[New morphometric criteria in the study of pathogenesis of normal-tension glaucoma]. / Novye morfometricheskie kriterii v izuchenii patogeneza glaukomy normal'nogo davleniya.

INTRODUCTION: Studying the factors that contribute to the disturbance of transmembrane pressure gradient is a topical task in the research of pathogenesis of normal-tension glaucoma (NTG). PURPOSE: To measure and compare the thickness and depth of lamina cribrosa (LCT and LCD), as well as optic nerve subarachnoid space width (ONSASW) in patients with NTG and healthy individuals. MATERIAL AND METHODS: The first group included 12 patients (23 eyes) aged from 58 to 74 years (average age 66.8±3.2 years) with NTG who all had normal intraocular pressure and arterial hypotension. The second (control) group consisted of 11 healthy individuals (22 eyes) aged from 51 to 69 years (average age 56.2±4.2 years). All patients underwent structural and functional assessment of the optic nerve head using OCT RTVue-100 (Optovue, USA), as well as Humphrey Visual Field Analyzer (HFA II 745i, Germany-USA) and our modification of Frequency Doubling Technology perimetry. In all subjects the central corneal thickness (CCT) was measured by Pentacam HR (Oculus, Germany), the LCT and LCD were measured by EDI (Enhanced Depth Imaging) mode of Topcon 3D OCT 2000 (Japan). To measure the ONSASW we used a cross-sectional image of the optic nerve taken 3 mm behind the eyeball with Magnetic Resonance Imaging (Siemens Magnetom Symphony 1.5 T, Germany). RESULTS: Statistically significant difference was found between the 1st and 2nd groups in the average LCT (217.60±36.92 and 345.86±33.29 µm respectively; p=0.0000), LCD (435.00±86.31 and 367.31±87.00 µm, respectively; p=0.014) and ONSASW (1.27±0.13 and 1.44±0.19 mm respectively; p=0.004); the difference wasn't significant in the average CCT (543.26±31.52 and 557.50±24.92 µm respectively; p=0.11). CONCLUSION: Patients with NTG had significantly higher value of the LCD with significantly lower values of the LCT and ONSASW compared with healthy individuals, which confirms the importance of these morphometric criteria in the study of NTG pathogenesis.

Digging deeper: structural background of PEGylated fibrin gels in cell migration and lumenogenesis.

Fibrin is a well-known tool in tissue engineering, but the structure of its modifications created to improve its properties remains undiscussed despite its importance, e.g. in designing biomaterials that ensure cell migration and lumenogenesis. We sought to uncover the structural aspects of PEGylated fibrin hydrogels shown to contribute to angiogenesis. The analysis of the small-angle X-ray scattering (SAXS) data and ab initio modeling revealed that the PEGylation of fibrinogen led to the formation of oligomeric species, which are larger at a higher PEG : fibrinogen molar ratio. The improvement of optical properties was provided by the decrease in aggregates' sizes and also by retaining the bound water. Compared to the native fibrin, the structure of the 5 : 1 PEGylated fibrin gel consisted of homogenously distributed flexible fibrils with a smaller space between them. Moreover, as arginylglycylaspartic acid (RGD) sites may be partly bound to PEG-NHS or masked because of the oligomerization, the number of adhesion sites may be slightly reduced that may provide the better cell migration and formation of continuous capillary-like structures.

Drug-templated mesoporous silica nanocontainers with extra high payload and controlled release rate.

The possibility of one-step creating of pH-sensitive mesostructured silica-based nanocontainers with exceptionally high payload using associates of two antiseptics (including hydrolyzable one) as templates is demonstrated. The effects of the template nature and the conditions of the sol-gel process on the porous structure of silica nanocontainers are studied and discussed. The kinetics of the templating drug release from such containers is studied and some features of this process are analyzed. It is shown that the drug release rate can be tuned by varying the medium pH. The bactericidal activity of two encapsulated antiseptics against the Staphylococcus aureus is evaluated in vitro by agar diffusion method with replacement of agar with agarose. The diameters of the inhibition zones for silica-based containers loaded with antiseptics increased with the pre-diffusion time at 4 °C. At the same time, empty containers (after elimination of antiseptics by etching) did not reveal any bactericidal properties.

X-Ray Diffraction Tomography Recovery of the 3D Displacement-Field Function of the Coulomb-Type Point Defect in a Crystal.

