Virosome engineering of colloidal particles and surfaces: bioinspired fusion to supported lipid layers.

Immunostimulating reconstituted influenza virosomes (IRIVs) are liposomes with functional viral envelope glycoproteins: influenza virus hemagglutinin (HA) and neuraminidase intercalated in the phospholipid bilayer. Here we address the fusion of IRIVs to artificial supported lipid membranes assembled on polyelectrolyte multilayers on both colloidal particles and planar substrates. The R18 assay is used to prove the IRIV fusion in dependence of pH, temperature and HA concentration. IRIVs display a pH-dependent fusion mechanism, fusing at low pH in analogy to the influenza virus. The pH dependence is confirmed by the Quartz Crystal Microbalance technique. Atomic Force Microscopy imaging shows that at low pH virosomes are integrated in the supported membrane displaying flattened features and a reduced vertical thickness. Virosome fusion offers a new strategy for transferring biological functions on artificial supported membranes with potential applications in targeted delivery and sensing.

The new 5- or 6-azapyrimidine and cyanuric acid derivatives of l-ascorbic acid bearing the free C-5 hydroxy or C-4 amino group at the ethylenic spacer: CD-spectral absolute configuration determination and biological activity evaluations.

We report on the synthesis of the novel types of cytosine and 5-azacytosine (1-9), uracil and 6-azauracil (13-18) and cyanuric acid (19-22) derivatives of l-ascorbic acid, and on their cytostatic activity evaluation in human malignant tumour cell lines vs. their cytotoxic effects on human normal fibroblasts (WI38). The CD spectra analysis revealed that cytosine (5 and 6), uracil (14-16), 6-azauracil (17) and cyanuric acid (21) derivatives of l-ascorbic acid bearing free amino group at ethylenic spacer existed as a racemic mixture of enantiomers, whereas L-ascorbic derivatives containing the C-5 substituted hydroxy group at the ethylenic spacer were obtained in (4R, 5S) enantiomeric form. The stereochemistry of 6-azauracil derivative of l-ascorbic acid (13) was confirmed by X-ray crystal structure analysis. The molecules are self-assembled by one N-H⋯O hydrogen bond, two C-H⋯O hydrogen bonds and two C-H⋯π interactions into three-dimensional framework. Cytostatic activity evaluation indicated that compounds did not show distinctive antiproliferative effects on tested cell line panel. However, the cytosine derivative of l-ascorbic acid (1) containing the C4-C5 double bond conjugated with the lactone moiety produced rather marked growth inhibitory effect on hepatocellular carcinoma (HepG2), metastatic breast epithelial carcinoma (MCF-7) and cervical carcinoma (HeLa) cell lines at micromolar concentrations, but also exerted strong cytostatic effect on WI38. 5-Azacytosine derivative of l-ascorbic acid (2) with a double bond at the C4-C5 conjugated with the lactone moiety displayed potent antitumour activity against tested tumour cell lines with meanIC(50) values ranging from 0.92 to 5.91 µM. However, this compound also exhibited pronounced cytotoxicity towards WI38. Flow cytometric analysis of the cell cycle revealed that compound 2 triggers S phase arrest, which clearly demonstrates its interference with DNA replication, a key event of cell proliferation. Marked anticancer efficacy of compound 2 supports further in vivo investigation into its possible clinical utility.

[Importance of adequate immobilization of the upper extremity in using the vascularized fibular graft]. / Znacaj adekvatne imobilizacije gornjeg ekstremiteta kod primene vaskularizovanog fibularnog grafta.

The most complications in patients after the reconstruction of the bone defect of the upper extremities are the fractures of the bone graft and pseudoarthrosis on one of the graft suture with defects of humerus. These complications influence on the primary efficiency of the reconstruction and prolong the recovery period. We registered five fractures, four pseudoarthrosis and two graft angulations in the prospective study on 25 patients where the defect of humerus, radius and ulna was compensated by the vascularized fibular graft. The analysis showed four fractures on the distal part of the reconstructed humerus graft and three pseudoarthrosis on the proximal part of reconstructed ulna. All osteogenic complications, apart from angulations which did not require additional interventions were solved by spongyoplasty according to Phemisters and more efficient postoperative immobilization.

[Fractures of the distal end of the tibia in adolescents ("transitional fractures")]. / Prelomi distalnog okrajka tibije u adolescenata ("prelazni prelomi").

Presented are experiences in the treatment of 6 adolescents with fractures of the distal tibial portion. Treatment was conservative in 4 cases and operative reposition and fixation was performed in 2 cases. Functional and anatomic results were excellent in all 6 patients. This type of fractures in adolescents is not known enough.