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Objective: To examine the toxic effects of fumonisin B1 (FB1)-containing culture material and deoxynivalenol (DON)-contaminated wheat diets on barrows., Animals: 24, 7-week-old crossbred barrows allotted to 4 equal groups of 3 replicates of 2 barrows/replicate., Procedure: Barrows were fed diets for 28 days that were formulated as follows: no additional FCM or DON/kg of feed (control); 100 mg FB1/kg of feed; 5 mg DON/kg of feed; or 100 mg FB1 plus 5 mg DON/kg of feed. Body weight and feed consumption were monitored weekly. On day 28, blood samples were obtained for serum biochemical, hematologic, and immunologic measurements. On day 29, barrows were euthanatized and necropsies were performed., Results: Analyzed mycotoxin content of diets were: none detected (control); 47 mg of FB1/kg of feed (FB1 diet); 4.5 mg of DON/kg of feed (DON diet); and 56 mg of FB1 and 3.7 mg of DON/kg of feed (FB1 plus DON diet). Differences were detected among groups of barrows for clinical performance, serum biochemical analytes, immunologic response, and histopathologic lesions., Conclusions: Combining FB1-containing material and DON-contaminated wheat in the diets of growing barrows induces a more toxic response than that induced by either toxin singly. For many variables, the response could be described as additive; however, for some variables, responses were interactive in a greater-than-additive manner., Clinical Relevance: Caution should be exercised when formulating swine diets that could contain FB1 and DON, because the condition induced by their combination is more severe than that predicted for each mycotoxin's toxicity.

Aflatoxin (AF)-contaminated and fumonisin B1 (FB1)-contaminated (culture material from Fusarium moniliforme) diets were fed singly and in combination to growing cross-bred barrows. Six barrows (3 replicates of 2 each; mean body weight, 17.5 kg) per group were fed: 0 mg of AF and 0 mg of FB1/kg of feed (control); 2.5 mg of AF/kg of feed; 100 mg of FB1/kg of feed; or 2.5 mg of AF plus 100 mg of FB1/kg of feed for 35 days. The effects on production performance, serum biochemical, hematologic, immunologic, and pathologic measurements were evaluated. Body weight, gain, and feed consumption were significantly (P < 0.05) decreased by AF and AF plus FB1 diets. The FB1 diet decreased feed consumption, and although body weight was numerically decreased, it was not statistically significant. Aflatoxin increased serum gamma-glutamyltransferase (GGT) activity and total iron concentration and decreased urea nitrogen concentration and unsaturated iron-binding capacity. The FB1-alone diet increased serum GGT activity, whereas the AF plus FB1 diet increased serum aspartate transaminase, cholinesterase, alkaline phosphatase, and GGT activities, increased RBC count, triglycerides, and total iron concentrations, and decreased unsaturated iron-binding capacity and urea nitrogen concentration. For the most part, the effects of the AF plus FB1 diet on body weight and hematologic measurements could be considered additive. However, the effect of the AF plus FB1 diet on cholinesterase and alkaline phosphatase activities was greater than additive and was a synergistic response. One pig in the FB1-diet group and 2 pigs in the combination-diet group died. Postmortem lesions in pigs of the FB1-diet group consisted of ascites and increased liver weight. Observations at necropsy for pigs of the AF plus FB1-diet group consisted of hydrothorax, ascites, pulmonary edema, gastric erosions and ulceration, and increased liver and spleen weights. The AF diet increased relative liver weight and resulted in liver that was pale, rubbery, and resistant to cutting. Histologic lesions consisted of hepatic necrosis or degeneration, or both, with variable degrees of bile duct proliferation in barrows of the AF-diet groups. Renal tubular nephrosis was observed in barrows of the FB1-diet group, but this was not consistent in the AF plus FB1-diet group. Cell-mediated immunity, as measured by mitogen-induced lymphoblastogenic stimulation index, was decreased in barrows of the AF and FB1-diet groups, and values in barrows given the combination diet were significantly decreased from those in barrows given the single toxin diets. It was concluded that AF and FB1 (from culture material), singly or in combination, can adversely affect clinical performance, serum biochemical, hematologic, and immunologic values and induce lesions in growing barrows. For most of the variables we evaluated under our study conditions and dosages of toxins, measurements were affected more by the combination diet than by either single toxin diet, and the toxic responses could be described as additive or more than additive, particularly for induction of liver disease.

Diets containing 200 mg fumonisin B1/kg of feed and .75 mg aflatoxin/kg of feed singly or in combination were fed to female turkey poults (Nicholas Large White) from day of hatch to 21 d of age. When compared with controls, 21-d body weight gains were reduced 10% by fumonisin B1, 39% by aflatoxins, and 47% by the combination. Relative weights (grams/100 g body weight) of the kidney and pancreas increased in poults fed the diet containing aflatoxins alone, whereas the relative weight of the liver decreased. Relative weights of the liver and pancreas increased in the poults fed the fumonisin diet. Relative weights of the kidney, pancreas, and gizzard increased in the poults fed the combination diet, whereas the relative weight of the liver decreased. Most serum constituents, hematology values, and activities of enzymes measured were altered in poults receiving the diets containing aflatoxins with or without fumonisin B1. No major histological lesions were observed in tissues from control poults or poults fed the diet containing fumonisin alone. Lesions associated with aflatoxins were only observed in the liver and occasionally in the kidney of poults fed the diets containing aflatoxins with or without fumonisin B1. The primary hepatic change was bile duct hyperplasia with some hepatocellular degeneration and necrosis and megalocytosis. Occasional necrotic and degenerating tubular epithelial cells were observed in the kidneys. The increased toxicity in poults fed the combination diet for most variables can best be described as additive, although some variables showed less than additive toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dietary aflatoxin (AF) and the antibiotics lincomycin (L) and tylosin (T) were evaluated in growing crossbred pigs. Six barrows (3 replicates of 2 each, mean body weight 14.0 kg) per group were assigned to 1 of 6 treatment groups (for a total of 36): 0 mg L, 0 mg T, and 0 mg AF/kg of feed (control); 220 mg L/kg of feed (200 g/ton); 110 mg T/kg of feed (100 g/ton); 2.5 mg AF/kg of feed; 2.5 mg AF plus 220 mg L/kg of feed; 2.5 mg AF plus 110 mg T/kg of feed. Barrows were administered their respective diets for 28 days. Body weight, body weight gain, and feed consumption were reduced by the AF alone, the AF plus L, and the AF plus T treatments, compared with control, L, and T treatments. Altered serum biochemical or hematologic measurements induced by AF treatments included increased serum activities of alkaline phosphatase and gamma-glutamyltransferase, increased hematocrit, hemoglobin, RBC count, WBC count, and mean cell hemoglobin, decreased serum concentrations of albumin, cholesterol, inorganic phosphorus, unsaturated iron binding capacity, total protein, and urea nitrogen, and decreased lymphoblastogenic response. Liver weight was increased, and microscopic lesions were consistent with those observed in cases of aflatoxicosis. With some other minor exceptions for hematologic and immunologic variables, these data indicate that the feed antibiotics lincomycin and tylosin, when added to aflatoxin-contaminated diets, do not have beneficial or detrimental effects on aflatoxicosis in growing swine.

