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PubMed2003

Medication of production animals--cure of malfunctioning animals or production systems?

Medication is used in all intensive animal productions. However, the increasing problems with resistant bacteria in all animal productions and in humans are supported by a number of reports. Special attention is given to the risk for transmitting food-borne (multi) resistant zoonotic agents to humans due to failure in antibiotic treatment resulting in lower cure rates or higher case fatality rates. The use of medication in humans per se is capable of selecting for resistance in human pathogens. Nevertheless, the amount of used medication/antimicrobials in treatment of Danish production animals goes far beyond the amount used for human consumption. The increase in consumption has not been followed by a similarly increased mortality, e.g. illustrated by the number of rendered animals, increased use of injection medicine for veterinary treatments of diseased animals, or increased number of remarks on the carcasses from the slaughterhouses. Medication in animal production is facing its limits and relevant economic alternatives have to be developed. The strategy for the future must concentrate on using medication only for clinically diseased animals and not as a strategic treatment of the whole herd in order to maximise growth and camouflage of suboptimal production systems and insufficient management.

Animal Husbandry↗
PubMed1990

Cytokine regulation of colony-stimulating factor production in cultured human synovial fibroblasts: I. Induction of GM-CSF and G-CSF production by interleukin-1 and tumor necrosis factor.

The cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), induce a dose-dependent production of both granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte CSF (G-CSF) in cultured human synovial cells, as measured by immunoassay. With IL-1, significant levels of both CSFs were first detected within 6 to 12 hours, with a maximum reached 24 to 48 hours after commencement of stimulation. A synergistic effect was detected between IL-1 and TNF in production of both CSFs in these cells. No evidence was obtained for the IL-1-induced effect to be mediated by induction of endogenous TNF nor for the TNF-induced stimulation to involve IL-1. IL-1-stimulated synovial cells were shown to secrete biologically active GM-CSF and G-CSF, which were specifically inhibited by their respective monoclonal antibodies. The transcription inhibitor, actinomycin D, and protein synthesis inhibitor, cycloheximide, inhibited the increase in GM-CSF and G-CSF production induced by IL-1 and TNF. Finally, other cytokines, IL-3, interferon gamma (IFN gamma), IL-2, platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha), failed to stimulate either GM-CSF or G-CSF production, whether alone or in the presence of IL-1. These results suggest that cytokine-stimulated synovial fibroblasts may be a major source of intraarticular CSF production in the joints of patients with inflammatory arthritis; as a result, monocyte/macrophages and granulocytes may be activated, leading to perpetuation of the inflammation and destructive events occurring in these lesions.

Cells, Cultured↗
PubMed2006

[Effects of terminal products on hydrogen production by ethanol hydrogen-producing microflora].

The effects of terminal products on hydrogen production were conducted in continuously stirred tank reactor (CSTR) by the acclimated ethanol hydrogen-producing bacteria. Glucose was added as carbon source and different ambient pH was carried out by buffer solution. High ethanol production was simultaneously achieved with high hydrogen production. The addition of 40 mol/L ethanol or acetic acid can result in the reduction of hydrogen production, the former was 34% and the latter was 84.3%. The ethanol fermentation formation for mixed microflora was attributed to the natural selection.

Bacteria, Anaerobic↗
PubMed1990

Enhanced production of IL-6 in tumor-bearing mice and determination of cells responsible for its augmented production.

IL-6 is a cytokine secreted in normal individuals by monocytes, fibroblasts, and endothelial cells. We have found increased levels of IL-6 in the sera from MH134 hepatoma- and CSA1M fibrosarcoma-bearing mice. Concerning the capacity of these tumor cells themselves to produce IL-6 in vitro, they exhibited the distinct contrast, i.e., the MH134 tumor cells produced high levels of IL-6 whereas the CSA1M generated a marginal level of IL-6. It was, however, demonstrated that appreciably enhanced IL-6 production was observed in spleen cell culture supernatants from both types of tumor-bearing mice when compared to those obtained from normal mice. More importantly, in contrast to the production of IL-6 by non-T cell compartment of normal spleen cells, enhanced IL-6 production of spleen cells from tumor-bearing mice was ascribed to T cell compartment. Analysis of T cell phenotype has revealed that enhanced IL-6 production was mediated predominantly by Lyt-2+ but not by L3T4+ T cell subset. Thus, these results indicate that increased circulating IL-6 is elicited in the tumor-bearing state and that irrespective of the potential of tumor cells themselves to produce IL-6, T cells, especially Lyt-2+ T cells from tumor-bearing mice are responsible for such a high level of IL-6 production.

