Human hepatocytes are the gold standard for toxicological studies but they have several drawbacks, like scarce availability, high inter-individual variability, a short lifetime, which limits their applicability. The aim of our investigations was to determine, whether HepaRG cells could replace human hepatocytes in uptake experiments for toxicity studies. HepaRG is a hepatoma cell line with most hepatic functions, including a considerable expression of uptake transporters in contrast to other hepatic immortalized cell lines. We compared the effect of cholestatic drugs (bosentan, cyclosporinA, troglitazone,) and bromosulfophthalein on the uptake of taurocholate and estrone-3-sulfate in human and rat hepatocytes and HepaRG cells. The substrate uptake was significantly slower in HepaRG cells than in human hepatocytes, still, in the presence of drugs we observed a concentration dependent decrease in uptake. In all cell types, the culture time had a significant impact not only on the uptake process but on the inhibitory effect of drugs too. The most significant drug effect was measured at 4 h after seeding. Our report is among the first concerning interactions of the uptake transporters in the HepaRG, at the functional level. Results of the present study clearly show that concerning the inhibition of taurocholate uptake by cholestatic drugs, HepaRG cells are closer to human hepatocytes than rat hepatocytes. In conclusion, we demonstrated that HepaRG cells may provide a suitable tool for hepatic uptake studies.

An unusual case of acute abdomen was caused by the inflammation of ectopic pancreatic tissue in a Meckel's diverticulum. A 49-year-old man presented with acute abdominal pain, and the clinical diagnosis of acute appendicitis was established. During laparotomy, a normal appendix of unusual localization near the gallbladder and a Meckel's diverticulum with an inflamed tip were found. Histological examination showed acute inflammation of heterotopic pancreatic tissue along with normal ectopic gastric and duodenal mucosa within the wall of the diverticulum. Fat necrosis was also ascertained. The authors believe that this is the first report of acute inflammation of ectopic pancreatic tissue and the presence of normal ectopic gastric and duodenal tissue in the same Meckel's diverticulum.

Although trastuzumab is an efficient drug, primary and acquired resistance is a challenging problem. The authors have previously shown in mouse xenograft experiments that masking ErbB2 by hyaluronan leads to diminished binding of the antibody and consequent resistance. In the current work, they correlated trastuzumab binding with the pericellular density of hyaluronan in ErbB2-overexpressing human breast cancer samples. A method for quantifying the relative binding of trastuzumab was developed involving constant and low-frequency background subtraction, segmenting the image to membrane and background pixels followed by evaluation of trastuzumab fluorescence, normalized with the expression level of ErbB2, only in the membrane. The normalized binding of trastuzumab showed a negative correlation with the pericellular density of hyaluronan ( r = −0.52) with the effect being the most pronounced in the extreme cases (i.e., low and high hyaluronan densities predicted strong and weak binding of trastuzumab, respectively). Removal of hyaluronan by hyaluronidase digestion unmasked the trastuzumab binding epitope of ErbB2 demonstrated by a significantly increased normalized binding of the antibody. The results show that the accumulation of pericellular hyaluronan plays a crucial role in masking ErbB2.

The relationship between the changes in portal venous and hepatic arterial blood flows, in the liver is a much disputed question, it has tremendous significance in the practice of transplantation, and an explanation has been available since 1981, when Lautt published the so-caled “adenosine washout theory”. According to our earlier observations the decrease of portal pressure or flow consistently led to an increase in hepatic artery flow. At the same time changes in hepatic artery flow or pressure seemed to produce only inconsistent effects on the portal circulation. In the present experiments liver transplantation (OLTX) was carried out on mongrel dogs by Starzl's method. Electromagnetic flow probes were placed on the hepatic artery and the portal vein before removal of recipient’s liver, and after completion of all vascular anastomoses to the newly inserted liver, during the recirculatory phase of OLTX. The flow probes were connected to a Hellige electromagnetic flowmeter, portal venous and systemic arterial pressures were also recorded. The control HAF was 241±23 ml/min, the average PVF was 517±47 ml/min before removal of the recipients's liver. In the recirculatory phase the HAF increased, by 71±12% (p < 0.001). The PVF decreased in most animals after OLTX. The decrease was in average –40.2±3.5% (p < 0.001). The THBF calculated by adding the HAF and PVF showed a small, but not significant decrease during recirculation. The systemic arterial pressure decreased slightly and portal vein pressure rose in most animals after OLTX. There was a substantial increase in portal inflow resistance and prehepatic arteriolar resistance and a decrease in hepatic artery resistance. The decrease of PVF after OLTX can be explained by progressive fluid accumulation in the liver parenchyma and increased sinusoidal and portal inflow resistance. The prolonged and continuous increase in hepatic artery flow during the recirculatory phase of OLTX may be due to the decrease of portal flow. The exact mechanism, by which a change in portal flow leads to arteriolar dilatation, can be most probably explained by the “adenosine washout theory” of Lautt.