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Biomedical subjects

V R Beasley

Publications and source records attributed to V R Beasley.

At least 73 records · Page 4Linked to original sources
PubMed1988

Analysis and purification of toxic peptides from cyanobacteria by reversed-phase high-performance liquid chromatography.

A simple, rapid and reliable chemical analysis method for microcystins (cyanoginosins) has been studied. Three different mobile phases for high-performance liquid chromatography were selected and optimized. Also the adsorptive powers of three commercially available C18 cartridges were compared and the results successfully applied to the clean up of three of the toxins. Finally a total system for the analysis and isolation of microcystins was established.

Chromatography, High Pressure Liquid↗
PubMed1988

Improved method for purification of toxic peptides produced by cyanobacteria.

The improved method consists of ODS-silica gel extraction, and separation on silica gel and HPLC with UV (238 nm) detector. The method has been successfully applied to the isolation of toxic peptides from the Monroe and M-228 strains of Microcystis aeruginosa. This method reduces toxin extraction and separation time, and so enables a rapid isolation of peptide toxins from cyanobacteria.

Chromatography, Gel↗
PubMed1988

Comparison of effects of anatoxin-a(s) and paraoxon, physostigmine and pyridostigmine on mouse brain cholinesterase activity.

Anatoxin-a(s), an alkaloid neurotoxin from the freshwater cyanobacterium, Anabaena flos-aquae NRC-525-17, was compared to paraoxon, physostigmine and pyridostigmine for effects on brain cholinesterase after i.p. injection into Balb/c mice. The duration of clinical signs in mice injected with anatoxin-a(s) persisted longer than in mice given the carbamates and was comparable with that of paraoxon. Anatoxin-a(s) did not inhibit brain cholinesterase activity suggesting that this toxin is unable to cross the blood-brain barrier.

Animals↗
PubMed1988

Experimental T-2 toxicosis in swine following inhalation exposure: clinical signs and effects on hematology, serum biochemistry, and immune response.

Nine- to ten-week-old, male castrated, specific pathogen-free derived pigs, weighing 34 to 42 kg, were exposed to a T-2 toxin aerosol (390 micrograms/liter, 1.5 microM mass median aerodynamic diameter) for a time period which allowed an amount equivalent to 8 mg/kg to be nebulized (six pigs). Control animals (five pigs) were exposed to an equivalent amount of the nebulized vehicle. Pigs were immunized subcutaneously with sheep red blood cells on Days 0 and 21. Whole blood and serum samples were taken periodically for clinical pathologic and immunologic studies. Pigs were closely observed, and daily rectal temperatures and weekly weights were measured. The T-2-treated pigs vomited and exhibited cyanosis, anorexia, lethargy, lateral recumbency, slightly elevated rectal temperature, and depressed body weight gain. The lymphocyte count decreased while the neutrophil count increased. The concentrations of total serum protein and hemoglobin declined. There was a marked increase in serum alkaline phosphatase activity on Day 1, followed by a marked and persistent decrease. Mitogen-induced (Con A, PHA, and PWM) blastogenic responses of peripheral blood mononuclear cells and hemagglutination titers to SRBC were also transiently decreased. Thus, inhalation exposure of pigs to a sublethal dose of T-2 toxin caused clinical signs of toxicity and adverse effects on clinical pathologic parameters and immune responses; however, most of these effects were short-lived. The changes described in our study resemble those reported in pigs given T-2 toxin by intravascular injection.

Administration, Inhalation↗
PubMed1988

Toxicologic evaluation of chlorpyrifos in cats.

Twenty-four male domestic shorthair cats were used to evaluate the acute and chronic effects of a single, toxic but sublethal, orally administered dose of chlorpyrifos. A dosage of 10 mg/kg of body weight did not induce clinical signs of toxicosis, but a dosage of 40 mg/kg induced clinical signs of toxicosis, and 1 of 12 cats died. Chlorpyrifos given at a dosage of 0.1 mg/kg to 2 cats reduced whole blood and plasma cholinesterase (Che) activities to values obtained after cats were given doses that induced clinical signs of toxicosis. Regeneration time for whole blood and plasma Che activities ranged from 7 to 28 days. Brain Che activity was considerably decreased in 1 cat that died 4.5 hours after dosing, but was normal in all others at 28 days after dosing. Other than decreased Che activity, significant changes were not seen in hematologic or serum biochemical values. Toxin-related lesions were not seen during macroscopic or microscopic examination.

