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Studies on toxicity of ochratoxin a to chromosomes of tumor cell-line.
1989
Yoon W.J. | Roh M.H. | Kim K.R.
This study was performed to investigate the toxicity of ochratoxin A (OA) to the chromosomes of K562 tumor cell-line in vitro. Chromosomes of K562 tumor cell-line resulted in pseudotriploidy on the control group. Chromosomes of K562 tumor cell-line treated with OA resulted in heteroploidy compared with the control group. The mean number of chromosomes in the karyotype of the control group (60) were 7 in the A group, 5 in the B group, 20 in the C+X group, 7 in the D group, 9 in the E group, 6 in the F group, and 6 in the G+Y group respectively. Treating with 0.7 micro M OA, the number of chromosomes were increased one in E and F group, two in G+Y group compared with control group. In treated with 1.5 micro M OA, the increasing number of chromosome was one in E and F group. In treated with 3 micro M OA, E and F group was increased one and G+Y group were increased two chromosome in G+Y group was decreased one. K562 tumor cell line treated with OA showed Philadelphia-Chromosome in the long arm of the G group karyotype chromosome. The rate of chromosome aberration in K562 tumor cell-line treated with OA was 77 % in 0.7 micro M OA group, 71 % in 1.5 micro M OA group, 82 % in 3 micro M OA group and 94 % in 6 micro M OA group respectively. The rate of chromosome aberration of K562 tumor cell-line treated with OA was high in the high dose level of OA, and chromosome aberration of K562 tumor cell-line treated with OA showed deletion, minute, dicentric-chromosome and translocation in the long arm of the C-group karyotype. As a result of this study, the toxicity of OA showed deletion, minute, dicentric-chromosome and translocation in the long arm of the C-group karyotype, and then, the toxicity of OA resulted in the damage to RNA and protein synthesis in K562 tumor cell-line, and the C-group karyotype of K562 tumor cell-line was target of the toxicity of OA.
Show more [+] Less [-]Effects of testosterone on the prevention of T-2 toxin-induced adrenocortical necrosis in mice
1989
Thurman, J.D. | Creasia, D.A. | Trotter, R.W.
To evaluate the effect of exogenous testosterone on the development of T-2 toxin-induced necrosis of adrenal glands, mice were allotted to 3 treatment groups. Each treatment group contained castrated male, and castrated and sexually intact female mice. Each mouse in group 1 was given 0.16 mg testosterone propionate at 48-hour intervals for a total of 12 infections, group-2 mice were given similar injections of only the vehicle, and group-3 mice were given no treatment. Twenty-four hours after the last injection, the mice in all 3 groups were exposed for 10 minutes to an aerosol of T-2 toxin. All mice alive at 24 hours after exposure were euthanatized and the adrenal glands and thymuses were examined histologically. Necrosis of the adrenal cortex was not found in any of the mice given preexposure treatment with exogenous testosterone, whereas all mice given vehicle only or no treatment had T-2 toxin-induced necrosis of the inner portion of the adrenal cortex. Lymphocytolysis in the cortex of the thymus confirmed that each mouse of all 3 treatment groups had experienced systemic mycotoxicosis. The uniform severity of the lesion in all mice suggests that the thymus was not protected by exogenous testosterone administration or by the castration status of the mice. We propose that T-2 toxin-induced adrenal necrosis in mice is prevented by the presence of testosterone.
Show more [+] Less [-]Diagnostic importance of vitamin K1 and its epoxide measured in serum of dogs exposed to an anticoagulant rodenticide
1989
Mount, M.E. | Kass, P.H.
