Possibilities of Endovascular Hemostasis in Treatment of Pancreatic Bleeding.

Pancreatic hemorrhage is one of the most severe complications of various pancreatic diseases that are difficult to treat even in multidisciplinary hospitals. Mortality from pancreatic hemorrhage can reach up to 80%. This study aimed to evaluate the possibility of maintaining endovascular homeostasis in the treatment of patients with pancreatic hemorrhage. This retrospective multicenter study included 45 patients (33 men and 12 women) in the age range of 27-84 years. More than 50% (n=23) of the patients were diagnosed with chronic pancreatitis. Malignant pancreatic lesions were observed in 22 patients; of whom11 patients had acute necrotizing pancreatitis. Acute bleeding was observed in 39 (86.6%) patients, and 6 (13.3%) patients showed chronic symptoms. Single-shot and recurrent bleeding was recorded in 22(48.9%) and 23 (51.1%) patients. In total, 57 patients underwent endovascular surgery. Moreover, 45 patients underwent primary surgery and another 12 (2.2%) underwent reoperation due to recurrent bleeding. Intraoperative complications occurred in 1 (2.2%) patient, and postoperative complications occurred in another. Out of all 45 patients, seven patients had 15 episodes of recurrent bleeding, of whom four patients showed recurrent bleeding at the in-hospital period, and the other three were under local supervision after the previous endovascular intervention. Out of the 45 patients, 35 (77.7%) survived and another 10 (22.2%) died due to multiple organ failure (n=8) and recurrent bleeding and hemorrhagic shock (n=2). Out of 10 patients who died, 4, 3, and 3patients showed malignant pancreatic lesions after surgery, acute pancreatitis, and chronic pancreatitis, respectively. Endovascular hemostatic interventions can significantly increase the survival rate in severe groups of patients with pancreatic bleeding. Endovascular hemostasis is a safe procedure and may be called the "method of choice" in the treatment of pancreatic bleeding, especially in combination with percutaneous draining, aspiration, and injection of liquid embolic agents into leakage of pancreatic juice.

Cationic Antiseptics Facilitate Pore Formation in Model Bacterial Membranes.

Antiseptics are an essential line of defense against bacterial and viral infections in modern medical practice. Many of them are supposed to act on microbial membranes. However, the detailed mechanisms of their action are still elusive. Here, we utilized coarse-grained molecular dynamics simulations to investigate interactions of different types of cationic antiseptics (CAs) with a model bacterial membrane. The simulations revealed qualitatively distinct patterns of dynamic and structural alterations of membrane induced by different types of antiseptics although none of them caused disintegration or solubilization of the bilayer even at the highest explored concentration. At the same time, the adsorption of antiseptics rendered membranes more vulnerable to poration under exposure to the external electric field. We further discuss the possible relation of the enhanced pore formation induced by CAs to their cytotoxic action.

[The remote results of treatment of ischemic stroke conditioned by atherosclerotic affection of carotid arteries].

The ischemic stroke is a disease that leads to dysfunctions in life of any individual. The mortality rate of cerebral infarcts reaches up to 39%. Besides, the most acute period of an ischemic stroke, which lasts up to 5-7 days, is especially problematic and is characterized by the highest mortality. The first day of disease results in 21.74% of deaths (out of the total annual number of deaths). The article presents the results of the analysis of treatment of the patients with ischemic stroke caused by the atherosclerosis of brachiocephalic arteries. The role of endovascular technologies in the treatment of the acute cerebrovascular cases has not been fully revealed. The retrospective analysis of treatment of 171 patients with atherosclerotic subtype of ischemic stroke was carried out. The patients were distributed in two groups: in the first group (83 patients) the applied conservative therapy was supplemented by endovascular intervention during the acute period of ischemic insult; in the second group (88 patients) the conservative therapy alone was applied. Both groups were comparable in terms of gender, age and associated diseases. The risk factors of ischemic insult were analyzed such as IHD that requires surgery; hypertensive disease; hypercholesterolemia; ischemic insult in medical history; heart dysrhythmia; diabetes mellitus. All patients had more than one risk factor. There mortality, incapacitation, degree of neurological impairment, frequency of symptoms of hemorrhagic suffusion and of hemorrhagic transformation were analyzed. The remote results were analyzed in sampling of 54 patients: 32 patients from the first group, 22 patients from the second group. The quality of life was measured using technique of non-specific survey SF-36 when its 36 items were grouped into eight scales: physical functioning, role activity, body pain, general health, vitality, social functioning, emotional state, psychological health. The degree of incapacitation was measured with the modified Rankin scale, the quality of life was examined with the SF-36 survey, the survival rate was measured with the Kaplan-Meier estimator. The statistical analysis was carried out with the help of the Statistica 6.0 software.

