Complement mediates binding and procoagulant effects of ultralarge HIT immune complexes.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by ultra-large immune complexes (ULICs) containing immunoglobulin G (IgG) antibodies to a multivalent antigen composed of platelet factor 4 and heparin. The limitations of current antithrombotic therapy in HIT supports the need to identify additional pathways that may be targets for therapy. Activation of FcγRIIA by HIT ULICs initiates diverse procoagulant cellular effector functions. HIT ULICs are also known to activate complement, but the contribution of this pathway to the pathogenesis of HIT has not been studied in detail. We observed that HIT ULICs physically interact with C1q in buffer and plasma, activate complement via the classical pathway, promote codeposition of IgG and C3 complement fragments (C3c) on neutrophil and monocyte cell surfaces. Complement activation by ULICs, in turn, facilitates FcγR-independent monocyte tissue factor expression, enhances IgG binding to the cell surface FcγRs, and promotes platelet adhesion to injured endothelium. Inhibition of the proximal, but not terminal, steps in the complement pathway abrogates monocyte tissue factor expression by HIT ULICs. Together, these studies suggest a major role for complement activation in regulating Fc-dependent effector functions of HIT ULICs, identify potential non-anticoagulant targets for therapy, and provide insights into the broader roles of complement in immune complex-mediated thrombotic disorders.

Nanohybrid Structures Based on Plasmonic or Fluorescent Nanoparticles and Retinal-Containing Proteins.

Rhodopsins are light-sensitive membrane proteins enabling transmembrane charge separation (proton pump) on absorption of a light quantum. Bacteriorhodopsin (BR) is a transmembrane protein from halophilic bacteria that belongs to the rhodopsin family. Potential applications of BR are considered so promising that the number of studies devoted to the use of BR itself, its mutant variants, as well as hybrid materials containing BR in various areas grows steadily. Formation of hybrid structures combining BR with nanoparticles is an essential step in promotion of BR-based devices. However, rapid progress, continuous emergence of new data, as well as challenges of analyzing the entire data require regular reviews of the achievements in this area. This review is devoted to the issues of formation of materials based on hybrids of BR with fluorescent semiconductor nanocrystals (quantum dots) and with noble metal (silver, gold) plasmonic nanoparticles. Recent data on formation of thin (mono-) and thick (multi-) layers from materials containing BR and BR/nanoparticle hybrids are presented.

3D surface topography imaging in SEM with improved backscattered electron detector: Arrangement and reconstruction algorithm.

We propose a new SFS (shape from shading) technique for improved 3D surface reconstruction and imaging of relatively smooth surface topography using the scanning electron microscope (SEM). The new arrangement of backscattered electrons detector plates allows decreasing the initial energy of the electron probe, which makes this SEM technique to be suitable for usage on radiation-sensitive samples like biological tissues. Experiments show high effectiveness of the method, which improves both the gradient sensitivity of the signal and the signal to noise ratio.

Multi-locus sequence analysis reveals a novel sequence type of Chlamydia trachomatis in Saratov Region, Russia.

Chlamydia trachomatis is the causative agent of a variety of chlamydial infections in humans with a predominantly (up to 80%) asymptomatic course of disease. In this study, a potentially novel C. trachomatis sequence type (ST) was detected in an asymptomatic man who has sex with a man among the nine STs revealed in urogenital swabs from individuals with chlamydia (n = 18). Phylogenetically this ST270 clustered separately as a single clade to an ST13-founded group of C. trachomatis strains and differed from the latter by a single allele, hflX. This finding emphasizes the importance of careful investigation of individuals with asymptomatic chlamydia infections.

Backscattered electron detector for 3D microstructure visualization in scanning electron microscopy.

A new configuration of semiconductor detectors for backscattered electrons for a scanning electron microscope (SEM) is presented. The result of the optimization was the possibility to extract the information about the spatial relief (3D topology) of the sample and its subsurface structure (3D tomography) in the simplest way. The detector consists of 8 sensors-semiconductor plates, positioned in a certain way. The proposed method was tested on real structures having a surface micro relief or a subsurface volume structure. Experiments and simple calculations show increased effectiveness and a high signal-noise ratio in the proposed method. This is important, particularly for studying the radiation-sensitive biomedical tissue in SEM.

Control over the relative reactivities of monomers in RAFT copolymerization of styrene and acrylic acid.