Diets containing 300 mg fumonisin B1 (FB1)/kg of feed and 5 mg T-2 toxin/kg of feed singly or in combination were fed to female turkey poults (Nicholas Large White) from day of hatch to 21 d of age. When compared with controls, 21-d body weight gains were reduced 21% by FB1, 26% by T-2, and 47% by the combination. the efficiency of feed utilization was adversely affected by FB1 and the combination of FB1 and T-2. Relative weights (grams/100 g BW) of the liver and gizzard were increased in poults fed the FB1 and the combination diets; whereas, the relative weight of the pancreas was increased in all treated groups. All poults were scored for oral lesions using a scale of 1 to 4 (1 = no visible lesions, 4 = severe lesions). Oral lesions were present in all poults fed the T-2 diet (average score of 3.29) or the combination diet (average score of 3.54). Serum concentration of cholesterol was decreased and lactate dehydrogenase activity was increased in poults fed the FB1 and combination diets. The activity of aspartate aminotransferase and the values for red blood cells, hemoglobin, and hematocrit were increased only in poults fed the combination diet. Inorganic phosphorus concentration was decreased only in poults fed the combination diet. The increased toxicity in poults fed the combination diet for most variables can best be described as additive, although some variables not altered by FB1 or T-2 singly were significantly affected by the combination, indicating that the combination may pose a potentially greater problem to the turkey industry than either of the mycotoxins individually.

To examine the effects of acute exposure to fumonisin-containing culture material (FCCM), 15 crossbred wether lambs were dosed intraruminally with FCCM containing 0 (CONTROL, n = 3), 11.1 (LOW, n = 4), 22.2 (MED, n = 4), or 45.5 (HIGH, n = 4) mg of total fumonisins (B1, B2, and B3)/kg BW daily for 4 d. Blood samples were collected daily, and on d 11 lambs were killed and necropsied. Changes in serum constituents in fumonisin-treated lambs indicative of liver damage, included increased (P < .05) activities of alkaline phosphatase, gamma-glutamyl transferase, aspartate aminotransferase, and lactate dehydrogenase. Serum concentrations of cholesterol, triglycerides, urea nitrogen, and creatinine were also increased (P < .05) in lambs dosed with FCCM. Hemoglobin tended to increase (P = .07) and white blood cell count tended to decrease (P = .08) in HIGH lambs and activated partial thromboplastin time tended to decrease (P < .10) in lambs dosed with LOW and MED treatments. Mitogen-induced lymphocyte blastogenesis was not different (P = .14) among treatments. Feed intake markedly decreased (P < .01) following the first dosing of FCCM and continued to decline throughout the study. Ruminal VFA concentrations and pH tended to decrease (P < .10) at d 11 in treated lambs. Relative liver and kidney weights (g/100 g of BW) increased (P < .05) in fumonisin-treated lambs. Histiolgical examination revealved tubular nephrosis and mild hepatopathy in dosed lambs. Lambs receiving the HIGH treatment died on d 3, 4, 5, and 7 of the study and on d 9 one lamb on the MED treatment died.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dietary ochratoxin A (OA) and T-2 toxin, fed singly and in combination, were evaluated in growing crossbred pigs. Thirty-six barrows (3 replicates of 3 for each of 4 treatment groups, mean body weight, 18.0 kg) were fed: 0 mg of OA and 0 mg of T-2/kg of feed (control); 2.5 mg of OA/kg of feed; 8.0 mg of T-2/kg of feed; or 2.5 mg of OA plus 8.0 mg of T-2/kg of feed; for 30 days. Production performance, serum biochemical, hematologic, immunologic, and pathologic evaluations were made. Body weight and body weight gain were decreased by all toxin treatments, but the combination toxin treatment reduced weight gain more than did either of the toxins administered singly and could be considered additive. Liver weight was decreased by combination treatment, whereas kidney weight was increased by OA treatment. Ochratoxin decreased serum cholesterol, inorganic phosphorus, and alkaline phosphatase values; reduced mean cell volume, hemoglobin concentration, and macrophage phagocytosis; and increased creatinine and total protein values. Consumption of T-2 toxin reduced hemoglobin and serum alkaline phosphatase values. The combination treatment decreased serum cholesterol, gamma-glutamyltransferase, alkaline phosphatase, mean cell volume, hematocrit, and hemoglobin values, as well as lymphoblastogenesis and phagocytosis, and increased serum creatinine concentration. We concluded that OA and T-2, singly or in combination, can affect clinical performance, serum biochemical, hematologic, and immunologic values, and organ weights of growing barrows. Although some analytes were affected more by the combination than by either toxin alone, the interactions could best be described as additive, not synergistic.

