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- Gozdzik, W, et al.
(author)
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Beneficial effects of inhaled nitric oxide with intravenous steroid in an ischemia-reperfusion model involving aortic clamping
- 2018
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In: International journal of immunopathology and pharmacology. - : SAGE Publications. - 2058-7384. ; 3132, s. 394632017751486-
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Journal article (peer-reviewed)abstract
- This study evaluated the effects of inhaled nitric oxide (iNO) therapy combined with intravenous (IV) corticosteroids on hemodynamics, selected cytokines, and kidney messenger RNA toll-like receptor 4 (mRNA TLR4) expression in ischemia–reperfusion injury animal model. The primary endpoint was the evaluation of circulatory, respiratory, and renal function over time. We also investigated the profile of selected cytokines and high-mobility group box 1 (HMGB1) protein, as well as renal mRNA TLR4 activation determined by quantitative real-time polymerase chain reaction analysis. Pigs (n = 19) under sevoflurane AnaConDa anesthesia/sedation were randomized and subjected to abdominal laparotomy and alternatively suprarenal aortic cross-clamping (SRACC) for 90 min or sham surgery: Group 1 (n = 8) iNO (80 ppm) + IV corticosteroids (25 mg ×3) started 30 min before SRACC and continued 2 h after SRACC release, followed with decreased iNO (30 ppm) until the end of observation, Group 2 (n = 8) 90 min SRACC, Group 3 (n = 3)—sham surgery. Renal biopsies were sampled 1 hr before SRACC and at 3 and 20 h after SRACC release. Aortic clamping increased TLR4 mRNA expression in ischemic kidneys, but significant changes were recorded only in the control group ( P = 0.016). Treatment with iNO and hydrocortisone reduced TLR4 mRNA expression to pre-ischemic conditions, and the difference observed in mRNA expression was significant between control and treatment group after 3 h ( P = 0.042). Moreover, animals subjected to treatment with iNO and hydrocortisone displayed an attenuated systemic inflammatory response and lowered pulmonary vascular resistance plus increased oxygen delivery. The results indicated that iNO therapy combined with IV corticosteroids improved central and systemic hemodynamics, oxygen delivery, and diminished the systemic inflammatory response and renal mRNA TLR4 expression.
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| 2. |
- Brauner, S., et al.
(author)
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Reduced expression of TRIM21/Ro52 predicts poor prognosis in diffuse large B-cell lymphoma patients with and without rheumatic disease
- 2015
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:3, s. 323-332
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Journal article (peer-reviewed)abstract
- ObjectiveTRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21 in patients with diffuse large B-cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker. Materials and methodsTRIM21 expression levels were assessed by immunohistochemistry in lymphoma biopsies from three cohorts of patients with DLBCL: 42 patients with rheumatic disease treated with a cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP)-like regimen, 76 CHOP-treated and 196 rituximab-CHOP-treated nonrheumatic patients. Expression was correlated with clinical and biomedical parameters. TRIM21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR and correlated with H-3-thymidine incorporation and propidium iodine staining. ResultsTRIM21 expression levels differed in the lymphomas compared to normal lymphoid tissue, with reduced expression correlating with shorter overall survival in all three cohorts. In the two larger cohorts, progression-free survival was assessed and was also found to correlate with TRIM21 expression. The association was independent of commonly used clinical prognostic scores, lymphoma subtype and several previously reported prognostic biomarkers. In agreement with this clinical observation, we noted an inverse correlation between TRIM21 expression and proliferation of leucocytes invitro. ConclusionsWe show that loss of TRIM21 expression is associated with more aggressive lymphoma and increased proliferation, whereas maintenance of TRIM21 expression is associated with better prognosis in patients with DLBCL. Based on our findings, we suggest that TRIM21 should be considered as a novel biomarker for lymphoma characterization and for predicting patient survival.
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| 4. |
- Geels, C., et al.
(author)
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Improved modelling of atmospheric ammonia over Denmark using the coupled modelling system DAMOS
- 2012
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In: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 9:7, s. 2625-2647
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Journal article (peer-reviewed)abstract
- A local-scale Gaussian dispersion-deposition model (OML-DEP) has been coupled to a regional chemistry-transport model (DEHM with a resolution of approximately 6 km x 6 km over Denmark) in the Danish Ammonia Modelling System, DAMOS. Thereby, it has been possible to model the distribution of ammonia concentrations and depositions on a spatial resolution down to 400 m x 400 m for selected areas in Denmark. DAMOS has been validated against measured concentrations from the dense measuring network covering Denmark. Here measured data from 21 sites are included and the validation period covers 2-5 years within the period 2005-2009. A standard time series analysis (using statistic parameters like correlation and bias) shows that the coupled model system captures the measured time series better than the regional- scale model alone. However, our study also shows that about 50% of the modelled concentration level at a given location originates from non-local emission sources. The local-scale model covers a domain of 16 km x 16 km, and of the locally released ammonia (NH3) within this domain, our simulations at five sites show that 14-27% of the locally (within 16 km x 16 km) emitted NH3 also deposits locally. These results underline the importance of including both high-resolution local-scale modelling of NH3 as well as the regional-scale component described by the regional model. The DAMOS system can be used as a tool in environmental management in relation to assessments of total nitrogen load of sensitive nature areas in intense agricultural regions. However, high spatio-temporal resolution in input parameters like NH3 emissions and land-use data is required.
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