Non-alcoholic fatty liver disease (NAFLD) is a major cause of morbidity and mortality in developed countries, resulting in steatohepatitis (NASH), fibrosis and eventually cirrhosis. Modulating inflammatory mediators such as chemokines may represent a novel therapeutic strategy for NAFLD. We recently demonstrated that the chemokine receptor CXCR6 promotes hepatic NKT cell accumulation, thereby controlling inflammation in experimental NAFLD. In this study, we first investigated human biopsies (n = 20), confirming that accumulation of inflammatory cells such as macrophages is a hallmark of progressive NAFLD. Moreover, CXCR6 gene expression correlated with the inflammatory activity (ALT levels) in human NAFLD. We then tested the hypothesis that pharmacological inhibition of CXCL16 might hold therapeutic potential in NAFLD, using mouse models of acute carbon tetrachloride (CCl4)- and chronic methionine-choline-deficient (MCD) diet-induced hepatic injury. Neutralizing CXCL16 by i.p. injection of anti-CXCL16 antibody inhibited the early intrahepatic NKT cell accumulation upon acute toxic injury in vivo. Weekly therapeutic anti-CXCL16 administrations during the last 3 weeks of 6 weeks MCD diet significantly decreased the infiltration of inflammatory macrophages into the liver and intrahepatic levels of inflammatory cytokines like TNF or MCP-1. Importantly, anti-CXCL16 treatment significantly reduced fatty liver degeneration upon MCD diet, as assessed by hepatic triglyceride levels, histological steatosis scoring and quantification of lipid droplets. Moreover, injured hepatocytes up-regulated CXCL16 expression, indicating that scavenging functions of CXCL16 might be additionally involved in the pathogenesis of NAFLD. Targeting CXCL16 might therefore represent a promising novel therapeutic approach for liver inflammation and steatohepatitis.
In the field of endoscopic solo surgery, the assistance received by the surgeon from ergonomical positioning devices is extremely important. They aid in both the retracting of instruments and the positioning of the endoscope. However, passive systems derived from open surgery have not proved satisfactory. Therefore, we set out to develop a remote-controlled arm capable of moving a rigid endoscope with about four degrees of freedom, while maintaining an invariant point of constraint motion coincident with the trocar puncture site through the abdominal wall. The system is driven by means of speaker-independent voice control or a finger-ring joystick clipped onto the instrument shaft close to the handle. When the joystick is used, the motion of the endoscope is controlled by the fingertip of the operating surgeon, which is inserted into the small ring of the controller in such a way as to make the motion of the fingertip correspond directly to the motion of the tip of the endoscope. A study was performed to compare the two different interfaces available for the system. With both interfaces, the guiding system allows for transparent and intuitive operation. Its set-up is easy; it is safe and reliable to use during the intervention; and it is faster than human assistance. With its improved ergonomy, this new generation of remote-controlled endoscope positioning system represents a further step toward the diffusion of solo surgery techniques in minimally invasive therapy. In our opinion, this prototype creates a valid compromise between human and robotic control of rigid endoscopes.
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