Poultry products represent a significant reservoir of Salmonella typhimurium. Ochratoxin A, a mycotoxin and natural contaminant of poultry feedstuffs, produces detrimental effects on the immune and other systems of the broiler chick. Because poultry products are possible sources of S. typhimurium contamination that can potentially infect humans, there is a need to know whether ochratoxin A can alter the growth of Salmonella in poultry. We investigated the pathological alterations of young male broiler chicks by S. typhimurium in the presence (3.0 mg/kg) or absence of ochratoxin A in the diet. Ochratoxin A alone in the diet decreased the body weight and increased the relative organ weights of the liver, kidney, gizzard, spleen, pancreas, and proventriculus. It did not affect the heart and bursa of Fabricius. The mycotoxin altered the serum concentrations of proteins, enzymes, calcium and phosphate salts, normal tissue constituents, and catabolic metabolites in a pattern that would suggest damage to skeletal muscle, liver, kidney, pancreas, and bone. Birds fed diets containing ochratoxin A had microcytic and hypochromic erythrocytes and a decrease in phytohemagglutin- and concanavalin A-stimulated blastogenesis. Salmonella typhimurium alone had no affect on the variables measured except for a decrease in body weight. With the exception of an increase in mortality (13.2%, a significant synergistic interaction) and decrease in body weight, Salmonella in combination with ochratoxin A did not alter the values of the remaining variables measured from those measured in the ochratoxin A diet alone. Cecal colony count of S. typhimurium was not affected by treatment with ochratoxin A.

Effects of dietary aflatoxin (AF) and supplemental vitamin E (d-alpha-tocopherol) were evaluated in growing crossbred pigs. Nine barrows (3 replicates of 3 each, mean body weight, 14.0 kg) per group were assigned to 1 of 4 treatment groups (for a total of 36 barrows): 0 IU of supplemental vitamin E and 0 mg of AF/kg of feed (control); 2,400 IU of vitamin E divided into equal doses and administered IM on days 1 and 16; 2.5 mg of AF/kg of feed; or 2.5 mg of AF/kg of feed plus 2,400 IU of vitamin E administered similarly to treatment 2. Barrows were administered their respective treatment for 32 days. Evaluations were made for group production performance and for serum biochemical, immunologic, hematologic, pathologic, serum and tissue tocopherol, and serum retinol variables. Body weight was reduced by AF-alone and AF plus vitamin E treatments, compared with control and vitamin E-alone treatments. Liver weight was increased for the AF alone-treated and the AF plus vitamin E-treated barrows, compared with control barrows. The AF alone-treated barrows had alterations in:serum values of alkaline phosphatase, gamma-glutamyltransferase, albumin, glucose, phosphorus, calcium, cholesterol, total iron, unsaturated iron-binding capacity, total iron-binding capacity, and urea nitrogen; RBC numbers, hematocrit, hemoglobin concentration, and prothrombin time; and mitogen-induced lymphoblastogenic responses. With the exception of some slight ameliorating effects on hematologic measurements, supplemental treatment with vitamin E did not prove beneficial against the toxicosis-associated AF treatment. The AF alone-treated barrows had decreased serum tocopherol and retinol concentrations, compared with control and pretest values, and decreased tocopherol concentration in cardiac tissue. High parenterally administered doses of vitamin E did not have sparing effect on AF-induced reductions of serum tocopherol or retinol concentration; however, compared with pretest values, serum tocopherol concentration was increased by vitamin E-alone treatment. Tocopherol concentration in cardiac tissue of the AF plus vitamin E-treated barrows was increased over that of the AF alone-treated barrows, indicating an ameliorating effect on AF-induced tissue concentrations reductions. These data indicate that vitamin E may not have a sparing effect on AF-induced toxicosis and that AF may reduce serum retinol and serum and tissue tocopherol concentrations.

Two formulations of hydrated sodium calcium aluminosilicate (HSCAS-1 and HSCAS-3), anti-caking agents for mixed feed, were added to the diets of growing barrows and were evaluated for their potential to diminish the clinical signs of aflatoxicosis. The experimental design consisted of 8 barrows (2 replicates of 4 each/treatment) assigned to 1 of the following 6 treatment diets (total of 48): 1) 0 g of HSCAS-1 or HSCAS-3 and 0 mg of aflatoxin (AF)/kg of feed (control); 2) 5 g HSCAS-1/kg of feed; 3) 5 g HSCAS-3/kg of feed; 4) 3 mg AF/kg of feed; 5) 3 mg AF plus 5 g HSCAS-1/kg of feed; or 6) 3 mg AF plus 5 g HSCAS-3/kg of feed. Barrows were maintained in indoor concrete-floored pens, with feed and water available for 28 days (from 8 to 12 weeks of age). Barrows were observed twice daily and weighed weekly, and blood samples were collected at day 28 for hematologic, immunologic, and serum biochemical measurements. At the termination of the study, barrows were euthanized and necropsied. Barrow body weight gains were diminished, compared to those of controls, by consumption of AF alone and both of the AF plus HSCAS diets; however, the AF plus HSCAS-1 and AF plus HSCAS-3 barrow body weight gains were significantly greater (P < 0.05) than those of the AF-alone barrows.(ABSTRACT TRUNCATED AT 250 WORDS)

A hydrated sodium calcium aluminosilicate (HSCAS) was incorporated into diets (.5%) containing 3.5 mg/kg aflatoxin (AF) and 5.0 mg/kg diacetoxyscirpenol (DAS) singly and in combination. Male broiler chicks received ad libitum access to their respective diets and water from 1 to 21 days of age. Body weight gains were significantly (P < .05) depressed by AF and DAS singly and a synergistic interaction occurred between AF and DAS for a further depression of body weight gains. Alterations in hematological and serum biochemical values, as well as serum enzyme activities, were observed for the AF and the AF and DAS combination. Additionally, a significant interaction occurred between AF and DAS for some biochemical values and enzyme activities. Adding HSCAS resulted in almost total protection against the effects caused by AF alone, limited protection against the combination, but no protection against the DAS alone. These findings indicate that HSCAS can diminish the adverse effects of AF but not of DAS.

