Diagnosis and management of iridocorneal endothelial syndrome

The iridocorneal endothelial (ICE) syndrome is a rare ocular disorder that includes a group of conditions characterized by structural and proliferative abnormalities of the corneal endothelium, the anterior chamber angle, and the iris. Common clinical features include corneal edema, secondary glaucoma, iris atrophy, and pupillary anomalies, ranging from distortion to polycoria. The main subtypes of this syndrome are the progressive iris atrophy, the Cogan-Reese syndrome, and the Chandler syndrome. ICE syndrome is usually diagnosed in women in the adult age. Clinical history and complete eye examination including tonometry and gonioscopy are necessary to reach a diagnosis. Imaging techniques, such as in vivo confocal microscopy and ultrasound biomicroscopy, are used to confirm the diagnosis by revealing the presence of "ICE-cells" on the corneal endothelium and the structural changes of the anterior chamber angle. An early diagnosis is helpful to better manage the most challenging complications such as secondary glaucoma and corneal edema. Treatment of ICE-related glaucoma often requires glaucoma filtering surgery with antifibrotic agents and the use of glaucoma drainage implants should be considered early in the management of these patients. Visual impairment and pain associated with corneal edema can be successfully managed with endothelial keratoplasty

Hepatocyte growth factor exerts multiple biological functions on bovine mammary epithelial cells.

The met proto-oncogene product Met is a member of the family of tyrosine kinase growth factor receptors, and hepatocyte growth factor/scatter factor (HGF/SF) has been identified as its only ligand. Bovine Met and HGF/SF have been recently cloned and their expression has been characterized in the mammary gland, but no data regarding the biological effects of this ligand/receptor couple in bovine mammary cells are yet available. We examined the role of HGF/SF and its receptor in a bovine mammary epithelial cell line (BME-UV). Expression of Met at the mRNA level in BME-UV mammary epithelial cells evaluated by real-time PCR was similar to the expression in MDCK cells, a widely used model for Met biology. Met expression in BME-UV at the protein level was confirmed by western blot. The analysis of some signal transductional pathways downstream from the Met receptor revealed that HGF/SF addition to BME-UV cells induced activation of the extracellular signal-regulated kinase 1/2 proliferative pathway and the Akt antiapoptotic pathway. The BME-UV cells treated with HGF responded with increased proliferation, cell scatter, and motility. Met activation by HGF induced degradation of the extracellular matrix and migration through matrigel coated transwells. Moreover, BME-UV cells included in a 3-dimensional matrix of collagen and treated with HGF developed tubular structures, reminiscent of the mammary gland ducts. These data indicate that HGF and Met might be important regulators of mammary gland growth, morphogenesis, and development in the bovine

Suppressor of Cytokine Signaling-3 (SOCS-3) induces Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) expression in hepatic HepG2 cell line

The suppressor of cytokine signaling (SOCS) proteins are negative regulators of the JAK/STAT pathway activated by proinflammatory cytokines, including the tumor necrosis factor (TNF-\u3b1). SOCS3 is also implicated in hypertriglyceridemia associated to insulin resistance. Proprotein convertase subtilisin kexin type 9 (PCSK9) levels are frequently found to be positively correlated to insulin resistance and plasma very low density lipoprotein (VLDL) triglycerides concentrations. The present study aimed to investigate the possible role of TNF-\u3b1 and JAK/STAT pathway on de novo lipogenesis and PCSK9 expression in HepG2 cells. TNF-\u3b1 induced both SOCS3 and PCSK9 in a concentration-dependent manner. This effect was inhibited by transfection with siRNA anti-STAT3, suggesting the involvement of the JAK/STAT pathway. Retroviral overexpression of SOCS3 in HepG2 cells (HepG2SOCS3) strongly inhibited STAT3 phosphorylation and induced PCSK9 mRNA and protein, with no effect on its promoter activity and mRNA stability. Consistently, siRNA anti-SOCS3 reduced PCSK9 mRNA levels, whereas an opposite effect was observed with siRNA anti- STAT3. In addition, HepG2SOCS3 express higher mRNA levels of key enzymes involved in the de novo lipogenesis, such as fattyacid synthase, stearoyl-CoA desaturase (SCD)-1, and apoB. These responses were associated with a significant increase of SCD-1 protein, activation of sterol regulatory element-binding protein-1c (SREBP-1), accumulation of cellular triglycerides, and secretion of apoB. HepG2SOCS3 show lower phosphorylation levels of insulin receptor substrate 1 (IRS-1) Tyr896 and Akt Ser473 in response to insulin. Finally, insulin stimulation produced an additive effect with SOCS3 overexpression, further inducing PCSK9, SREBP-1, fatty acid synthase, and apoB mRNA. In conclusion, our data candidate PCSK9 as a gene involved in lipid metabolism regulated by proinflammatory cytokine TNF- in a SOCS3-dependent manner

