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    Val Beasley

    Cellular uptake of neutral red dye (NR) is currently used as an indirect measure of viable cells in cultures. We used E-63 rat skeletal muscle cells to identify causes of NR assay variability and to develop modifications that... more
    Cellular uptake of neutral red dye (NR) is currently used as an indirect measure of viable cells in cultures. We used E-63 rat skeletal muscle cells to identify causes of NR assay variability and to develop modifications that substantially reduce it. Three methods of NR preparation and/or addition to cells were used. When NR medium was prepared, incubated overnight, and filtered to remove precipitates, the amount of dye precipitated varied greatly. Coefficients of variation (CVs) in NR uptake were greater than 25% between assays. Higher NR concentrations, longer incubation times, increased pH, and decreased temperature promoted NR precipitation in media. NR media prepared and filtered just prior to use or direct addition of prefiltered NR stock solution to cell cultures resulted in much smaller CVs between assays. NR was cytotoxic to E-63 rat muscle and primary quail myoblasts in a time- and concentration-dependent manner. NR exposure to E-63 cells for greater than 1.25 and 2 hr at 157 or 127 microg/ml, respectively, was associated with swelling and rupture of lysosomes. By contrast, there was no evidence of cytotoxicity when E-63 cells were exposed to NR for 1 hr at either 127 or 157 microg/ml. Primary quail myoblasts developed lysosomal swelling and ruptured more rapidly than E-63 cells when exposed to NR at either 127 or 157 microg/ml. For confluent 10-day cultures of E-63 cells exposed to NR at 127 microg/ml for 1 hr, the CVs within assay and between assays were 3.3-3.9% and 5.1%, respectively. For similarly exposed, actively replicating 3-day cultures of E-63 cells, the CVs within and between assays were 6.2-9.6% and 2.4%, respectively. NR uptake by the E-63 cells was linear with respect to viable cell number.
    Insufficient data from existing surveillance systems underlie societal tolerance of acute and slow-onset health disasters that threaten, harm, and kill vast numbers of humans, animals, and plants. Here we describe barriers to integrated... more
    Insufficient data from existing surveillance systems underlie societal tolerance of acute and slow-onset health disasters that threaten, harm, and kill vast numbers of humans, animals, and plants. Here we describe barriers to integrated "One Health" surveillance, including those related to a lack of medical services, professional divisions, incompatible vocabularies, isolated data sets, and territorial borders. We draw from publications of experts who justify broader and more integrated surveillance, education, and stewardship focused on preventing and mitigating disease emergence and re-emergence. In addition, we highlight efforts from Illinois, the United States and the broader world, pointing to examples of relevant education; ways to acquire, compile, and analyze diagnostic and syndromic data; mapping of diseases of humans and animals; and rapid communication of findings and recommendations. For the future, we propose using needed outcomes for health and sustainability...
    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,... more
    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.
    Harmful cyanobacterial blooms have adversely impacted human and animal health for thousands of years. Recently, the health impacts of harmful cyanobacteria blooms are becoming more frequently detected and reported. However, reports of... more
    Harmful cyanobacterial blooms have adversely impacted human and animal health for thousands of years. Recently, the health impacts of harmful cyanobacteria blooms are becoming more frequently detected and reported. However, reports of human and animal illnesses or deaths associated with harmful cyanobacteria blooms tend to be investigated and reported separately. Consequently, professionals working in human or in animal health do not always communicate findings related to these events with one another. Using the One Health concept of integration and collaboration among health disciplines, we systematically review the existing literature to discover where harmful cyanobacteria-associated animal illnesses and deaths have served as sentinel events to warn of potential human health risks. We find that illnesses or deaths among livestock, dogs and fish are all potentially useful as sentinel events for the presence of harmful cyanobacteria that may impact human health. We also describe ways to enhance the value of reports of cyanobacteria-associated illnesses and deaths in animals to protect human health. Efficient monitoring of environmental and animal health in a One Health collaborative framework can provide vital warnings of cyanobacteria-associated human health risks.
    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,... more
    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.
    ABSTRACT Objectives: The objectives of this study were to assess whether the Envirovet programme served to increase the number of practising ecosystem health professionals, as well as to measure the lasting professional and personal... more
    ABSTRACT Objectives: The objectives of this study were to assess whether the Envirovet programme served to increase the number of practising ecosystem health professionals, as well as to measure the lasting professional and personal impact of the programme on participants.
    Research Interests:
    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,... more
    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.
    We suggest each of us take on the daily challenge of writing and speaking to the public on scientific matters, always being certain to include at least one statement about how our clinical practice, our research, and our daily work as... more
    We suggest each of us take on the daily challenge of writing and speaking to the public on scientific matters, always being certain to include at least one statement about how our clinical practice, our research, and our daily work as veterinarians influences, and is ...
