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Inflammatory Stage (inflammatory + stage)
Selected AbstractsAgonists of proteinase-activated receptor-2 affect transendothelial migration and apoptosis of human neutrophilsEXPERIMENTAL DERMATOLOGY, Issue 10 2007Victoria M. Shpacovitch Abstract:, Skin is the first barrier preventing microorganism invasion in host. Wounds destroy this defense barrier and, without an appropriate care, may lead to sepsis. Neutrophil activation and immigration plays an important role at the inflammatory stage of wound healing. Neutrophils are known to express proteinase-activated receptors (PARs), which can be activated by serine proteases, also by enzymes involved in wound healing. We previously reported that PAR2 agonists up-regulate cell adhesion molecule expression and cytokine production by human neutrophils. Here, we demonstrate that PAR2 agonists (serine proteases as well as synthetic peptides) reduce transendothelial migration of neutrophils and prolong their life in vitro. Synthetic PAR2 agonist also enhanced protective interferon (IFN),-induced Fc,RI expression at neutrophil cell surface. Of note, IFN, is a cytokine, which was used in clinical trials to reactivate human neutrophil functions during sepsis. Moreover, we observed a significant increase of PAR2 expression on cell surface of neutrophils from septic patients as compared with healthy volunteers. Together, our results indicate that PAR2 may be involved in the pathophysiology of neutrophil-endothelial interactions during wound healing or later during sepsis in humans, potentially by affecting neutrophil apoptosis, transendothelial migration and Fc, receptor-mediated phagocytosis. [source] A12. IPL therapy in the inflammatory stage of rosaceaJOURNAL OF COSMETIC DERMATOLOGY, Issue 2 2002M Rone The inflammatory stage of Rosacea iscommonly treated with topical or oral antibiotics. However, if additional erythema and telangiectasias are present, antibiotics are not successful. IPL (intense pulsed light) is mostly involved when only initial or residual telangiectasias are present. Application of IPL simultaneously with topical or oral medicine could be an effective form of treatment in the inflammatory stage of rosacea. This study was performed in order to detect the effect of IPL application with simultaneous topical antibiotics in inflammatory rosacea and to assess the efficacy of IPL therapy in routine treatment of rosacea. Twenty patients aged between 34 and 70 with papulopustular rosacea (14 female and 7 male) were included in the study. Ten patients (group I) were treated for 21 weeks with topical metronidazole. The other ten patients (group II) received an additional 3 sessions with IPL 515,755 nm Photoderm VL technology over 4 weeks. Treatment affectivity was recorded by digital visualisation and patient satisfaction scale before each IPL session. In all patients, significant reductions in papulopustular elements were observed. Eight out of 10 patients (group I) still showed permanent erythema and telangiectasias despite topical treatment. In 3/10 patients a few telangiectasias remained following the treatment in contrast to 5/10 satisfied group I patients. The most effective treatment was the application of 570 nm and 590 nm wavelength at a fluence of 25,55 J/cm2. Application of IPL in inflammatory rosacea is equally as safe and effective in residual or initial lesions. Moreover, in combination with antibiotics, it promotes reduction of all symptoms, is less time-consuming and is more successful for patients. The pathogenetic influence of IPL in rosacea seems not only to be limited to selective photothermolysis of dilated blood vessels, but may also have immunomodulatory effects on inflammatory processes and possibly on collagen remodelling. The combination of IPL and antibiotics from theoutset of rosacea therapy is considered to be highly effective. [source] Current Experimental Perspectives on the Clinical Progression of Alcoholic Liver DiseaseALCOHOLISM, Issue 10 2009Katja Breitkopf Chronic alcohol abuse is an important cause of morbidity and mortality throughout the world. Liver damage due to chronic alcohol intoxication initially leads to accumulation of lipids within the liver and with ongoing exposure this condition of steatosis may first progress to an inflammatory stage which leads the way for fibrogenesis and finally cirrhosis of the liver. While the earlier stages of the disease are considered reversible, cirrhotic