AIM: To evaluate if the administration of an enteral diet supplemented with glutamine, arginine and omega-3-fatty acids modulates inflammatory and immune responses after surgery. METHODS: A prospective randomized doub...AIM: To evaluate if the administration of an enteral diet supplemented with glutamine, arginine and omega-3-fatty acids modulates inflammatory and immune responses after surgery. METHODS: A prospective randomized double-blind, clinical trial was performed. Forty-eight patients with gastrointestinal cancer were randomized into two groups, one group was given an isocaloric and isonitrogenous standard diet and the other was fed with the supplemented diet with glutamine, arginine and omega-3-fatty acids. Feedings were started within 48 hours after operation, and continued until day 8. All variables were measured before operation and on postoperative day 1 and 8. Immune responses were determined by phagocytosis ability, respiratory burst of polymorphonuclear cells, total lymphocytes lymphocyte subsets, nitric oxide, cytokines concentration, and inflammatory responses by plasma levels of C-reactive protein, prostaglandin E2 level. RESULTS: Tolerance of both formula diets was excellent.There were significant differences in the immunological and inflammatory responses between the two groups. In supplemented group, phagocytosis and respiratory burst after surgery was higher and C-reactive protein level was lower (P【0.01) than in the standard group. The supplemented group had higher levels of nitric oxide, total lymphocytes, T lymphocytes, T-helper cells, and NK cells. Postoperative levels of IL-6 and TNF-alpha were lower in the supplemented group (P 【0.05). CONCLUSION: It was clearly established in this trial that early postoperative enteral feeding is safe in patients who have undergone major operations for gastrointestinal cancer. Supplementation of enteral nutrition with glutamine, arginine, and omega-3-fatty acids positively modulated postsurgical immunosuppressive and inflammatory responses.展开更多
The discharge of organic waste from the petrochemical industry into the Mercier lagoons caused major groundwater contamination. The objective of this study was to determine the immunotoxic potential of three groundwat...The discharge of organic waste from the petrochemical industry into the Mercier lagoons caused major groundwater contamination. The objective of this study was to determine the immunotoxic potential of three groundwater wells at increasing distance from the incinerator dumping site （1.17, 2.74 and 5.40 km）. Rainbow Trout were exposed to increasing concentrations of water from three groundwater wells for 14 days. Immunocompetence was characterized by phagocytosis, mitogen-stimulated proliferation of lymphocytes, cell cycle analysis and apoptosis. A significant increase in innate （phagocytosis） and specific immune response （B lymphocyte proliferation） was observed in trout exposed to water collected from the well at 2.74 km. However, phagocytosis activity was suppressed in groups at 1.17 and 5.40 km. The proportion of lymphocytes in S phase was significantly increased in groups at 2.74 and 5.40 kin, while lymphocytes in G0/G1 phase were decreased in all three exposure groups. Additionally, dexamethasone （DEX）-induced apoptosis of lymphocytes was significantly reduced in the group at 2.74 km, which suggests decreased lymphocyte turnover. Furthermore, the ratio of DEX- induced apoptosis/apoptosis was lower in the groups at 2.74 and 5.40 km. In summary, our experiments have shown that exposure to the mixture of organic compounds present in Mercier groundwater modulates phagocytosis and cell proliferation, disrupts the cell cycle and reduces the ratio of DEX- induced apoptosis/apoptosis. It is concluded that groundwater collected in the vicinity of an incinerator containment field could impact immunocompetence in fish.展开更多
Pulmonary carcinomas have developed mechanisms by which they escape the attack of immune cells.Immune checkpoint molecules programmed death 1-programmed death ligand 1(PD1-PDL1)and the cytotoxic T-lymphocyte antigen 4...Pulmonary carcinomas have developed mechanisms by which they escape the attack of immune cells.Immune checkpoint molecules programmed death 1-programmed death ligand 1(PD1-PDL1)and the cytotoxic T-lymphocyte antigen 4 system have gained attention.The expression of PDL1 by tumor cells causes immune tolerance,and further influences the microenvironment via orchestration by cytokines.Therapy with PDL1 antibodies could restore the cytotoxicity of T-lymphocytes towards tumor cells.Many patients will respond to this treatment.However,resistance mechanisms will counteract this therapy.New investigations have identified additional immune checkpoint inhibitors such as lymphocyte activation gene 3 and T cell immunoglobulin and mucin-domain containing-3.Tumor cells also induce tolerance by manipulating cells of the innate immune system.Macrophages are polarized to tumor-friendly M2,neutrophils into N2 types,and dendritic cells and myeloid suppressor cells are switched to assist tumor cells.Regulatory T cells enter the tumor microenvironment and signal tolerance to cytotoxic cells,inhibiting the influx of NK cells.Soluble mediators either released by tumor cells or cells of the tumor stroma induce immune tolerance,examples including tryptophan and indolamine dioxygenases,arginine and adenosine.Treatment options to counteract these molecules are currently being tested.The tumor stroma has been classified as immune-inflamed,immune-excluded,and immune-desert types.The latter might be switched to an inflamed type by induction of tertiary lymph follicles.Dendritic cells and macrophages normally phagocytose tumor antigens,but inhibitors of phagocytosis can block this.Interference with these molecules is another option for re-establishing the cytotoxic action of the immune system against tumor cells.In this review we will discuss these aspects with a special emphasis on non-small cell lung cancer.展开更多
