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The discovery of cyclosporine A was a milestone in organ transplantation and the treatment of autoimmune diseases. However, developing an efficient oral delivery system for this drug is complicated by its poor biopharmaceutical characteristics (low solubility and permeability) and the need to carefully monitor its levels in the blood. Current research is exploring various approaches, including those based on emulsions, microspheres, nanoparticles, and liposomes. Although progress has been made, none of the formulations is flawless. This review is a brief description of the main pharmaceutical systems and devices that have been described for the oral delivery of cyclosporine A in the context of the physicochemical properties of the drug and the character of its interactions with lipid membranes.
Despite the enormous progress in understanding the process of bacterial pathogenesis and interactions of pathogens with eucaryotic cells the infectious diseases still remain the main cause of human premature deaths. It is now recognized that Helicobacter pylori infects about half of the world's population. Based on results of clinical studies the World Health Organization has assigned H. pylori as a class I carcinogen. The review presents new achievements aimed at construction efficient and safe anti-Helicobacter vaccine. We discuss the new global technologies such as immunoproteomics employed for selecting new candidates for vaccine construction as well as new vaccine delivery systems. The review presents also our knowledge concerning H. pylori interaction with immune system which might facilitate modulation of the host immune system by specific adjuvant included into vaccine.
Six isolates of Trichoderma spp. (belonging to species: Trichoderma harzianum and T. longibrachiatum) were applied as seed or soil treatments to suppress damping-off of seedlings of ten cotton cultivars under greenhouse conditions. In most cases, cultivar x isolate interaction was a highly significant (p < 0.01) source of variation in the tested seedling growth parameters: incidence of disease, seedling height, and seedling dry weight. This interaction implies that a single isolate of Trichoderma can be highly effective in controlling the disease on a cotton cultivar but may have minimal efficiency in controlling the disease on another cultivar. It was also found that, in most cases, cultivar x isolate x application method was a highly significant source of variation (p < 0.01) in the tested growth parameters. Cotton cultivars showed differences in the disease reaction to the biocontrol agents. In the experiments evaluating the Trichoderma antagonists and their effect on seedling disease, a highly significant (p < 0.01) experimental treatment interaction was found. This interaction suggests that the outcome of cultivar x isolate interaction is markedly affected by the application method. Thus, the application method should be chosen to maximize the outcome of this interaction. The degree of the control of seedling disease in cotton differed according to the isolates of antagonists, the application method and cultivars.
Experimental Allergic Encephalomyelitis (EAE) is the animal model of Multiple Sclerosis (MS), human chronic and progressive autoimmunological disease that lead to neurodegeneration in Central Nervous System (CNS). Although there are some hypothesis, like genetic, environmental or viral factors involvement, cause and patophysiology of MS remains still unknown, and that is the reason why there is no sufficient MS treatment so far. Most common MS therapy is use of immunosupressive drugs, but that is not very effective and costs number of health complications. Also new targeted therapies are burdened with the risk of side effects, which may be even lethal. Therefore, the efficient alternative treatment is urgently needed. The autoimmune base of the disease directed treatment searching into immunological mechanisms. Few years ago we proposed application of animal spinal cord hydrolysate for inducing oral tolerance, which effect lies in reducing of immunoresponse for previously fed antigen. We presented the effectiveness of this type of treatment in EAE rat model. The success of oral tolerance with mixture of peptides stimulates us to development bacteria that may express active peptide related to myelin fragment. As far as it is known, that the dose of fed antigen is crucial in evoking oral tolerance, the aim of our study, was to investigate which dose or doses of Lactococcus lactis expressing myelin peptides is sufficient for EAE treatment. We used autolising strain of Lactococcus lactis, producing one of three myelin peptides, which are considered to be crucial in MS developement: Myelin Basic Protein (MBP aa85-97), Proteolipid Protein (PLP aa139- 151) or Myelin Oligodendrocyte Protein (MOG aa35-55). We mixed all three peptide variants, and made whole-cell extracts. For our experiments we used female Lewis rats (180–200 g), which were fed with ball-pointed needle with mixed bacteria extracts for 20 days. Doses of preparations ranged from 101 to 108 cells/rat/feeding suspended in 0.5 ml PBS. At the 10th day of feeding, EAE was evoked by hind paw injection of guinea pig spinal cord homogenate in Freund Adjuvant with Mycobacterium tuberculosis. During the whole experiment animals were weighted, and clinical symptomes were observed. The obtained results demonstrated, that the sufficient doses of Lactococcus lactis expressing myelin peptides, given orally to animals are 103 and 106 cells/rat/feeding. Further experiments including cytokine level measurement and microscopic observation of rats spinal cord are in progress.
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