Commercially available zeolitic ore compounds, when incorporated into the diets at 0.5%, were evaluated for their ability to reduce the deleterious effects of 3.5 mg aflatoxin/kg feed on growing broiler chickens from 1 day to 3 weeks of age. In a series of four experiments, the compounds used included the following: mordenite (particle size of -20 mesh; Zeomite); clinoptilolite (particle size of -20 mesh; Zeobrite); SC Zeolite (particle size of -20 mesh); and clinoptilolite (particle size of -35 mesh; Clino 1) or clinoptilolite (particle sizes of -20 plus +35 mesh; Clino 2). Results demonstrated that 0.5% Zeobrite, Clino 1, or Clino 2 added to aflatoxin-contaminated diets did not significantly (P < 0.05) diminish the toxicity of high concentrations of aflatoxin to growing broiler chicks. Zeomite mordenite ore reduced the toxicity of aflatoxin to growing chicks by 41%, as indicated by weight gains, liver weight, and serum biochemical measurements, which compares favorably with its in vitro binding capacity to aflatoxin. SC Zeolite reduced weight-gain toxicity of aflatoxin by approximately 29%.

Ochratoxin A (OA) was incorporated in the diets of growing gilts (mean body weight, 20.1 kg) at a concentration of 2.5 mg of OA/kg of feed and was fed continuously for 35 days. Humoral and cell-mediated immunologic measurements were evaluated to determine the effects of OA on immune function in swine. Cutaneous basophil hypersensitivity to phytohemagglutinin (PHA), delayed hypersensitivity to tuberculin, PHA-induced lymphocyte blastogenesis, interleukin-2 production, total and isotype immunoglobulin concentrations, antibody response to chicken RBC, and macrophage activation were used to evaluate immune function. Gilts treated with OA had reduced cutaneous basophil hypersensitivity response to PHA, reduced delayed hypersensitivity to tuberculin, decreased stimulation index for lymphoblastogenesis, decreased interleukin-2 production when lymphocytes were stimulated with concanavalin A, and decreased number and phagocytic activity of macrophages. Differences were not observed for total and isotype immunoglobulin concentrations, or humoral hemagglutination (chicken RBC) titer. These data indicate that OA may suppress cell-mediated immune response in growing swine.

One-day-old broilers were reared until 35 days of age at both natural low (100 m) and simulated high altitude (2133 m) to assess the incidence and development of ascites syndrome. Clinical measurements were conducted at 7, 14, 21, 28, and 35 days of age. Birds reared at 2133 meters exhibited significantly (P less than or equal to 0.05) reduced body weights at 7 through 28 days of age. Total serum calcium and biochemical enzyme activities were found to be altered at 35 days of age. In addition, the high-altitude group had significantly (P less than or equal to 0.05) higher erythrocyte counts, hematocrits, and hemoglobin at 14, 21, 28, and 35 days of age and higher serum inorganic phosphorus at each weekly sample time than birds at the low altitude. Total mortality was 20.3% at 2133 meters and 4.6% at 100 meters. The incidence of ascites syndrome in the high-altitude group ranged from 16.6% to 61.1% during the 5-week experimental period.

Effects of adding .5% of a hydrated sodium calcium aluminosilicate (HSCAS) to diets containing 1 or .5 mg aflatoxin (AF)/kg were determined in male turkey poults from 1 day to 3 wk of age. Body weight gains were significantly reduced by 51 and 19% in turkey poults fed 1 and .5 mg AF/kg, respectively; efficiency of feed utilization was not affected. There were no deaths in poults fed .5 mg AF/kg; however, the mortality rate was 88% in poults fed 1 mg AF/kg. The addition of .5% dietary HSCAS resulted in a 68% decrease in mortality to 28% for the 3-wk experimental period. Treatment-related changes in relative organ weights, hematological values, serum biochemical values, and enzyme activities were observed. The HSCAS in the absence of AF did not alter any of the parameters measured. The HSCAS diminished the adverse effects of AF on body weight gains, most relative organ weights, hematological values, serum biochemical values, and enzyme activities associated with .5 mg AF/kg, but not 1 mg AF/kg. These findings indicate that HSCAS may diminish many of the adverse effects of AF in an AF-sensitive species, the turkey.

Inclusion of lactose in the diets of chickens has been determined to reduce cecal colonization with Salmonella typhimurium. We hypothesized, therefore, that dietary lactose may be a practical means for reducing the prevalence of Salmonella contamination of chicken products. Because some strains of Salmonella are atypical and ferment lactose, we investigated the effects of dietary lactose on cecal colonization with lactose-fermenting S typhimurium. Broiler chicks were inoculated intracloacally with Lac+ S typhimurium selected for resistance to novobiocin and rifampicin. The chicks also were inoculated orally with certain anaerobes that do not effectively inhibit colonization by S typhimurium, but do appear essential for lactose mediated inhibition of cecal colonization. Control chicks were not given dietary lactose, and chicks in the experimental group were fed a diet containing 7% lactose. Enumeration of Lac+ S typhimurium in cecal contents revealed dietary lactose to be effective at controlling this organism. Control was correlated with changes in cecal pH and increases in undissociated volatile fatty acids, especially propionic acid.