A successive approach to the solution of the inverse problem of the X-ray diffraction tomography (XRDT) is proposed. It is based on the semi-kinematical solution of the dynamical Takagi-Taupin equations for the σ-polarized diffracted wave amplitude. Theoretically, the case of the Coulomb-type point defect in a single crystal Si(111) under the exact conditions of the symmetric Laue diffraction for a set of the tilted X-ray topography 2D-images (2D projections) is considered provided that the plane-parallel sample is rotated around the diffraction vector [[Formula: see text]20]. The iterative simulated annealing (SA) and quasi-Newton gradient descent (qNGD) algorithm codes are used for a recovery of the 3D displacement-field function of the Coulomb-type point defect. The computer recovery data of the 3D displacement-field function related to the one XRDT 2D projection are presented. It is proved that the semi-kinematical approach to the solution of the dynamical Takagi-Taupin equations is effective for recovering the 3D displacement-field function even for the one XRDT 2D projection.

Comparison of the Size and Properties of the Cytochrome c/Cardiolipin Nanospheres in a Sediment and Non-polar Medium.

Apoptosis, as the major type of programmed cell death, plays an important role in the organism renewal and removal of defective and transformed cells, including cancer cells. One of the earliest apoptotic events is lipid peroxidation in the inner mitochondrial membrane catalyzed by a complex of cytochrome c (CytC) with the mitochondrial phospholipid cardiolipin (CL). It was shown that mixing CytC and CL solutions results in the formation of CytC/CL complexes (Cyt-CL nanospheres) with a diameter of 11-12 nm composed of the molten globule protein molecule and a CL monolayer. Using the methods of dynamic light scattering for the Cyt-CL chloroform solution and small-angle X-ray scattering for the Cyt-CL sediment, it was found that in both cases, Cyt-CL formed nanospheres with a diameter of 8 and 11 nm, which corresponded to the earlier determined lipid/protein ratios of 13-14 and 35-50, respectively. These results showed that the Cyt-CL nanospheres can form not only during crystallization but also in a hydrophobic medium. CytC in the complex exists as a molten globule, as evidenced by the emergence of tryptophan and tyrosine fluorescence (absent in the native protein) due to the Förster resonance transfer of the electron excitation energy onto the heme. At the same time, the coordinate bond between the heme iron and the sulfur atom of methionine 80 in Cyt-CL is disrupted (the absorption band at ~700 nm disappears). Similar disruption of the iron-sulfur bond in Cyt-CL was observed in 50% methanol. These changes were reversible, which corroborates the conclusion on the CytC transition to the molten globule conformation in methanol-containing solutions.

Combined treatment of nonresectable cholangiocarcinoma complicated by obstructive jaundice.

BACKGROUND: The five-year survival rate for successful surgical treatment of cholangiocellular cancer is only 20-40%, and in the case of an unresectable tumor, the life expectancy does not usually exceed 6 months. Survival decreases with the presence of jaundice, due to the spread of the tumor process along the bile ducts, leading to their obstruction. We report outcomes of patients with nonresectable bile duct carcinoma complicated by obstructive jaundice treated with Photodynamic Therapy (PDT). METHODS: Combined diagnosis and treatment included percutaneous cholangiostomy, intraductal video fluorescence diagnostics, photodynamic therapy, and bile duct stenting. All patients were treated at the Sechenov University Oncology Center in Moscow. The results of treatment of 33 patients have been presented. The intraductal diagnosis of malignant bile duct lesions was performed after cholangiostomy using the endovideofluorescence module for minimally invasive surgery and endoscopy. With the use of this method, it is the first time in Russia that it has become possible to obtain a videofluorescent image of the tumor and to determine the high level of photosensitizer accumulation in all cholangiocarcinoma patients. The preparations Photolon, Radachlorin, and Photosens were employed as photosensitizers (PS). Intraductal photodynamic therapy was used to achieve the antitumor effect. Laser power density was about 200 mW/cm2. RESULTS: We present initial results, improved the diagnostic possibilities in this difficult localization of carcinoma, and demonstrated the feasibility of prolongation of life without significant deterioration of its quality. The average survival time in the treatment group is 9.5 months. CONCLUSION: The treatment of patients with nonresectable cholangiocarcinoma with Photodynamic Therapy should be an available option. In this context, the additional use of intraductal endovideofluorescence diagnostics is a highly specific technique that allows reliable detection of the photosensitizer accumulation predominantly by the tumor tissue and appears promising. As shown by our experience, flourescent localization followed by Photodynamic Therapy, enabled us to improve diagnostic techniques and treat the tumor with improved outcome.

