β-1,3-glucan Given Orally Modulates Immunomyelopoietic Activity And Enhances The Resistance Of Tumour-bearing Mice

β-Glucans have been reported to be potent adjuvants in stimulating innate and adaptive immune responses. The aim of the present study was to determine the immunohematopoietic effects of Imunoglucan (HEBRON) following its oral administration to normal and Ehrlich ascites tumour (EAT)-bearing mice. Mice were treated with 250, 500 and 1000 mg/kg per day, p.o., Imunoglucan (β-1,3-glucan extracted from Saccharomyces cerevisae) for 18 consecutive days. Treatment started 10 days prior to and ended 8 days after tumour inoculation. At 500 and 1000 mg/kg per day, Imunoglucan enhanced the life span of EAT-bearing mice and prevented myelosuppression and splenomegaly caused by the tumour by increasing the number of granulocyte-macrophage progenitors in the bone marrow and increasing colony-stimulating activity in the serum. At 500 mg/kg, Imunoglucan restored the reduced ability of stromal cells to display myeloid progenitors in long-term bone marrow cultures of EAT-bearing mice and upregulated the production of interleukin (IL)-6 and IL-1α by these cells, consistent with a higher number of non-adherent cells. Moreover, 500 mg/kg Imunoglucan restored natural killer cell activity in tumour-bearing mice, consistent with the increased production of interferon (IFN)-γ observed. The results of the present study suggest that Imunoglucan given orally indirectly modulates immune activity and probably disengages tumour-induced suppression by producing a higher reserve of myeloid progenitors in the bone marrow in consequence of biologically active cytokine release (colony-stimulating factors, IL-1α, IL-6 and IFN-γ). © 2011 The Authors Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.393209217Fecchio, D., Sirois, P., Russo, M., Jancar, S., Studies on inflammatory response induced by Ehrlich tumor in mice peritoneal cavity (1990) Inflammation, 14, pp. 125-132Queiroz, M.L.S., Valadares, M.C., Bincoletto, C., Ehrlich ascites tumor as a tool in the development of compounds with immunomodulatory properties (2004) Immunopharmacol. Immunotoxicol., 26, pp. 511-525Valadares, M.C., Klein, S.I., Queiroz, M.L.S., Titanocene modulation of cytokine imbalance induced by Ehrlich ascites tumor progression (2004) Eur. J. 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The Effect Of A Titanocene Dichloride Derivative, Ti Iv (c5h5)2 Ncs2, On The Haematopoietic Response Of Ehrlich Tumour-bearing Mice

The effects of the [Ti IV (C5H5)2 NCS2] metallocene (BCDT), a Titanocene Dichloride derivative, on the growth and differentiation of granulocyte-macrophage progenitor cells [colony-forming unit-granulocyte-macrophage (CFU-GM)] and bone marrow cellularity in normal and Ehrlich ascites tumour-bearing mice were studied. As expected for the Ehrlich ascites tumour-model, concomitant myelosuppression, increased number of spleen CFU-GM and changes in bone marrow cellularity were observed. The treatment of Ehrlich ascites tumour-bearing mice with BCDT (10-30 mg/kg/day) produced a dose-dependent increase in myelopoiesis, a reduction in splenic colonies and a restoration in the total and differential marrow cell counts. We also observed an increase in CFU-GM number when bone marrow cells obtained from normal mice were incubated in vitro with serum from normal mice treated with BCDT. 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The Effects Of Chlorella Vulgaris In The Protection Of Mice Infected With Listeria Monocytogenes. Role Of Natural Killer Cells

