Increased sample asymmetry and memory of cardiac time-series following endotoxin administration in cirrhotic rats.

Sepsis, and other causes of acute systemic inflammation, can reduce heart rate variability (HRV) and increase cardiac cycle regularity in mammals. Thus, HRV monitoring has been used for early detection of sepsis in adults and neonates. Liver cirrhosis is associated with reduced basal HRV and the development of tolerance to the cardiac chronotropic effects of bacterial endotoxin. This may pose limitations on the use of heart rate monitoring in early detection of sepsis in this patient population. In a study to develop a physiomarker for the detection of sepsis in cirrhosis, we observed that endotoxin administration in adult cirrhotic rats leads to the development of transient heart rate decelerations, a phenomenon which has been reported in neonates with sepsis, and quantified using sample asymmetry analysis. In the present study, cirrhosis was induced by surgical ligation of the bile duct in rats. Cirrhotic rats were given intraperitoneal injections of either saline or endotoxin (1 mg kg-1). Changes in sample asymmetry and memory length of cardiac time-series were studied in conscious rats using implanted telemetric probes. Cirrhotic (but not control) rats exhibited increased sample asymmetry following endotoxin injection, which was consistent with the development of transient heart rate deceleration. Endotoxin administration in cirrhotic rats was associated with prolongation of memory length for observing decelerating perturbations in the cardiac rhythm. These findings may have application in the development of an HRV monitoring system for early detection of sepsis in cirrhosis.

Preparation and characterization of silk fibroin/oligochitosan nanoparticles for siRNA delivery.

siRNA therapy offers hope treating diseases caused by genetic defects as well as viral infections and cancers, although it has been limited by the low stability of siRNA and its rapid degradation in the presence of nucleases as well as its low cellular uptake. In this study, oligochitosan (OC) combined with silk fibroin (SF) was formulated and proposed as a novel carrier for siRNA. The obtained SF/OC/siRNA nanoparticles (NPs) were characterized according to their physicochemical properties, such as their size, zeta potential, loading efficiency, stability, cytotoxicity, cellular uptake and transfection efficiency, and their properties were compared with those of OC polyplexes. The mean diameter of SF/OC/siRNA NPs was not significantly different compared to polyplexes, and the particle size ranged between 250 and 450 nm. Increased amounts of SF in NPs enhanced their loading efficiency, and NPs showed excellent stability in the presence of FBS and heparin compared with OC polyplexes. Additionally, MTT assays demonstrated that SF/OC/siRNA NPs had lower cytotoxicity. NPs showed better gene silencing with or without FBS, which could be attributed to increased loading efficiency, serum stability and cellular uptake. These properties suggest that SF/OC/siRNA NPs have a strong potential as gene carriers.