Structural Study of the Complex Formed by Ceruloplasmin and Macrophage Migration Inhibitory Factor.

Macrophage migration inhibitory factor (MIF) is a key proinflammatory cytokine. Inhibitors of tautomerase activity of MIF are perspective antiinflammatory compounds. Ceruloplasmin, the copper-containing ferroxidase of blood plasma, is a noncompetitive inhibitor of tautomerase activity of MIF in the reaction with p-hydroxyphenylpyruvate. Small-angle X-ray scattering established a model of the complex formed by MIF and ceruloplasmin. Crystallographic analysis of MIF with a modified active site supports the model. The stoichiometry of 3 CP/MIF trimer complex was established using gel filtration. Conformity of novel data concerning the interaction regions in the studied proteins with previous biochemical data is discussed.

[About the Spatial Organization of Double-stranded DNA Molecules in the Cholesteric Liquid-crystalline Phase and Dispersion Particles of this Phase].

The answer to a question on the organization of molecules in a cholesteric phase is well enough proved in case of low molecular mass compounds. However, in case of double-stranded nucleic acids molecules the unequivocal answer to such question is a subject of discussions. In this work an attempt to generalize the well known literary data on the structure of the cholesteric phase formed by double-stranded DNA molecules was undertaken. Besides the experimental results of authors describing the packing of these molecules in the cholesteric liquid-crystalline dispersion particles are added to these data. Comparison of the results obtained offers the possibility to come out with an assumption of high probability of the existence of both the short-range positional and long-range orientational order in arrangement of double-stranded DNA molecules in a liquid-crystalline phase, and in the particles of dispersions of this phase generated under certain conditions. The occurrence of the orientational order, i.e. rotation of 'quasinematic' layers of double-stranded DNA molecules by a small angle, defines the formation of spatially twisted (cholesteric) structure with characteristic for it physical and chemical properties.

Surface modification of PTMSP membranes by plasma treatment: Asymmetry of transport in organic solvent nanofiltration.

For the first time, the effect of asymmetry of the membrane transport was studied for organic solvents and solutes upon their nanofiltration through the plasma-modified membranes based on poly(1-trimethylsilyl-1-propyne) (PTMSP). Plasma treatment is shown to provide a marked hydrophilization of the hydrophobic PTMSP surface (the contact angle of water decreases from 88 down to 20°) and leads to the development of a negative charge of -5.2 nC/cm(2). The XPS measurements prove the formation of the oxygen-containing groups (Si-O and C-O) due to the surface modification. The AFM images show that the small-scale surface roughness of the plasma-treated PTMSP sample is reduced but the large-scale surface heterogeneities become more pronounced. The modified membranes retain their hydrophilic surface properties even after the nanofiltration tests and 30-day storage under ambient conditions. The results of the filtration tests show that when the membrane is oriented so that its modified layer contacts the feed solution, the membrane permeability for linear alcohols (methanol-propanol) and acetone decreases nearly two times. When the modified membrane surface faces the permeate, the membrane is seen to regain its transport characteristics: the flux becomes equal to that of the unmodified PTMSP. The well-pronounced effect of the transport asymmetry is observed for the solution of the neutral dye Solvent Blue 35 in methanol, ethanol, and acetone. For example, the initial membrane shows the negative retention for the Solvent Blue 35 dye (-16%) upon its filtration from the ethanol solution whereas, for the modified PTMSP membrane, the retention increases up to 17%. Various effects contributing to the asymmetry of the membrane transport characteristics are discussed.

[Tanning lamp radiation-induced photochemical retinal damage].

On the basis of original clinical research a rare case of bilateral retinal damage due to tanning lamp radiation exposure is presented. Along with significant decrease of visual acuity and light sensitivity of central visual field as well as color vision impairment, bilateral macular dystrophy was found during an ophthalmoscopy and confirmed by optical coherent tomography and fluorescent angiography. Intensive retinoprotective, vascular, and antioxidant therapy was effective and led to functional improvement and stabilization of the pathologic process associated with photochemical retinal damage. A brief review of literature compares mechanisms of retinal damage by either short or long-wave near visible radiation.

[Regarding the so called posterior approach for posterior eye wall foreign body removal].

Disadvantages of the posterior approach for the optic nerve head foreign body removal, especially with associated intraocular hemorrhage, have been analyzed. In such circumstances the transvitreal approach is of an evident benefit since it also allows removing the intraocular hemorrhage which is a potential source of severe vitreoretinal proliferation.

Double-resolution electron holography with simple Fourier transform of fringe-shifted holograms.