Animals↗
PubMed1990

Interferon-gamma production closely related to antibody production in lymphocyte cultures stimulated with mumps virus.

Enzyme-linked immunosorbent assay (ELISA) antibody to mumps virus and virus specific interferon (IFN)-gamma production were investigated in lymphocyte cultures stimulated with mumps virus before and after immunization with live mumps vaccine. Synthesis of immunoglobulin (Ig) M but not Ig G was enhanced after vaccination. Spontaneous production of mumps ELISA antibodies in lymphocyte culture increased after vaccination and substantially higher levels of antibodies were produced when lymphocytes were stimulated with mumps virus after vaccination. The production of mumps ELISA antibodies was closely related to IFN-gamma production (r = 0.326, p less than 0.01) but not to IFN-alpha production (r = 0.084, p greater than 0.05).

Antibodies, Viral↗
PubMed1990

IL-4 production by T cells from naive donors. IL-2 is required for IL-4 production.

Utilizing a sensitive and selective assay for IL-4, it was shown that lymph node T cells from naive mice could produce small amounts of this lymphokine in response to anti-CD3 antibodies adsorbed to culture dishes. The capacity of these cells to produce IL-4 in response to plate-bound anti-CD3 was substantially enhanced by the addition of IL-2 to the culture and was strikingly inhibited by monoclonal anti-IL-2 antibody. Thus, IL-2 appears to be essential for IL-4 production by anti-CD3 antibody-stimulated T cells from naive mice. The effect of IL-2 was not mediated either by preferential proliferation or survival of precursors of IL-4 producing cells, indicating that IL-2 regulates T cell production of IL-4. IL-4 producing capacity of T cells from naive mice was found mainly among CD4+ T cells. Large T cells produced much more IL-4, on a per cell basis, than did small T cells. In contrast, small T cells appeared to be equal or superior to large T cells in producing IL-2. The superiority of large T cells in IL-4-producing capacity was not accounted for by a lack of an accessory cell population from the small T cells as addition of large spleen cells depleted of both B and T cells did not enhance IL-4 production by small lymph node T cells. These results suggest that the bulk of IL-4 production by T cell populations, from normal mice, in response to anti-CD3 depends upon cells that are already activated and that IL-2 is required for such production.

Animals↗
PubMed1990

In vitro effect of larval Schistosoma mansoni excretory-secretory products on phagocytosis-stimulated superoxide production in hemocytes from Biomphalaria glabrata.

The in vitro production of the reactive oxygen metabolite superoxide (O2-) was confirmed in hemocytes from the schistosome intermediate host Biomphalaria glabrata. Active forms of the enzyme superoxide dismutase (SOD) inhibited reduction of nitroblue tetrazolium (NBT) to formazan in cells that had phagocytozed zymosan particles, whereas an inactivated form of SOD did not. Moreover, based on the prevalence of O2(-)-positive hemocytes and the relative intensity of NBT staining reactions, hemocytes from the Schistosoma mansoni-resistant 10-R2 strain of B. glabrata possessed an overall greater capacity for generating superoxide than did those from S. mansoni-susceptible M-line snails. Schistosoma mansoni excretory-secretory (E-S) products, released during in vitro transformation of miracidia to sporocysts, inhibited phagocytosis of zymosan particles and superoxide activity in hemocytes from both snail strains, but 10-R2 hemocytes maintained higher levels of phagocytosis and superoxide production than did M-line hemocytes. The dose-dependent decreases in phagocytosis observed in both snail strains in the presence of E-S products could not account fully for the concomitant decrease in superoxide levels detected, indicating that either a single E-S factor differentially affects phagocytosis and superoxide production, or that different E-S factors are involved in the specific interference of each of these hemocyte functions.