Administration of vitamin K1, SC, to anticoagulant-poisonsed (diphenadione) dogs provided diagnostic information within 4 hours, when vitamin K1 and its epoxide were measured in canine sera. Twelve dogs (2 groups of 6) were given 2.5 mg of diphenadione/kg of body weight for 3 days. Dogs were treated with vitamin K1, 2.5 (n = 6) or 5 mg/kg/day (n = 6) SC for 21 days, and their responses were compared. Four nonexposed control dogs were given 5 mg of vitamin K1/kg/day. Serum concentration of vitamin K epoxide was significantly (P less than 0.02) higher in diphenadione-exposed dogs than in control dogs 1 to 4 hours after the initial vitamin K1 treatment on day 4. Vitamin K epoxide/vitamin K1 ratios were similarly higher and became more distinct. Cessation of vitamin K1 therapy on day 24 resulted in prolongation of one-stage prothrombin times in diphenadione-exposed dogs, becoming clearly evident on day 27. Serum vitamin K1 concentrations were not detectable on day 27 in diphenadione-exposed dogs, whereas serum vitamin K1 concentrations were readily detectable in control dogs. One stage prothrombin time changes, during days 24 to 32, indicated 5 mg of vitamin K1/kg provided better protection than did 2.5 mg of vitamin K1/kg. Coagulopathy in the dogs was resolved by day 32.
Show more [+] Less [-]Effects of aflatoxin, deoxynivalenol, and their combinations in the diets of growing pigs
1989
Harvey, R.B. | Kubena, L.F. | Huff, W.E. | Corrier, D.E. | Clark, D.E. | Phillips, T.D.
In 2 studies, the effects of dietary aflatoxin (AF) and deoxynivalenol (DON) were evaluated in growing crossbred barrows. The first study consisted of 4 treatments of 5 barrows each (6 weeks old) at dosages of 0 mg of DON and AF (control), 2.5 mg of DON/kg of feed, 0.75 mg of AF/kg of feed, and 2.5 mg of DON + 0.75 mg of AF/kg of feed. Pigs were fed their respective diets for 21 days. Treatment with DON caused decreases in weight gains, but no other treatment-related differences could be attributed to diets. In a second study, the experimental design consisted of 4 treatments of 5 barrows each (6 weeks old) at dosages of 0 mg of DON and AF (control), 3 mg of DON/kg of feed, 3 mg of AF/kg of feed, and 3 mg of DON + 3 mg of AF/kg of feed fed ad libitum for 28 days. The pigs were observed twice daily for clinical signs, hematologic and serum biochemical measurements were made weekly, and body weights and feed consumption were determined weekly. Body weight gains were significantly depressed by the AF and the AF + DON treatments for days 7, 14, 21, and 28. Body weights and body weight gains were only slightly reduced in the DON treatment. Changes in serum enzymatic activities of alkaline phosphatase, aspartate transaminase, creatine kinase, and gamma-glutamyl transferase were noticed in pigs given treatments with AF alone and those given AF + DON. Total iron binding capacity and serum total protein, albumin, cholesterol, BUN, and glucose concentrations were decreased, whereas prothrombin and activated thromboplastin times were increased by AF and AF + DON treatments. Lesions in the AF-treated groups were compatible with a diagnosis of aflatoxicosis. The control and DON-treated pigs had no abnormalities. These data provide a description of the effects of dietary AF and DON, singly and in combination, in growing barrows.
Show more [+] Less [-]Effects of Pasteurella haemolytica leukotoxin on cultured bovine lymphoma cells
1989
Clinkenbeard, K.D. | Mosier, D.A. | Timko, A.L. | Confer, A.W.