We propose a fringe-shifting holographic method with an appropriate image wave recovery algorithm leading to exact solution of holographic equations. With this new method the complex object image wave recovered from holograms appears to have much less traditional artifacts caused by the autocorrelation band present practically in all Fourier transformed holograms. The new analytical solutions make possible a double-resolution electron holography free from autocorrelation band artifacts and thus push the limits for phase resolution. The new image wave recovery algorithm uses a popular Fourier solution of the side band-pass filter technique, while the fringe-shifting holographic method is simple to implement in practice.

ATP-dependent DNA ligase from Thermococcus sp. 1519 displays a new arrangement of the OB-fold domain.

DNA ligases join single-strand breaks in double-stranded DNA by catalyzing the formation of a phosphodiester bond between adjacent 5'-phosphate and 3'-hydroxyl termini. Their function is essential for maintaining genome integrity in the replication, recombination and repair of DNA. High flexibility is important for the function of DNA ligase molecules. Two types of overall conformations of archaeal DNA ligase that depend on the relative position of the OB-fold domain have previously been revealed: closed and open extended conformations. The structure of ATP-dependent DNA ligase from Thermococcus sp. 1519 (LigTh1519) in the crystalline state determined at a resolution of 3.02 Šshows a new relative arrangement of the OB-fold domain which is intermediate between the positions of this domain in the closed and the open extended conformations of previously determined archaeal DNA ligases. However, small-angle X-ray scattering (SAXS) measurements indicate that in solution the LigTh1519 molecule adopts either an open extended conformation or both an intermediate and an open extended conformation with the open extended conformation being dominant.

Adlayers of palladium particles and their aggregates on porous polypropylene hollow fiber membranes as hydrogenization contractors/reactors.

Principal approaches for the preparation of catalytic membrane reactors based on polymer membranes containing palladium nanoparticles and for the description of their characteristics are presented. The method for the development of adlayers composed of palladium nanoparticles and their aggregates on the surface of hydrophobic polypropylene porous hollow fiber membranes is proposed, and their comprehensive study is performed. Various regimes of the deposition of palladium on individual fibers and on membrane surface inside membrane modulus are considered. The sizes of primary Pd particles range from 10 to 500 nm, and dimensions of their aggregates vary from 200 nm to tens of microns. The sizes of primary particles in a free state and in their aggregates are estimated by the methods of X-ray analysis and scanning electron microscopy. The proposed approach is used for the preparation of catalytic membrane contactors/reactors for the removal of dissolved oxygen from water. In the systems under study, the limiting stage of dissolved oxygen removal is concerned with diffusion-controlled delivery of oxygen to the surface of catalytic particles.

SAXS-data-based structural modeling of DNA-gadolinium complexes fixed in particles of cholesteric liquid-crystalline dispersions.

Structure of cholesteric liquid-crystalline dispersions (CLCDs) formed by double-stranded DNA molecules and treated with gadolinium salts was studied by small-angle X-ray scattering (SAXS). The obtained SAXS data open the way for structural modeling of these complexes to obtain a reasonable explanation for the correlated decrease in amplitude of an abnormal negative band in the circular dichroism (CD) spectra and the characteristic Bragg peak in the experimental small-angle X-ray scattering curves observed on treatment of CLCD by gadolinium salts. Model simulations of different kinds of structural organizations of the DNA-gadolinium complex were performed using novel SAXS data analysis methods in combination with several new, complementary modeling techniques, enabling us to build low-resolution three-dimensional structural models of DNA-gadolinium complexes fixed in CLCD particles. The obtained models allow us to suggest that a change takes place in the helical twist of quasinematic layers formed by these molecules at high concentrations of gadolinium salt. This change in the twist can be used to explain the experimentally observed increase in amplitude of an abnormal band in the CD spectra of DNA CLCD.

Effect of solvent phase transitions on enzymatic activity and structure of laccase from Coriolus hirsutus.

The effect of solvent phase transitions on catalytic activity and structure of the active site of laccase produced by the Basidiomycetes Coriolus hirsutus 072 was studied. As shown by small-angle X-ray scattering, laccase exists in solution as a mixture of monomeric and aggregated particles in the percent ratio 85:15. This ratio did not change on phase transitions. A complex nature of laccase activity dynamics during thawing and further heating to 20 degrees C was shown. Spontaneous oxidation of T1 copper center in the temperature range 12-20 degrees C was not observed. According to spectral data, the structure of laccase active sites including all copper centers of types T1, T2, and T3 changes during the phase transition.