Analysis of Variance↗
PubMed1990

Expression of the mammalian mitochondrial genome. Role for membrane potential in the production of mature translation products.

Protein synthesis was investigated in isolated mitochondria under conditions which either inhibited electron transport or uncoupled oxidative phosphorylation. In a medium containing an exogenous source of ATP and oligomycin, an inhibitor of the ATP synthase complex, incorporation of [35S]methionine into proteins is stimulated in the presence of inhibitors of the electron transport chain; substituting uncouplers of oxidative phosphorylation for the latter leads, in contrast, to a decrease in the rate of incorporation of the labeled amino acid into mitochondrial translation products. Studies on the metabolic stability of mitochondrial translation products revealed that "mature" polypeptides made in isolated mitochondria are stable as indicated by the absence of degradation during a 50 min "chase" period. Under conditions which reduce or dissipate the membrane potential, 50-60% of the newly made polypeptides (pulse) are degraded within 50 min. The kinetics of the degradation process for individual mitochondrial gene products reveal that the largest proportion of polypeptides degraded to an acid-soluble form during the chase period are abnormal proteins, likely the result of premature chain termination. Emerging as a common denominator in these studies is a role for a transmembrane potential across the inner membrane in the production of mature "stable" mitochondrial gene products.

Animals↗
PubMed1985

Evidence that production of platelet fibrinogen is synchronous with platelet production in the turpentine-induced acute phase response.

Fibrinogen is synthesized by both hepatocytes and megakaryocytes, and available evidence indicates that cellular production of this protein is controlled by a single gene. We evaluated platelet and plasma fibrinogen production in rats injected with turpentine to induce the acute phase response. After turpentine injection, plasma fibrinogen levels, as expected, rose to more than double the baseline values within 48 hours and then declined to the upper limit of the normal range in 6 days. When levels were expressed as a percentage of total plasma protein, a rise form 4.2% to 10.0% occurred. Thrombocytosis was not observed until day 4; platelet counts returned to the normal range by day 8. The mean fibrinogen content per platelet did not change significantly (P greater than 0.05) during this period of observation. Thus, in contrast to the abrupt rise in the level of plasma fibrinogen, changes in the blood level of platelet fibrinogen paralleled changes in the platelet count. We interpret these findings to indicate that platelet fibrinogen production is synchronized with platelet production by megakaryocytes and thus suggest that fibrinogen production is regulated differently in these cells than it is in hepatocytes.

Acute-Phase Proteins↗
PubMed1988

The effect of products from bronchoalveolar-derived neutrophils on oxidant production and phagocytic activity of alveolar macrophages.

Neutrophils and alveolar macrophages are found together in the alveolar region during pulmonary inflammation where neutrophil products could influence important macrophage defensive functions. We set out therefore to investigate the ability of neutrophil products to modulate alveolar macrophage phagocytosis and oxidant production. Neutrophils derived from acutely inflamed rat lung were incubated along with a range of potential triggers of neutrophil secretion and supernatants collected. Using two quantitative assays of rat alveolar macrophage phagocytosis, the supernatants were found to have no effect except for the quartz supernatant, which slightly enhanced phagocytosis via non-specific receptors and the PMA supernatant, which caused reduction in phagocytosis via non-specific and Fc receptors; this reduction could however be mimicked by PMA alone. None of the supernatants affected macrophage production of superoxide anion or hydrogen peroxide except for the PMA supernatant and once again the inhibitory effect of the PMA supernatant could be mimicked with PMA alone. It is concluded that products of inflammatory neutrophils do not affect phagocytosis or oxidative metabolism of alveolar macrophages, although in quartz-exposed lung neutrophils may exert a small enhancing effect on macrophage phagocytosis.

Animals↗
PubMed1986

Interleukin 2 production in HTLV-III/LAV infection: evidence of defective antigen-induced, but normal mitogen-induced IL-2 production.

