| 1. |
- Koussounadis, Antonis I., et al.
(författare)
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Analysis of Fish IL-1beta and Derived Peptide Sequences Indicates Conserved Structures with Species-Specific IL-1 Receptor Binding: Implications for Pharmacological Design
- 2004
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Ingår i: Current Pharmaceutical Design. - : Bentham Science Publishers Ltd.. - 1873-4286 .- 1381-6128. ; 10:31, s. 3857-3871
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Tidskriftsartikel (refereegranskat)abstract
- A large number of IL-1 protein sequences have become available recently from a range of vertebrate species and especially from bony fish. However, 3D structures are still only known for mammalian IL-1. In this review, we use a multiple sequence alignment of all published non-mammalian vertebrate IL-1beta proteins to locate the structurally important residues critical for maintaining the beta-trefoil fold and we investigate the degree to which functionally important residues involved in receptor binding are conserved across vertebrate species. We find that although there is a high level of variability of positions involved in receptor binding, the mode of binding and overall shape of the ligand-receptor complex is probably maintained. This implies that each species has evolved its own unique interleukin-1 signalling system through ligand-receptor co-evolution. Nonetheless, the IL-1beta processing mechanism in non-mammalian vertebrates remains unclear because, with the exception of three bony fish, all non-mammalian IL-1beta sequences discovered so far lack an ICE (Interleukin Converting Enzyme) cut site. The IL-1 system has become an important drug target because of its significance in inflammatory diseases. Research on peptides derived from IL-1beta has identified peptides that possess agonist activity in humans and in trout, and peptides with antagonist activity. The agonist peptides map to two distinct loop regions of IL-1beta that are known to interact with the flexible domain III of the corresponding receptor. Further analysis of the IL-1 system may prove useful in engineering IL-1 with improved features and in suggesting new avenues for therapeutic intervention.
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| 2. |
- Rostami, Elham, 1979-, et al.
(författare)
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Microdialysis in neurointensive care.
- 2004
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Ingår i: Current pharmaceutical design. - : Bentham Science Publishers Ltd.. - 1381-6128 .- 1873-4286. ; 10:18, s. 2145-2152
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Tidskriftsartikel (refereegranskat)abstract
- Microdialysis is a technique for sampling the chemistry of the interstitial fluid of tissues and organs in animal and man. It is minimally invasive and simple to perform in a clinical setting. Although microdialysis samples essentially all small molecular substances present in the interstitial fluid the use of microdialysis in neurointensive care has focused on markers of ischemia and cell damage. The lactate / pyruvate ratio is a well-known marker of changes in the redox state of cells caused by ischemia Glycerol is an integral component of cell membranes. Loss of energy due to ischemia eventually leads to an influx of calcium and a decomposition of cell membranes, which liberates glycerol into the interstitial fluid. Thus the lactate / pyruvate ratio and glycerol have become the most important markers of ischemia and cell membrane damage. While the primary insult at the site of the accident is beyond our control, secondary insults during intensive care should be avoided by all means. Therefore, the single most important finding from microdialysis studies is the dramatic difference in the vulnerability of the penumbra surrounding a lesion as compared to normal brain tissue allowing early detection of secondary insults after traumatic brain injury as well as the onset of vasospasm after subarachnoid hemorrhage.
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| 3. |
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| 4. |
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| 5. |
- Korsgren, Magnus
(författare)
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NK cells and asthma.
- 2002
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Ingår i: Current Pharmaceutical Design. - : Bentham Science Publishers Ltd.. - 1381-6128. ; 8:20, s. 1871-1876
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Forskningsöversikt (refereegranskat)abstract
- NK cells have been associated with immune surveillance of tumor cells and defense mechanisms against various pathogens. However, by their capacity for immunoregulation NK cells may also play a role in determining the response to allergens. The novel possibility that NK cell activity may in part decide development of allergic airway inflammation and thus potentially be involved in the inception of asthma is discussed in this review article.
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| 6. |
- Pullerits, Teet, 1967
(författare)
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Cytokine modulation for anti-allergic treatment.
- 2002
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Ingår i: Current pharmaceutical design. - 1381-6128. ; 8:20, s. 1845-53
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Forskningsöversikt (refereegranskat)abstract
- In the complex pathogenesis of airway inflammation seen in asthma, several cytokines are recognized to play a crucial role. Modulation of the effect of these cytokines can provide alternative and more specific treatment approach to currently widely-used systemic immunosuppression by glucocorticoids. Theoretically, cytokine modulation can be achieved via several pathways, including inhibition of released cytokines by using antibodies or soluble receptors, blocking cytokine receptors, inhibiting signal transduction or preventing cytokine gene transcription. Also, some cytokines are known to possess anti-inflammatory effects in allergic inflammation, being thus themselves potentially used as a therapeutic agent. The current review discusses the present knowledge on the involvement of cytokines in the pathogenesis of allergic asthma and the experience on modulation of the effect of these cytokines in clinical situations.
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| 7. |
- Turesson, Carl
(författare)
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Endothelial expression of MHC class II molecules in autoimmune disease
- 2004
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Ingår i: Current Pharmaceutical Design. - : Bentham Science Publishers Ltd.. - 1381-6128. ; 10:2, s. 129-143
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Forskningsöversikt (refereegranskat)abstract
- Major histocompatibility complex (MHC) class II molecules are up-regulated on endothelial cells in human allografts, and are thought to be involved in graft rejection. The MFIC class 11 subtypes HLA-DR, DQ and DP regulate T cell dependent immune responses, and aberrant expression could be important in autoimmunity. Increased endothelial MHC class II expression has been demonstrated in several autoimmune diseases, including myocarditis with dilated cardiomyopathy, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Recent data suggest that there is an association between endothelial expression of MHC class II molecules and diffuse endothelial dysfunction, which may be part of the explanation of the increased risk of cardiovascular disease in patients with RA, SLE and other chronic inflammatory conditions. MHC class II transcription is in part genetically determined. Cytokine induced up-regulation of MHC class II molecules can be inhibited in vitro by antioxidants and different drugs, such as cyclosporin and statins. Research on the development of new treatments for systemic autoimmune diseases and cardiovascular disease should include evaluation of effects on endothelial activation, including MHC class II expression. This review also discusses the genetic basis of MHC class II expression and its implications for understanding MHC genotype associations with autoimmune diseases. Recent studies of interactions between endothelial cells and T cells are reviewed. Such interactions could be of major importance in the pathogenesis of autoimmune and vascular diseases.
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| 8. |
- Wimo, A, et al.
(författare)
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Economic aspects on drug therapy of dementia
- 2004
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Ingår i: Current pharmaceutical design. - : Bentham Science Publishers Ltd.. - 1381-6128. ; 10:3, s. 295-301
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Tidskriftsartikel (refereegranskat)
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