    T-2 toxin given as a single intravascular dose to swine produced a shock syndrome. Dosages of 0.6 or 4.8 mg/kg were administered to different groups of swine. Shock was characterized by reductions in cardiac output and blood pressure, and... more
    T-2 toxin given as a single intravascular dose to swine produced a shock syndrome. Dosages of 0.6 or 4.8 mg/kg were administered to different groups of swine. Shock was characterized by reductions in cardiac output and blood pressure, and increased plasma concentrations of epinephrine, norepinephrine, thromboxane B2, 6-keto PGF1 alpha, and lactate. Total peripheral resistance was unchanged in the high-dose group but decreased in the low-dose group. Pulmonary vascular resistance increased in both groups. Decreases occurred in arterial pH and arterial oxygen partial pressure. No alterations occurred in plasma concentrations of histamine or serotonin.
    ... Val Richard Beasley, Project Coordinator Roseanne M. Lorenzana, Researcher Steven P. Swanson, Project Coordinator ... 4-deacetylneosolaniol, T-2 tetracl and their conjugates were also present. The concentration of free T-2 was... more
    ... Val Richard Beasley, Project Coordinator Roseanne M. Lorenzana, Researcher Steven P. Swanson, Project Coordinator ... 4-deacetylneosolaniol, T-2 tetracl and their conjugates were also present. The concentration of free T-2 was negligible in all samples following the ...
    ABSTRACT
    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... more
    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.
    Page 373. CHAPTER 26 Trichothecene Mycotoxins WANDA M. HASCHEK AND VAL R. BEASLEY I. INTRODUCTION The ideal biologic warfare agent is lethal, easy, and inex-pensive to produce in large quantities, stable as ...
    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... more
    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.
    Background/Question/Methods Biodiversity can strongly influence disease transmission in wildlife populations and the dilution effect is a well-studied example of this phenomenon. We examined the potential for biodiversity among predators... more
    Background/Question/Methods Biodiversity can strongly influence disease transmission in wildlife populations and the dilution effect is a well-studied example of this phenomenon. We examined the potential for biodiversity among predators of trematode cercariae to reduce the risk of trematode infections in amphibians. Free swimming cercariae are vulnerable to predation from a wide variety of aquatic organisms, but larval odonates appear to be particularly voracious consumers of cercariae. We used a multi-factorial approach to assess the independent and combined effects of larval odonate richness and density on the survival, behavior, and trematode infection load of Rana clamitans tadpoles. The experiment included two treatment variables, odonate diversity (8 levels) and odonate density (2 levels). The eight odonate diversity levels included a full-factorial treatment design with the presence/absence of three early-instar odonates: Ischnura verticalis, Pachydiplax longipennis and Eryt...
    T-2 toxin was given as a single intravascular dose at either 0.6 or 4.8 mg/kg to different groups of 50-kg female swine. Blood samples were taken at hourly intervals for determination of concentrations or activities of the following... more
    T-2 toxin was given as a single intravascular dose at either 0.6 or 4.8 mg/kg to different groups of 50-kg female swine. Blood samples were taken at hourly intervals for determination of concentrations or activities of the following substances in serum or plasma: creatinine, blood urea nitrogen, inorganic phosphorus, total calcium, ultrafilterable calcium, magnesium, sodium, potassium, chloride, total protein, albumin, cholesterol, glucose, alkaline phosphatase, aspartate aminotransferase, and total bilirubin. Coagulation analyses included prothrombin time, partial thromboplastin time, activated coagulation time, and fibrin degradation products. Red blood cell, white blood cell, and platelet counts, hemoglobin concentrations, and hematocrits were determined from whole blood samples. An initial leukocytosis was followed by a leukopenia. The numbers of red cells, the hemoglobin concentration, and the hematocrit were increased. Nucleated red blood cells were seen in the blood smears. T...
    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.... more
    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 la...
