Abnormal regulation of fibronectin production by fibroblasts in psoriasis.

BACKGROUND: Data indicate that in psoriasis, abnormalities are already present in nonlesional skin. Transforming growth factor-ß and keratinocyte growth factor (KGF), together with fibronectin and α5ß1 integrin, were suggested to play a crucial role in the pathogenesis of psoriasis by influencing inflammation and keratinocyte hyperproliferation. OBJECTIVES: To investigate the expression of KGF, fibroblast growth factor receptor (FGFR)2, fibronectin (FN) and extra domain A (EDA)-positive FN in healthy and nonlesional psoriatic skin, and to study the effect of KGF on the regulation of FN and EDA(+) FN production by fibroblasts. METHODS: Healthy, nonlesional psoriatic skin and lesional psoriatic skin were immunostained for α5 integrin, KGF, FGFR2, EDA(+) FN and signal transducer and activator of transcription (STAT)1. KGF-treated cell cultures were analysed for FN and EDA(+) FN mRNA and protein by real-time reverse-transcriptase polymerase chain reaction and flow cytometry, respectively. The major downstream signalling of KGF was investigated by blocking experiments using inhibitors of mitogen-activated protein kinase (MAPK) kinase (MEK1), AKT1/2, STAT1 and STAT3. RESULTS: The expression of α5 integrin, EDA(+) FN, KGF and its receptor FGFR2 is elevated in psoriatic nonlesional skin compared with healthy skin. KGF mildly induced EDA(+) FN, but not FN expression in healthy fibroblasts through MAPK signalling. Fibroblasts express the FGFR2-IIIc splice variant. STAT1 negatively regulates both FN and EDA(+) FN expression in healthy fibroblasts, and this regulation is compromised in fibroblasts derived from nonlesional psoriatic dermis. We detected active STAT1 in healthy and lesional skin, similarly to a previous report. However, in the nonlesional skin STAT1 activation was absent in tissues far away from lesions. CONCLUSIONS: The production of FN and EDA(+) FN by fibroblasts and the signalling of STAT1 are abnormally regulated in psoriatic nonlesional skin.

The utility of the predictive scores in polytrauma with abdomino-pelvic injuries: a series of 38 patients.

UNLABELLED: Trauma is the principal cause of mortality among the population under 40 years. The aim of our study was to compare predictive trauma scores and demonstrate their utility in the evaluation of the quality of care in polytrauma. MATERIAL AND METHODS: A retrospective study was performed between 2000-2011 including polytrauma patients with abdominal lesions and pelvic fracture who under went emergency laparotomy. We calculated ISS, GCS, RTS,TRISS, ASCOT trauma scores and W score for evaluation of treatment quality. RESULTS: We obtained the necessary data to calculate the predictive scores in 38 cases. Comparing the scores of the survivals and non-survivals we noted the following regarding mortality predictive scores: GCS 13.74 vs. 6.13 (p 0.0001),ISS 28.52 vs. 35 (p=0.0169), RTS 6.96 vs. 3.07 (p 0.0001),TRISS 84.67% vs. 28.7% (p 0.0001), ASCOT 10.34% vs.64.32% (p 0.0001). The W score in TRISS and ASCOT methodology was -2.05 (p=0.7997) and -7.81 (p=0.336),respectively. There was no statistically significant difference between actual and predicted mortality, the former being 39.47%. CONCLUSION: We did not observe differences between the two methodologies TRISS and ASCOT in mortality prediction (p=0.5401). Both of them can be used to predict polytrauma patient evolution. The W score is useful in treatment quality assessment.