Primary human hepatocytes (hHeps) are still gold standard to perform human drug metabolism studies, but their availability is limited by donor organ scarcity. Therefore, hepatoma cell lines are widely used as alternatives, although their phases I and II drug-metabolizing activities are substantially lower compared with hHeps. The major advantage of these cell lines is immediate availability, standardized culture conditions and unlimited life span. Therefore, the aim of this study was to investigate the drug-metabolizing profile of five human hepatoma cell lines (HepG2, Hep3B, HCC-T, HCC-M and Huh-7) over a culture period of 10 passages. Fluorescent-based assays for seven different cytochrome P450 (CYP) isoforms and seven different phase II enzymes were performed and compared with enzymatic activities of hHeps. CYP activities were much lower in the cell lines (5-15% of hHeps), whereas phase II enzyme activities that are involved in buffering oxidative stress (e.g., Glutathione-S-transferase) reached levels comparable with hHeps. Furthermore, phases I and II enzyme activities in hepatoma cell lines vary strongly during culture time. Interestingly, the most constant results were obtained with Huh-7 cells. Huh-7 cells as well as HCC-T cells exhibited a drug-metabolizing profile closest to hHeps between passages two and four. Toxicity studies with Diclofenac, Paracetamol and Verapamil in both cell lines show dose-response characteristics and EC(50) values similar to hHeps. Therefore, we propose that due to the more consistent results throughout the passages, Huh-7 could be an alternative system to the limitedly available hHeps and frequently used HepG2 cell line in the study of drug metabolism.

The recently introduced dual-layer stents have a higher risk of acute occlusion compared with single-layer stents in the treatment of acute stroke.

In-stent stenosis is a common finding on short term follow-up after the treatment with flow diverters but improves over time.

Background Endovascular stents are commonly used during neurointerventional procedures; however, the concomitant use of dual anti-platelet treatment (DAPT) can limit their use. There is a need to develop stent coatings that mitigate requirement for DAPT. Methods The hydrophilic polymer coating is a novel glycan-based multilayer polymer that inhibits platelet adhesion. After Institutional Animal Care and Use Committee approval, 18 New Zealand white rabbits (mean weight 4.02 ± 0.51 kg) were commenced on DAPT (ASA 10 mg/kg/day and clopidogrel 10 mg/kg/day). A bare nitinol pCONUS and coated pCONUS HPC were implanted into the common carotid arteries of each rabbit. Histological examinations were performed at 30 days ( n = 9) and 180 days ( n = 8) to assess the acute and chronic inflammatory reactions to the pCONUS HPC. Wilcoxon/Kruskal–Wallis and ANOVA were used with p value < 0.05 considered as significant. Results There is no statistically significant difference in inflammation within the intima/media or adventitia at 30 days ( p = 0.3901 and p = 1, respectively) or at 180 days ( p = 0.144 and p = 1, respectively) between pCONUS and pCONUS HPC cohorts. There is no significant difference in the presence of granulomas or giant cells between the cohorts at either 30 days ( p = 1 and p = 0.8363) or 180 days ( p = 1.00 and p = 0.149). At 30 days and 180 days, there was near-complete endothelialisation of the stent struts and no significant difference between the pCONUS or pCONUS HPC ( p = 0.7832 and p = 0.334, respectively). Conclusion pCONUS HPC stents do not elicit an acute or chronic inflammatory response in vivo with no significant difference in the tissue response to bare nitinol pCONUS stents or pCONUS HPC stents.

The Derivo Embolization Device provides excellent occlusion of elastase-induced aneurysms while preserving branch arteries.

BackgroundFlow diverters (FDs) are widely used in the treatment of intracranial aneurysms, but the required medication increases the risk of haemorrhagic complications and limits their use in the acute setting. Surface modified FDs may limit the need for dual antiplatelet therapy (DAPT). Hydrophilic polymer coating (HPC) may reduce the need of medication.MethodsThis explorative study, approved by the local authorities and the local welfare committee, compared stent behaviour and overall tissue response between HPC-coated FDs and uncoated FDs, both implanted into the common carotid arteries of eight New Zealand white rabbits. Endothelialisation, inflammatory response, and performance during implantation were assessed. Angiographic follow-up was performed to observe the patency of the devices after implantation and after 30 days. Histological examinations were performed at 30 days to assess foreign body reaction and endothelialisation. Kruskal-Wallis and Wilcoxon tests were used to compare non-parametric variables.ResultsAngiography showed that both coated and uncoated FDs performed well during implantation. All devices remained patent during immediate follow-up and after 30 days. Histopathology showed no significant difference in inflammation within the vessel wall between the two cohorts (2.12 ± 0.75 vs. 1.96 ± 0.79, p = 0.7072). Complete endothelialisation of the stent struts was seen with very similar (0.04 ± 0.02 mm vs. 0.04 ± 0.03 mm, p = 0.892) neoendothelial thickness between the two cohorts after 30 days.ConclusionTaking into account the limitation in sample size, non-significant differences between the HPC-coated and uncoated FDs regarding implantation, foreign body response, and endothelialisation were found.

Purpose Mechanical thrombectomy (MT) is an effective treatment for patients suffering from acute ischemic stroke. However, recanalization fails in about 16.5% of interventions. We report our experience with unsuccessful MT and analyze technical reasons plus patient-related parameters for failure. Methods Five hundred ninety-six patients with acute ischemic stroke in the anterior circulation and intention to perform MT with an aspiration catheter and/or stent retriever were analyzed. Failure was defined as 0, 1, or 2a on the mTICI scale. Patients with failing MT were analyzed for interventional progress and compared to patients with successful intervention, whereby parameters included demographics, medical history, stroke presentation, and treatment.Results One hundred of the 596 (16.8%) interventions failed. In 20 cases, thrombus could not be accessed or passed with the device. Peripheral arterial occlusive disease is common in those patients. In 80 patients, true stent retriever failure occurred. In this group, coagulation disorders are associated with poor results, whereas atrial fibrillation is associated with success.The administration of intravenous thrombolysis and intake of nitric oxide donors are associated with recanalization success. Intervention duration was significantly longer in the failing group. Conclusion In 20% of failing MT, thrombus cannot be reached/passed. Direct carotid puncture or surgical arterial access could be considered in these cases.In 80% of failing interventions, thrombus can be passed with the device, but the occluded vessel cannot be recanalized. Rescue techniques can be an option. Development of new devices and techniques is necessary to improve recanalization rates. Assessment of pre-existing illness could sensitize for occurring complications.

The tested flow diverter achieved near-complete and complete aneurysm occlusion under double antiplatelet therapy of elastase-induced aneurysms in 78 %, while preserving branch arteries.