    Fumonisin B1 is hepatotoxic in all species, but nephrotoxicity has only been reported in rats. It is a specific inhibitor of sphinganine N-acyltransferase. Our objective was to determine the target organs for fumonisin toxicosis in the... more
    Fumonisin B1 is hepatotoxic in all species, but nephrotoxicity has only been reported in rats. It is a specific inhibitor of sphinganine N-acyltransferase. Our objective was to determine the target organs for fumonisin toxicosis in the rabbit. We administered fumonisin B1 ( > 95% pure) intravenously to adult rabbits and examined selected clinical, biochemical, and histological parameters for up to 5 days. In a pilot study, rabbits were given fumonisin B1 at 1, 0.5, 0.3, 0.15, or 0 mg/kg daily for 4 or 5 days and then euthanized. Additional rabbits were given a single dose of fumonisin B1 at 1 mg/kg and euthanized on day 2 or 4. In the formal time-course study, rabbits were given a single dose of fumonisin B1 at 0 or 1.25 mg/kg and euthanized on days 1, 3, or 5. Rabbits given multiple doses of fumonisin B1 were lethargic and anorectic, and had decreased urine production. Liver- and renal-associated clinical chemistry parameters were elevated. Renal lesions consisted of severe proximal tubular necrosis. Liver lesions were variable and consisted of mild necrosis, hepatocyte vacuolation, and bile stasis. The sphinganine-to-sphingosine ratio, in both target and nontarget tissues, was markedly elevated in treated rabbits. A single dose of fumonisin B1 induced renal but not hepatic injury. Therefore, the target organs for fumonisin B1 toxicity in rabbits are kidney and liver, with the kidney being more sensitive.
    Microcystin-LR (MCLR) is a commonly encountered blue-green algal hepatotoxin and a known inhibitor of cellular protein phosphatase types 1 and 2A. The toxin causes alterations in, and redistribution of, intermediate filaments,... more
    Microcystin-LR (MCLR) is a commonly encountered blue-green algal hepatotoxin and a known inhibitor of cellular protein phosphatase types 1 and 2A. The toxin causes alterations in, and redistribution of, intermediate filaments, microtubules, and actin microfilaments (MFs) in affected cells. In this study, the effect of MCLR on the sequence of alterations in MFs and actin-associated proteins (AAPs) of isolated hepatocytes was examined in an effort to determine whether morphologic changes induced in MFs by microcystins are a result of prior dislocation of AAPs. We studied the effects of MCLR exposure on alpha-actinin and talin, two AAPs that play a role in the orientation of the MFs. Primary hepatocytes were incubated with 10 microns MCLR for 0-64 min. The distribution of actin, alpha-actinin, and talin were examined using fluorescence microscopy. MCLR induced similar changes in the distribution of actin and the AAPs. Actin filament redistribution was first observed after 12 min of MCLR exposure, and was characterized by detachment of MFs from the cell periphery, followed by condensation at distinct focal points and progressive collapse into the interior of affected cells. Changes in alpha-actinin and talin distribution were first observed after 20 min of toxin exposure. The AAPs appeared to detach from focal contacts on the cytoplasmic surface of the plasma membrane, condense into cytoplasmic aggregates, and ultimately collapse into a juxtanuclear bundle. The results of this study indicate that, in hepatocytes exposed to MCLR, the collapse of actin MFs occurs prior to the dislocation of alpha-actinin and talin. Changes in these actin associated proteins are not likely to account for the initial changes in actin MFs.
    Declines of amphibians have been attributed to many factors including habitat degradation. The introduction of grass carp (Ctenopharyngodon idella) as a biological agent for aquatic plant control in ponds and lakes managed narrowly for... more
    Declines of amphibians have been attributed to many factors including habitat degradation. The introduction of grass carp (Ctenopharyngodon idella) as a biological agent for aquatic plant control in ponds and lakes managed narrowly for human recreation has likely contributed to amphibian declines through massive plant removal and associated habitat simplification and thus degradation. This research examined the interactions among grass carp and three Midwestern aquatic plants (Jussiaea repens, Ranunculus longirostris, and R. flabellaris) that may be of value in rehabilitation of habitats needed by amphibians. The feeding preference study found that C. idella avoided eating both J. repens and R. longirostris. Ranunculus species studied to date contain a vesicant toxin called ranunculin that is released upon mastication. The study that compared the effects of R. flabellaris, J. repens and a control food administered by tube feeding to C. idella found significant lesions only in the mu...
    The cyanobacterial hepatotoxin, microcystin-LR (MCLR), is a potent protein phosphatase inhibitor that disrupts actin microfilament, cytokeratin intermediate filament, and microtubule networks in hepatocytes. To determine ultrastructural... more
    The cyanobacterial hepatotoxin, microcystin-LR (MCLR), is a potent protein phosphatase inhibitor that disrupts actin microfilament, cytokeratin intermediate filament, and microtubule networks in hepatocytes. To determine ultrastructural and biochemical changes that develop concurrently with microcystin-induced cytoskeletal disorganization, isolated rat livers were perfused with MCLR at 0.1 to 5.0 micrograms/ml for 5 to 40 min. Lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase changed over time, but trends for toxin-treated and control livers did not differ. The earliest toxin-induced ultrastructural changes, observed in livers perfused at 0.1 microgram/ml for 15-20 min or at 0.3 microgram/ml for 5-10 min, were loss of hepatocyte microvilli in the space of Disse, widening of sinusoidal fenestrae, disruption of sinusoidal endothelium, dilation of bile canaliculi with loss of microvilli, and widening of hepatocyte intercellular spaces. Lesions progressed with increasing toxin concentrations and exposure times. In livers perfused with MCLR at 0.5 microgram/ml for 10-20 min, hepatocytes had plasma membrane blebs and concentric whorls of rough endoplasmic reticulum, and there was marked disassociation of hepatocytes resulting in disrupted hepatic cords. At toxin concentrations of 2.0 or 5.0 micrograms/ml for 10-20 min, there was mild dilation of mitochondrial cristae, cytoplasmic vacuolization or invagination of plasma membranes, redistribution of organelles, and sometimes nuclear degenerative change. Some hepatocytes exhibited clusters of plasma membrane blebs radiating from round cytoplasmic structures, which may be composed primarily of condensed microfilaments.