In this work we have demonstrated the effects of oral administration of Chlorella vulgaris (CV) on Natural Killer cells (NK) activity of mice infected with a sublethal dose of viable Listeria monocytogenes. The treatment with C. vulgaris produced a significant increase on NK cells activity in normal (non-infected) animals compared to the animals that received only vehicle (water) (p < 0.0001). Similarly, the infection alone produced a significant increase on NK cells activity, which was observed at 48 and 72 hours after the inoculation of L. monocytogenes. Moreover, when CV was administered in infected animals, there was an additional increase in NK cells activity which was significantly higher than that found in the infected groups (p < 0.0001) CV treatment (50 and 500mg/Kg) of mice infected with a dose of 3x105 bacteria/animal, which was lethal for all the non- treated controls, produced a dose-response protection which led to a 20% and 55% survival, respectively (p < 0.0001).213609619Bancroft, G.J., The role of natural killer cells in innate resistance to infection (1993) Curr. Op. Immunol., 5, p. 503Bancroft, G.J., Schreiber, R.D., Bosma, G.C., Bosma, M.J., Unanue, E.R., T cell independent mechanism of macrophage activation by interferon gamma (1987) J. Immunol., 139, p. 1104Bancroft, G.J., Schreiber, R.D., Unanue, E.R., Natural immunity: A T-cell independent pathway of macrophage activation defined in the scid mouse (1991) Immunol. Rev., 124, p. 5Brombacher, F., Kopf, M., Innate versus acquired immunity in listeriosis (1996) Res. Immunol., 147, p. 505Collet, D., (1994) Modeling Survival Data in Medical Research, pp. 1-13. , Texts in Statistical Science-Chapman & Hall, LondonDenis, M., Interferon-gamma-treated murine macrophages inhibit growth of tubercle bacilli via the generation of reactive nitrogen intermediates (1991) Cell. Immunol., 132, p. 150Dunn, P.L., North, R.J., Early gamma interferon production by natural killer cells is important in defense against murine listeriosis (1991) Infect. Immunity, 59, p. 2892Hasegawa, T., Okuda, M., Nomoto, K., Augmentation of the resistance against Listeria monocytogenes by oral administration of a hot water extract of Chlorella vulgaris in mice (1994) Immunopharmacol. Immunotoxicol., 16, p. 191Kaufmann, S.H.E., Immunity to intracellular bacteria (1993) Annu. Rev. Immunol., 11, p. 129Konishi, F., Tanaka, K., Kumamoto, S., Hasegawa, T., Okuda, M., Yano, I., Yoshikai, Y., Nomoto, K., Enhanced resistance against Escherichia coli infection by subcutaneous administration of the hot-water extract of Chlorella vulgaris in cyclophosphamide-treated mice (1990) Cancer Immunol. Immunother., 32, p. 1Mackaness, G.B., Cellular resistance to infection (1962) J. Exp. Med., 116, p. 381Nathan, C.F., Murray, H.W., Wiebe, M.B., Rubin, B.Y., Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity (1983) J. Exp. Med., 158, p. 670Romagnani, S., Induction of Th1 and Th2 immune responses: A key role for the natural immune response (1992) Immunol Today, 13, p. 379Tanaka, K., Tomita, Y., Tsuruta, M., Konishi, F., Okuda, M., Himeno, K., Nomoto, K., Oral administration of Chlorella vulgaris augments concomitant antitumor immunity (1990) Immunopharmacol. Immunotoxicol., 12, p. 277Teixeira, H.C., Kaufmann, S.H.E., Role of NK1.1+ cells in experimental listeriosis (1994) J. Immunol., 152, p. 1873Ladel, C.H., Blum, C., Kaufmann, S.H.E., Control of Natural Killer cell-mediated innate resistance against the intracellular pathogen listeria monocytogenes by γ/δ T lymphocytes (1996) Infect. Immun., 64, p. 1744Kearns, R.J., Leu, R.W., Modulation of Natural Killer activity in mice following infection with Listeria monocytogenes (1984) Cell. Immunol., 84, p. 361Goossens, P.L., Jovin, H., Milon, G., Dynamics of lymphocytes and inflammatory cells recruited in liver during murine listeriosis (1991) J. Immunol., 147, p. 3514Hasegawa, T., Yoshikai, Y., Okuda, M., Nomoto, K., Accelerated restoration of the leukocyte number and augmented resistance against Escherichia coli in cyclophospamide-treated rats orally administered with a hot water extract of Chlorella vulgaris (1990) Int. J. Immunopharmacol., 12, p. 88

Hematopoietic Response Of Rats Exposed To The Impact Of An Acute Psychophysiological Stressor On Responsiveness To An In Vivo Challenge With Listeria Monocytogenes: Modulation By Chlorella Vulgaris Prophylactic Treatment

In this study, we investigated the hematopoietic response of rats pretreated with CV and exposed to the impact of acute escapable, inescapable or psychogenical stress on responsiveness to an in vivo challenge with Listeria monocytogenes. No consistent changes were observed after exposure to escapable footshock. Conversely, the impact of uncontrollable stress (inescapable and psychogenical) was manifested by an early onset and increased severity and duration of myelossuppression produced by the infection. Small size CFU-GM colonies and increased numbers of clusters were observed, concurrently to a greater expansion in the more mature population of bone marrow granulocytes. No differences were observed between the responses of both uncontrollable stress regimens. CV prevented the myelossuppression caused by stress/infection due to increased numbers of CFU-GM in the bone marrow. Colonies of cells tightly packed, with a very condensed nucleus; in association with a greater expansion in the more immature population of bone marrow granulocytes were observed. Investigation of the production of colony-stimulating factors revealed increased colony-stimulating activity (CSA) in the serum of normal and infected/stressed rats treated with the algae. CV treatment restored/enhanced the changes produced by stress/infection in total and differential bone marrow and peripheral cells counts. Further studies demonstrated that INF-γ is significantly reduced, whereas IL-10 is significantly increased after exposure to uncontrollable stress. Treatment with CV significantly increased INF-γ levels and diminished the levels of IL-10. Uncontrollable stress reduced the protection afforded by CV to a lethal dose of L. monocytogenes, with survival rates being reduced from (50%) in infected rats to 20% in infected/stressed rats. 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Petiveria Alliacea L. Extract Protects Mice Against Listeria Monocytogenes Infection - Effects On Bone Marrow Progenitor Cells

In this study we have investigated the effects of Petiveria alliacea on the hematopoietic response of mice infected with Listeria monocytogenes. Our results demonstrate a protective effect of the crude extract of P. alliacea since the survival of the treated/infected was higher than that in the infected group. Moreover, the number of granulocyte/macrophage colonies (CFU- GM) and the serum colony stimulating activity levels were increased in the treated/infected mice in relation to the infected group. 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Hydroxyurea Promotes The Reduction Of Spontaneous Bfu-e To Normal Levels In Ss And S/β Thalassemic Patients

