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Biomedical subjects

S J Cysewski

Publications and source records attributed to S J Cysewski.

At least 19 recordsLinked to original sources

Toxicologic evaluation of diisopropyl methylphosphonate and dicyclopentadiene in cattle.

Diisopropyl methylphosphonate (DIMP), and dicyclopentadiene [3a,4,7,7a-tetrahydro-4,7-methyanoindene] (DCPD), were found as contaminants of groundwater in Colorado. Since there was a potential for cattle to be exposed to these chemicals by drinking well water, a study of their effects was initiated. Eight-to-ten week old calves were given a single dose of either DIMP at 62.5, 125, 250, 500 and 1000 mg/kg of body weight (b.w.) or DCPD at 250, 500, 1000 or 2000 mg/kg of b.w. The calves given DIMP developed tympanitis and ataxia, followed by depression, prostration, and death within two hr after dosing. A slight but significant increase in activated partial thromboplastin time was the only change observed in any of the clinical pathologic parameters. The only gross pathologic changes were acute gastroenteritis with hemorrhages in calves given 1000 mg/kg of b.w. Mild signs of intoxication, ataxia and excess salivation, were observed in calves given 250 mg of DCPD/kg of b.w. At higher doses, these signs were intensified; in addition, calves fell and, while prostrate, exhibited running movements and tonic, clonic spasms. The severity of the signs observed increased as the dose of DCPD increased. All calves given 2000 mg/kg of b.w. and one calf given 1000 mg/kg of b.w. died before seven days after dosing. The only clinical pathologic changes found were increased serum levels of creating phosphokinase, glutamic-oxalacetic transaminase, and glutamic pyruvic transaminase. The only consistent gross pathologic change was congestion in a variety of tissues in calves given 2000 mg/kg of b.w. A variety of histologic changes were observed in tissues from calves treated with both chemicals. However, these changes were not consistent for any one dose level and were not dose dependent. DIMP was slightly toxic for calves, since no signs of intoxication were observed at doses less than 1000 mg/kg of b.w. DCPD exerted detrimental effects on calves at 250 mg/kg of b.w. and was classified as moderately toxic.

Alanine Transaminase↗

High pressure liquid chromatographic determination of penicillic acid in chicken tissues.

Penicillic acid (PA) is a mycotoxin with reported cytotoxic, cardiotoxic, and carcinogenic activity and it can occur in high concentration in corn. The occurrence of PA in contaminated poultry feed represents a potential public health hazard. A reverse phase high pressure liquid chromatographic (HPLC) method is proposed for determining PA residues in chicken tissues. Optimization of chromatography was achieved for PA using a mobile phase consisting of acetonitrile: H2O. PA was detected by ultraviolet absorption at 254 nm, identified by retention time, and quantitated by peak area integration. Blood, parenchymal tissues, muscle, and alimentary tract contents were homogenized, sonicated, and acid treated followed by extraction with ethyl acetate and analysis by HPLC. Acute oral dosing of chickens with PA over a range of 50 to 550 mg/kg body weight resulted in detectable levels of the mycotoxin (confirmed by gas liquid chromatography) in gizzard muscle and contents, liver, kidney, heart, and intestinal contents. This method should prove useful both for the rapid and sensitive detection of PA residues in poultry and in further studies on the distribution and metabolism of this mycotoxin.

Animals↗

Ultrastructural observations in ponies after treatment with monensin.

Ultrastructural studies were made of myocardium, diaphragm, appendicular muscle, liver, and kidney of 3 ponies acutely poisoned with a single oral dose of monensin (4 mg/kg of body weight). These ponies developed severe signs of toxicosis and were killed 28 to 72 hours after treatment. Severe mitochondrial damage (swelling) and lipoidosis in myocardial tissues were observed in 2 of the 3 ponies; similar, but less severe, changes were observed in the 3rd pony. The hepatocytes of the 3 ponies were characterized by increased amounts of smooth endoplasmic reticulum, large numbers of lipid droplets, vacuoles bounded by fibrous material, and a 2-fold increase in the number of peroxisomes per cell. Some hepatocytes also contained a membrane-bounded protein-like body. The observations indicate that heart mitochondria are primary targets of monensin poisoning in ponies.

Animals↗

Implications of mycotoxins in animal disease.

Mycotoxins are formed on animal feeds when conditions of moisture and temperature permit the growth of naturally occurring toxigenic fungi. In general, mycotoxins are low molecular weight, nonantigenic substances, many of which are relatively heat stable. Mycotoxins can cause acute disease episodes when animals consume critical quantities of them. Specific toxins affect specific organs or tissues such as the liver, kidney, oral and gastric mucosa, brain, or reproductive tract. In acute mycotoxicoses, the signs of disease often are marked and directly referable to the affected target organs. Most frequently, however, concentrations of mycotoxin in feeds are below those that cause acute disease. At lower concentrations, the effects of mycotoxins are more protean. They reduce the growth rate of young animals, and some interfere with native mechanisms of resistance and impair immunologic responsiveness, making the animals more susceptible to infection. These effects on immunity and resistance are difficult to recognize because the signs of disease are associated with the infection rather than with the mycotoxin that predisposed the animal to infection. Animals vary in their susceptibility to some mycotoxins, according to the species and age of animal; young growing animals are more susceptible to certain mycotoxins than are adults. The major effects, sources, and dose response relationships of mycotoxins important to the health of food-producing animals are presented in accompanying tables.