Acetylcholinesterase↗
PubMed1987

Assessment of potential therapies for acute T-2 toxicosis in the rat.

The efficacy of a variety of approaches for the treatment of animals with acute T-2 toxicosis was assessed utilizing young female rats. A single large dose of the water soluble salt of methylprednisolone significantly prolonged survival times in T-2 toxin treated animals. The use of diltiazem hydrochloride, dazemgrel, N-acetylcysteine, dimethyl sulfoxide, adenosine triphosphate (ATP), ATP combined with magnesium chloride, ascorbic acid, and aprotinin did not prolong survival times at the dosages administered. Trichodermin, a trichothecene similar in structure and biochemical activity to T-2 toxin but much less acutely toxic, had a detrimental effect on survival times whether given 1 hr prior to or after T-2 toxin.

Adenosine Triphosphate↗
PubMed1987

Distribution of blood flow to the gastrointestinal tract of swine during T-2 toxin-induced shock.

Swine (6 per group) were used to study gastrointestinal blood flow during T-2 toxin-induced shock. Low- and high-dose groups were given T-2 toxin at 0.6 or 2.4 mg/kg via the pulmonary artery; controls were given the ethanol vehicle. Radiolabeled microspheres were administered into the left atrium to assess organ blood flow predosing and at 90-min intervals for 6 hr. Gastric blood flow decreased in both T-2 groups, and at 6 hr the high-dose group's value was 17% of the predose value. In the low-dose group, the lowest gastric blood flow (30% of predose) was observed 3 hr postdosing. Small-intestinal blood flow of the control group declined to 64% of the predose value. In the high-dose group, small-intestinal blood flow at 3 hr was 174% of predose, followed by a reduction to 62% at 6 hr, coinciding with a severe decline in cardiac output. Small-intestinal blood flow of the low-dose group was 159% of predose at 1.5 hr, then declined to the control value. The high-dose group's large-intestinal blood flow increased to 177% of predose at 3 hr, then declined to 66% at 6 hr. The low-dose group's large-intestinal blood flow increased to 200% of the predose value. The severe decline in gastric blood flow is probably related to the development in swine (given high doses of T-2 toxin) of a grossly bright red gastric fundus, with histologic evidence of vascular congestion and mucosal deterioration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Experimental T-2 toxicosis in swine. III. Morphologic changes following intravascular administration of T-2 toxin.

The gross and microscopic changes in swine following a single intravascular (iv) dose of T-2 toxin are described and evaluated quantitatively. T-2 toxin, in 70% ethanol, was given iv at 0 (5 pigs), 0.6 (5 pigs), 1.2 (1 pig), 4.8 (5 pigs), or 5.4 (2 pigs) mg/kg to 40 to 60 kg female crossbred pigs. The 4.8 and 5.4 mg/kg group pigs died between 5 and 10.5 hr after treatment, while the 0, 0.6, and 1.2 mg/kg pigs were killed at 24, 24, and 12 hrs after treatment, respectively. Morphologic examination was performed at the gross and light microscopic levels. In addition, a quantitative evaluation of microscopic changes present in lymphoid tissues and intestinal tract was performed using a semiquantitative scoring system. Gross lesions in the T-2-treated pigs consisted of edema, congestion, and hemorrhage of the lymph nodes and pancreas; congestion and hemorrhage of the gastrointestinal mucosa, subendocardium, adrenal gland, and meninges; and edema of the gall bladder. Histologic examination confirmed the gross observations. Additional microscopic lesions included widespread degeneration and necrosis of the lymphoid tissues as well as of the surface and crypt epithelium of the gastrointestinal mucosa; mild scattered necrosis of pancreatic acinar cells, myocardium, bone marrow cells, adrenal cortical cells, and tubular epithelium of renal medulla; and mild interstitial pneumonia. A dose-dependent increase in lesion severity was observed except for the pancreatic lesion which was slightly more apparent in the pigs from the 0.6 mg/kg group. These findings indicate that T-2 toxin-induced lesions in the lymphoid tissues and gastrointestinal tract of pigs are similar to those of other species the pancreas and heart should be considered as additional target organs in the pig, and both rapidly dividing cells and those with little or no turnover are damaged by T-2 toxin.