The relative monomer reactivities in the reversible addition-fragmentation chain transfer (RAFT) radical copolymerization of styrene (S) and acrylic acid (AA) in a solution of the polar solvent N,N-dimethylformamide are found to be dependent on the chemical nature of the RAFT agent. Polymeric RAFT agents based on polyacrylic acid enhance the difference in monomer reactivities (dithiobenzoate - r AA = 0.09 ± 0.02, r S = 3.5 ± 1.2, trithiocarbonate - r AA = 0.08 ± 0.04, r S = 3.03 ± 1.78) compared to low molecular weight RAFT agents (dibenzyl dithiobenzoate - r AA = 0.14 ± 0.01, r S = 1.00 ± 0.01, dibenzyl trithiocarbonate - r AA = 0.08 ± 0.01, r S = 0.85 ± 0.03). The opposite effect on the relative reactivity of acrylic acid is observed when polymeric RAFT agents based on polystyrene are used (dithiobenzoate - r AA = 3.3 ± 0.4, r S = 0.72 ± 0.05, trithiocarbonate - r AA = 0.11 ± 0.01, r S = 0.54 ± 0.03). In all the investigated systems the copolymers formed are characterized by narrow MWD due to the high efficiency of the chosen RAFT agents.

Supramolecular nanostructures based on bacterial reaction center proteins and quantum dots.

Design of the nanostructures based on membrane proteins (the key functional elements of biomembranes) and colloid nanoparticles is a fascinating field at the interface of biochemistry and colloids, nanotechnology and biomedicine. The review discusses the main achievements in the field of ultrathin films prepared from bacterial reaction center proteins and light-harvesting complexes, as well as these complexes tagged with quantum dots. The principles of preparation of these thin films and their structure and properties at different interfaces are described; as well as their characteristics estimated using a combination of the modern interfacial techniques (absorption and fluorescence spectroscopy, atomic force and Brewster angle microscopy, etc.) are discussed. Further approaches to develop the nanostructures based on the membrane proteins and quantum dots are suggested. These supramolecular nanostructures are promising prototypes of the materials for photovoltaic, optoelectronic and biosensing applications.

Fabrication of digital rainbow holograms and 3-D imaging using SEM based e-beam lithography.

Here we present an approach for creating full-color digital rainbow holograms based on mixing three basic colors. Much like in a color TV with three luminescent points per single screen pixel, each color pixel of initial image is presented by three (R, G, B) distinct diffractive gratings in a hologram structure. Change of either duty cycle or area of the gratings are used to provide proper R, G, B intensities. Special algorithms allow one to design rather complicated 3D images (that might even be replacing each other with hologram rotation). The software developed ("RainBow") provides stability of colorization of rotated image by means of equalizing of angular blur from gratings responsible for R, G, B basic colors. The approach based on R, G, B color synthesis allows one to fabricate gray-tone rainbow hologram containing white color what is hardly possible in traditional dot-matrix technology. Budgetary electron beam lithography based on SEM column was used to fabricate practical examples of digital rainbow hologram. The results of fabrication of large rainbow holograms from design to imprinting are presented. Advantages of the EBL in comparison to traditional optical (dot-matrix) technology is considered.

Dynamic spin polarization by orientation-dependent separation in a ferromagnet-semiconductor hybrid.

Integration of magnetism into semiconductor electronics would facilitate an all-in-one-chip computer. Ferromagnet/bulk semiconductor hybrids have been, so far, mainly considered as key devices to read out the ferromagnetism by means of spin injection. Here we demonstrate that a Mn-based ferromagnetic layer acts as an orientation-dependent separator for carrier spins confined in a semiconductor quantum well that is set apart from the ferromagnet by a barrier only a few nanometers thick. By this spin-separation effect, a non-equilibrium electron-spin polarization is accumulated in the quantum well due to spin-dependent electron transfer to the ferromagnet. The significant advance of this hybrid design is that the excellent optical properties of the quantum well are maintained. This opens up the possibility of optical readout of the ferromagnet's magnetization and control of the non-equilibrium spin polarization in non-magnetic quantum wells.

[Clinical peculiarities of posttraumatic arteriovenous fistulas].

Analysed herein are clinical manifestations of, and outcomes of successful surgical management for postoperative arteriovenous fistulas.

The spatial dynamics of fibrin clot dissolution catalyzed by erythrocyte-bound vs. free fibrinolytics.