Aflatoxins↗

Plasma progesterone concentration in the bovine before abortion or parturition in pregnant animals exposed to Sarcocystis cruzi, Campylobacter fetus, or Aspergillus fumigatus.

Pregnant cows in the 4th and 5th month of the gestation were exposed to Sarcocystis cruzi, Campylobacter fetus, or Aspergillus fumigatus. Plasma progesterone concentrations were determined at intervals from before the cows were exposed until they had aborted or calved. The plasma progesterone concentration of the exposed pregnant cattle remained at 3.95 +/- 2.0 ng/ml until 24 to 48 hours before abortion or parturition, when it decreased to below 1.00 ng/ml. This pattern was similar for cattle exposed to each of the infective agents. Thus, changes in progesterone concentrations in bovine plasma cannot be used as a diagnostic tool for fetal distress or fetal death.

Abortion, Veterinary↗

Exposure of rabbits to spores of Aspergillus fumigatus or Penicillium sp: survival of fungi and microscopic changes in the respiratory and gastrointestinal tracts.

Rabbits were exposed to spores of Aspergillus fumigatus by 1 of 2 routes: exposure to aerosols of dry spores or introduction of liquid suspensions of spores directly into the stomach. Rabbits also were exposed to aerosols containing spores of a Penicillium sp. Cultural and microscopic examinations of tissues from the respiratory and gastrointestinal tracts indicated fungi were distributed throughout the gastrointestinal tract of the rabbits within 1 hour after exposure to aerosols of A fumigatus or Penicillum spores. Viable A fumigatus and Penicillium were detected in lung tissues of rabbits for 2 or 3 weeks after inhalation of spores. Aspergillus fumigatus was isolated from the gastrointestinal tract no more than 1 week after aerosol exposure, and Penicillium, not beyond 48 hours. However, when large numbers of A fumigatus spores were introduced directly into the stomach, fungi were isolated from tissues for as long as 16 days after exposure even though the intestinal contents were negative 4 to 7 days after introduction of spores. Tests for precipitating antibody were negative, with one exception, among 26 rabbits surviving for 2 weeks or more. Microscopic changes were more pronounced in rabbits exposed to spores of A fumigatus than in rabbits exposed to Penicillium spores.

Animals↗

Comparison of effects of dietary T-2 toxin on growth, immunogenic organs, antibody formation, and pathologic changes in turkeys and chickens.

The effect of T-2 toxin (trichothecene mycotoxin) consumption on Broad-Breasted White turkey poults and White Leghorn chicks was studied. Groups of ten 8-day-old poults were fed rations containing T-2 at 10 ppm, 2ppm, or 0 ppm (controls) for a period of 4 weeks; a 4th group (inanition control) was fed control rations equal to the amount consumed by the group fed rations containing T-2 at 10 ppm during the previous 24 hours. A similar experimental design was used to study the effect of the toxin on 1-day-old chicks. The thymus glands of the poults given the feed containing 10 ppm were markedly decreased in size compared with thymus glands from poults in the control group, 0.182 vs 0.331 (percentage of body weight). There was no significant (P less than or equal to 0.05) decrease in thymus gland size in poults given 2 ppm or in the inanition controls. Dietary treatment did not appear to affect the size of the bursa or spleen of the poults. Histopathologic examination of thymus glands from poults given 10 ppm of T-2 revealed a depletion of cortical lymphocytes. Chicks appeared less sensitive to T-2 toxin than did the poults. There was no effect by any dietary treatment on the size of the thymus gland, bursa, or spleen of chicks. Reductions were noticed in feed efficiency and weight gain. There was no effect of T-2 toxin on agglutinating antibody formation to Pasteurella multocida bacterin.

Animals↗

Complement activity, serum protein, and hepatic changes in guinea pigs given sterigmatocystin or aflatoxin, alone or in combination.

Effects of either sterigmatocystin or aflatoxin, alone or in combination, given orally to guinea pigs were studied. Sterigmatocystin and aflatoxin B1 given alone and in combination at 4.2 mg/day and 0.01 mg/day, respectively, markedly reduced body weight. Although changes in total serum protein were not marked in any of the guinea pigs in this study, sterigmatocystin given alone and aflatoxin given alone significantly ( less than 0.05) decreased alpha2-globulin. The combination of toxins significantly (P less than 0.01) increased albumin and significantly (P less than 0.01) decreased both alpha2- and beta-globulins. Sterigmatocystin depressed complement activity, although not significantly. However, the combination of sterimatocystin with 0.01 mg of aflatoxin B1/day (an amount that does not affect complement activity alone) significantly (P less than 0.01) reduced complement activity. Increased severity of lesions was not found in guinea pigs given aflatoxin at 0.01 mg of B1 equivalents/day in addition to the sterigmatocystin.