The individual and combined effects of kojic acid and aflatoxin were studied in male broiler chicks (Peterson x Hubbard). The experiment had a two by two factorial arrangement of treatments with dietary treatments of 0 and 2,500 mg kojic acid/kg feed and 0 and 2.5 mg aflatoxin/kg feed. The broilers were obtained at 1 day of age and housed in electrically heated batteries with feed and water available for ad libitum intake until they reached 3 wk of age. The toxicity of kojic acid was characterized by significant (P less than .05) reductions in body weight, the relative weight of the bursa of Fabricius, serum cholesterol concentration, and serum alkaline phosphatase activity, and by significant (P less than .05) increases in the relative weight of the pancreas, proventriculus, and gizzard, and serum concentrations of uric acid and triglycerides. Aflatoxicosis was characterized by significant (P less than .05) reductions in body weight, serum concentrations of total protein, albumin, cholesterol, and inorganic phosphorus, serum glutamic oxalacetic transaminase activity, and mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Significant (P less than .05) increases in the relative weight of the liver, kidney, spleen, pancreas, proventriculus, and heart, and the serum pyruvic transaminase activity were also caused by aflatoxin alone. The only significant (P less than .05) interaction between kojic acid and aflatoxin, which can best be described as antagonistic, was seen through an increase in mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. These data indicate that kojic acid is not an aflatoxin synergist at the levels used in the present study.

The effects of dietary aflatoxin (AF) and diacetoxyscirpenol (DAS), singly and in combination, were evaluated in growing crossbred barrows. The experimental design consisted of 4 treatments of 9 barrows each fed diets containing 1) 0 mg AF and 0 mg DAS/kg feed (control), 2) 2.5 mg AF/kg feed, 3) 2.0 mg DAS/kg feed, or 4) 2.5 mg AF + 2.0 mg DAS/kg feed for 28 days (10-14 weeks of age). Production performance, serum biochemical, hematologic, and pathologic measurements were made. Body weight and body weight gain were significantly decreased by each toxin but more so by the combination treatment. The effects were additive in nature. Liver and spleen weights, as percentages of body weight, were increased by the AF and AF + DAS treatments, and AF or AF + DAS treatments induced diffuse hepatocellular vacuolar change, early portal fibrosis, and early bile duct hyperplasia. Aflatoxin increased serum values of creatinine and gamma glutamyl transferase, cholinesterase, and alkaline phosphatase activities; increased packed cell volume and hemoglobin; and decreased urea nitrogen and total iron binding capacity. DAS reduced serum iron binding capacity. The AF + DAS treatment increased serum gamma glutamyl transferase and alkaline phosphatase activities, increased hemoglobin, and decreased serum iron binding capacity. Generally, the combination treatment could be described as additive or less than additive, with most of the effects attributable to AF. Under the conditions and parameters monitored in this study, AF and DAS had no synergistic toxic effects when incorporated into diets of growing barrows.

The toxicological effects induced by the administration of kojic acid were characterized in young male broiler chickens (Hubbard x Peterson). The experimental design consisted of six dietary treatments of kojic acid (0, .5, 1, 2, 4, and 8 g/kg feed) and four replicates of 10 broilers per replicate. Kojic acid significantly (P less than .05) decreased growth rates at concentrations greater than 2 g basic acid/kg feed. Kojic acid in higher concentrations also significantly increased the relative weights of the proventriculus, gizzard, pancreas, and liver, and significantly decreased the relative weight of the bursa of Fabricius at necropsy (Day 21). Hematological changes included a significant increase in the number of red blood cells, a significant increase in packed-cell volume, and a significant decrease in mean corpuscular volume. Also occurring was a significant increase in the serum concentrations of total protein, albumin, cholesterol, and triglycerides. Hepatotoxicity of dietary kojic acid was evident through a significant increase in the activities of serum glutamic oxalacetic transaminase and creatine kinase and a significant decrease in the activity of alkaline phosphatase. A significant increase in serum uric acid concentration was indicative of nephrotoxicity, and a significant increase in serum glucose concentration was indicative of pancreatic toxicity. A significant decrease in colonic temperature was also observed. Because the toxic effects of kojic acid were only observed at concentrations greater than 2 g kojic acid/kg feed, this mycotoxin alone does not appear to pose a serious economic threat to the poultry industry.

Hydrated sodium calcium aluminosilicate (HSCAS), an anticaking agent for mixed feed, was added to the diets of growing wethers (mean body weight, 34.0 kg) and was evaluated for its ability to diminish the clinical signs of aflatoxicosis. The experimental design consisted of 4 treatment groups of 5 wethers each, consuming concentrations of 0 g of HSCAS and 0 g of aflatoxin (AF)/kg of feed (control; group 1); 20 g of HSCAS/kg (2.0%; group 2), 2.6 mg of AF/kg (group 3); or 20 g of HSCAS (2.0%) plus 2.6 mg of AF/kg (group 4). Wethers were maintained in indoor pens, with feed and water available ad libitum for 42 days. Lambs were observed twice daily and weighed weekly, and blood samples were obtained every 2 weeks for hematologic and serum biochemical analyses and for measurement of mitogen-induced lymphocyte-stimulation index. At the termination of the study, wethers were euthanatized and necropsied. Body weight gain was diminished significantly (P less than 0.05) by consumption of 2.6 mg of AF/kg of feed, whereas body weight of lambs consuming HSCAS plus AF did not differ from that of control wethers. The AF-alone treatment increased serum aspartate transaminase and gamma-glutamyltransferase activities, prothrombin time, and cholesterol, uric acid, and triglyceride values and decreased albumin, glucose, and urea nitrogen values, and urea-to-creatine ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

One-day-old broiler chicks were divided into four groups: untreated controls and three groups treated with the immunosuppressive drugs cyclophosphamide, cyclosporin, or dexamethasone on days 1-4 of age. On day 5, all groups were challenged orally with 10(4) Salmonella typhimurium. Suppression of immunocompetency was demonstrated in the treatment groups by significant decrease (P less than 0.05) in weights of bursas of Fabricius, and diminished mitogen-induced T and B lymphocyte blastogenesis and cutaneous basophil hypersensitivity responses. There were no significant differences among the four groups in the number of Salmonella in the cecal contents or in the number of cecal-culture-positive chicks on day 10 post-challenge at 15 days of age. Results indicated that impairment of B or T lymphocyte responses had little influence on the resistance of young chicks to Salmonella cecal colonization.