We studied mitogen- and antigen-induced interleukin 2 (IL-2) production in HTLV-III/LAV infected and non-infected individuals and compared the results with T cell subpopulations, and with mitogen- and antigen-induced DNA synthesis and production of leucocyte migration inhibitory factor (LIF) in order to understand the controversial findings related to IL-2 production in HTLV-III/LAV infection. The HTLV-III/LAV antibody positive group showed immunological defects: low T helper (Th) cells, high T-suppressor (Ts) cells, reduced mitogen- and antigen-induced DNA-synthesis, but LIF production comparable to the HTLV-III/LAV antibody negative group. The total amount of IL-2, produced either as a response to a mitogenic stimulus or as a response to a soluble antigenic (purified protein derivative of tuberculin, PPD) stimulus, was lower in the HTLV-III/LAV antibody positive group. However, adjusting the IL-2 production to the amount of Th-cells showed that the IL-2 produced by a standard number of Th-cells after mitogen induction was similar in HTLV-III/LAV infected and non-infected individuals. In contrast, the ability of Th-cells of infected persons to produce IL-2, or to proliferate as a response to a soluble antigenic stimulus, was considerably diminished. We conclude that HTLV-III infection leads to a selective incapability to mount a specific Th-cell response either due to an intrinsic defect in the Th-cell population or due to metabolic and/or functional disturbances in antigen-processing and presenting accessory cells.

Acquired Immunodeficiency Syndrome↗
PubMed1979

PPD-induced immunoglobulin production in human peripheral blood lymphocytes. II. Separation of PPD-reactive helper T cells from PWM-reactive helper T cells in polyclonal immunoglobulin production of human peripheral blood lymphocytes.

We investigated the relationship bewteen PPD-reactive helper T cells and PWM-reactive helper T cells in polyclonal Ig production of human PBL. Elimination of PPD-reactive T cells by BUdR + light treatment resulted in a loss of helper function in PPD-induced Ig production, but had no effect on helper function in PWM-induced Ig production. On the other hand, elimination of PWM-reactive T cells resulted in a loss of helper function in both PPD-induced Ig production and PWM-induced Ig production. A blast cell-enriched fraction that was generated by PPD and separated by the velocity sedimentation method contained helper function in both responses. On the other hand, blast cell-depleted fractions did not contain PPD-reactive helper function, although the PWM-reactive helper function was evident. These results strongly suggest that PPD-reactive helper T cells are included in PWM-reactive helper T cells.

Bromodeoxyuridine↗
PubMed1988

Physicochemical, toxicological and hygienic aspects of ethylene oxide application for the sterilization of medical products. III. Setting hygienic norms in sterilized medical products.

Some of the drawbacks are discussed associated with hygienic norms for gaseous sterilizing agents in polymeric products for medical applications. A new approach is proposed for regulating ethylene oxide (EO) in such products. To this end, limiting types of biological effect and its pathways have been determined and substantiated as well as the reliability factor for establishing hygienic norms for EO in medical products. Daily threshold EO limit values were calculated for momentary and repeated exposure of humans. The duration of long-term and short-term exposure of the patient to sterilized products was evaluated on the basis of EO extraction kinetics from a variety of materials. Using daily threshold limit values, threshold residual values (TRV) of EO were calculated for different groups of polymeric products for medical applications.

Animals↗
PubMed1982

Modulation of collagen production following bleomycin-induced pulmonary fibrosis in hamsters. Presence of a factor in lung that increases fibroblast prostaglandin E2 and cAMP and suppresses fibroblast proliferation and collagen production.