Animals↗
PubMed1987

The toxicity of T-2 toxin in swine following topical application. I. Clinical signs, pathology, and residue concentrations.

T-2 toxin at 0 or 15 mg/kg in 0.75 ml dimethyl sulfoxide was topically applied to 11- to 12-week-old specific-pathogen-free derived crossbred female pigs. Animals were killed on Days 1, 3, 7, or 14 after treatment. Clinical signs and morphologic changes in the skin and internal organs, as well as the residual concentrations of T-2 toxin and its metabolites in plasma, bile, urine, skin, and subcutaneous tissue, were examined. The T-2-treated pigs had signs of lethargy, anorexia, posterior weakness or paresis, and persistent fever. The skin at the site of application was red and swollen initially and progressively became dark red and then purple. By Day 7, at the margin of the exposed area, clefts had formed and were covered by serosanguinous exudate. By Day 14, the affected skin was focally separated from the underlying tissue and covered by a thick scab. The initial skin lesions were characterized as a spongiotic dermatitis and were located mainly in the dermal papillae and stratum germinativum of the epidermis. These lesions progressed to a locally extensive necrotizing dermatitis between Days 3 and 7 that was still evident at Day 14. Healing began on Day 7 and was more prominent on Day 14. Morphologic changes in the internal organs were minimal. They consisted of necrosis of single cells in the follicles of lymphoid tissues and in the exocrine pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1987

The toxicity of T-2 toxin in swine following topical application. II. Effects on hematology, serum biochemistry, and immune response.

T-2 toxin at 0 (6 pigs) or 15 mg/kg (8 pigs) in 0.75 ml of dimethyl sulfoxide was topically applied to 9- to 10-week-old, male castrated, specific-pathogen-free derived pigs which were immunized subcutaneously with sheep red blood cells (SRBC) on Days 0 and 21. Whole blood and serum samples were taken periodically for clinical pathologic and immunologic evaluations. The pigs were observed daily and weighed weekly; their rectal temperatures were measured periodically. The T-2-treated pigs displayed anorexia, lethargy, posterior weakness and paresis, persistent high fever, and reduced body weight gain. Prominent neutrophilia, decreased serum glucose, albumin, and alkaline phosphatase activity, and increased serum globulin were seen in the T-2-treated group. The responses of enriched peripheral blood mononuclear cells to mitogens concanavalin A, phytohemagglutinin, and pokeweed mitogen of the T-2-treated group were significantly lower than those of the control group both at early (3 to 5 days) and late (20 to 28 days) postdosing intervals. No significant effects were noted in the hemagglutination titer to SRBC. Thus, in addition to the severe local dermal injury reported previously, topical exposure of swine to a sublethal dose of T-2 toxin, 15 mg/kg, can cause significant systemic effects on parameters such as body weight gain, rectal temperature, hematology, serum biochemistry, and cellular immune response.

Administration, Topical↗
PubMed1987

Experimental T-2 toxicosis in swine following inhalation exposure: effects on pulmonary and systemic immunity, and morphologic changes.