High Density Lipoproteins Inhibit Oxidative Stress-Induced Prostate Cancer Cell Proliferation

Recent evidence suggests that oxidative stress can play a role in the pathogenesis and the progression of prostate cancer (PCa). Reactive oxygen species (ROS) generation is higher in PCa cells compared to normal prostate epithelial cells and this increase is proportional to the aggressiveness of the phenotype. Since high density lipoproteins (HDL) are known to exert antioxidant activities, their ability to reduce ROS levels and the consequent impact on cell proliferation was tested in normal and PCa cell lines. HDL significantly reduced basal and H2O2-induced oxidative stress in normal, androgen receptor (AR)-positive and AR-null PCa cell lines. AR, scavenger receptor BI and ATP binding cassette G1 transporter were not involved. In addition, HDL completely blunted H2O2-induced increase of cell proliferation, through their capacity to prevent the H2O2-induced shift of cell cycle distribution from G0/G1 towards G2/M phase. Synthetic HDL, made of the two main components of plasma-derived HDL (apoA-I and phosphatidylcholine) and which are under clinical development as anti-atherosclerotic agents, retained the ability of HDL to inhibit ROS production in PCa cells. Collectively, HDL antioxidant activity limits cell proliferation induced by ROS in AR-positive and AR-null PCa cell lines, thus supporting a possible role of HDL against PCa progression

Power Block Off-design Control Strategies for Indirect Solar ORC Cycles

AbstractThe performance of a 5MWel indirect ORC cycle coupled to linear solar collectors with different technologies is assessed, aiming at evaluating the effect of different control strategies on annual electricity output. Two different solutions are considered for solar collectors: a state-of-the-art parabolic trough collector with Therminol VP1 as heat transfer fluid (HTF), reaching 390°C as maximum temperature within the solar field, and a cheaper Linear Fresnel Reflector (LFR) with Therminol 55, limited to an operating temperature of 310°C. A simplified procedure is firstly proposed in order to identify the organic fluid that guarantees the highest performance under design conditions. Toluene is the selected working fluid in a saturated regenerative Rankine cycle configuration. After fluid selection, a more detailed analysis involving turbine sizing and piping estimate is carried on in order to set optimal on-design parameters such as the evaporating pressure of the working fluid. Finally, yearly electricity production is calculated taking into account off-design performance of all plant components as a function of the effective solar radiation. Two different off-design control strategies are considered for the turbine, namely sliding pressure and constant pressure at the turbine inlet. The levelized cost of electricity (LCOE) is computed for both cases. For high temperature collectors the LCOE results respectively about 180 €/MWh with partial admission and 175 €/MWh with sliding pressure off-design control strategy. LFR technology leads to similar LCOE when its specific cost is about half than the parabolic trough collector

Biological role of the HGF/MET ligand/receptor couple in bovine mammary epithelial cells

The mammary gland is an organ in which numerous remodelling events follow each other during the development and the reproductive cycle of the animal. After puberty and during pregnancy morphogenesis and proliferation transform the primordial epithelium to an extended network composed of hollow tubules and secreting acini. The development of the mammary gland requires several locally-derived growth factors such Hepatocyte Growth Factor (HGF). Hepatocyte Growth Factor (HGF) is a cytokine originally described as a mitogenic factor for hepatocytes during liver regeneration. HGF is secreted by mesenchymal/stromal cells and acts as a paracrine factor on adjacent epithelial cells that express the c-met tyrosine kinase receptor (Sonnenberg et al., 1993). Binding of HGF to its receptor induces multiple biological responses including proliferation, motility, invasion of the extracellular matrix, resistance to apoptosis and activation of angiogenesis (Bussolino et al., 1992; Brinkmann et al., 1995; Bardelli et al., 1996; Medico et al., 1996). HGF and c-met are expressed and temporally regulated during mammary development and differentiation; some mammary epithelial cell lines grown in a three dimensional collagen matrix with HGF generate tubules (Soriano et al., 1995) with a morphology resembling mammary ducts. Recently, bovine HGF and c-met have been analyzed for their expression in the mammary gland, but no data regarding their biological roles are yet available. We have therefore investigated whether the bovine mammary epithelial cell line BME-UV1 was responsive to HGF and what the biological effects induced by this cytokine were