SUMMARY BACKGROUND: Coupling fibrinolytic plasminogen activators to red blood cells (RBCs) has been proposed as an effective, yet safe method of thromboprophylaxis, because of increased circulation lifetime and reduced propensity to induce hemorrhage by selectivity for nascent thrombi rather than pre-formed hemostatic clots. OBJECTIVES AND METHODS: We used confocal microscopy of fluorescently labeled fibrin and erythrocytes in plasma-derived clots to study the spatial dynamics of lysis catalyzed by RBC-coupled vs. free plasminogen activators (RBC-PA vs. PA). RESULTS: Clot lysis catalyzed by free PA progressed gradually and uniformly. In contrast, distinct holes formed surrounding RBC-PA while the rest of the clot remained intact until these holes enlarged sufficiently to merge, causing sudden clot dissolution. Compared with naïve RBCs within clots lysed by free PA, RBC-PA moved faster inside the fibrin network prior to clot dissolution, providing a potential mechanism for spatial propagation of RBC-PA induced lysis. We also showed the focal nature of fibrinolysis by RBC-PA as dense loading of PA onto RBCs initiates more efficient lysis than equal amounts of PA spread sparsely over more RBCs. In an in vitro model of clots exposed to buffer flow, incorporated RBC-PA increased permeability and formed channels eventually triggering clot dissolution, whereas clots containing free PA remained intact. CONCLUSIONS: Clot lysis by RBC-PA begins focally, has a longer lag phase when measured by residual mass than homogeneous lysis by PA, is propagated by RBC-PA motility and provides more effective clot reperfusion than free PA, making RBC-PA attractive for short-term thromboprophylaxis.

[Efficacy of prostaglandin E1 and systemic antibacterial therapy application in patients with diabetes mellitus and purulent-necrotic lesions of the foot].

The results of prostaglandin E1 et systemic antibacterial therapy use in 1836 patients, suffering purulent-necrotic affection of foot, were summarized. There was established, that cefuroxym constitutes the first line preparation for the ostheoarthropathy focus elimination, when the affection is limited and the patient state is stable, and meronem--for extended affection and unstable patient's state. In the pronounced ischemia of the foot the initial administration of cefepim is the most effective. For purulent-necrotic affection as a consequence of the foot wounding, erysipelas or operative intervention it is expedient to use carbapenem or meropenem. The systemic antibacterial therapy administration had promoted significant reduction of the treatment duration and improvement of its result.

[A case report of successful surgical management for a combined wound of the neck with a rare variant of an injury of the vertebral artery].

Presented herein is a clinical case report regarding successful surgical management of a male patient presenting with a concomitant injury of the neck and involvement of the second portion of the contralateral vertebral artery.

Immunohistochemical analysis of beta-defensin-2 expression in human lung tumors.

AIM: The present research was directed on analysis of the expression patterns of human beta-defensin-2 (hBD-2) in human lung tumors. MATERIALS AND METHODS: Specimens of surgically resected human lung tumors (n = 31) of different histological type (1 case of small cell lung cancer, and 30 cases of non-small cell lung cancer (1 case of clear cell carcinoma, 9 cases of squamous cell carcinoma (SCC), and 20 cases of adenocarcinoma (AC)) were analyzed for expression of hBD-2 with the use of immunohistochemical analysis. RESULTS: Immunohistochemical analysis has revealed that all lung tumor samples independently on their histological type express hBD-2 peptide, however at different levels (from < 5% to 100% cells). According to our observations, low-differentiated AC differs from moderately differentiated AC by significantly lower hBD-2 expression levels (p < 0.05). No correlation between hBD-2 expression patterns and PCNA or Bcl-2 expression has been found. CONCLUSION: Human beta-defensin-2 expression levels may depend on differentiation grade of lung adenocarcinoma.

[A case report of successful surgical management of lower-limb critical ischaemia on the background of femoropopliteal atherosclerotic aneurysms].

Presented herein is a case report of successful surgical management of a male patient presenting with lower-limb critical ischaemia on the background of thrombosis of femoropopliteal atherosclerotic aneurysms and the presence of a necrobiotic process on the stump of the foot. The reconstructive intervention performed resulted in salvation of the extremity, followed by uneventful wound healing on his left foot with complete medical and social rehabilitation of the patient.

Organization of butadienyl dyes containing benzodithiacrown-ether or dimethoxybenzene in monolayers at the air/aqueous salt solution interface.

