Capillaroscopy in 2016 : new perspectives in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disorder of unknown etiology characterized by early impairment of the microvascular system. Nailfold microangiopathy and decreased peripheral blood perfusion are typical clinical aspects of SSc. The best method to evaluate vascular injury is nailfold videocapillaroscopy, which detects peripheral capillary morphology, and classifies and scores the abnormalities into different patterns of microangiopathy. Microangiopathy appears to be the best evaluable predictor of the disease development and has been observed to precede the other symptoms by many years. Peripheral blood perfusion is also impaired in SSc, and there are different methods to assess it: laser Doppler and laser speckle techniques, thermography and other emerging techniques

Assessment of treatment effects on digital ulcer and blood perfusion by laser speckle contrast analysis in a patient affected by systemic sclerosis

Laser speckle contrast analysis (LASCA) is a good tool to evaluate the variation in peripheral blood perfu-sion during long-term follow-up andis able to safely monitor digital ulcer evolution inscleroderma patients. It evaluates blood perfusion in different areas within the skin lesions and surrounding them during standard treatment

[17beta-Estradiol and testosterone influence the mRNA expression and the time course of inflammatory cytokines in activated human monocytic cell line (THP-1)].

Objective: The aim of this study was to evaluate the effects of 17b-estradiol (E2) and testosterone (T) on the mRNA expression of IL-1b, IL-6, TNF-a and TGF-b in cultured human monocytic cells (THP-1) after INF-g activation. Methods: THP-1 were cultured with E2 and T (10 nM) for 24 hs and then activated with INF-g (500 U/ml), during different periods of time (1, 3, 6, and 12 hs). After total RNA extraction, all samples were analyzed by multiple RT-PCR to detect mRNA expression of the selected cytokines. Results: Cells cultured without hormonal treatment expressed IL-1b mRNA after 1 h; on the contrary TNF-a, TGF-b and IL-6 mRNA were expressed only after 3 hs. At 6 and 12 hs only IL-6 mRNA was still expressed. Interestingly, cells cultured with testosterone never expressed IL-1b nor TNF-a mRNA and showed an IL-6 mRNA expression similar to the untreated controls at 3, 6 and 12 hours. On the contrary, cells treated with E2 showed the expression of all cytokines at 3 and 12 hs, and in general showed an higher expression of all the analyzed cytokines mRNA when compared to the other conditions. Conclusions: This study suggests that sex hormones may modulate the cytokine mRNA expression in the inflammatory cells. In fact, T inhibits TNF-a production at all the tested times, whereas E2 seems to accelerate and to enhance the inflammatory response. Therefore, the altered sex hormone ratio, as observed in the synovial fluid of RA patients (high E2/low T), might contribute to the occurrence and last of synovitis

Subclinical dermal involvement is detectable by high frequency ultrasound even in patients with limited cutaneous systemic sclerosis.

Background: The aim of the study was to detect by skin high-frequency ultrasound (US) possible subclinical skin involvement in patients affected by limited cutaneous systemic sclerosis (lcSSc), in those skin areas apparently not affected by the disease on the basis of a normal modified Rodnan skin score (mRSS). Differences in dermal thickness (DT) in comparison with healthy subjects were investigated. Methods: Fifty patients with lcSSc (age 62 \ub1 13 years (mean \ub1 SD), disease duration 5 \ub1 5 years) and 50 sex-matched and age-matched healthy subjects (age 62 \ub1 11 years) were enrolled. DT was evaluated by both mRSS and US at the usual 17 skin areas (zygoma, fingers, dorsum of the hands, forearms, upper arms, chest, abdomen, thighs, lower legs and feet). Non-parametric tests were used for the statistical analysis. Results: Subclinical dermal involvement was detected by US even in the skin areas in patients with lcSSc, who had a normal local mRSS. In addition, statistically significantly higher mean DT was found in almost all skin areas, when compared to healthy subjects (p < 0.0001 for all areas). In particular, DT was significantly greater in patients with lcSSc than in healthy subjects in four out of six skin areas with a normal mRSS (score = 0) (upper arm, chest and abdomen), despite the clinical classification of lcSSc. Conclusions: This study strongly suggests that subclinical dermal involvement may be detectable by US even in skin areas with a normal mRSS in patients classified as having lcSSc. This should be taken into account during SSc subset classification in clinical studies/trial

Microvascular damage evaluation in systemic sclerosis : the role of nailfold videocapillaroscopy and laser techniques

Microvascular damage and a decrease in peripheral blood perfusion are typical features of systemic sclerosis (SSc) with serious clinical implications, not only for a very early diagnosis, but also for disease progression. Nailfold videocapillaroscopy is a validated and safe imaging technique able to detect peripheral capillary morphology, as well as to classify and to score any nailfold abnormalities into different microangiopathy patterns. Capillaroscopic analysis is now included in the ACR/EULAR classification criteria for SSc. The decrease in peripheral blood perfusion is usually associated with microvascular damage in SSc, which may be studied by different methods. Several of these make use of safe laser technologies. This paper focuses on these new clinical aspects to assess SSc microvascular impairment