Leukotoxin activity from culture supernatants of Pasteurella haemolytica serotype 1 in logarithmic growth phase caused rapid (less than 5 min) release of intracellular K+, uptake of extracellular Ca2+, and swelling of cultured bovine lymphoma cells (BL3 cells). Release of 51CrO(4)(2-) and lactate dehydrogenase (LDH) from BL3 cells began after 15 minutes of incubation with leukotoxin at 37 C and was completed between 60 and 120 minutes of incubation. In addition, leukotoxin exposure of BL3 cells resulted in cell aggregation and adherence to glass surfaces. Scanning electron microscopy indicated that after 10 minutes of leukotoxin exposure, BL3 cells increased in size, and large membrane defects developed between 20 and 60 minutes of exposure. The rate of release of LDH from leukotoxin-exposed BL3 cells was proportional to the amount of leukotoxin added. At high cell concentrations, the activity of LDH released at completion was directly proportional to the amount of leukotoxin added. Leukotoxin-induced release of LDH required a divalent cation, whereas K+ release and cell swelling did not. The addition of Ca2+, Mn2+, and Ba2+ resulted in increased leukotoxin-induced release of LDH. Divalent cation concentrations of 0.5 to 2.5 mM resulted in 50% of maximal stimulation. Ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid blocked increased release of LDH caused by Ca2+ addition, but had no effect on K+ release or cell swelling. Leukotoxin action on BL 3 cells (K+ release, cell swelling, Ca2+ uptake, and release of LDH) was prevented by incubation at 4 C.
Show more [+] Less [-]Complement, bacteriostatic, and enzymatic activities in sera from guinea pigs given aflatoxin and/or rubratoxin
1989
Thurston, J.R. | Sacks, J.M. | Richard, J.L. | Peden, M. | Driftmier, K.
The relationship of serum complement activity and bacteriostatic activity was investigated in male guinea pigs given aflatoxin and/or rubratoxin. In experiment 1, guinea pigs were given 0.6 mg of aflatoxin/kg of body weight, PO, once. In experiment 2, guinea pigs were given 0.02 mg of aflatoxin/kg, PO, and/or 8 mg of rubratoxin, PO, 11 times. Aflatoxin (0.02 mg/kg) had no effect given alone, but potentiated the effect of rubratoxin. In both experiments, changes in complement activity were accompanied by similar but not always significant (P less than 0.05) changes in bacteriostatic activity of serum. Guinea pigs given 0.06 mg of aflatoxin/kg had significant (P less than 0.05) changes in complement titers and in serum alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase activities. Guinea pigs given repeated oral doses of aflatoxin and/or rubratoxin had changes in complement titers, bacteriostasis, and alkaline phosphatase and aspartate aminotransferase activities, but not in alanine aminotransferase activities. Significant differences were detected only when average values for all guinea pigs given rubratoxin or rubratoxin with aflatoxin were compared with average values for guinea pigs not given rubratoxin.
Show more [+] Less [-]Phenolsulfonphthalein pharmacokinetics and renal morphologic changes in adult pony mares with gentamicin-induced nephrotoxicosis
1989
Hinchcliff, K.W. | McGuirk, S.M. | MacWilliams, P.S. | Cooley, A.J.
Changes in renal function, determined by pharmacokinetics of phenolsulfonphthalein (PSP), and renal morphologic features were examined in adult pony mares given 20 mg of gentamicin sulfate/kg of body weight, IV, q 8 h (group A) n = 7 or isotonic saline solution, IV, q 8 h, n = 5 (group B) for 14 days. Susceptibility of ponies to gentamicin-induced nephrotoxicosis was varied. Two group-A ponies developed acute renal failure and were euthanatized before treatment day 14, whereas 5 group-A ponies did not develop physical or behavioral abnormalities after 14 days of gentamicin administration. All group-A ponies but none of group-B ponies developed ultrastructural abnormalities of the proximal tubular epithelium, consistent with gentamicin-induced nephrotoxicosis. Significant (P less than 0.05) differences were not detected in pharmacokinetic values of either group. Clearance of PSP was reduced in 4 group-A ponies that developed the most severe gentamicin-induced nephrotoxicosis. Changes in clearance of PSP were significantly (P less than 0.05) correlated with changes in the serum creatinine concentration.
Show more [+] Less [-]Effect of clindamycin on Factor-VII activity in healthy cats
1989
Four healthy cats were given clindamycin orally in daily doses of 25 or 50 mg/kg of body weight for 6 weeks. Significant change in Factor-VII activity was not found, compared with pretreatment values. In 2 cats tested, toxin produced by Clostridium difficile was not detected in fecal samples obtained before treatment and at 6 weeks after treatment, suggesting that intestinal overgrowth by C difficile did not develop. Results of the study seemed to indicate that orally administered clindamycin does not measurably reduce synthesis of vitamin K-dependent clotting factors in healthy cats.
