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Biomedical subjects

M H Elissalde

Publications and source records attributed to M H Elissalde.

At least 19 recordsLinked to original sources

Immunotoxicity of ochratoxin A to growing gilts.

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.

Animals

Cocontamination of swine diets by aflatoxin and diacetoxyscirpenol.

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.

Aflatoxins

Toxic effects of kojic acid in the diet of male broilers.

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.

Animal Feed

The individual and combined toxicity of kojic acid and aflatoxin in broiler chickens.

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.

Aflatoxins

Effects of a hydrated sodium calcium aluminosilicate on growing turkey poults during aflatoxicosis.

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.

Aluminum Silicates

Diminution of aflatoxin toxicity to growing lambs by dietary supplementation with hydrated sodium calcium aluminosilicate.

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)

Aflatoxins

Colonization control of lactose-fermenting Salmonella typhimurium in young broiler chickens by use of dietary lactose.

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.

Animals

Stimulation and release of prostaglandins and thromboxane from macrophages by cotton dust associated lipopolysaccharides.

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.

Animals

Effect of alkali treatment on physiological activity of cotton condensed tannin.

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.

Animals

Ascites in growing broilers: a research model.

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.

Altitude

Effect of T-2 toxin on resistance to systemic Salmonella typhimurium infection of newly hatched chickens.

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.

Aflatoxins

Maturation of resistance to salmonellosis in newly hatched chicks: inhibition by cyclosporine.

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.

Age Factors

Inhibition of macrophage adenylate cyclase by the alpha-methylene-gamma-lactone moiety of sesquiterpene lactones from forage plants.

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.

Adenylyl Cyclase Inhibitors

Effects of dietary cobalt on testicular structure.

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.

Animals

Histamine release from mast cells by terpenoid aldehydes isolated from glanded varieties of cotton.

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.

Aldehydes

Testicular degeneration and necrosis induced by dietary cobalt.

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.

Animals

The role of cyclic AMP and cyclic GMP in byssinosis.

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.

Animals