destruction of the liver architecture beyond certain limits causes irreversible damage of the organ and often represents the basis for cancer development. This review will summarize current knowledge about the molecular mechanisms underlying the different stages of alcoholic liver disease (ALD). Recent observations have led to the identification of new molecular mechanisms and mediators of ALD. For example, plasminogen activator inhibitor 1 was shown to play a central role for steatosis, the anti-inflammatory adipokine, adiponectin profoundly regulates liver macrophage function and excessive hepatic deposition of iron is caused by chronic ethanol intoxication and increases the risk of hepatocellular carcinoma development. [source] The cannabinoid receptor CB2 exerts antifibrotic effects in experimental dermal fibrosisARTHRITIS & RHEUMATISM, Issue 4 2009Alfiya Akhmetshina Objective The cannabinoid receptor CB2 is predominantly expressed in non-neuronal tissue and exerts potent immunomodulatory effects. This study was undertaken to evaluate the role of CB2 in the pathogenesis of dermal fibrosis. Methods Mice deficient in CB2 (CB2,/, mice) and their wild-type littermates (CB2+/+ mice) were injected with bleomycin to induce experimental fibrosis. Mice were treated with selective agonists and antagonists of CB2. Lesional skin was evaluated for dermal thickness and numbers of infiltrating leukocytes. Bone marrow transplantation experiments were performed. Results CB2,/, mice were more sensitive to bleomycin-induced dermal fibrosis than were CB2+/+ mice, and showed increased dermal thickness. Leukocyte counts were significantly higher in the lesional skin of CB2+/+ mice. Increased dermal fibrosis was also observed upon treatment with the CB2 antagonist AM-630. In contrast, the selective CB2 agonist JWH-133 reduced leukocyte infiltration and dermal thickening. The phenotype of CB2,/, mice was mimicked by transplantation of CB2,/, bone marrow into CB2+/+ mice, whereas CB2,/, mice transplanted with bone marrow from CB2+/+ mice did not display an increased sensitivity to bleomycin-induced fibrosis, indicating that leukocyte expression of CB2 critically influences experimental fibrosis. Conclusion Our findings indicate that CB2 limits leukocyte infiltration and tissue fibrosis in experimental dermal fibrosis. Since selective CB2 agonists are available and well tolerated, CB2 might be an interesting molecular target for the treatment of early inflammatory stages of systemic sclerosis. [source] Treatment with imatinib prevents fibrosis in different preclinical models of systemic sclerosis and induces regression of established fibrosisARTHRITIS & RHEUMATISM, Issue 1 2009Alfiya Akhmetshina Objective Imatinib is a small-molecule tyrosine kinase inhibitor capable of selective, dual inhibition of the transforming growth factor , and platelet-derived growth factor (PDGF) pathways. Imatinib has previously been shown to prevent the development of inflammation-driven experimental fibrosis when treatment was initiated before administration of the profibrotic stimulus. The aim of this study was to confirm the efficacy of imatinib in a murine model of systemic sclerosis (SSc) that is less driven by inflammation and to investigate whether imatinib is also effective for the treatment of established fibrosis. Methods The tight skin 1 (TSK-1) mouse model of SSc was used to evaluate the antifibrotic effects of imatinib in a genetic model of the later stages of SSc. In addition, the efficacy of imatinib for the treatment of preestablished fibrosis was analyzed in a modified model of bleomycin-induced dermal fibrosis in which the application of bleomycin was prolonged and the onset of treatment was late. Results Treatment with imatinib reduced dermal and hypodermal thickening in TSK-1 mice and prevented the differentiation of resting fibroblasts into myofibroblasts. In the model of preestablished dermal fibrosis, imatinib not only stopped further progression of fibrosis but also induced regression of preexisting dermal fibrosis, with a reduction in dermal thickness below pretreatment levels. Conclusion These results indicate that combined inhibition of the tyrosine kinase c-Abl and PDGF receptor might be effective in the later, less inflammatory stages of SSc and for the treatment of established fibrosis. Thus, imatinib might be an interesting candidate for clinical trials in patients with longstanding disease and preexisting tissue fibrosis. [source] | ||||||||||