The role of macrophages in the development of biliary injury in a lipopolysaccharide-aggravated hepatic ischaemia-reperfusion model

Introduction: Endotoxins, in the form of lipopolysaccharides (LPS), are potent inducers of biliary injury. However the mechanism by which injury develops remains unclear. We hypothesized that hepatic macrophages are pivotal in the development of endotoxin-induced biliary injury and that no injury would occur in their absence. Material and methods: Clodronate liposomes were used to deplete macrophages from the liver. Forty-eight rats were equally divided across six study groups: sham operation (sham), liposome treatment and sham operation (liposomes + sham), 1. mg/kg LPS i.p. (LPS), liposome treatment and LPS administration (liposomes + LPS), hepatic ischaemia-reperfusion injury with LPS administration (IRI + LPS) and liposome treatment followed by IRI + LPS (liposomes + IRI + LPS). Following 6. h of reperfusion, blood, bile, and liver tissue was collected for further analysis. Small bile duct injury was assessed, serum liver tests were performed and bile composition was evaluated. The permeability of the blood-biliary barrier (BBB) was assessed using intravenously administered horseradish peroxidase (HRP). Results: The presence of hepatic macrophages was reduced by 90% in LPS and IRI + LPS groups pre-treated with clodronate liposomes (

A Cellular Potts Model simulating cell migration on and in matrix environments

Cell migration on and through extracellular matrix plays a critical role in a wide variety of physiological and pathological phenomena, and in scaffold-based tissue engineering. Migration is regulated by a number of extracellular matrix- or cell-derived biophysical parameters, such as matrix fiber orientation, gap size, and elasticity, or cell deformation, proteolysis, and adhesion. We here present an extended Cellular Potts Model (CPM) able to qualitatively and quantitatively describe cell migratory phenotype on both two-dimensional substrates and within three-dimensional environments, in a close comparison with experimental evidence. As distinct features of our approach, the cells are represented by compartmentalized discrete objects, differentiated in the nucleus and in the cytosolic region, while the extracellular matrix is composed of a fibrous mesh and of a homogeneous fluid. Our model provides a strong correlation of the directionality of migration with the topological ECM distribution and, further, a biphasic dependence of migration on the matrix density, and in part adhesion, in both two-dimensional and three-dimensional settings. Moreover, we demonstrate that the directional component of cell movement is strongly correlated with the topological distribution of the ECM fibrous network. In the three-dimensional networks, we also investigate the effects of the matrix mechanical microstructure, observing that, at a given distribution of fibers, cell motility has a subtle bimodal relation with the elasticity of the scaffold. Finally, cell locomotion requires deformation of the cell's nucleus and/or cell-derived proteolysis of steric fibrillar obstacles within rather rigid matrices characterized by small pores, not, however, for sufficiently large pores. In conclusion, we here propose a mathematical modeling approach that serves to characterize cell migration as a biological phenomen in health, disease and tissue engineering applications. The research that led to the present paper was partially supported by a grant of the group GNFM of INdA

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Systematic review of the influence of chemotherapy-associated liver injury on outcome after partial hepatectomy for colorectal liver metastases

Background: The impact of chemotherapy-associated liver injury (CALI) on postoperative outcome in patients undergoing partial hepatectomy for colorectal liver metastases (CRLM) remains controversial. The objective of this study was to clarify the effect of CALI (sinusoidal dilatation (SD), steatosis and steatohepatitis) on postoperative morbidity and mortality by investigating a large data set from multiple international centres. Methods: PubMed and Embase were searched for studies published between 1 January 2004 and 31 December 2013 with keywords 'chemotherapy', 'liver resection', 'outcome' and 'colorectal metastases' to identify potential collaborating centres. Univariable and multivariable analyses were performed using binary logistic regression models, with results presented as odds ratios (ORs) with 95 per cent confidence intervals. Results: A consolidated database comprising 788 patients who underwent hepatectomy for CRLM in eight centres was obtained. In multivariable analyses, severe SD was associated with increased major morbidity (Dindo-Clavien grade III-V; OR 1.73, 95 per cent c.i. 1.02 to 2.95; P = 0.043). Severe steatosis was associated with decreased liver surgery-specific complications (OR 0.52, 95 per cent c.i. 0.27 to 1.00; P = 0.049), whereas steatohepatitis was linked to an increase in these complications (OR 2.08, 1.18 to 3.66; P = 0.012). Subgroup analysis showed that lobular inflammation was the sole component associated with increased overall morbidity (OR 2.22, 1.48 to 3.34; P = 0.001) and liver surgery-specific complications (OR 3.35, 2.11 to 5.32; P <0.001). Finally, oxaliplatin treatment was linked to severe SD (OR 2.74, 1.67 to 4.49; P <0.001). Conclusion: An increase in postoperative major morbidity and liver surgery-specific complications was observed after partial hepatectomy in patients with severe SD and steatohepatitis. Postoperative liver failure occurred more often in patients with severe SD. Presented to the International Liver Congress 2016, Barcelona, Spain, April 2016, and the 12th World Congress of the International Hepato-Pancreato-Biliary Association, Sao Paulo, Brazil, April 2016; published in abstract form as J Hepatol 2016; 64: S235 and HPB 2016; 18(Suppl 1): e5