Decreases in the ventilation capacity of human lungs following the inspiration of cotton dust correlates more closely with the concentration of endotoxin in the dust than with any other parameter measured thus far. A lipopolysaccharide isolated from the endotoxin of Enterobacter agglomerans, a common bacterial contaminant of cotton fiber, stimulated isolated rat macrophages to produce and release prostaglandins 6 keto-PGF1 alpha, PGF2 alpha, PGE2, PGD2, PGA2, and PGB2 and thromboxane B2. If in vivo human pulmonary macrophages respond in a similar fashion by releasing these arachidonic acid metabolites or their immediate precursors in response to stimulation by cotton dust associated lipopolysaccharides, some of the acute pulmonary changes observed in humans following inspiration of cotton dust could be caused by increased release of these biologically active compounds. Daily release of arachidonic acid metabolites at concentrations significantly above normal homeostatic levels could produce some of the pathophysiologic pulmonary changes observed in byssinotics. This paper reports the results of an experiment to quantitate arachidonic acid metabolite production following macrophage stimulation by E. agglomerans lipopolysaccharide. Procedures are described for the stimulation of macrophages by cotton dust associated lipopolysaccharide, for the separation and identification of arachidonic acid and its metabolites by high-performance liquid chromatography, and for the quantification of those products by radioisotope techniques.

Newly hatched chickens were treated with the trichothecene mycotoxin, T-2 toxin, during the first day of life. Control chickens were treated with other agents known to cause immunosuppression--cyclosporine, cyclophosphamide, and aflatoxin. Chickens were infected on day 6 (5 days after treatment with T-2 toxin) by intraperitoneal inoculation with Salmonella typhimurium. Blood samples were collected from treated chickens (noninfected) and used to assess the responsiveness of blood lymphocytes to T-cell or B-cell mitogens, phytohemagglutinin, or lipopolysaccharide, respectively. The T-2 toxin had a profound negative effect on the ability of the chickens to resist salmonellosis, as measured by survival. However, the toxin effect in reducing phytohemagglutinin- and lipopolysaccharide-stimulated mitogenesis, though significant (P greater than 0.05), was not severe. Our data indicate a direct effect of T-2 toxin on native resistance to systemic salmonellosis, which was not accompanied by marked alteration in T- or B-cell responses to mitogenic stimulation.

Cotton dusts contain condensed tannins and endotoxins, which are suspected of contributing to the development of acute and chronic biological responses in some cotton textile mill workers. Condensed tannin extracted from cotton dust was coated on to cellulose powder, and the tannin coated powder was treated with an alkali solvent system previously developed to reduce the endotoxin content and pulmonary toxicity of cotton dust. Physiological activities of the dusts and powders were compared by assaying the production of the arachidonic acid metabolites prostaglandin F2 alpha (PGF2 alpha), thromboxane A2 (TxA2) (the precursor to thromboxane B2 (TxB2], leukotriene C4 (LTC4), and prostaglandin E2 (PGE2) by guinea pig pulmonary cells obtained by lung lavage. Cotton dust stimulated the pulmonary cells to produce a total of 29 pg metabolites per 10(6) cells. Production of metabolites by cells stimulated with tannin coated cellulose powder was reduced to 8.3 pg/10(6) cells. Alkali treatment of the tannin coated cellulose powder resulted in a further decrease in its ability to stimulate the cells, producing 3.5 pg metabolites per 10(6) cells. The ability of the dusts and powders to stimulate production of metabolites of arachidonic acid by pulmonary cells from guinea pigs was highly correlated with tannin content of the materials, but not with endotoxin content as measured by the Limulus amoebocyte lysate (LAL) assay.

The combined effect of treatments with dietary lactose plus anaerobic organisms on cecal colonization of broiler chicks by Salmonella typhimurium was evaluated. Chickens treated with a combination of anaerobic organisms and 7% dietary lactose were resistant to cecal colonization by S. typhimurium. The number of recoverable S. typhimurium cells per gram of cecal contents taken on days 10 and 15 after infection was significantly reduced. Treatment with anaerobes without the addition of lactose did not effectively control cecal colonization. Intracloacal inoculations with bacterial concentrations that varied by 10,000-fold resulted in roughly similar levels of colonization. The treatments resulted in reduced cecal pH and elevated levels of undissociated volatile fatty acids. Statistically significant correlations (P less than 0.01) were observed between the S. typhimurium concentrations in cecal material and the concentrations of undissociated fatty acids (r = -0.79, and between the bacterial counts and pH (r = 0.72).

A method was developed to experimentally produce ascites in broiler chickens. High-altitude simulation (treatment group) was conducted to study the development of ascites in broiler chickens. In each of three experiments, 15 male broiler chicks (1 wk old) were placed in a hypobaric chamber (principal groups) for 5 wk and 15 other chicks were reared in batteries (control groups). Ascites occurred among chicks in the principal groups recorded at 13, 27, and 80% at simulated altitudes of 1,980, 2,438, and 2,896 m, respectively. No ascites were observed in the controls at 100 m (the altitude at College Station, Texas). Body weight was significantly (P less than .05) reduced for broilers in the principal groups versus the controls-especially at 2,896 m, where the principals weighed 500 g less than the controls. The counts for hematocrit, hemoglobin, and red blood cells were significantly (P less than .05) increased in all treatment groups; while at 2,438 and 2,896 m, corticosterone was significantly reduced. Histopathology indicated consistent, mild, cardiopulmonary lesions similar to those observed in the spontaneous ascites of broiler chickens. The high-altitude simulation model will be useful in studying the etiological factors and interactions causing ascites.