Two amphiphilic butadienyl dyes 1 and 2 form stable monolayers at the air/water interface in the presence of various salts. Dye 1 consists of the basic amphiphilic butadienyl chromophore. In dye 2, the dimethoxybenzene part of dye 1 is substituted by benzodithia-15-crown-5. The monolayers have been characterized by surface pressure-area and surface potential-area isotherms as well as Brewster angle microscopy and reflection spectroscopy. In contrast to dye 1, dye 2 interacts specifically with Hg(2+) and Ag(+) cations forming complexes. No complex formation was observed with alkali and earth alkali metal ions. The nature of the anion (Cl(-) or ClO(4)(-)) influences the monolayer behaviour of both dyes. At the air/water interface, besides monomers of the dyes, two types of associates are coexisting in the pure dye monolayers on aqueous salt solutions, attributed to dimers and aggregates, respectively. Their equilibria depend on the nature of both cations and anions in the subphase, as in the case of dye 2, or only anions, as in the case of dye 1. The dimers may be organized as head-to-tail dimers with the intermolecular distances 0.38 and 0.45nm for dye 1 and dye 2, respectively. According to the extended dipole model, we propose formation of aggregates in which the chromophores are parallel to each other with the same intermolecular distances as in the dimers, and the centers of their transition moments shifted by 0.95nm (dye 1) and 1.2nm (dye 2).

Fabrication and analysis of Cr-doped ZnO nanoparticles from the gas phase.

High quality Cr-doped ZnO nanoparticles from the gas phase were prepared and investigated with respect to their structural, optical and magnetic properties. The extended x-ray absorption fine structure and the x-ray absorption near edge structure of the particles verify that after nanoparticle preparation Cr is incorporated as Cr3+ ) at least partially on sites with a 4-fold oxygen configuration, most likely on a Zn site, into the wurtzite lattice. Despite the fact that Cr is known to act as an efficient non-radiative loss centre for near band gap emission (NBE), a pronounced NBE is obtained up to room temperature even for a nominal Cr concentration of 10 at.%. Annealing at 1000 degrees C results in a significant improvement of the photoluminescence efficiency and a reduced PL linewidth down to 2.9 meV at low temperatures while the structural and magnetic data indicate the formation of ZnCr2O4 clusters.

The imidazoline RX871024 induces death of proliferating insulin-secreting cells by activation of c-jun N-terminal kinase.

An insufficient number of insulin-producing beta-cells is a major cause of defective control of blood glucose in both type 1 and type 2 diabetes. The aim of this study was to clarify whether the insulinotropic imidazolines can affect the survival of highly proliferating insulin-secreting cells, here exemplified by the MIN6 cell line. Our data demonstrate that RX871024, but not efaroxan, triggered MIN6 cell death and potentiated death induced by a combination of the pro-inflammatory cytokines interleukin-1beta, interferon- gamma and tumor necrosis factor-alpha. These effects did not involve changes in nitric oxide production but correlated with stimulation of c-jun N-terminal kinase (JNK) activity and activation of caspases-1, -3, -8 and -9. Our results suggest that the imidazoline RX871024 causes death of highly proliferating insulin-secreting cells, putatively via augmentation of JNK activity, a finding that may impact on the possibility of using compounds of similar activity in the treatment of diabetes.

[A case of successful surgical management of a patient with acute thrombosis of the abdominal aorta and complicated gastric ulcer].

The authors describe a case report of surgical management of a patient presenting with a clinical picture of ascending thrombosis of the abdominal aorta on the background of Leriche's syndrome and perforated gastric ulcer complicated by penetration and haemorrhage.

Arachidonic acid signaling is involved in the mechanism of imidazoline-induced KATP channel-independent stimulation of insulin secretion.

The mechanism by which the novel, pure glucose-dependent insulinotropic, imidazoline derivative BL11282 promotes insulin secretion in pancreatic islets has been investigated. The roles of KATP channels, alpha2-adrenoreceptors, the I1-receptor-phosphatidylcholine-specific phospholipase (PC-PLC) pathway and arachidonic acid signaling in BL11282 potentiation of insulin secretion in pancreatic islets were studied. Using SUR1(-/-) deficient mice, the previous notion that the insulinotropic activity of BL11282 is not related to its interaction with KATP channels was confirmed. Insulinotropic activity of BL11282 was not related to its effect on alpha2-adrenoreceptors, I1-imidazoline receptors or PC-PLC. BL11282 significantly increased [3H]arachidonic acid production. This effect was abolished in the presence of the iPLA2 inhibitor, bromoenol lactone. The data suggest that potentiation of glucose-induced insulin release by BL11282, which is independent of concomitant changes in cytoplasmic free Ca2+ concentration, involves release of arachidonic acid by iPLA2 and its metabolism to epoxyeicosatrienoic acids through the cytochrome P-450 pathway.