We have studied the effects of hydroxyurea on growth and differentiation of early erythroid progenitor cells (BFU-e) from peripheral blood of sickle cell disease patients (five SS and two Hb S/β-thalassemia) in the presence or absence of exogenous stimulating factors. When the mononuclear cells from the sickle cell disease patients were cultured at diagnosis (before hydroxyurea treatment), there was an increased number of BFU-e in relation to controls (p < 0.05, Wilcoxon test) when cells were grown in the presence or absence of 5637 conditioned medium and erythropoietin. Colonies that developed in the absence of added growth factors were considered "spontaneous". A significant difference was observed after hydroxyurea treatment in the number of BFU-e obtained in the presence and absence of stimulus, with a higher reduction in the spontaneous BFU-e number. As expected, there was an increased Hb F level in these patients when compared with their pretreatment levels. There was no correlation between spontaneous BFU-e and hemoglobin levels in all patients studied.25117Bincoletto, C., Saad, S.T.O., Silva, E., Queiroz, M.L.S., Bcl-2 expression and autonomous proliferation in patients with acute myeloid leukaemia (1999) Eur. J. Haematol., 62, pp. 38-42Löwenberg, B., Van Putten, W.L.J., Touw, I.P., Delwel, R., Santini, V., Autonomous proliferation of leukemic cells in vitro as a determinant of prognosis in adult acute myeloid leukemia (1993) N. Engl. J. Med., 328, pp. 614-619Hunter, A.E., Rogers, S.Y., Roberts, I.A.G., Barrett, A.J., Russell, N., Autonomous growth of blast cells is associated with reduced survival in acute myeloblastic leukemia (1993) Blood, 82, pp. 899-903Norgaard, J.M., Langkjer, S.T., Palshof, T., Clausen, N., Pedersen, B., Hokland, P., Relation of blast cell survival and proliferation to chemotherapy resistance in AML (1996) Br. J. 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Immunoglgbulin Levels And Cellular Immune Function In Lead Exposed Workers

The immunological status of lead acid batters workers with blood lead levels and urinary delta-aminolevulinic acid (ALA-U) concentrations ranging from safe to toxic levels has been examined and compared with those of non-exposed, age and sex matched controls. No differences in the serum concentrations of IgG, IgA and IgM between the populations were observed and there existed no correlation between blood lead level or ALA-U concentrations and serum immunoglobulin levels. In addition assessment was made of the capacity of peripheral blood mononuclear cells to respond to the mitogen phytohaemagglutin in (PHA), a correlate of T cell function. As before, there was no difference between exposed and control populations and no correlation between reactivity and blood lead concentration. Our data suggest that chronic exposure to lead fail to compromise lymphocyte function in man. © 1994 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.16111512

Antitumour activity of [1,2-di(cyclopentadienyl)-1,2-di(p-N,N-dimethylaminophenyl)-ethanediyl] titanium dichloride in xenografted Ehrlich's ascites tumour

The effects of a new titanocene compound with an ansa ligand in the cyclopentadienyl rings, the 1,2-di(cyclopentadienyl)-1,2-di(p-NNdimethylaminophenyl)-ethanediyl] titanium dichloride (TITANOCENE X), on the growth and differentiation of granulocyte-macrophage progenitor cells [colony-forming unit-granulocyte-macrophage (CFU-GM)] and Natural killer (NK) cell activity in Ehrlich's ascites tumour (EAT)-bearing mice were studied. Myelosuppression concomitant with increased numbers of spleen CFU-GM was observed in tumour-bearing mice. Treatment of these animals with TITANOCENE X (2.5-50mg/kg/day) produced an increase in myelopoicsis, in a dose-dependent manner, and reduced spleen colony formation. In addition, the treatment of EAT-bearing mice with 3 doses of 20 or 50 mg/kg TITANOCENE X restored to normal values the reduced Natural killer cell function observed during tumour growth. In parallel, TITANOCENE X prolonged, in a dose-dependent manner, the survival of mice inoculated with Ehrlich's ascites tumour. The highest dose of 50 mg/kg prolonged in 50% the survival time of EAT-bearing mice, compared to non-treated tumour-bearing controls. In comparison with previous results from our laboratory addressing the effects of titanocenes on haematopoiesis, we observed with TITANOCENE X a similar effective profile as for bis(cyclopentadienyl) dithiocyanate titanium(IV), being both less effective than di(cyclopentadienyl) dichloro titanium(IV), since the latter not only prolonged, but also increased the rate of survival. These differences in efficacy may be due to the nature of the ansa-cyclopentadienyl ligand used in TITANOCENE X, since the C, bridge between the two cyclopentadienyl groups will increase the hydrolytic stability by an organometallic chelate effect. Also, the introduction of two dimethylamino substituents increases the water solubility of TITANOCENE X when compared to titanocene dichloride itself (c) 2006 Elsevier B.V. All rights reserved