Thirty-four, 9- to 11-week-old, male castrated, crossbred, specific pathogen-free derived pigs were exposed to a T-2 toxin aerosol at a nebulized dose of 0 or 9 mg/kg in pairs, each pair consisting of 1 control and 1 T-2 treated pig which were exposed on the same day. Twenty to 30% of the toxin (1.8 to 2.7 mg/kg) was retained by the pigs. Five pairs were killed on each of 1, 3 and 7 days after dosing. Two pairs of pigs were designated as a 0.33-day group when one T-2 treated pig died and the other was killed in a moribund state at 8 to 10 hours after dosing. The pulmonary and systemic immunity and morphologic changes of the lungs and other organs were examined. Bronchoalveolar lavage was performed to obtain alveolar macrophages (AM) and pulmonary lymphocytes (PL). The phagocytic ability of AM and mitogen-induced blastogenic responses of enriched PL and peripheral blood lymphocytes were evaluated. Clinically, all of the T-2 treated pigs vomited and were cyanotic, anorexic, lethargic and laterally recumbent. In the 0.33-, 1-, and 3-day T-2 treated pigs, there was a marked reduction in AM phagocytosis and mitogen-induced blastogenic responses of PL but not of peripheral blood lymphocytes. Mild to moderate, multifocal interstitial pneumonia was seen in the majority of the T-2 treated pigs. In pigs dying following inhalation of T-2 toxin, there was a more severe pneumonia, as well as marked necrosis of lymphoid tissues, severe necrohemorrhagic gastroenteritis and edema of the gall bladder wall, and multifocal necrosis of the heart and pancreas. Thus, inhalation exposure to T-2 toxin can result in clinical signs and morphologic changes resembling those reported previously in pigs given T-2 toxin intravascularly (iv) at a dose of 1.2 mg/kg (approximate LD50) or greater, as well as death. Mild pulmonary injury as well as transient impairment of pulmonary immunity was present in pigs surviving inhalation exposure.

Administration, Inhalation↗
PubMed1987

Assessment of a general therapeutic protocol for the treatment of acute T-2 toxicosis in swine.

T-2 toxin, a trichothecene mycotoxin suspected of being used as a chemical warfare agent, was administered iv to swine at a dose of 3.6 mg/kg body weight (iv LD50 approximately 1.2 mg/kg). Four different therapeutic protocols were assessed for their efficacy in the treatment of the resultant acute T-2 toxicosis syndrome. One therapeutic protocol included the combined use of metoclopramide, activated charcoal, magnesium sulfate, dexamethasone sodium phosphate, sodium bicarbonate and normal saline. The other 3 protocols utilized the same agents less 1 of the following: the combination of activated charcoal and magnesium sulfate, sodium bicarbonate, or normal saline. All 4 treatment groups showed improved survival times compared to a positive T-2 control group. Within the limits of the study, it would appear that the removal of activated charcoal and magnesium sulfate was most detrimental to the T-2 toxin-dosed swine.

Animals↗
PubMed1987

Blue-green algae (Microcystis aeruginosa) hepatotoxicosis in dairy cows.

Twenty cows from a dairy herd consisting of 60 healthy, lactating Holsteins developed clinical signs of anorexia, mental derangement, dehydration, recumbency, and ruminal atony after ingesting water containing blue-green algae. Of the 20 cows, 9 died. The algal bloom, which developed in a stagnant pond during hot, dry weather, was identified as the cyanobacterium Microcystis aeruginosa, a potentially hepatotoxic algae. One week after the onset of toxicosis, affected cows seemed healthy, although liver-associated enzyme activities (alkaline phosphatase, gamma-glutamyl transferase, aspartate transaminase, and lactate dehydrogenase) were increased. Intraruminal administration of the intact wet bloom to a healthy 125-kg Angus heifer was followed by hepatic necrosis and death. The liver was large, friable, and gun-metal blue, with microscopically evident hepatocyte dissociation, degeneration, and necrosis. The ingesta of the heifer contained typical clumps of cells that were identified as M aeruginosa. The intraperitoneal administration of lyophilized cell material from that bloom to 18 mice caused marked hepatic enlargement. The intraperitoneal median lethal dose of the dried bloom was estimated to be 10 mg/kg of body weight. A cyclic peptide toxin purified from the algae seems to be similar structurally to toxins from other characterized hepatotoxic blooms of M aeruginosa.

Animals↗
PubMed1986

Effects of an insecticidal dip containing d-limonene in the cat.

A study was undertaken to determine the effects of a single dermal application of a commercial insecticidal dip containing 78.2% d-limonene in cats. At the manufacturer's recommended concentration of 1.5 oz/gal of water, no clinical signs or lesions of toxicosis were seen. At 5 times the recommended concentration, clinical signs were mild and consisted of hypersalivation of short duration, ataxia, and muscle tremors resembling shivering. At 15 times the recommended concentration, clinical signs included hypersalivation lasting 15 to 30 minutes, moderate-to-severe ataxia lasting 1 to 5 hours, muscle tremors resembling shivering lasting 1 to 4 hours, and severe hypothermia beginning soon after treatment and lasting 5 hours. Gross lesions were confined to excoriation of the scrotal and perineal areas of the treated male cats at the 15 X concentration. No deaths or other lasting effects were seen at any dosage.