The development of resistance to salmonellosis and the basis of resistance in newly hatched chickens were investigated. Newly hatched chickens are inherently susceptible to salmonellosis but develop resistance rapidly to Salmonella infection during the first 5 days of life. Newly hatched chickens were treated with cyclosporine, the thymic (T)-cell-specific, immunosuppressive agent (T-cell). The resultant changes in T-cell responsiveness to mitogens, in vivo delayed-type hypersensitivity, and resistance to salmonellosis were measured. The results demonstrated that cyclosporine reduced in vitro T-cell responses to T-cell-specific mitogens, suppressed in vivo delayed-type hypersensitivity (tuberculin skin-test reactions), and impaired the development of native resistance to salmonellosis. These results indicate that development of resistance to salmonellosis in newly hatched chicks depends on a fully functional capacity for cell-mediated immunity. Therefore, the development of effective vaccines for reducing the contamination of live birds with Salmonella probably should include strategies for enhancing the early development of cellular immunity.

Hexachlorobenzene, which is a widespread contaminant of meat and meat animal by-products throughout the world, had a profound effect on the homeostatic mechanism which controls the serum testosterone concentrations in the mouse. Significant increases in the mean hepatic weight, the concentrations of hepatic microsomal protein, cytochrome P-450, cytochrome b5, and cytochrome c reductase activity occurred in the aminals given a ration containing 250 mg of hexachlorobenzene/kg for 21 days, when compared with their nontreated controls. These increases in cytochrome concentrations and enzyme activity of the hepatic microsomes are reflected by significant increases in the in vitro metabolism of [3H]testosterone and a decrease in the serum concentrations of testosterone with a concomitant decrease in the weights of the seminal vesicles and ventral prostate of the mouse.

Sera from Babesia bovis-infected cross-bred cows and purebred steers were evaluated throughout the course of acute Babesia bovis infection for cholesterol and cortisol concentrations. Cholesterol and cortisol values of surviving cattle became markedly reduced (less than 50% of normal values) during the acute phase of the disease, Days 10-15 postinoculation, and returned to essentially normal values by the end of the 35 day experimental period. The combined control group values were approximately 2.98 mM/l cholesterol and 0.085 mM/l cortisol throughout the experimental period. The results suggest that if normal synthesis of cholesterol by hepatocytes or other tissues is not maintained, then cholesterol-derived compounds such as cortisol may not be produced at levels adequate to protect against the effects of stress and cell damage during the disease process.

Mast cell degranulation was quantitated by measuring percentage of histamine release, 45Ca2+ ion influx, or c-AMP cellular levels after stimulation with various concentrations of the sesquiterpene lactones hymenovin, helenalin, or tenulin. Hymenovin and helenalin, which contain an alpha-methylene-gamma-lactone moiety, produced extensive degranulation. Alkylation of the alpha-methylene-gamma-lactone group of these compounds with the amino acid cysteine before mast cell stimulation drastically reduced the capacity of these lactones to stimulate histamine release. Tenulin, which does not contain an alpha-methylene-gamma-lactone moiety, generally stimulated degranulation approximately equal to that of cysteine-treated hymenovin or helenalin. These data indicate that sesquiterpene lactones containing alpha-methylene-gamma-lactone are potent stimulators of mast cell degranulation. This phenomenon may have a significant role in the toxicity of some sesquiterpene lactones of poisonous plants when ingested by livestock.

Female guinea pigs were perfused via the pulmonary artery with Tyrode's solution containing 0, 10(-6), 10(-5), or 10(-4) g/mL of lyophilized aqueous extracts of cotton dust. The perfusate was collected via the pulmonary vein and analyzed for prostaglandin F2 alpha, its metabolite 15-keto-13, 14-dihydro-prostaglandin F2 alpha and histamine. The histamine content of the pulmonary parenchyma was also analyzed. Prostaglandin F2 alpha, its metabolite, and the percentage of total histamine released increased in a dose related fashion and were significantly higher in the perfusate of the animals which had received the two highest doses than that of the controls. Since prostaglandin F2 alpha can increase airway resistance and bronchial smooth muscle contraction and decrease pulmonary tidal volume, its liberation into the respiratory system could play a role, along with histamine, in the acute bronchial constriction that follows the inhalation of cotton, flax, or hemp dust.

The lungs of female guinea pigs, either untreated or previously sensitized with aqueous extracts of cotton dust (AECD) were perfused via the pulmonary artery with 0, 10-6, 10-5 or 10-4 g/mL of lyophilized AECD in Tyrodes solution. Pressure changes in the pulmonary artery were monitored during this period. After perfusion, the pulmonary parenchyma was excised, frozen, and later analyzed for c-AMP, c-GMP, histamine, and total protein. Levels of c-AMP and histamine decreased while levels of c-GMP and pulmonary arterial pressure increased with increasing doses of AECD. Correlation coefficients, between the parameters measured, indicate that the ratio of c-AMP to c-GMP (c-AMP/c-GMP) was a better indicator of histamine depletion or change in pulmonary arterial pressure than was the level of either c-AMP or c-GMP alone. Comparisons of the relative changes in c-AMP, c-GMP, c-AMP/c-GMP, histamine, and pulmonary arterial pressure between sensitized and nonsensitized guinea pigs support the hypothesis that the acute changes in pulmonary function that follow breathing of cotton dust are due to the effects of pharmacoactive compounds and not to antigen-antibody response.

The effects of social stress (crowding) on hexachlorobenzene (HCB) toxicity in male rats was evaluated by a morphometrical analysis of adrenal cortex mitochondria. The social stress was produced by transferring singly-housed rats from cages of ample size (1000 cm2 floor space) into small cages (100 cm2 floor space) each containing four rats. Differences in cage design as well as size may have contributed to the overall stress experienced by the rats. The food of the treated rats was supplemented with 250 ppm HCB. Structural changes in mitochondrial volume, surface area, or cristae area were not significant in HCB-treated or in crowded animals when compared with those of the controls. However, increases in mitochondrial volume and diameter were significant in those animals simultaneously challenged by HCB and crowding. The results strongly suggest that even a relatively mild social stress may adversely affect the ability of an animal to resist the effects of some exogenous chemicals.

