Effector Mechanisms in Low-Dose Streptozotocin-induced Diabetes

The cellular and molecular requirements for β-cell damages in an immune-mediated toxininduced insulin-dependent diabetes mellitus have been studied in the model of multiple low-dose streptozotocin-induced diabetes in rats and mice. It was found that strain-related susceptibility to diabetes induction correlated with a higher level of IL-2, IFN-γ, and TNF-α production, whereas such differences were not observed when IL-1 and NO production by macrophages were analyzed; elimination of immunoregulatory RT6+T cells that increases IFN-γ production, enhances susceptibility to MLD-STZ-induced diabetes; mercury-induced Th-2 cells downregulated the disease; IFN-γ-mediated macrophage activation to produce proinflammatory cytokines rather than NO is an important event in early diabetogenic effects of invading macrophages; inhibition of IL-1 activity downregulates diabetes induction; and generation of NO in β cells appears to be important for diabetogenic effects. Taken together, data indicate that MLD-STZ diabetes is induced by Th-1 lymphocytes that secrete soluble effector molecules that activate macrophages and promote destruction of β cells possibly by both nitric oxide and nonnitric oxide-mediated mechanisms

Separation of rhenium (VIII) from tungsten (VI)

Examined were the conditions for an effective separation of tungsten(VI) and rhenium(VII) on alumina if the solution of 0.20 mol dm-3 NaCl, pH=2-6, is used as the aqueous phase. Under the given experimental conditions alumina was found to be much better adsorbent for tungsten than for rhenium. The breakthrough and saturation capacities of alumina at pH = 2 are 24 and 78 mg W/g Al2O3, respectively. With the increase of pH these values decrease. So, at pH = 6 they are only 4 and 13 mg W/g Al2O3, respectively. The elution volume for rhenium for the given column dimensions and the quantity of the adsorbent, is about 16 ml. These results were confirmed by the experiments of the radiochemical separations. Tungsten-187 remains firmly bound to alumina. The radionuclidic purity of the eluted 186,188 Re at pH = 2 is very high.Physical chemistry 2004 : 7th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 21-23 September 200

Pentoxifylline Prevents Autoimmune Mediated Inflammation in Low Dose Streptozotocin Induced Diabetes

Xanthine derivative, pentoxifylline (PTX), has been recently shown to exert a protective effects in certain animal models of autoimmunity, including diabetes in NOD mice. In the present study, the immunomodulatory potential of PTX was investigated in autoimmune diabetes induced by multiple low doses of streptozotocin (MLD-SZ) in genetically susceptible CBA/H mice (tested with 40 mg SZ/kg b.w. for 5 days) and DA rats (tested with 20 mg/kg b.w. for 5 days). In both species, 2 – 3 weeks following the MLD-SZ treatment, sustained hyperglycemia developed, as an outcome of inflammatory reaction with endothelial cell activation and accumulation of mononuclear cells. Although there was no evidence of typical insulitis in early disease development (day 10), in both rats and mice, macrophages, CD4+ and CD8+ cells were present in the islets of Langerhans as diffuse mononuclear infiltrates with the expression of IFN-γ and inducible NO synthase (iNOS). Administration of PTX (200 mg/kg/day for 10 days) in combination with MLD-SZ reduced insulitis and the production of mediators tested, and prevented the development of hyperglycemia. These results suggest that beneficial effects of PTX involve down-regulation of local proinflammatory cytokine-mediated NO synthase pathway. They also demonstrate that in addition to ameliorating spontaneous autoimmunity in NOD mice, PTX may be effective in downregulating an inflammatory autoimmune process triggered in susceptible host by an external agents, such as streptozotocin

Latent Murine Cytomegalovirus Infection Contributes to EAE Pathogenesis

ABSTRACT Viral infection has been identified as the most likely environmental trigger of multiple sclerosis (MS). There are conflicting data regarding the role of cytomegalovirus (CMV) in MS pathogenesis. We utilised experimental autoimmune encephalomyelitis (EAE)-resistant BALB/c mice and murine cytomegalovirus (MCMV), the murine homolog of CMV, to examine the mechanism by which viral infection enhances autoimmune neuroinflammation. Mice subjected to latent neonatal MCMV infection developed the typical characteristics of EAE. Similar to MS, the MCMV-infected EAE-induced mice developed infiltrates in the central nervous system (CNS) composed of similar percentages of CD4+ and CD8+ T cells. The influx of both Th 1 and Th 17 cells into the CNS of MCMV- infected EAE-induced mice was observed. Interestingly, the development of autoimmune neuroinflammation after latent MCMV infection was accompanied by a significant influx of Tc17 cells (CD8+IL-17+ and CD8+RoRγt+) but not Tc1, cells. Our results suggest that latent MCMV infection affects the development of inflammatory lymphocytes that exhibit encephalitogenic potential, thereby mediating increased CNS pathology following EAE induction, and that CMV represents a possible environmental factor in the pathogenesis of MS and other autoimmune disease

Murine cytomegalovirus infection induces susceptibility to eae in resistant BalB/c Mice

In contrast to C57BL/6 mice, BALB/c mice are relatively resistant to the induction of experimental autoimmune encephalomyelitis (EAE) after challenge with MOG35–55 peptide. Here, we provide the first evidence that infection with murine cytomegalovirus (MCMV) in adulthood abrogates this resistance. Infected BALB/c mice developed clinical and histological signs similar to those seen in susceptible C57BL/6 mice. In addition to CD4+ cells, large proportion of cells in the infiltrate of diseased BALB/c mice was CD8+, similar with findings in multiple sclerosis. CD8+ cells that responded to ex vivo restimulation with MOG35–55 were not specific for viral epitopes pp89 and m164. MCMV infection favors proinflammatory type of dendritic cells (CD86+CD40+CD11c+) in the peripheral lymph organs, M1 type of microglia in central nervous system, and increases development of Th1/Th17 encephalitogenic cells. This study indicates that MCMV may enhance autoimmune neuropathology and abrogate inherent resistance to EAE in mouse strain by enhancing proinflammatory phenotype of antigen-presenting cells, Th1/Th17, and CD8 response to MOG35–55

Interleukin-33/ST2: A new signaling pathway in immunity and immunopathology

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Galectin-3 deficiency preserves pancreatic islets function in basal conditions and under cytotoxic stimuli

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Galectin-3 deficiency preserves pancreatic islets function in basal conditions and under cytotoxic stimuli

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Galectin-3 deficiency confers resistance to cytokine-induced apoptosis of pancreatic islets - role of mitochondrial pathway

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