文摘AIM: To evaluate if the administration of an enteral diet supplemented with glutamine, arginine and omega-3-fatty acids modulates inflammatory and immune responses after surgery. METHODS: A prospective randomized double-blind, clinical trial was performed. Forty-eight patients with gastrointestinal cancer were randomized into two groups, one group was given an isocaloric and isonitrogenous standard diet and the other was fed with the supplemented diet with glutamine, arginine and omega-3-fatty acids. Feedings were started within 48 hours after operation, and continued until day 8. All variables were measured before operation and on postoperative day 1 and 8. Immune responses were determined by phagocytosis ability, respiratory burst of polymorphonuclear cells, total lymphocytes lymphocyte subsets, nitric oxide, cytokines concentration, and inflammatory responses by plasma levels of C-reactive protein, prostaglandin E2 level. RESULTS: Tolerance of both formula diets was excellent.There were significant differences in the immunological and inflammatory responses between the two groups. In supplemented group, phagocytosis and respiratory burst after surgery was higher and C-reactive protein level was lower (P【0.01) than in the standard group. The supplemented group had higher levels of nitric oxide, total lymphocytes, T lymphocytes, T-helper cells, and NK cells. Postoperative levels of IL-6 and TNF-alpha were lower in the supplemented group (P 【0.05). CONCLUSION: It was clearly established in this trial that early postoperative enteral feeding is safe in patients who have undergone major operations for gastrointestinal cancer. Supplementation of enteral nutrition with glutamine, arginine, and omega-3-fatty acids positively modulated postsurgical immunosuppressive and inflammatory responses.
基金supported by the Canada Research Chairin Environmental Immunotoxicology(Dr.M.Fournier)
文摘The discharge of organic waste from the petrochemical industry into the Mercier lagoons caused major groundwater contamination. The objective of this study was to determine the immunotoxic potential of three groundwater wells at increasing distance from the incinerator dumping site （1.17, 2.74 and 5.40 km）. Rainbow Trout were exposed to increasing concentrations of water from three groundwater wells for 14 days. Immunocompetence was characterized by phagocytosis, mitogen-stimulated proliferation of lymphocytes, cell cycle analysis and apoptosis. A significant increase in innate （phagocytosis） and specific immune response （B lymphocyte proliferation） was observed in trout exposed to water collected from the well at 2.74 km. However, phagocytosis activity was suppressed in groups at 1.17 and 5.40 km. The proportion of lymphocytes in S phase was significantly increased in groups at 2.74 and 5.40 kin, while lymphocytes in G0/G1 phase were decreased in all three exposure groups. Additionally, dexamethasone （DEX）-induced apoptosis of lymphocytes was significantly reduced in the group at 2.74 km, which suggests decreased lymphocyte turnover. Furthermore, the ratio of DEX- induced apoptosis/apoptosis was lower in the groups at 2.74 and 5.40 km. In summary, our experiments have shown that exposure to the mixture of organic compounds present in Mercier groundwater modulates phagocytosis and cell proliferation, disrupts the cell cycle and reduces the ratio of DEX- induced apoptosis/apoptosis. It is concluded that groundwater collected in the vicinity of an incinerator containment field could impact immunocompetence in fish.
文摘Pulmonary carcinomas have developed mechanisms by which they escape the attack of immune cells.Immune checkpoint molecules programmed death 1-programmed death ligand 1(PD1-PDL1)and the cytotoxic T-lymphocyte antigen 4 system have gained attention.The expression of PDL1 by tumor cells causes immune tolerance,and further influences the microenvironment via orchestration by cytokines.Therapy with PDL1 antibodies could restore the cytotoxicity of T-lymphocytes towards tumor cells.Many patients will respond to this treatment.However,resistance mechanisms will counteract this therapy.New investigations have identified additional immune checkpoint inhibitors such as lymphocyte activation gene 3 and T cell immunoglobulin and mucin-domain containing-3.Tumor cells also induce tolerance by manipulating cells of the innate immune system.Macrophages are polarized to tumor-friendly M2,neutrophils into N2 types,and dendritic cells and myeloid suppressor cells are switched to assist tumor cells.Regulatory T cells enter the tumor microenvironment and signal tolerance to cytotoxic cells,inhibiting the influx of NK cells.Soluble mediators either released by tumor cells or cells of the tumor stroma induce immune tolerance,examples including tryptophan and indolamine dioxygenases,arginine and adenosine.Treatment options to counteract these molecules are currently being tested.The tumor stroma has been classified as immune-inflamed,immune-excluded,and immune-desert types.The latter might be switched to an inflamed type by induction of tertiary lymph follicles.Dendritic cells and macrophages normally phagocytose tumor antigens,but inhibitors of phagocytosis can block this.Interference with these molecules is another option for re-establishing the cytotoxic action of the immune system against tumor cells.In this review we will discuss these aspects with a special emphasis on non-small cell lung cancer.
