Chitosan-based multi-liposomal complexes: Synthesis, biodegradability and cytotoxicity.

Anionic liposomes were electrostatically adsorbed onto the surface of cationic chitosan particles cross-linked by sulfate anions, forming multi-liposomal containers (MLCs) for encapsulation and delivery of bioactive substances. An increase in molecular mass of chitosan from 30 to 300 kDa results in a size increase of chitosan particles, from 200 to 400 nm. Being saturated by liposomes, chitosan particles give MLCs of 320-540 nm. Each chitosan particle carries between 60 and 200 liposomes. The proteolytic complex Morikrase, a mixture of enzymes with various specificities, induces degradation of MLCs down to particles of size 10-15 nm; the higher the molecular mass of chitosan, the slower the enzyme-induced MLCs' degradation. pH variation within 5.5-7 and cholesterol incorporation into the liposomal membrane both have a minor effect on the rate of MLCs' biodegradation. Both the MLCs and the products of their biodegradation show low cytotoxicity. These results are of interest for constructing biodegradable capacious carriers of bioactive substances.

NMR Chemical Shift of a Helium Atom as a Probe for Electronic Structure of FH, F-, (FHF)-, and FH2.

In this work, we present the first results of outer electronic shell visualization by using a 3He atom as a probe particle. As model objects we have chosen F-, FH, and FH2+ species, as well as the hydrogen-bonded complex FH···F- at various H···F- distances (3.0, 2.5, 2.0, and 1.5 Å and equilibrium at ca. 1.14 Å). The interaction energy of investigated objects with helium atom (CCSD/aug-cc-pVTZ) and helium atom chemical shift (B3LYP/pcS-2) surfaces were calculated, and their topological analysis was performed. For comparison, the results of standard quantum mechanical approaches to electronic shell visualization were presented (ESP, ELF, ED, ∇2ED). We show that the Laplacian of helium chemical shift, ∇2δHe, is sensitive to fluorine atom lone pair localization regions, and it can be used for the visualization of the outer electronic shell, which could be used to evaluate the proton accepting ability. The sensitivity of ∇2δHe to lone pairs is preserved at distances as large as 2.0-2.5 Å from the fluorine nucleus (in comparison with the distance to ESP minima, located at 1.0-1.5 Å or maxima of ELF, which are as close as 0.6 Å to the fluorine nucleus).

[Nutrition value of national milk products with the addition of wild berries and wild food plants of Yakutia].

Results of an assessment of the actual food of the population in various medicoeconomic zones of the republic (industrial, agricultural, Arctic) by method of the frequency analysis of food consumption are presented in the article. The analysis of control of compliance of quality and safety of foodstuff in the Republic of Sakha (Yakutia), according to requirements of the legislation of the Russian Federation, acts of the Customs union has been made. Decreased consumption of such foodstuff as milk, fish and meat products including products from local food staples and national dishes has been established. The data obtained are medic-biological justification for search of ways of optimization of population nutrition, creation of specialized products with a functional purpose and for the prevention of the states and diseases connected with nutrition violation. They also define innovative development of the republic in questions of biotechnologies of the production of specialized foods for various groups of the population. Results of chemical composition research of the most used wild-growing food plants of Yakutia are given. The questions connected with the nutrition and biological value of the dairy products of a functional purpose with use of wild-growing food herbs and berries of Yakutia are discussed.

Complexation of polycations to anionic liposomes: composition and structure of the interfacial complexes.

Poly(N-ethyl-4-vinylpyridinium bromide) (a polycation with a degree of polymerization of 1100) was adsorbed onto liposomes composed of egg lecithin with a 0.05-0.20 molar fraction (nu) of anionic headgroups provided by cardiolipin (a doubly anionic lipid). According to electrophoretic mobility data, this led to total charge neutralization of the liposomes, whereupon the liposomes adopted a positive charge as additional polymer continued to adsorb. Although the liposomes aggregated at the charge-neutralization point, they disassembled into individual liposomes after becoming positively charged. The degree of polymer adsorption was shown to reach a limit. Thus, by measuring the free polymer content in a liposome suspension, it was possible to determine the polymer concentration at which the liposome surface became saturated with polymer. Beyond this point, an electrostatic/steric barrier at the surface suppressed further adsorption. Dynamic light scattering studies of liposomes with and without adsorbed polymer allowed calculation of the polymer film thickness which ranged from 22 to 35 nm as the molar fraction of cardiolipin (nu) increased from 0.05 to 0.20. The greater the content on the anionic lipid in the bilayer, the thicker the polymer film. The maximum number of polymer molecules adsorbed onto the liposomes was estimated: 1-2 molecules for nu = 0.05; 3 molecules for nu = 0.1; 4- molecules for nu = 0.15; and 6 molecules for nu = 0.2. The polymer appears to lie on the liposome surface, rather than embedding into the bilayer, because addition of NaCl easily dislodges the polymer from the liposome into the bulk water.