Influence of pH and ionic strength on electrostatic properties of ferredoxin, FNR, and hydrogenase and the rate constants of their interaction.

Ferredoxin (Fd) protein transfers electrons from photosystem I (PSI) to ferredoxin:NADP+-reductase (FNR) in the photosynthetic electron transport chain, as well as other metabolic pathways. In some photosynthetic organisms including cyanobacteria and green unicellular algae under anaerobic conditions Fd transfers electrons not only to FNR but also to hydrogenase-an enzyme which catalyzes reduction of atomic hydrogen to H2. One of the questions posed by this competitive relationship between proteins is which characteristics of thylakoid stroma media allow switching of the electron flow between the linear path PSI-Fd-FNR-NADP+ and the path PSI-Fd-hydrogenase-H2. The study was conducted using direct multiparticle simulation approach. In this method protein molecules are considered as individual objects that experience Brownian motion and electrostatic interaction with the surrounding media and each other. Using the model we studied the effects of pH and ionic strength (I) upon complex formation between ferredoxin and FNR and ferredoxin and hydrogenase. We showed that the rate constant of Fd-FNR complex formation is constant in a wide range of physiologically significant pH values. Therefore it can be argued that regulation of FNR activity doesn't involve pH changes in stroma. On the other hand, in the model rate constant of Fd-hydrogenase interaction dramatically depends upon pH: in the range 7-9 it increases threefold. It may seem that because hydrogenase reduces protons it should be more active when pH is acidic. Apparently, regulation of hydrogenase's affinity to both her reaction partners (H+ and Fd) is carried out by changes in its electrostatic properties. In the dark, the protein is inactive and in the light it is activated and starts to interact with both Fd and H+. Therefore, we can conclude that in chloroplasts the rate of hydrogen production is regulated by pH through the changes in the affinity between hydrogenase and ferredoxin.

The role of electrostatic interactions in the process of diffusional encounter and docking of electron transport proteins.

Electrostatic interaction of plastocyanin and cytochrome f in the process of protein-protein complex formation was investigated by computer simulation methods. It was shown that long-range electrostatic interaction promotes energetically favorable mutual orientation of protein molecules at distances between their cofactors shorter than 5 nm. At distances shorter than 3 nm, these electrostatic interactions lead to a significantly detectable increase in the rate of convergence of the cofactors.

[Identification of Intermediate States of Electron Transfer Proteins Plastocyanin and Cytochrome f in the Process of Diffusional Encounter].

The Brownian dynamics method is used for qualitative analysis of events leading to formation of a functionally active plastocyanin-cytochrome f complex. Intermediate states of this process are identified by density-based hierarchical clustering. Diffusive entrapment of plastocyanin by cytochrome f is a key point of the suggested putative scenario of protein-protein approaching. Mobility of plastocyanin is characterized for different values of protein-protein electrostatic interaction energy.

[Brownian dynamics simulations of protein-protein interactions in photosynthetic electron transport chain].

The application of Brownian dynamics for simulation of transient protein-protein interactions is reviewed. The review focuses on theoretical basics of Brownian dynamics method, its particular implementations, advantages and drawbacks of the method. The outlook for future development of Brownian dynamics-based simulation techniques is discussed. Special attention is given to analysis of Brownian dynamics trajectories. The second part of the review is dedicated to the role of Brownian dynamics simulations in studying photosynthetic electron transport. Interactions of mobile electron carriers (plastocyanin, cytochrome c6, and ferredoxin) with their reaction partners (cytochrome b6f complex, photosystem I, ferredoxin:NADP-reductase, and hydrogenase) are considered.

[Multiparticle computer simulation of protein interactions in the photosynthetic membrane].

The basic principles of the design of direct multiparticle models and the results of multiparticle computer simulation of electron transfer by mobile protein carriers in the photosynthetic membrane of a chloroplast thylakoid are presented. The reactions of complex formation of the protein plastocyanin with the protein cytochrome f and the pigment-protein complex of photosystem I, as well as of the protein ferredoxin with the protein FNR and photosystem 1 are considered. The role of diffusion and electrostatic interactions is discussed, and the effect of the shape of the reaction volume and ionic strength on the rate of electron transport are discussed.

Direct computer simulation of ferredoxin and FNR complex formation in solution.