    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... more
    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.
    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... more
    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.
    The toxicokinetics of tritiated dihydromicrocystin-LR ([3H]2H-MCLR) were studied in anesthetized, specific-pathogen-free pigs. Pigs were dosed with radiolabeled plus non-labeled 2H-MCLR at 25 or 75 micrograms/kg i.v., or via an isolated... more
    The toxicokinetics of tritiated dihydromicrocystin-LR ([3H]2H-MCLR) were studied in anesthetized, specific-pathogen-free pigs. Pigs were dosed with radiolabeled plus non-labeled 2H-MCLR at 25 or 75 micrograms/kg i.v., or via an isolated ileal loop at 75 micrograms/kg. The i.v. doses were rapidly removed from the blood. At either i.v. dose, more than half the radiolabel from [3H]2H-MCLR present in the blood at 1 min postdosing was cleared by 6 min. The blood clearance at the 75 micrograms/kg dose was slower than at the 25 micrograms/kg dose. Accordingly, at the high dose, the concentrations of the toxin in blood were disproportionately higher from 10 min after dosing until the study ended 4 hr later. The decreased clearance is presumably due to decreased elimination from the blood as a consequence of the hepatic injury that was observed histologically. Following administration of [3H]2H-MCLR at 75 micrograms/kg via the ileum, the maximal toxin concentration in blood was achieved at 90 min after dosing. At that time the [3H]2H-MCLR concentration in portal venous blood was 3.6 times higher than in peripheral venous blood. Although bile production varied, following i.v. dosing radioactivity was detected in bile as early as 12 min postdosing in one animal. This study demonstrated that [3H]2H-MCLR is rapidly removed from the blood of anesthetized swine and that excretion of the radiolabel into bile may begin within 30 min of dosing.
    The distribution of tritiated dihydromicrocystin [3H]2H-MCLR was studied in anesthetized specific-pathogen-free pigs. Two doses were administered i.m. and one dose was given via an isolated ileal loop. At 4 hr after i.v. administration of... more
    The distribution of tritiated dihydromicrocystin [3H]2H-MCLR was studied in anesthetized specific-pathogen-free pigs. Two doses were administered i.m. and one dose was given via an isolated ileal loop. At 4 hr after i.v. administration of the toxin at 25 micrograms/kg, 64.6% of the total dose (%TD) was located in the liver, with smaller amounts distributed to the kidneys (1.2% TD), lungs (1.75% TD), heart (0.22% TD), ileum (0.13% TD) and spleen (0.04% TD). A similar distribution was found at 4 hr postdosing in pigs given 75 micrograms/kg, although the liver contained a lower fraction of the total dose, at 46.99% TD, and the kidneys had somewhat more, at 2.19% TD, than the low dose. At the high dose, the fractions of the amount given accounted for by the lungs (0.55% TD), heart (0.23% TD), ileum (0.20% TD) and spleen (0.07% TD) were similar to those at the low dose. The livers of the pigs given 75 micrograms/kg via the ileal loop, at 5 hr postdosing, contained 49.5% TD and the ileum had 33.94% TD. Smaller amounts were distributed to kidneys (1.04% TD), lungs (0.65% TD), heart (0.81% TD) and spleen (0.16% TD). The livers of both groups dosed at 75 micrograms/kg contained higher concentrations of toxin, but lower percentages of the total dose, than the livers of pigs dosed at 25 micrograms/kg. Larger increases in serum arginase in the two 75 micrograms/kg groups were associated with histological evidence of more severe liver damage than at the 25 micrograms/kg dose. Analysis of radiolabeled compounds from hepatic tissue using fast atom bombardment mass spectrometry determined that the primary constituent was [3H]2H-MCLR, but two minor radioactive components were also isolated. These findings indicate that [3H]2H-MCLR is rapidly concentrated in the liver of swine, whether given i.v. or via an isolated ileal loop, that at extremely toxic doses uptake is slowed, and that it is as toxicologically active as the parent compound.

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