[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.

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.

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.

[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.

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.

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.

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.

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.

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.

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.

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.

Position-sensitive diffractive imaging in STEM by an automated chaining diffraction algorithm.

The diffractive imaging process used for retrieval of an aberration-free exit-wave function of a complex-valued object is optimized with a newly developed automated chaining diffraction (ACD) algorithm. Our algorithm enables automatic recovery of the amplitude and phase of the complex-valued objects with diffraction-limited resolution, starting from selected-area electron diffraction (SAED) patterns recorded from partially overlapping regions in STEM/CTEM. Based on a 'differential map' (DM) approach, the ACD algorithm meets very general requirements and, similar to 'hybrid input-output' (HIO) algorithm, can be applied to non-periodic, real or complex structures. In contrast to many other algorithms, it is not limited by the object's finite size or tight object support. Wide-field-of-view reconstructions for the complex-object-wave amplitude and phase made with ACD algorithm from SAED patterns down to sub-Angström resolution show the potential of diffractive imaging for quantitative analysis of functional materials at different length scales in terms of absorption and scattering mechanisms. The method can be applied also for imaging magnetic properties of samples by the electron or neutron microscopy and/or imaging of non-periodic objects with X-ray microscopy.

[Effect of weak static magnetic fields on the excitability of a neuron].

Changes in the excitability of the neuron (amplitude, excitability threshold, rate of action potential transduction), as well as changes in the viscosity of the plasma membrane of the nerve and membranes of subcellular organelles, induced by the action of a weak magnetic field, have been studied by the methods of extracellular registration of membrane potential and combination scattering. It was found that only the threshold of excitability in intact nervous fibers increases by the action of this field. It was proven that the conformation of C40 carotenoids localized not only in plasma membranes but also in subcellular membranes of the neuron changes in a weak magnetic field. It is assumed that the changes in the excitability of the neuron by the action of weak magnetic field are due to changes in the orderliness of membrane lipids and the content of oxygen in the cytoplasm.

[Yustova's threshold tables for examination of color vision and the results of their clinical application].

The paper describes the stages of development of unique tests for strict threshold estimation of the color power of each retinal color (red, green, and blue) perception under the direction of Ye. N. Yustova. These threshold tables are shown to be more informative in the diagnosis of both congenital and acquired color visual disorders than all other existing appliances intended for either evaluation of color anomaly or detection of chromaticity (rather than color as an item of three components!). Due to their high informative value and, at the same time, easiness-to-use, and cheapness, the tables developed by Yustova et al. should be an obligatory attribute of an ophthalmologist's work place. For this, they should be reissued, by taking into account comments on the first edition, which are mentioned in the paper.

[Present-day battle injury to the eye and principles of delivery of specialized ophthalmological care to victims].

The paper considers the armament development ultimately resulting in the predominance of using minor blasting assemblies and accordingly to a drastic prevalence (as high as 80%) of mine explosion injuries among other battle injuries to the eye. The particular severity of these injuries requires their efficient subdivision into types and severity, which is alleviated by the introduction of a new classification of mechanical injuries into the eyeball. It is obligatory for each ophthalmologist to know this classification. It is the ophthalomologist who may be the first specialist to start rendering an aid to the victim. In terms of the highest level of development of modern ophthalmological diagnosis and intraocular eye surgery, delivery of a patient to a specialized eye traumatological center where he/she will be given a comprehensive aid, including an intraocular one, in 3-7 days rather than the promptest surgical debridement (generally as just wound closure) is a master link in obviating the losses associated with eye injury. There is evidence that the same interregional centers as the army centers that have operated in Kabul and Rostov-on-Don should be set up preferably on the basis of multidisciplinary hospitals in the civil health care system. They could become an original testing area for researches of explosive injuries to the eye and a source of materials for making the centralized national register of eye injury.

Solution scattering structural analysis of the 70 S Escherichia coli ribosome by contrast variation. II. A model of the ribosome and its RNA at 3.5 nm resolution.

Selectively deuterated 70 S E. coli ribosomes and isolated 30 S and 50 S subunits were analyzed by X-ray and neutron solution scattering. The resulting contrast variation data set (42 curves in total) was proven to be consistent in describing the ribosome as a four-phase system composed of the protein and rRNA moieties of both subunits. This data set thus provides ten times more information than a single scattering curve. A solid body four-phase model of the 70 S ribosome at low resolution was built from the envelope functions of the 30 S and 50 S subunits and of those of the corresponding RNA moieties. The four envelopes were parameterized at a resolution of 3.5 nm using spherical harmonics and taking into account interface layers between the phases. The initial approximation for the envelopes of the subunits was taken from electron microscopic data presented recently by J. Frank and co-workers (Albany); the rRNA envelopes were initially approximated by spheres. The optimization and the refinement of the model proceeded by non-linear least squares minimization fitting the available experimental data. The refined envelopes of the subunits differ by about 10% from the starting approximation and the shape of the final 70 S model lies between the outer envelopes of the models by Frank and by M. von Heel & R. Brimacombe (Berlin). The rRNA moiety in the 30 S subunit is more anisometric than the subunit itself, whereas the rRNA of the 50 S subunit forms a compact core. The rRNAs protrude to the surfaces of the subunits and occupy approximately 30 to 40% of the corresponding surface areas. X-ray scattering curves of the two main functional elongation 70 S complexes (pre- and post-translocational) differ only marginally from those of the non-programmed ribosomes, suggesting that the low resolution four-phase model is also valid for the elongating 70 S ribosome.