Adult male rats were maintained on a diet containing 265 ppm cobalt for up to 98 days. Three rats were sacrificed weekly and assayed for testicular damage by light and electron microscopy. Testicular damage was first apparent after 70 days of treatment, followed by a progressive deterioration of cell architecture and decrease in testicular volume. The degenerative changes were of a very general nature; e.g., thickening of basal lamina and basement membranes, increased packing of red blood cells in veins and arteries, formation of "giant" cells, loss of sperm tail filaments, and degeneration of sperm mitochondria. No cobalt residues could be detected by energy dispersive x-ray microanalysis. These data indicate that testicular degeneration was not a primary response to cobalt and suggest that the testes become hypoxic due both to blockage of veins and arteries by red blood cells and to changes in permeability caused by thickening of basal lamina and basement membranes.

In vivo and in vitro experiments have strongly indicated that mast cell degranulation, with its release of histamine and other pharmacoactive compounds, plays a major role in the acute respiratory response of humans following inhalation of cotton textile dust. Thirteen terpenoid aldehydes isolated from the glands of the two major Gossypium species used for cotton production, stimulated significant release of histamine from mast cells at concentrations of 1 micrograms/mL. Eleven of the thirteen compounds produce significant mast cell degranulation at concentrations well below the levels of free terpenoid aldehydes that could be expected to enter the lungs during an eight hour work day under the current permissible card room standards of 200 micrograms per cubic meter. Daily mast cell degranulation, stimulated by these terpenoid aldehydes could account for many of the pathophysiological changes found in the chronic byssinotic.

Previously reported fat biopsy techniques (either omental or subcutaneous) require extensive restraint of the animal, require anesthesia methods, are time-consuming to do, or demand much postoperative care. The biopsy technique reported in the present paper involves the subcutaneous fat located around the tailhead of sheep. With minimal restraint of the sheep and local anesthesia, up to 1 g of subcutaneous fat can be obtained using this surgical procedure. Michel clips facilitate closure of the surgical wound, making this method brief in operative time.

Dietary cobalt (265 ppm Co) induced polycythemia and consistent degenerative and necrotic lesions in the seminiferous tubules of rats. Cyanosis and engorgement of testicular vasculature on day 35 and thereafter was followed on day 70 by degenerative and necrotic changes in the germinal epithelium and Sertoli cells. Spermatogonia, primary spermatocytes and round spermatids were markedly affected, while elongated spermatids, spermatozoa, and sertoli cells were more resistant. Damaged tubules, often present side by side with normal tubules, contained multinucleated giant cells composed of degenerated and necrotic spermatocytes and/or spermatids, sloughed germinal and Sertoli cells, and calcified necrotic debris. Necrotic tubules were frequently collapsed and devoid of epithelium except for occasional spermatogonia and surviving Sertoli cells. Lesions were not observed in the Leydig cells, cauda epididymis or seminal vesicles.

Inhibition of murine macrophage adenylate cyclase activity by sesquiterpene lactones isolated from toxic forage plants was highly correlated with the presence of the alpha-methylene-gamma-lactone moiety on the molecule (ie, hymenovin and helenalin). Tenulin, a sesquiterpene lactone which does not contain this reactive moiety, caused minimal inhibition of the enzyme. Reaction of the alpha-methylene-gamma-lactone moiety of hymenovin and helenalin with cysteine decreased the number of reactive moieties available to alkylate the enzyme, thus decreasing the inhibition of adenylate cyclase by these 2 sesquiterpene lactones. As the reaction time available for the reduction by cysteine of the alpha-methylene-gamma-lactone moiety decreases, the amount of adenylate cyclase inhibition increases. Stimulation of the hymenovin- or helenalin-inhibited adenylate cyclase by prostaglandin E1 or E2 or by sodium fluoride did not reverse the inhibition of the enzyme, but did stimulate the undamaged adenylate cyclase in the sesquiterpene lactone treatment groups to the same degree as in the nontreated control. These data indicate that sesquiterpene lactones containing an alpha-methylene-gamma-lactone moiety are potent inhibitors of macrophage adenylate cyclase activity. This moiety may have a significant role in the toxicity of some sesquiterpene lactones in poisonous plants when ingested by livestock.

The effects of hexachlorobenzene (HCB) on the ability of male rats to adapt to a crowded environment were investigated. Eighty male rats were individually housed (1000 cm2 floor space per rat) and given either feed containing 250 ppm HCB or control feed. After 4 w, half of the rats from each diet group were transferred to smaller cages with four rats per cage (100 cm2 floor space per rat). After 1, 2, 4, 7, and 10 d, four rats each from the four treatment groups were sacrificed and organs removed for analysis. The HCB diet alone had no effect on the body weight of the rats. Crowding resulted in severe loss of body weight, an effect that was potentiated by the HCB diet. The HCB diet resulted in increased liver and kidney weight but had no effect on brain weight. Livers and kidneys of crowded rats weighed less than those of singly housed rats. Rats fed HCB then crowded had higher tissue residues of HCB and higher mortality than rats given HCB and not crowded or rats crowded but not given HCB.

The effects of shipping stress, increased serum cortisol concentrations, and levamisole treatment on the hematologic values of cattle were studied. Complete blood counts were done on blood samples from 40 calves; samples were collected 9 times during a period that began immediately after the calves were weaned and continued through an auction barn-truck transport cycle plus 5 weeks. The object of the study was to determine whether the combination of shipping stress and levamisole treatment would alter the hematologic values (granulocytic series). There was no effect observed.

Alteration of mast cell cyclic AMP levels have been implicated in the acute respiratory symptoms in mill workers following inspiration of cotton, flax, or hemp textile dusts. This paper describes the inverse relationship between the cellular levels of cyclic AMP and the degranulation in pure culture of mast cells in response to aqueous cotton bract extracts of glanded and glandless varieties.

A method is presented for studying the absorption of the lipophilic toxin polychlorinated biphenyl (PCB) from the intestine to the lymphatic system. Concentrations of the toxin were high in mesenteric lymph nodes and in the thoracic duct lymph.