A b s t r a c t Background and aim:To evaluate the accuracy of the three-dimensional (3D) printing of cardiovascular structures. To explore whether utilisation of 3D printed heart replicas can improve surgical and catheter interventional planning in patients with complex congenital heart defects. Methods:Between December 2014 and November 2015 we fabricated eight cardiovascular models based on computed tomography data in patients with complex spatial anatomical relationships of cardiovascular structures. A Bland-Altman analysis was used to assess the accuracy of 3D printing by comparing dimension measurements at analogous anatomical locations between the printed models and digital imagery data, as well as between printed models and in vivo surgical findings. The contribution of 3D printed heart models for perioperative planning improvement was evaluated in the four most representative patients. Results:Bland-Altman analysis confirmed the high accuracy of 3D cardiovascular printing. Each printed model offered an improved spatial anatomical orientation of cardiovascular structures.Conclusions: Current 3D printers can produce authentic copies of patients` cardiovascular systems from computed tomography data. The use of 3D printed models can facilitate surgical or catheter interventional procedures in patients with complex congenital heart defects due to better preoperative planning and intraoperative orientation.

Phospholipid bilayers represent a complex, anisotropic environment fundamentally different from bulk oil or octanol, for instance. Even "simple" drug association to phospholipid bilayers can only be fully understood if the slab-of-hydrocarbon approach is abandoned and the complex, anisotropic properties of lipid bilayers reflecting the chemical structures and organization of the constituent phospholipids are considered. The interactions of drugs with phospholipids are important in various processes, such as drug absorption, tissue distribution, and subcellular distribution. In addition, drug-lipid interactions may lead to changes in lipid-dependent protein activities, and further, to functional and morphological changes in cells, a prominent example being the phospholipidosis (PLD) induced by cationic amphiphilic drugs. Herein we briefly review drug-lipid interactions in general and the significance of these interactions in PLD in particular. We also focus on a potential causal connection between drug-induced PLD and steatohepatitis, which is induced by some cationic amphiphilic drugs.

Phospholipidosis, the accumulation of phospholipids in cells, is a relatively frequent side effect of cationic amphiphilic drugs. In response to the industry need, several methods have been recently published for the prediction of the phospholipidosis-inducing potential of drug candidates. We describe here a high-throughput physicochemical approach, which is based on the measurement of drug-phospholipid complex formation observed by their effect on the critical micelle concentration (CMC) of a short-chain acidic phospholipid. The relative change due to the drug, CMC(DL)/CMC(L) provides a direct measure of the energy of the drug-phospholipid association, irrespective of the nature of the interaction. Comparison of results for 53 drugs to human data, animal testing, cell culture assays, and other screening methods reveals very good correlation to their phospholipidosis-inducing potential. The method is well suited for screening already in early phases of drug discovery.

We have studied the physical properties of monolayers formed by calix[4]resorcinarene and in mixtures with dipalmitoyl phosphatidylcholine (DPPC) in various molar ratios formed at the air-water interface and at presence of dopamine in water subphase by means of measurements of surface pressure and dipole potential. We showed that both calix[4]resorcinarene as well as its mixture with DPPC form stable monolayers at the water subphase. The presence of dopamine resulted in an increase of the mean molecular area and in a decrease of the compressibility modulus of the monolayers. For mixed monolayers at higher content of calix[4]resorcinarene (> 0.2 molar fraction) a deviation from ideal miscibility took place especially for monolayers in a solid state. This can be connected with formation of aggregates of calix[4] resorcinarene. Lowest miscibility and weakest interaction of dopamine with a monolayer was observed for calix[4]resorcinarene molar fraction of 0.33 in the monolayer.

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