the control of fleas and ticks on cats. Suspected fenvalerate/Deet toxicosis in cats is associated with tremors, hypersalivation, ataxia, vomiting, depression, and seizures.

Animals↗

PubMed1990

Isolation and characterization of the minor components associated with microcystins LR and RR in the cyanobacterium (blue-green algae).

Two structurally similar analogues of microcystins LR and RR, cyclic peptide hepatotoxins from Microcystis, were isolated by chromatographic methods. Although they have the same mol. wt and amino acid compositions as those of the parent toxins, they do not possess similar toxicities. Ultraviolet and 1H-NMR spectral data for both components demonstrate clear structural difference of these cyclic peptides from the parent toxins, which are probably responsible for the marked decreases in their observed toxicities.

Amino Acids↗

PubMed1990

Management of toxicoses.

This article provides information on the detoxification of and supportive care for poisoned animals. Involved are measures to control life-threatening manifestations of toxicoses, to remove agents from the digestive tract, skin, or eyes, and to promote removal of systemically absorbed toxicants. The use of these methods is often of paramount importance in an effort to limit organ damage and to enable a poisoned animal to survive.

Animals↗

PubMed1990

Toxicology of selected pesticides, drugs, and chemicals. Smoke inhalation.

Animals with smoke inhalation should be given a thorough diagnostic evaluation. Optimal care relies on the information derived, as well as judicious choice of therapeutic measures. Careful attention to such animals by the veterinarian and allied staff is important to minimize suffering and to enhance not only the likelihood of survival, but also the extent of recovery.

Animals↗

PubMed1990

Pathophysiologic effects of anatoxin-a(s) in anaesthetized rats: the influence of atropine and artificial respiration.

The pathophysiologic effects of anatoxin-a(s) from the cyanobacterium Anabaena flos-aquae NRC-525-17 were investigated in anaesthetized adult male Sprague Dawley rats given the toxin by continuous intravenous infusion until death. Rats (n = 6) pretreated with atropine sulfate (50 mg/kg) intraperitoneally survived significantly longer (P less than 0.05) than non-atropinized rats (n = 6), suggesting that the muscarinic effects of anatoxin-a(s) were important in the lethal syndrome. In contrast to rats only given toxin, rats that were pretreated with atropine had a decrease in heart rate and mean blood pressure that followed profound reductions in respiratory tidal and minute volume, suggesting that neuromuscular blockade of the muscles of respiration was the cause of death. Even when survival time of rats was increased by pretreatment with atropine, phrenic nerve amplitude increased, indicating a lack of a depressive effect of anatoxin-a(s) on central mediation of respiration. Rats (n = 3) continuously ventilated during toxin infusion survived a dose more than 4 fold greater than a consistently lethal dose of the toxin. Thus, the cardiovascular effects of anatoxin-a(s) alone could not account for the death of rats. Electromyographic activity recorded from the diaphragms of rats (n = 5) during continuous toxin administration revealed an increase in muscular electrical activity that became more random and finally decreased prior to death, suggesting a toxin-induced neuromuscular blockade in vivo which ultimately was the cause of death of the anatoxin-a(s) dosed rats.

Anesthesia, Inhalation↗

PubMed1990

Microcystin-LR-induced ultrastructural changes in rats.

The ultrastructure of hepatic, pulmonary, and renal lesions was evaluated in rats injected intraperitoneally with a lethal dose of microcystin-LR (MCLR, 160 micrograms/kg), a cyclic heptapeptide hepatotoxin produced by the blue-green algae, Microcystis aeruginosa. Hepatic lesions were first seen at 10 minutes post-dosing and consisted of mild widening of hepatocyte intercellular spaces centrilobularly. At 20 minutes post-dosing, hepatocyte plasma membrane alterations were more pronounced, consisting of plasma membrane invagination with formation of variably sized and shaped intracytoplasmic vacuoles, loss of microvilli along the sinusoidal face, and widespread, pronounced hepatocyte separation. By 30 minutes, the space of Disse was markedly widened. At 60 minutes post-dosing, centrilobular areas contained necrotic cells and apparently intact, isolated, organelles intermingled with erythrocytes and platelets. In less severely affected regions there was prominent hepatocyte rounding, and erythrocytes and platelets were present in the widened space of Disse. Large amounts of hepatocellular debris and intact hepatocytes were present in the pulmonary vasculature, while smaller amounts of debris were also seen in the glomerular and peritubular capillaries of the renal cortex. This study shows that initial lesions are confined to shape changes in the plasma membrane of hepatocytes. These changes are consistent with the hypothesis that microcystin-LR induces alterations in the hepatocyte cytoskeleton. Later changes consist of hepatocyte disassociation and necrosis, as well as endothelial damage, which allow release of hepatocytes and debris into the circulation with microembolism in lungs and kidneys.

Animals↗