Show more [+] Less [-]Hematologic changes induced by intravenous administration of diacetoxyscirpenol in pigs, dogs, and calves
1989
Coppock, R.W. | Hoffman, W.E. | Gelberg, H.B. | Bass, D. | Buck, W.B.
Diacetoxyscirpenol (DAS) was given IV to pigs (0, 0.5, and 1.0 mg/kg of body weight), cattle (0 and 0.5 mg/kg), and dogs (0 and 0.5 mg/kg). Blood was collected and hemograms were done at 0.5-hour intervals for 8 hours. The animals were euthanatized at 8 hours after treatment, and bone marrow samples were taken and examined by light microscopy. Moderate to severe necrosis of bone marrow hematopoietic elements was found in animals given DAS. The sequential increase in the type and number of abnormal cells in the blood suggested a successive destruction of the hematopoietic elements. A marked left shift in the neutrophil population was found in animals given DAS. Metarubricytes and large platelets were found in the blood of animals given DAS. Lymphocytes were replaced with immature cells. Pathologic changes were most severe in the pigs given a dosage of 1.0 mg of DAS/kg. The order of species sensitivity to DAS was pigs greater than dogs much greater than cattle.
Show more [+] Less [-]Comparative effects of cholera toxin, Salmonella typhimurium culture lysate, and viable Salmonella typhimurium in isolated colon segments in ponies
1989
Murray, M.J. | Doran, R.E. | Pfeiffer, C.J. | Tyler, D.E. | Moore, J.N. | Sriranganathan, N.
Isolated segments of left dorsal colon and a side-to-side colocolostomy (between the left ventral colon and left dorsal colon) were surgically created in 6 adult ponies. Four segments, each separated by an empty segment, were inoculated (20 ml) with 1 of the following 4 solutions: phosphate buffered saline solution (PBSS)/1% polyethylene glycol (PEG); purified cholera toxin in PBSS/1% PEG (5 micrograms cholera toxin/ml of PBSS/1% PEG); lyophilized Salmonella typhimurium UCD 1755 culture lysate, reconstituted in PBSS/1% PEG; and viable S typhimurium UCD 1755 (10(8) organisms/ml of PBSS/1% PEG). Twenty hours following inoculation of the treatment solutions into the isolated colon segments, the ponies were reanesthetized. Fluid accumulation in the isolated segments was measured, and tissue samples from isolated segments were taken for examination by light microscopy and electron microscopy, and for measurement of mucosal cyclic adenosine monophosphate levels. There was fluid accumulation in segments inoculated with cholera toxin in 4 ponies (29.5 +/- 12.7 ml), and in segments inoculated with S typhimurium UCD 1755 culture lysate in 3 ponies. (14.0 +/- 8.7 ml). There was no fluid accumulation in segments inoculated with either the control solution (PBSS/1% PEG) or viable S typhimurium UCD 1755. There was significantly (P less than 0.05) less cyclic adenosine monophosphate in segments inoculated with cholera toxin, Salmonella lysate, and viable Salmonella, compared with control segments. Histologically, there were minimal changes in control segments, consisting of mild to moderate submucosal edema and capillary congestion. Changes in the other segments were more pronounced and included neutrophilic infiltration and exocytosis, with the changes increasing in severity in the segments inoculated with cholera toxin, S typhimurium culture lysate UCD 1755, and viable S typhimurium UCD 1755, respectively. Ultrastructurally, mucosa from control segments was normal. Mucosa from segments inoculated with cholera toxin had swollen endoplasmic reticula and basolateral separation of surface epithelial cells. Mucosa from segments inoculated with S typhimurium UCD 1755 culture lysate and viable S typhimurium UCD 1755 had swollen smooth and rough endoplasmic reticula, separation of epithelial cells, degeneration of microvilli, and goblet cell degeneration.
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