Aflatoxins↗

Effects of aflatoxin on the development of acquired immunity to swine erysipelas.

The effect of aflatoxin consumption on the development of acquired immunity to swine erysipelas was studied. Twenty-four pigs were divided into 4 groups (6 pigs/group). Two groups were fed a normal diet and 2 groups were fed the same diet but containing aflatoxin. One group from each diet treatment was given a single injection of an erysipelas bacterin, and 21 days later all pigs were given a challenge inoculum of virulent Erysipelothrix rhusiopathiae organisms. On the basis of the response to the challenge inoculation, pigs were classified as immune, partially immune (PI), or susceptible. Three of the vaccinated pigs fed the normal diet were immune, 2 were PI, and 1 was susceptible, whereas none of the vaccinated pigs given the aflatoxin diet were immune, only 1 was PI, and the remainder were susceptible. Two of the nonvaccinated pigs fed the normal diet were PI and 4 were susceptible; all of the nonvaccinated pigs fed the aflatoxin diet were susceptible. It was concluded that aflatoxin consumption interfered with the development of acquired immunity and apparently increased the severity of the E rhusiopathiae infection in unvaccinated pigs.

Aflatoxins↗

Effects of aflatoxin on the cellular immune system.

Observations of aflatoxin induced thymic involution were followed by studies of other parameters of cellular immunity. Guinea pigs treated with 0.03 to 0.35 mg aflatoxin B1 for 3 to 5 weeks were tested for the development of cutaneous hypersensitivity, migration inhibition factor activity, and stimulation of lymphocyte transformation. A significant suppression of cutaneous hypersensitivity to a Nocardia asteroides sensitin in sensitized aflatoxin recipients was demonstrated. In vitro reductions in migration inhibition factor (MIF) and depressed stimulation indices (Phytohemagglutinin) of peripheral blood lymphocytes were also demonstrated in aflatoxin recipients but did not reach significant levels.

Aflatoxins↗

Cystine aminopeptidase (oxytocinase) activity in plasma and tissues of normal and infected pregnant cattle.

Cystine aminopeptidase (CAP) activity in tissues and in plasma from pregnant cows was measured at various stages of gestation by using the substrate S-benzyl-L-cysteine-4-nitroanilide. The CAP activity was as high or higher in hepatic and renal tissues as in cotyledonary tissue. Plasma CAP activity was low and did not change with length of gestation, nor did it change when placentation was disrupted by infection with Aspergillus fumigatus.

Abortion, Veterinary↗

Penitrem A intoxication of calves: blood chemical and pathologic changes.

An isolate of Penicillium puberulum, obtained from moldy silage, was found to produce a tremorgenic mycotoxin, penitrem A. Dried ground mycelium of this isolate was administered orally to calves either in increasing daily doses or in a single dose that equalled the amount given over a 3-day period in the increasing daily-dose schedule. Signs of intoxication included tremor, ataxia, muscular rigidity, and convulsive episodes. Marked increases in plasma concentrations of lactic acid, pyruvic acid, glucose, and creatine phosphokinase activity were found coincident with the development of severe tremor. The only gross or microscopic change observed in tissues of intoxicated animals was an accumulation of fat in the liver. Changes in the various plasma constituents were interpreted as a secondary effect of the intoxication.

Administration, Oral↗

Effect of aflatoxin on susceptibility of hamsters to Mycobacterium paratuberculosis.

After oral administration of Mycobacterium paratuberculosis to hamsters, the organism passed the epithelial barrier of the intestine, and infection was established in the small intestine and mesenteric lymph nodes. The addition of aflatoxin to the ration of hamsters did not increase their susceptibility to M paratuberculosis but, rather, seemed to decrease susceptibility to the bacillus. Hamsters not treated with aflatoxin and infected with M paratuberculosis had higher bacterial counts in intestinal tract and mesenteric lymph node on necropsy than did infected hamsters that had been treated with aflatoxin. Aflatoxin-treated hamsters grew slowly, had an unthrifty appearance, and developed lesions of megalocytosis regardless of whether they were infected with M paratuberculosis.

Administration, Oral↗

Antibody formation in rabbits exposed to aerosols containing spores of Aspergillus fumigatus.

Rabbits were exposed once a day for 1 to 10 consecutive days to aerosols containing spores of Aspergillus fumigatus. The number of spores used at each 5-minute exposure during an experiment was constant, but the level of exposure was different for each of the 4 experiments. Precipitating antibodies were detected only in serums from rabbits that had inhaled at least 1.6 X 10-6 spores/g of lung tissue at each of 6 exposures or 1.8 X 10-6 spores at 2 exposures. A single exposure to 3.6 X 10-5 spores was sufficient to stimulate antibody detectable in passive hemagglutination (HA) tests. None of the rabbits died from aspergillosis, and signs of infection were transient.

Aerosols↗