To elucidate mechanisms involved in the regulation of lung collagen content we studied hamsters with bleomycin-induced pulmonary fibrosis. Lung collagen in this model is increased as the result of greatly increased lung collagen synthesis rates. However, collagen synthesis rates are subsequently restored to normal. Hamster lung explants from both normal and bleomycin-exposed hamsters were cultured, and the effects of explant conditioned medium (CM) on lung fibroblast (IMR-90) proliferation and collagen production in vitro were determined. Lung explant CM increased fibroblast prostaglandin (PG)E2 production and intracellular cAMP, and decreased both fibroblast proliferation and collagen production in a dose-dependent manner. Greater activity was observed with lung explant CM from bleomycin-exposed lungs. Incubation of fibroblasts with indomethacin prior to addition of CM blocked CM-mediated changes in PGE2 and cAMP and inhibited changes in fibroblast proliferation and collagen production. Exogenous PGE2 or dibutyryl cAMP also suppressed fibroblast proliferation and collagen production. The suppressive activity in lung-conditioned medium is nondialyzable, has an apparent molecular weight of 15,000-20,000 by gel filtration, and is heat-stable. It is not species-restricted since CM from hamster lung affected human and hamster lung fibroblasts similarly. Activity is present preformed in lung and bronchoalveolar lavage fluid, although bronchoalveolar macrophages produce a nondialyzable factor in culture which suppresses fibroblast proliferation. The suppressive activity identified in fibrotic lung may represent a means for limiting collagen accumulation following tumor injury.

Animals↗
PubMed1984

Difference in requirement of macrophage products for concanavalin A-induced production of eosinophil chemotactic factor and macrophage chemotactic factor from guinea pig lymphocytes in vitro.

Differences between the conditions for an eosinophil chemotactic factor (ECF) and macrophage chemotactic factor (MCF) production by lymphoid cells of mesenteric lymph nodes and spleen were studied in guinea pigs. If lymphoid cells were washed less than 4 hr after concanavalin A (Con A) stimulation and were cultured for an additional 24 hr, they failed to produce ECF, whereas Con A stimulation for 1 hr before washing was sufficient to stimulate them to produce MCF. Subsequently, it was shown that heat-labile soluble factors (termed ECF-PF) with potentiating activity for ECF production are produced from macrophages by 5 micrograms/ml Con A activation. When ECF-PF were added to the cell culture with 5 micrograms/ml Con A, the lymphoid cells could produce ECF even when they were washed 2 hr after Con A stimulation and were cultured for an additional 24 hr, suggesting that ECF-PF plays a critical role in the early stage of ECF production. The lymphoid cells were also able to produce ECF even when they were cultured with ECF-PF and a suboptimal dose of Con A (1 microgram/ml) for ECF production. Protein synthesis seemed to be essential for ECF-PF production. The ECF-PF activity was associated with two separated molecular fractions with m.w. of about 50,000 to 70,000 and of 10,000 to 20,000. It is thus suggested that ECF is produced from T cells by Con A stimulation under conditions which differ, at least, from those for MCF in the requirement of ECF-PF.

Animals↗
PubMed1983

Utilization of fodder yeast and agro-industrial by-products in production of spores and biologically - active endotoxins from Bacillus thuringiensis.

A number of newly-devised fermentation media were evaluated with respect to their ability to support sporulation and biosynthesis of endotoxins by strains of Bacillus thuringiensis that are biologically active against Spodoptera littoralis, Heliothis armigera, and Spodoptera exigua. Fodder yeast from dried cells of Saccharomyces cerevisiae could be used as a complete mono-component medium for production of highly active spore-delta-endotoxin complexes from B. thur., vars. entomocidus, kurstaki and galleriae. Highest sporulation titers were obtained at 2% fodder yeast concentration with endotoxin yields ranging between 7 to 9 grams per liter of medium. Ground horse beans and kidney bean seeds could also be used successfully as complete media for sporulation and endotoxin production. Extracts of potato tubers and sweet potato roots were efficient media for active endotoxin production from B. thur. var. kurstaki, although the obtained yields were much lower than those produced in fodder yeast media. The utilization of fish meal, cotton seed meal, and residues of chicken from the slaughter-house as media for the production of endotoxins active against Spodoptera littoralis, was not successful. On the other hand, minced citrus peels, ground seeds of dates, and wheat bran could be successfully used in combination with fodder yeast as media for production of endotoxins, active against Heliothis armigera and Spodoptera exigua. Re-utilization of culture supernatants in a second fermentation cycle after supplementation with some nutrients gave promising results with some of the strains tested. The data obtained are discussed in view of their feasibility of application.

