In vivo efficacy of Ingavirin against pandemic A (H1N1/09)v influenza virus

Ingavirin was shown to be efficient in inhibition of the pandemic influenza virus strains A/California/04/2009 (H1N1)v, A/California/07/2009 (H1N1)v, A/Moscow/225/2009 (H1N1)v and A/Moscow/226/2009 (H1N1)v. as well as the influenza virus strain A/Aichi/2/68 (H3N2) in the lungs of the infected mice. After oral administration of Ingavirin the titers of the influenza virus strains in the lung homogenates lowered.     

Effect of polylysine on transformations and permeability of negative vesicular membranes

Small (40-60 nm in diameter) and large (300-350 nm) negative vesicles were complexed with a cationic polypeptide, poly-L-lysine (PL). Laser microelectrophoresis experiments showed that in small vesicles rendered anionic with the addition of cardiolipin (CL(2-)), only the CL(2-) in the outer leaflet is involved in the complexation with PL. Calorimetric and other data demonstrate that the binding of PL to the membrane surface causes domains ("rafts") of CL(2-) to form in the outer leaflet, and it is these domains that electrostatically bind the polymer. The kinetics of transmembrane permeation of doxorubicin (Dox, a fluorescent anti-tumor drug) was monitored with and without PL binding to the outer surface of the vesicles. It was found that PL mediates the permeation of Dox into the vesicle interior. In the absence of PL, the Dox molecule (possessing an amino group of pK(a)=8.6) binds to the anionic vesicles in the protonated form and, consequently, suffers an impaired mobility through the membrane. On the other hand, when the PL covers the vesicle surface, Dox passes though the membrane with greater ease. The effects of salt and polyanion on the stability of PL-vesicle complexes and the PL-mediated Dox permeation are also discussed.     

Unusual metastasis of papillary thyroid carcinoma to larynx and hypopharynx a case report

Background  

Although direct infiltration of papillary carcinoma of thyroid to larynx, trachea and esophagus is well recognized, lymphatic and vascular metastases to larynx and hypopharynx have rarely been reported.     

Pluronic micelles as a tool for low-molecular compound vector delivery into a cell: effect of Staphylococcus aureus enterotoxin B on cell loading with micelle incorporated fluorescent dye.

Micelles of pluronic P85 (poly(oxyethylene)-poly(oxypropylene) block copolymer) are used as microcontainers for in vitro delivery of fluorescein into Jurkat and MDCK cells. In order to target the fluorescein containing micelles into the cell, Staphylococcus aureus enterotoxin B (SEB) is covalently conjugated with a pluronic molecule and the conjugate is incorporated into the micelle content. The incorporation of SEB capable of receptor-mediated endocytosis results in a drastic enhancement of the efficiency of cell loading with the fluorescent dye. This effect is not observed under the conditions (4 degrees C) when endocytosis is abolished.     

Synthesis and evaluation of a star amphiphilic block copolymer from poly(epsilon-caprolactone) and poly(ethylene glycol) as a potential drug delivery carrier

A star polymer composed of amphiphilic block copolymer arms has been synthesized and characterized. The core of the star polymer is polyamidoamine (PAMAM) dendrimer, the inner block in the arm is lipophilic poly(epsilon-caprolactone) (PCL), and the outer block in the arm is hydrophilic poly(ethylene glycol) (PEG). The star-PCL polymer was synthesized first by ring-opening polymerization of epsilon-caprolactone with a PAMAM-OH dendrimer as initiator. The PEG polymer was then attached to the PCL terminus by an ester-forming reaction. Characterization with SEC, (1)H NMR, FTIR, TGA, and DSC confirmed the star structure of the polymers. The micelle formation of the star copolymer (star-PCL-PEG) was studied by fluorescence spectroscopy. Hydrophobic dyes and drugs can be encapsulated in the micelles. A loading capacity of up to 22% (w/w) was achieved with etoposide, a hydrophobic anticancer drug. A cytotoxicity assay demonstrated that the star-PCL-PEG copolymer is nontoxic in cell culture. This type of block copolymer can be used as a drug delivery carrier.     

The influence of differentiation-inducing agents on plasma membrane surface characteristics of THP-1 cells

Undifferentiated THP-1 cells from Cell Culture Collection of the Institute of Cytology, RAS (St. Petersburg), are characterized by weak expression of Toll-like receptor-4 (TLR4) on the cell surface (up to 2%) and by almost undetectable expression of CD14 and CD11b receptors. Differentiation agent phorbol-12-myristate-13-acetate independently of its concentration (2 × 10⁻⁷ M or 10⁻⁸ M) and incubation time (24 or 48 h) did not initiate CD11b surface expression and did not change the parameter S_app (0.605 ± 0.005 at 37°C) reflecting the cell membrane viscosity. Differentiation of THP-1 cells induced by another differentiation agent, 1α,25-dihydroxyvitamin D₃, caused expression of CD14 (up to 70–80%) and CD11b (up to 15–20%) receptors, again without changes in plasma membrane viscosity. The rate constants of the reduction of 5- and 16-doxyl-stearic acids by THP-1 cells were in the range of 6–8 × 10⁻³ s⁻¹ at 37°C. During cell differentiation significant changes in cell electrophoretic mobility (EM, μm s⁻¹ V⁻¹ cm) were observed. Mean value of EM for undifferentiated THP-1 cells was −1.332 ± 0.011, whereas for phorbol-12-myristate-13-acetate- and 1α,25-dihydroxyvitamin D₃-treated cells it was −1.432 ± 0.030 and −1.212 ± 0.016, respectively.     