Seismo-stratigraphic and morpho-bathymetric analysis revealing recent fluid-rising phenomena on the Adventure Plateau (northwestern Sicily Channel)

The northwestern region of the Sicily Channel hosts a great number of morphological highs, the widest of which is the Adventure Plateau that is part of the Sicilian Maghrebian Fold and Thrust Belt system, formed since the Neogene. The Adventure Plateau was shaped in the Early Pliocene by an extensional phase that produced high-angle normal faults mostly WNW-ESE to N-S oriented. Through these faults, magmatic fluids ascended and produced widespread volcanic manifestations often associated to fluid flow processes. The interpretation of multibeam echosounder, seismic reflection (sparker, airgun) and well-log data allow us to identify several features related to the presence of fluids in the study area. The morpho-structural analysis showed a NW–SE oriented fault system and a string of pockmarks that follow the same trend. A detailed well-log analysis confirmed the presence of oil traces, at a depth of ~ 250 m, and gas (i.e., CO2) at a depth of ~ 450 m. The seismo-stratigraphic analysis highlighted seismic signals located below the pockmarks, (e.g. seismic chimneys, bright spots) which suggest the presence of fluids that would rise to a few meters’ depth. Based on the observations, two sources and two corresponding rising mechanisms have been identified. Morphometric analysis of pockmarks has been performed to delineate their possible interaction with the bottom currents. A fluids pathway model has been reconstructed, revealing the source of fluids emissions at depth in the Adventure Plateau, and providing new insights into the identification of fluid leakage pathways

Morphology of the submerged Ferdinandea Island, the ‘Neverland’ of the Sicily Channel (central Mediterranean Sea)

We present the bathy-morphological map at a scale of 1: 50,000 of the area around the submerged Ferdinandea Island, the ‘Neverland’ of the Sicily Channel (central Mediterranean Sea). We investigate an area of 100 km2, between 10 and 350 m, which is part of a triangular morphological high, 360 km2 wide, representing the SE-wards prolongation of the Adventure Bank. The study is based on the morphometric analysis based on high resolution multibeam, and sub-bottom CHIRP profiles collected in 2015. The area around the remains of Ferdinandea Island is morphologically shaped by the interplay between volcanic, tectonic, fluid seepage, and oceanographic processes. Since the study area is considered a hot spot of biodiversity affected by maritime traffic (especially in Ferdinandea Channel) and hosting communication pipelines, this map provides insights both for habitat mapping purposes and preliminary marine geohazard assessment due to the occurrence of historically active submarine volcanoes, pockmarks, and mass transport deposits

Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages.

Background Alternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing profibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its profibrotic effects through the interaction with its receptors (ETA and ETB). The study investigated the possible role of ET-1 in inducing the transition from cultured human macrophages into M2 cells. Methods Cultured human monocytes (THP-1 cell line) were activated into macrophages (M0 macrophages) with phorbol myristate acetate and subsequently maintained in growth medium (M0-controls) or treated with either ET-1 (100nM) or interleukin-4 (IL-4, 10ng/mL, M2 inducer) for 72 hours. Similarly, primary cultures of human peripheral blood monocyte (PBM)-derived macrophages obtained from healthy subjects, were maintained in growth medium (untreated cells) or treated with ET-1 or IL-4 for 6 days. Both M0 and PBM-derived macrophages were pre-treated with ET receptor antagonist (ETA/BRA, bosentan 10-5M) for 1 hour before ET-1 stimulation. Protein and gene expression of CD204, CD206, CD163, TGFbeta1 were analysed by immunocytochemistry, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Gene expression of interleukin(IL)-10 and macrophage derived chemokine (CCL-22) was evaluated by qRT-PCR. MMP-9 production was investigated by gel zymography. Results ET-1 significantly increased the expression of M2 phenotype markers CD204, CD206, CD163, IL-10 and CCL-22, and the production of MMP-9 in both cultures of M0 and PBMderived macrophages compared to M0-controls and untreated cells. In cultured PBMderived macrophages, ET-1 increased TGFbeta1 protein and gene expression compared to untreated cells. The ET-1-mediated effects were contrasted by ETA/BRA treatment in both cultured cell types. Conclusion ET-1 seems to induce the M2 phenotype in cultured human macrophages, a process apparently contrasted by the action of the ETA/BRA, suggesting possible clinical implications in those fibrotic diseases characterized by increased ET-1 concentrations, such as systemic sclerosis but also type 2 diabetes