Bacillus thuringiensis↗
PubMed1995

Growth factor consumption and production in perfusion cultures of human bone marrow correlate with specific cell production.

Perfusion cultures of human bone marrow mononuclear cells (BMMNC) provide a unique in vitro model of hematopoiesis, supporting growth of both accessory and hematopoietic elements. In this study, bioreactors were used to analyze the consumption and production of growth factors (GFs) in relation to each other and to the cells produced. The exogenously added GFs interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), and erythropoietin (Epo) each exhibited different, but reproducible, consumption kinetics. Epo and IL-3 were consumed slowly for the first 5-7 days, and then the consumption rate of both increased. Epo consumption reached a plateau by day 10, whereas IL-3 consumption continued to increase. Consumption of SCF was similar to that of Epo, but began 2-3 days earlier. GM-CSF was consumed throughout the culture period in an accelerating manner. Consumption of SCF and Epo were related, because omission of Epo from the growth medium reduced SCF consumption by 53% and omission of SCF reduced Epo consumption by 82%. A reproducible relationship between cumulative GF consumption and total cell production was observed. Epo was most potent, with 5900 molecules consumed per cell produced, whereas 69,400 molecules of SCF were consumed per cell generated. More specifically, Epo consumption was correlated (r = 0.92 and 0.96) with the number of glycophorin A-positive (glyA+) cells produced, and the rate of Epo consumption varied with the progression of cells through the erythroid lineage. Consequently, measurement of GF consumption rates may be useful for quantifying the types of cells present in a culture. Endogenous GF production was also examined. G-CSF and MIP-1 alpha were present at high levels during the first 4 days but then declined rapidly. LIF first appeared in the second week and steadily increased thereafter. Omission of SCF from the medium allowed the detection of endogenous SCF production, and the kinetics was similar to that of LIF. IL-6 production was biphasic, with a peak and decline in week 1 and an increase during week 2. TGF-beta was below the level of detection in these cultures. The results suggest that perfusion supports accessory and hematopoietic elements which interact and therefore represent a partially functional tissue ex vivo. This system provides a useful model for studying relationships within GF networks and for elucidating the conditions that result in primitive cell expansion ex vivo.

Bone Marrow↗
PubMed1993

Excessive production of transforming growth factor-beta by bone marrow stromal cells in B-cell chronic lymphocytic leukemia inhibits growth of hematopoietic precursors and interleukin-6 production.

To explore the pathogenesis of marrow failure in B-cell type chronic lymphocytic leukemia (B-CLL), we have examined the production of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage CSF (GM-CSF) by the adherent cell population of bone marrow (BM) derived from B-CLL patients and their capacity to support hematopoietic cell proliferation. Lipopolysaccharide-stimulated B-CLL stromal cells produced G-CSF and GM-CSF in amounts similar to normal stromal layers, whereas IL-6 production was significantly decreased. Using the blast-colony forming cell assay (BI-CFC) and the classical colony-forming unit granulocyte macrophage (CFU-GM) assay, we found that: (1) marrow stromal cells of B-CLL were able to support only 25% of the BI-CFC growth supported by normal marrow stromal cells; (2) this anomaly was partially corrected by the addition of exogenous IL-6; (3) the colony-stimulating activity (CSA) of the conditioned medium (CM) of B-CLL stromal cells was lower than that of normal CM; (4) that this was the result of the presence of an inhibitor rather that of a growth factor defect; (5) this inhibition could be abrogated by addition of anti-transforming growth factor-beta (TGF-beta) neutralizing antibody; (6) this antibody corrected the deficient colony supportive activity of the B-CLL stromal cells; (7) TGF-beta production by marrow stromal cells was significantly increased in CLL compared with normal; and (8) that this was not caused by the effect of the B-CLL lymphocytes on the stromal cells. It is concluded that this increased TGF-beta production in B-CLL is probably responsible for the decreased IL-6 production by stromal cells and for the inhibiting activity on hematopoietic precursors as well. We hypothesize that TGF-beta generated at a high level by B-CLL marrow stromal cells could play a major role in the pathophysiology of the BM failure seen in advanced stages of B-CLL.

Aged↗