Systemic Sclerosis Sera Impair Angiogenic Performance of Dermal Microvascular Endothelial Cells: Therapeutic Implications of Cyclophosphamide

In systemic sclerosis (SSc), dermal capillaries are progressively lost with consequent chronic tissue hypoxia insufficiently compensated by angiogenesis. Clinical studies reported that intravenous cyclophosphamide (CYC) may improve SSc-related peripheral microvascular damage. Recently, we showed that CYC treatment may normalize SSc sera-induced abnormalities in endothelial cell-matrix interactions. Our objective was to evaluate in vitro the effects of sera from treatment-naïve or CYC-treated SSc patients on dermal blood microvascular endothelial cell (dMVEC) angiogenesis, migration, proliferation and apoptosis. dMVECs were challenged with sera from 21 SSc patients, treatment-naïve (n = 8) or under CYC treatment (n = 13), and 8 healthy controls. Capillary morphogenesis on Geltrex matrix was significantly reduced upon challenge with sera from naïve SSc patients compared with healthy controls. When dMVECs were challenged with sera from CYC-treated SSc patients, their angiogenic capacity was comparable to that of cells treated with healthy sera. Wound healing capacity and chemotaxis in Boyden chamber were both significantly decreased in the presence either of naïve or CYC-treated SSc sera compared with healthy sera. WST-1 assay revealed that cell proliferation was significantly decreased in dMVECs challenged with sera from naïve SSc patients compared with healthy sera. Conversely, dMVEC proliferation was not impaired in the presence of sera from CYC-treated SSc patients. Accordingly, the percentage of TUNEL-positive apoptotic dMVECs was significantly higher in the presence of sera from naïve SSc patients than healthy controls, while CYC-treated SSc sera did not induce dMVEC apoptosis. Levels of the angiostatic mediators endostatin, pentraxin 3, angiostatin and matrix metalloproteinase-12 were all significantly elevated in sera from naïve SSc patients compared with sera from both healthy controls and CYC-treated SSc patients. In SSc, CYC treatment might boost angiogenesis and consequently improve peripheral microangiopathy through the normalization of the endothelial cell-matrix interactions, reduction of endothelial cell apoptosis and rebalance of dysregulated angiostatic factors

Endothelial and Metabolic Function Interactions in Overweight/Obese Children.

AIM: Although the underlined mechanisms are still unknown, metabolic/coagulation alterations related to childhood obesity can induce vascular impairments. The aim of this study was to investigate the relationship between metabolic/coagulation parameters and endothelial function/vascular morphology in overweight/obese children. METHODS: Thirty-five obese/overweight children (22 pre-pubertal, mean age: 9.52±3.35 years) were enrolled. Body mass index (BMI), homeostasis model assessment index (HOMAIR), metabolic and coagulation parameters, [adiponectin, fibrinogen, high molecular weight adiponectin (HMW), endothelin-1, and vonWillebrand factor antigen] ultrasound early markers of atherosclerosis [flow-mediated dilatation (FMD), common carotid intima-media thickness (C-IMT), and anteroposterior diameter of infra-renal abdominal aorta (APAO)] were assessed. RESULTS: APAO was related to anthropometric (age: r=0.520, p=0.001; height: r=0.679, p＜0.001; weight: r=0.548, p=0.001; BMI: r=0.607, p＜0.001; SBP: r=0.377, p=0.026) and metabolic (HOMAIR: r=0.357, p=0.035; HMW: r=－0.355, p=0.036) parameters. Age, height, and systolic blood pressure were positively related to increased C-IMT (r=0.352, p=0.038; r=0.356, p=0.036; r=0.346, p=0.042, respectively). FMD was not related to any clinical and biochemical characteristics of the pediatric population. Age, HOMAIR, fasting glucose levels, and HMW were independent predictors for APAO increase. Each unit decrease in HMW concentrations (1 μg/ml) induced a 0.065 mm increase in APAO. CONCLUSION: High molecular weight adiponectin is related to cardiovascular risk in overweight/obese children

An experimental study on earth plasters for earthen building protection: the effect of different admixtures and surface treatments

In rainy climates, the external surfaces of earthen buildings suffer water erosion. In this paper, the properties of earth plasters have been investigated considering the specific relationship with the underlying substrate. Ten typologies of earth plasters containing different admixtures and surface treatments, a cob wall and a rammed earth wall were produced in laboratory. The aim is to evaluate the effectiveness of the coatings in protecting the earthen walls against weathering. An in situ procedure consisting of a shrinkage test followed by an adhesion strength test was performed in order to identify the earth/sand ratio optimal for the plaster manufacturing. Then, a series of tests was carried out both on the plasters and the two walls: compression, water vapor permeability, surface color, wettability, water absorption and erosion. The results demonstrate that all the plasters are physically and mechanically compatible with the earthen substrates and that the most important differences are in the specific relationship with water. The earth plaster treated with the silane–siloxane product was found to be the best one: it is fully compatible, water-repellent and highly resistant to water erosion. Hence, there is a potential for the use of earth plasters for the protection of earthen buildings against weathering