18 Possible extraterrestrial life: a quantum-chemical look on the silicon analogs of carbon biomolecules

The uniqueness of life on our planet has been an important topic of discussion in scientific literature for many decades. The most particular findings are in the fields of the structure of biomolecules and the mechanisms of their conformational and chemical transfers since they underlie all the biospheric processes of our planet. The compounds based on carbon are the subject of study of organic chemistry, which has an appropriate thoroughly developed classification of such substances; a number of approaches have been proposed for the analysis of composition and structure of the organic compounds, and a theoretical basis has been created, which describes the character of various chemical bonds involving carbon atoms. At the same time, since quite a while, there is a widely discussed hypothesis (Alison, 1968) concerning the possibility of existence of compounds, which are similar to organic, but are based on silicon atoms. Even in interstellar medium, among all the diversity of molecules detected, 84 are based on carbon, and 8 on silicon (Lazio, 2000), including four hybrid types, i.e. containing both silicon and carbon. According to approximate evaluations, the contents ratio of carbon to silicon in the space equals to 10:1, though the Earth’s crust consists of 87% of silicon in the form of oxides. In the Periodic Table, silicon is situated in the same group IV, like carbon. These two elements are largely similar in the structure of their valent electronic shells, and their noteworthy that previously it was stated (Lazio, 2000) that silicon-containing compounds are not as diverse in structure as carbon compounds. Despite having higher mass and radius, the atoms of silicon form double and triple covalent bonds (Wang et al., 2008). Therefore, the issue concerning the existence of silicon structures similar to carbon biomolecules, as well as the question of hypothetical “biochemical” processes involving non-carbonic analogs of aminoacids, carbohydrates, proteins, lipids, and other biomolecules, is still a matter of discussion in scientific and popular science literature. It is particularly notable that the modern methods of computational chemistry allow carrying out the estimating calculations of the structure and dynamics of such compounds, which is quite similar to the known approaches of substance modeling de novo in drug design. For instance, first by calculations (Nagase, Kudo, & Aoki, 1985), and later on experimentally (Abersfelder, White, Rzepa, & Scheschkewitz, 2010), aromaticity of cyclic carbohydrate-like derivatives of silicon was studied. In the present study, we used quantum-chemical semiempirical PM3 and ab initio B3LYP/6-311G(d,p) level of theory to investigate the peculiarities of several structural and thermodynamic parameters of molecules, which can be assumed as complete silicon analogs of carbonic L-amino acids and other biomolecules, so-called bricks of life: carbohydrates, nitrogenous bases, fatty acids, as well as vitamins and caffeine. The quantum-mechanical calculations that we made displayed that the molecules of silicon amino acids possess higher thermodynamic stability compared to carbon analogs. Thereby, silicon amino acids have a similar conformation freedom, increased values of dipole moment, as well as more pronounced electron-donor characteristics. Silicon analogs of carbohydrates, fatty acids, and nitrogenous bases are as well considered as heavier thermodynamically stable compounds, having special features in 3D-organization and worth further experimental study. The present work also deals with the question of the existence and stability of “alpha-helices” composed of silicon amino acids, because in the molecules of Si-analogs of aspartate and glutamate, we have discovered effective formation of intramolecular hydrogen bond (due to the side chain), which is highly important for Pauling–Corey alpha helix formation in natural L-amino acids (Kondratyev, Kabanov, & Komarov, 2010). Our estimations show that an “alpha helix” composed of 10 silicon alanine analogs is more stable in isolated state than a linear form of such macromolecule, which was not observed for a molecule of the same composition having a carbon backbone.     

Synthesis,biological evaluation,X-ray molecular structure and molecular docking studies of RGD mimetics containing 6-amino-2,3-dihydroisoindolin-1-one fragment as ligands of integrin αIIbβ3

A series of novel RGD mimetics containing phthalimidine fragment was designed and synthesized. Their antiaggregative activity determined by Born’s method was shown to be due to inhibition of fibrinogen binding to α_IIbβ₃. Molecular docking of RGD mimetics to α_IIbβ₃ receptor showed the key interactions in this complex, and also some correlations have been observed between values of biological activity and docking scores. The single crystal X-ray data were obtained for five mimetics.