Reversibility of structural rearrangements in the negative vesicular membrane upon electrostatic adsorption/desorption of the polycation.

Interaction of small unilamellar vesicles (SUVs), composed of negative diphosphatidylglycerol (cardiolipin, CL(2-)) and neutral dipalmitoylphosphatidylcholine (DPPC), with poly(N-ethyl-4-vinylpyridinium bromide) (PEVP) was studied in water solution above and below the vesicular membrane melting point by means of differential scanning calorimetry, photon correlation spectroscopy, microelectrophoresis, conductometry, and fluorescence techniques. It has been found that CL(2-) species are homogeneously distributed within DPPC-CL(2-) SUV membrane leaflets and between them. Interaction of PEVP with DPPC-CL(2-) SUVs led to drastic structural rearrangements in the membrane if it was in the fluid state (liquid SUVs). Negative CL(2-) molecules migrated from the inner to the outer membrane leaflet and segregated in the vicinity of adsorbed PEVP chains. In addition, PEVP adsorption terminated completely the exchange of lipid molecules between the SUVs. At the same time, the integrity of liquid SUVs contacting PEVP remained unchanged. Since the interaction of PEVP with liquid SUVs was predominantly electrostatic in nature, the polycation could be completely removed from the vesicular membrane by addition of an excess of polyacrylic acid (PAA) polyanions forming a more stable electrostatic complex with PEVP. Removal of PEVP resulted in complete resumption of the original distribution of lipids in lateral and transmembrane directions as well as intervesicular lipid exchange. In contrast, PEVP interacting with DPPC-CL(2-) SUVs formed defects in the vesicular membrane if it was in the gel state (solid SUVs). Such interaction was contributed not only by electrostatic but most likely by hydrophobic interactions involving the defected membrane sites. PEVP kept contacting solid SUVs in the presence of an abundant amount of PAA. The established phenomena may be important for understanding the biological effects of polycations.

Reversibility of structural rearrangements in lipid membranes induced by adsorption-desorption of a polycation.

Interaction of poly(N-ethyl-4-vinylpyridinium bromide) with mixed cardiolipin/phosphatidyl-choline (1/9) liposomes was studied by differential scanning calorimetry and photon correlation spectroscopy. It was found that the adsorption of polycation on the surface of liquid liposomes was accompanied by transmembrane migration of negatively charged cardiolipin molecules from the inner to outer membrane leaflet and lateral lipid segregation. At the same time, the liposome integrity was retained, and the adsorbed polycation can be displaced from the membrane by recomplexation with polyanions. As a result, the initial transmembrane and lateral lipid distribution in the membrane was restored.

[Comparative evaluation of the effectiveness of vaccination of newborn infants with BCG and BCG-M vaccines]. / Sravnitel'naia otsenka éffektivnosti vaktsinatsii novorozhdennykh vaktsinami BTsZh i BTsZh-M.

A comparative effectiveness of the newborn BCG- and BCG-M vaccination was analysed as to the indices of primary infection, morbidity and its structure. The rate of postvaccination complications in 1,645,360 children, aged under 3 years, and living in the areas with different epidemiological situations for tuberculosis was studied too. 2,142,292 and 799486 healthy newborns were BCG- and BCG-M-vaccinated, respectively. The studies were carried out in Moscow, Kiev, Vilnius++ and Tashkent. The obtained results indicate that the number of complications in the form of regional lymphadenitis induced by BCG-M vaccine is 5 times less frequent than those caused by BCG. Under favourable epidemiological conditions, the primary infection and morbidity are alike, while under unfavourable ones the former is higher, particularly in infants in their first year as compared to the BCG-vaccinated. On the basis of the available data BCG-M can be recommended for the vaccination of all the newborns living in the areas with a favourable epidemiological situation for tuberculosis, thus increasing the newborn vaccination coverage and bringing the morbidity down.

[Effect of air pollution on the incidence and course of allergic diseases in children]. / Vliianie zagriazneniia vozdushnoi sredy na rasprostranennost' i techenie allergicheskikh boleznei u detei.

Allergic diseases occupy the leading position in the structure of childhood pathology. The rates of the growth of the allergic disease incidence among children are considerably higher than those among adults. It has been revealed that the prevalence and the course of allergic diseases in children are influenced by atmospheric air and house air medium pollution with chemical agents.