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Many Pathological Conditions (many + pathological_condition)
Selected AbstractsThe role of reactive oxygen species and nitric oxide in mast cell-dependent inflammatory processesIMMUNOLOGICAL REVIEWS, Issue 1 2007Emily J. Swindle Summary:, Reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS), including nitric oxide, are produced in cells by a variety of enzymatic and non-enzymatic mechanisms. At high levels, both types of oxidants are used to kill ingested organisms within phagocytes. At low levels, RNOS may diffuse outside cells where they impact the vasculature and nervous system. Recent evidence suggests that low levels of ROS produced within cells are involved in cell signaling. Along with these physiological roles, many pathological conditions exist where detrimental high-level ROS and RNOS are produced. Many situations in which ROS/RNOS are associated also involve mast cell activation. In innate immunity, such mast cells are involved in the immune response toward pathogens. In acquired immunity, activation of mast cells by cross-linking of receptor-bound immunoglobulin E causes the release of mediators involved in the allergic inflammatory response. In this review, we describe the principle pathways for ROS and RNOS generation by cells and discuss the existence of such pathways in mast cells. In addition, we examine the evidence for a functional role for ROS and RNOS in mast cell secretory responses and discuss evidence for a direct relationship between ROS, RNOS, and mast cells in mast cell-dependent inflammatory conditions. [source] Enhanced formation of advanced oxidation protein products in IBDINFLAMMATORY BOWEL DISEASES, Issue 6 2008Malgorzata Krzystek-Korpacka PhD Abstract Background: Advanced oxidation protein products (AOPPs) are new protein markers of oxidative stress with pro-inflammatory properties, accumulated in many pathological conditions. The issue of their enhanced formation in IBD has not been addressed yet. Methods: The concentration of relative AOPPs (rAOPP; concentration of AOPPs divided by albumin level) were measured in 68 subjects with ulcerative colitis (UC), 50 subjects with Crohn's disease (CD) and 45 healthy volunteers, and related to disease phenotype, clinical and biochemical activity, and therapeutic strategy. Diagnostic utility of rAOPP was evaluated by ROC analysis. Results: In comparison with controls (1.367 ,mol/g), rAOPP were increased in inactive (1.778 ,mol/g, P = 0.053) and active (1.895 ,mol/g, P = 0.013) UC and in active (1.847 ,mol/g, P = 0.003) CD. In CD, but not UC, rAOPP correlated with disease activity (r = 0.42, P = 0.013). Significant correlations with the inflammatory/malnutrition indices-erythrocyte sedimentation rate (ESR) (r = 0.53), leukocytes (r = 0.33), platelets (r = 0.38), IL-6 (r = 0.36), and transferrin (r = ,0.35) were demonstrated in CD. In UC, rAOPP correlated only with ESR (r = 0.35) and IL-6 (r = 0.30). Instead, associations with antioxidant dismutase (r = 0.29) and catalase (r = 0.22) were observed. The diagnostic power of rAOPP in discriminating diseased from non-diseased subjects was less than that of C-reactive protein (CRP). Simultaneous determination of rAOPP and CRP did not significantly improve the power of single CRP determination. Conclusions: IBD was associated with enhanced formation of AOPP, which differed between C and UC with respect to the relationship between rAOPP and disease activity, inflammatory and antioxidant response. These differences may reflect divergent ways that oxidative stress develops in CD and UC. The diagnostic power of rAOPP was insufficient for its clinical application. (Inflamm Bowel Dis 2008) [source] Methylene blue inhibits angiogenesis in chick chorioallontic membrane through a nitric oxide-independent mechanismJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2006N. Zacharakis Abstract Angiogenesis is the process of generating new blood vessels from preexisting vessels and is considered essential in many pathological conditions. The purpose of the present study was to evaluate the effect of methylene blue in chick chorioallantoic membrane angiogenesis model in vivo. In this well characterized model, methylene blue inhibited angiogenesis in a concentration-dependent manner. In addition, when methylene blue was combined with sodium nitroprusside, a spontaneous generator of nitric oxide, an inhibition of angiogenesis was evident which was comparable with that observed by the application of methylene blue alone. Sodium nitroprusside, alone, caused a significant inhibition in basal angiogenesis. These results provide evidence that methylene blue inhibits angiogenesis independently of nitric oxide pathway and suggest that methylene blue may be useful for treating angiogenesis-dependent human diseases. [source] Assessment of tissue redox status using metabolic responsive contrast agents and magnetic resonance imagingJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2008Fuminori Hyodo Regulation of tissue redox status is important to maintain normal physiological conditions in the living body. Disruption of redox homoeostasis may lead to oxidative stress and can induce many pathological conditions such as cancer, neurological disorders and ageing. Therefore, imaging of tissue redox status could have clinical applications. Redox imaging employing magnetic resonance imaging (MRI) with nitroxides as cell-permeable redox-sensitive contrast agents has been used for non-invasive monitoring of tissue redox status in animal models. The redox imaging applications of nitroxide electron paramagnetic resonance imaging (EPRI) and MRI are reviewed here, with a focus on application of tumour redox status monitoring. While particular emphasis has been placed on differences in the redox status in tumours compared to selected normal tissues, the technique possesses the potential to have broad applications to the study of other disease states, inflammatory processes and other circumstances