Ferredoxin reduced by Photosystem I in light serves as an electron donor for the reduction of NADP(+) to NADPH, and this reaction is catalyzed by enzyme ferredoxin:NADP(+)-reductase (FNR). Kinetics and mechanisms of this reaction have been extensively studied experimentally by site-specific mutagenesis, laser flash photolysis and stopped-flow methods. We have applied a method of multiparticle computer simulation to study the effects of electrostatic interactions upon the reaction rate of Fd-FNR complex formation. Using the model we calculated rate constants of Fd-FNR complex formation for the wild-type proteins and some mutant forms of FNR at different values of ionic strength. Simulation revealed that electrostatic interactions play an important role in Fd-FNR complex formation and define its specificity.

[Mathematical and computer modeling of primary processes of photosynthesis].

The results of recent works on kinetic and direct multipartial computer modeling of processes in the photosynthetic membrane, performed at the chair of biophysics of the Biological faculty of the Moscow State University are reviewed. The models take the current experimental data on the heterogeneous structure and kinetic characteristics of the system into account. The generalized kinetic model describes the processes in multienzyme complexes of Photosystems 1 and 2 and the cytochrome complex, coupled transmembrane ionic currents, and the generation of electric and electrochemical potential. The identification of the parameters of the models allows one to estimate the rate constants for reactions that cannot be measured experimentally. The multicomponent models give a clear picture of the interaction of components of the electron transport chain in the lumen and the tylakoid stroma and simulate in an explicit form the Brown diffusion and electrostatic interactions of protein carriers. The combination of different methods of description (differential equations and formalism of Brown dynamics) allows one to model the processes in a complex three-dimensional interior of a vegetative cell that collectively provide a high efficiency of energy transformation in photosynthesis.

[Computer simulation of complex formation between plastocyanine and cytochrome f in thylakoid lumen].

The diffusion of the protein plastocyanine and complex formation between plastocyanine and cytochrome f (a subunit of a cytochrome b6/f complex) in the chloroplast thylakoid lumen has been studied. A 3D computer simulation model of diffusion and binding of plastocyanine and cytochrome f has been constructed, which considers their electrostatic interaction. Based on the experimental data, the parameters of the model for complex formation between plastocyanine and cytochrome f in solution have been estimated. The dependence of the rate of plastocyanine-cytochrome f reaction on the size of the luminal space has been studied. It was shown that the contraction of the luminal space leads to a decrease in the reaction rate, which is in agreement with the experimental data on the inhibition of the reaction under hyperosmotic stress.

[Multiparticle computer simulation of photosynthetic electron transport in a thylakoid membrane].

A method for multiparticle computer simulation of photosynthetic electron transport in a thylakoid membrane has been developed. The basic principles of this method were described previously. The method is used to describe the cyclic electron flow around photosystem I. The effects of size and shape of the reaction volume on the kinetics of interaction of a mobile carrier with a protein complex and the limited diffusion of reactants were studied. It was shown that the kinetic parameters of photosynthetic electron transport processes depend on the distribution of protein complexes in the membrane. It was shown that the limited nature of diffusion of plastoquinone molecules in the membrane leads to a tenfold decrease in the efficient diffusion coefficient. It was shown that the occurrence of two phases of dark reduction of photooxidized P700+ is due to a heterogeneous spatial organization of the thylakoid membrane of a chloroplast.

Direct simulation of plastocyanin and cytochrome f interactions in solution.

Most biological functions, including photosynthetic activity, are mediated by protein interactions. The proteins plastocyanin and cytochrome f are reaction partners in a photosynthetic electron transport chain. We designed a 3D computer simulation model of diffusion and interaction of spinach plastocyanin and turnip cytochrome f in solution. It is the first step in simulating the electron transfer from cytochrome f to photosystem 1 in the lumen of thylakoid. The model is multiparticle and it can describe the interaction of several hundreds of proteins. In our model the interacting proteins are represented as rigid bodies with spatial fixed charges. Translational and rotational motion of proteins is the result of the effect of stochastic Brownian force and electrostatic force. The Poisson-Boltzmann formalism is used to determine the electrostatic potential field generated around the proteins. Using this model we studied the kinetic characteristics of plastocyanin-cytochrome f complex formation for plastocyanin mutants at pH 7 and a variety of ionic strength values.

[Experimental and theoretical study of processes of cyclical electron transport around photosystem I]. / Ekspeirmental'noe i teoreticheskoe issledovanie protsessov tsiklicheskgo élektronnogo transporta vokrug fotosistemy I.

The kinetics of photoinduced EPR I signals at different concentrations of ferredoxin was studied on isolated pea chloroplasts. A kinetic model of ferredoxin-dependent electron transport around photosystem I was suggested. A multiparticle model was constructed, which makes it possible to "directly" model the processes of electron transfer in multiprotein complexes and limited diffusion in different compartments of the system (stroma, lumen, and intermembrane space). A comparison of the kinetic and "direct" models revealed an important role of spatial organization of the system in the kinetics of redox turnover of P700.