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W B Buck

Publications and source records attributed to W B Buck.

At least 55 records · Page 3Linked to original sources
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

Comparative in vitro metabolism of T-2 toxin by hepatic microsomes prepared from phenobarbital-induced or control rats, mice, rabbits and chickens.

Hepatic microsomes were prepared from phenobarbital (PB)-treated and control rats, mice, rabbits and chickens and were incubated with T-2 toxin (100 micrograms/mg microsomal protein). Additional microsomes from PB-induced animals were incubated with T-2 toxin and the esterase inhibitor paraoxon (PA) at 2.5 nmol/mg microsomal protein. The major metabolite in microsomal preparations from both control and PB-induced rats, rabbits and mice was HT-2. In microsomes isolated from PB-treated chickens, 3'-hydroxy T-2 was the major metabolite, but 30 and 79% of the added T-2 toxin remained unmetabolized at 60 min in incubations from PB-induced and control birds, respectively. The percentage of hydroxylated metabolites formed in the microsomal preparations of the four species studied was significantly increased following PB treatment compared with the non-treated controls. The addition of PA to the incubation system effectively inhibited the hydrolysis of the ester groups in T-2 toxin, resulting in 1.4- and 1.25-fold increases in the percentage of 3'-hydroxy T-2 in the mouse and rat microsomal samples, respectively. In the rabbit microsomal preparations, 3'-hydroxy T-2, which was not detected in the absence of PA, represented 11% of the added substrate in the PB/PA incubation samples. Addition of PA did not cause a significant change in the amount of 3'-hydroxy T-2 formed in chicken microsomal samples, since competition between hydrolysis and hydroxylation pathways for the T-2 toxin substrate was not an important factor in this species. Two new metabolites, designated RLM-2 and RLM-3 were detected in chicken, rat and mouse microsomal preparations. On the basis of gas chromatography/mass spectrometry data, the compounds were tentatively identified as isomers of 3'-hydroxy T-2.

Animals↗
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

Pharmacokinetics of diacetoxyscirpenol in cattle and swine: effects of halothane.

In swine and cattle given 0, 0.1, or 0.5 and 0, 0.5 mg of diacetoxyscirpenol (DAS)/kg of body weight, IV, respectively; DAS had a large volume of distribution and total body clearance. The shortness of the interval between halothane and DAS exposures significantly (P greater than 0.05) decreased DAS biotransformation. Urinary excretion of DAS as a parent compound was not an important route of elimination. In swine and cattle, DAS was transformed by sequential deacetylation to monoacetoxyscirpenol and scirpentriol.

Anesthesia, General↗
PubMed1986

Rapid screening procedure for the detection of trichothecenes in plasma and urine.

A rapid and easy procedure to screen for trichothecenes in plasma and urine is presented. The toxins are extracted using a Clin-Elut column, hydrolyzed to their corresponding parent alcohols and cleaned up with a silica cartridge followed by derivatization for gas chromatographic analysis. The detection of any of the parent alcohols in plasma or urine would indicate an exposure to trichothecenes. Recoveries in urine are between 78 and 119% at levels of 50-1000 ng/ml and recoveries in plasma are between 80 and 116% at levels of 50-500 ng/ml. The limit of detection is better than 25 ppb.

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↗
PubMed1986

Excretion of deoxynivalenol and its metabolite in milk, urine, and feces of lactating dairy cows.

Corn contaminated with deoxynivalenol was added to the diets of three dairy cows for 5 d and milk, urine, and 3 d following feeding of the diets. Dietary concentrations of deoxynivalenol averaged 66 mg/kg. Following exposure to deoxynivalenol, unconjugated deepoxydeoxynivalenol, a metabolite of deoxynivalenol, was present in milk at concentrations up to 26 ng/ml. Deoxynivalenol was not detected in the milk. Approximately 20% of the deoxynivalenol fed was recovered in the urine and feces in the unconjugated forms as deepoxydeoxynivalenol (96%) and deoxynivalenol (4%). After incubating urine with beta-glucuronidase, the concentration of unconjugated deepoxydeoxynivalenol increased by 7 to 15-fold whereas unconjugated deoxynivalenol increased 1.6 to 3-fold. Detectable concentrations of unconjugated deepoxydeoxynivalenol were found in urine and feces up to 72 h after the last oral exposure. Thus, urine and feces are the diagnostic specimens of choice for the determination of deoxynivalenol exposure in cows. Feeding deoxynivalenol-contaminated diets for 5 d did not alter feed intake or milk production nor were the milk concentrations of calcium, phosphorus, sodium, potassium, magnesium, or nitrogen altered.

Animals↗
PubMed1986

Preferential grazing by cattle on glyphosate-treated fescue pastures.

Cattle grazing preferences on fescue pastures treated with the herbicide glyphosate at a rate of 2.52 kg/ha by surface application were determined, and the time course of the effect was characterized. An initial grazing preference for treated pasture was observed for the first 5 to 7 days. Over the next 15 days, this preference was lost because of decreasing amounts of herbicide on the herbage and/or desiccation of the herbage.

Animal Feed↗
PubMed1985

The acute toxicopathy of intravenous diacetoxyscirpenol (anguidine) administration in swine.

Diacetoxyscirpenol (DAS, anguidine) was given intravenously to swine at 0.0, 0.5, and 1.0 mg/kg body wt. In mitotically and metabolically active tissues such as gastrointestinal epithelium and lymphoid aggregates the effects of DAS mimicked radiation poisoning. A quadratic dose-response relationship between the cytotoxicity of DAS and damage to enterocytes was found. Enterocytes in different anatomical regions of the bowel had differing susceptibilities to the toxic effects of DAS. In lymphoid tissues, DAS was preferentially cytotoxic to B-lymphocyte-rich tissues as compared to T-lymphocyte-rich tissues. In all pigs dosed with DAS the bone marrow was void of hemopoietic elements. DAS was cytotoxic to cells with specialized ion pumps, namely, renal tubular, gastric parietal, and salivary ducts. Cell damage in the exocrine and endocrine pancreas and adrenal gland accounted for changes in blood glucose. Endothelial necrosis and hemorrhage were observed in the brain. These findings were compared with those reported for other 12,13-epoxytrichothecenes and ionizing radiation and we concluded that a similar mechanism of cytotoxicity could exist.

Animals↗