Animals↗
PubMed1986

Pharmacokinetics of the trichothecene mycotoxin, T-2 toxin, in swine and cattle.

The pharmacokinetics of the trichothecene mycotoxin, T-2 toxin, were determined in growing gilts and heifers. Following intra-aortal administration in swine and intravenous administration in calves, the disappearance of the parent T-2 toxin followed a 2-compartment open model. Mean elimination phase half-lives were 13.8 and 17.4 min and mean apparent specific volumes of distribution were 0.366 and 0.376 l/kg in swine and calves, respectively. The fraction of T-2 toxin eliminated as parent compound in the urine was negligible. In spite of administration of a lethal oral dose in swine (2.4 mg/kg) and toxic oral doses (up to 3.6 mg/kg) in calves, no parent T-2 toxin was detected in plasma or urine. After intra-aortal administration in swine, tissue concentrations of T-2 toxin were consistently highest in lymphoid organs. Tissue residues of T-2 toxin were rapidly depleted such that, in spite of administration of a potentially lethal intra-aortal dose, no quantifiable T-2 toxin was present in any of the tissues collected at 4 hr after dosing. No T-2 toxin could be detected in liver, even at 1 hr after dosing.

Animals↗
PubMed1986

Systemic distribution of blood flow during T-2 toxin induced shock in swine.

Three groups of swine (6 per group) were used to determine hemodynamic and blood flow alterations induced by T-2 toxin. Two groups were dosed at 0.6 or 2.4 mg/kg T-2 toxin, and one group served as a vehicle control (70% ethanol). Organ blood flow was determined at 0 hr (predosing) and at 90-min intervals for 6 hr postdosing using 15-micron diameter radionuclide labeled microspheres injected into the left atrium. Hemodynamic parameters were obtained at the same time points. The infusion of T-2 toxin resulted in reductions in cardiac output. This trend appeared to reverse itself in the low dose animals after 3 hr, whereas in the high dose group, cardiac output continued to decline. Mean aortic pressure (MAP) declined in a dose dependent fashion which tended to parallel the reduction observed in cardiac output. Heart rate was increased in both groups treated with T-2 toxin. Blood flow, to the brain, heart, and kidneys decreased following exposure to the toxin. The relative percentage of cardiac output received by these organs, however, was maintained despite the drop in blood flow. Pancreatic and splenic blood flows were the most severely compromised as a result of T-2 toxicosis. Consequently, the percentage of cardiac output going to the pancreas and spleen was dramatically reduced. Adrenal, hepatic, and total gastrointestinal blood flows increased or did not change from control values. As a result, the percentage of cardiac output supplying these organs increased.

Animals↗
PubMed1986

Myocardial and pancreatic lesions induced by T-2 toxin, a trichothecene mycotoxin, in swine.

Myocardial and pancreatic lesions induced by sublethal doses of T-2 toxin in swine were characterized by light and electron microscopy. Toxin was given intravenously to six 17- to 18-week-old pigs. Pigs were killed 24 or 48 hours after treatment. Grossly, subendocardial hemorrhages, multifocal pinpoint white foci in myocardium, and pancreatic edema occurred in one treated pig. Histologic changes in myocardium of treated pigs consisted of multifocal edema, mononuclear cell infiltration, myofiber hyalinization, vacuolation, and contraction bands with nuclear pyknosis. Ultrastructurally, there were areas of edema, myofibrillar disorganization, dilation of sarcoplasmic reticulum, and formation of hypercontraction bands. Myocardial mineralization was seen in the pig with gross lesions. Pancreatic changes in treated pigs consisted of multifocal acinar degeneration and necrosis. Ultrastructural changes included irregular dilation of rough endoplasmic reticulum and abnormal zymogen granules. Thus, in addition to radiomimetic lesions of the gastrointestinal tract and lymphoid organs, heart and pancreas are target organs of T-2 toxin in swine.

Animals↗