Soil contamination by microplastics in relation to local agricultural development as revealed by FTIR, ICP-MS and pyrolysis-GC/MS

Plastic film mulching and use of wastewaters for irrigation have been common agricultural practices for over half a century in Tunisia, especially in arid regions, resulting in the undesired creation of a pathway for microplastics (MPs) to enter farmland soil. In order to assess the extent and characteristics of soil contamination by MPs in the Moknine province, an area of intensive agricultural practices, 16 farmland soil samples were collected and characterized. The total concentration of targeted MPs was 50-880 items/kg; among them, the most common MPs type being polypropylene (PP), mainly occurring as white/transparent fibers with small size (cross section <0.3 mm). SEM images of MPs surfaces revealed multiple features related to environmental exposure and degradation. ATR-FTIR spectroscopy and pyrolysis-GC/MS analyses enabled the accurate identification of MPs separated from the embedding soil micro and macro-aggregates. Finally, contamination of the polymeric microparticles with a broad range of metals was found by ICP-MS analysis, suggesting that MPs can be5 vectors for transporting heavy metals in the soil and indicators of soil contamination as a result of mismanagement of industrial wastewaters

Valutazione degli effetti della stimolazione acustica bimodale (impianto cocleare e protesi controlaterale) sulla qualità della voce

Valutazione degli effetti della stimolazione acustica bimodale (impianto cocleare e protesi controlaterale) sulla qualità della voc

Two novel compound heterozygous SAG mutations in an Italian patient with Oguchi disease: A genetic and multimodal retinal imaging study

Oguchi disease is a rare autosomal recessive retinal dystrophy, characterized by congenital stationary blindness and caused by pathogenic variants in SAG and GRK1 genes. The present study aimed to report an Italian patient affected by Oguchi disease, evaluated by means of a multimodal retinal imaging study and harboring two novel heterozygous pathogenic variants in the SAG gene

Systemic sclerosis sera affect fibrillin-1 deposition and focal adhesion molecule expression by dermal blood microvascular endothelial cells: Therapeutic implications of cyclophosphamide

Systemic sclerosis (SSc, scleroderma) is characterized by fibrosis of the skin and internal organs, autoantibodies and diffuse microangiopathy. In SSc, fibrillin-1 microfibrils are disorganized and unstable. Mutations in FBN1 gene and anti-fibrillin- 1 autoantibodies have also been reported in SSc patients. Fibrillin-1 microfibrils sequester in the extracellular matrix the latent form of the potent pro-fibrotic cytokine transforming growth factor-β (TGF-β). We herein report the effects of SSc sera on the deposition of fibrillin-1 and microfibril-associated glycoprotein-1 (MAGP-1) and the expression of focal adhesion molecules by dermal blood (B-MVECs) and lymphatic (Ly-MVECs) microvascular endothelial cells. Cells were challenged with sera from SSc patients, naïve or under cyclophosphamide (CYC) treatment, and healthy controls. Fibrillin-1/MAGP-1 synthesis and deposition and the expression of αvβ3 integrin/ phosphorylated-FAK and vinculin/actin were evaluated by immunofluorescence and quantified by morphometric analysis. Fibrillin-1 and MAGP-1 co-localized in all experimental conditions, forming a honeycomb pattern in B-MVECs and a dense mesh of short segments in Ly-MVECs. In B-MVECs, fibrillin-1/MAGP-1 production and αvβ3 integrin expression significantly decreased upon challenge with sera from naïve SSc patients compared with healthy controls. Vinculin was overexpressed in the cells exposed to the serum of naïve patients with the diffuse form of SSc. B-MVECs challenged with sera from CYC-treated SSc patients showed fibrillin-1, αvβ3 integrin and vinculin levels comparable to those of controls. Ly-MVECs challenged with SSc sera did not differ from controls in the expression of any of the molecules assayed. Due to the critical role of fibrillin-1 in sequestering TGF-β in the extracellular matrix, its decreased deposition by B-MVECs challenged with SSc sera might contribute to dermal fibrosis. CYC treatment might limit fibrosis through the maintenance of physiologic fibrillin-1 synthesis and deposition by B-MVECs. CYC-induced normalization of αvβ3 integrin expression may restore effective interaction of endothelial cells with fibrillin. Since vinculin is necessary for angiogenesis, its normalization upon CYC treatment may contribute to restore the impaired angiogenesis found in SSc