where oxidative stress is implicated. [source] Insulin-like growth factor binding protein-3 induces angiogenesis through IGF-I- and SphK1-dependent mechanismsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2007R. GRANATA Summary. Angiogenesis is critical for development and repair, and is a prominent feature of many pathological conditions. Based on evidence that insulin-like growth factor binding protein (IGFBP)-3 enhances cell motility and activates sphingosine kinase (SphK) in human endothelial cells, we have investigated whether IGFBP-3 plays a role in promoting angiogenesis. IGFBP-3 potently induced network formation by human endothelial cells on Matrigel. Moreover, it up-regulated proangiogenic genes, such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP)-2 and -9. IGFBP-3 even induced membrane-type 1 MMP (MT1-MMP), which regulates MMP-2 activation. Decreasing SphK1 expression by small interfering RNA (siRNA), blocked IGFBP-3-induced network formation and inhibited VEGF, MT1-MMP but not IGF-I up-regulation. IGF-I activated SphK, leading to sphingosine-1-phosphate (S1P) formation. The IGF-I effect on SphK activity was blocked by specific inhibitors of IGF-IR, PI3K/Akt and ERK1/2 phosphorylation. The disruption of IGF-I signaling prevented the IGFBP-3 effect on tube formation, SphK activity and VEGF release. Blocking ERK1/2 signaling caused the loss of SphK activation and VEGF and IGF-I up-regulation. Finally, IGFBP-3 dose-dependently stimulated neovessel formation into subcutaneous implants of Matrigel in vivo. Thus, IGFBP-3 positively regulates angiogenesis through involvement of IGF-IR signaling and subsequent SphK/S1P activation. [source] Anti-angiogenic drugs: from bench to clinical trialsMEDICINAL RESEARCH REVIEWS, Issue 4 2006Ana R. Quesada Abstract Angiogenesis, the generation of new capillaries through a process of pre-existing microvessel sprouting, is under stringent control and normally occurs only during embryonic and post-embryonic development, reproductive cycle, and wound repair. However, in many pathological conditions (solid tumor progression, metastasis, diabetic retinopathy, hemangioma, arthritis, psoriasis and atherosclerosis among others), the disease appears to be associated with persistent upregulated angiogenesis. The development of specific anti-angiogenic agents arises as an attractive therapeutic approach for the treatment of cancer and other angiogenesis-dependent diseases. The formation of new blood vessels is a complex multi-step process. Endothelial cells resting in the parent vessels are activated by an angiogenic signal and stimulated to synthesize and release degradative enzymes allowing endothelial cells to migrate, proliferate and finally differentiate to give rise to capillary tubules. Any of these steps may be a potential target for pharmacological intervention. In spite of the disappointing results obtained initially in clinical trials with anti-angiogenic drugs, recent reports with positive results in phases II and III trials encourage expectations in their therapeutic potential. This review discusses the current approaches for the discovery of new compounds that inhibit angiogenesis, with emphasis on the clinical developmental status of anti-angiogenic drugs. © 2006 Wiley Periodicals, Inc. Med Res Rev, 26, No. 4, 483,530, 2006 [source] Vascular endothelial growth factor and the nervous systemNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 5 2004A. Brockington Vascular endothelial growth factor (VEGF) is an angiogenic factor essential for the formation of new blood vessels during embryogenesis and in many pathological conditions. A new role for VEGF as a neurotrophic factor has recently emerged. In the developing nervous system, VEGF plays a pivotal role not only in vascularization, but also in neuronal proliferation, and the growth of coordinated vascular and neuronal networks. After injury to the nervous system, activation of VEGF and its receptors may restore blood supply and promote neuronal survival and repair. There is a growing body of evidence that VEGF is essential for motor neurone survival, and that aberrant regulation of VEGF may play a role in the degeneration of neurones in diseases such as amyotrophic lateral sclerosis. [source] Studies of phospholipid oxidation by electrospray mass spectrometry: From analysis in cells to biological effectsBIOFACTORS, Issue 1-4 2005Corinne M. Spickett Abstract The oxidation of lipids is important in many pathological conditions and lipid peroxidation products such as 4-hydroxynonenal (HNE) and other aldehydes are commonly measured as biomarkers of oxidative stress. However, it is often useful to complement this with analysis of the original oxidized phospholipid. Electrospray mass spectrometry (ESMS) provides an informative method for detecting oxidative alterations to phospholipids, and has been used to investigate oxidative damage to cells, and low-density lipoprotein, as well as for the analysis of oxidized phosphatidylcholines present in atherosclerotic plaque material. There is increasing evidence that intact oxidized phospholipids have biological effects; in particular, oxidation products of 1-palmitoyl-2-arachidonoyl- sn -glycerophosphocholine (PAPC) have been found to cause inflammatory responses, which could be potentially important in the progression of atherosclerosis. The effects of chlorohydrin derivatives of lipids have been much less studied, but it is clear that free fatty acid chlorohydrins and phosphatidylcholine chlorohydrins are toxic to cells at concentrations above 10 micromolar, a range comparable to that of HNE and oxidized PAPC. There is some evidence that chlorohydrins have biological effects that may be relevant to atherosclerosis, but further work is needed to elucidate their pro-inflammatory properties, and to understand the mechanisms and balance of biological effects that could result from oxidation of complex mixtures of lipids in a pathophysiological situation. [source] | ||||||||||