Features of Bacteriochlorophylls Axial Ligation in the Photosynthetic Reaction Center of Purple Bacteria.

This review focuses on recent experimental data obtained by site-directed mutagenesis of the reaction center in purple nonsulfur bacteria. The role of axial ligation of (bacterio)chlorophylls in the regulation of spectral and redox properties of these pigments, as well as correlation between the structure of chromophores and nature of their ligands, are discussed. Cofactor ligation in various types of reaction centers is compared, and possible reasons for observed differences are examined in the light of modern ideas on the evolution of photosynthesis.

[Specific Features of Pharmacotherapy of Patients With Chronic Heart Failure and Preserved Left Ventricular Ejection Fraction].

The review is devoted to pharmacotherapy of chronic heart failure (CHF) with preserved left ventricular ejection fraction. In this review we discuss data of meta-analyzes of randomized clinical trials and observational studies, as well as the indications for use of inhibitors of the renin-angiotensin-aldosterone system, ß-blockers, and antagonists of mineralocorticoid receptors in these patients in current clinical guidelines. New approaches to therapy of CHF from the perspective of influence on myocardial fibrosis are considered in this review.

The site-directed mutation I(L177)H in Rhodobacter sphaeroides reaction center affects coordination of P(A) and B(B) bacteriochlorophylls.

To explore the influence of the I(L177)H single mutation on the properties of the nearest bacteriochlorophylls (BChls), three reaction centers (RCs) bearing double mutations were constructed in the photosynthetic purple bacterium Rhodobacter sphaeroides, and their properties and pigment content were compared with those of the correspondent single mutant RCs. Each pair of the mutations comprised the amino acid substitution I(L177)H and another mutation altering histidine ligand of BChl P(A) or BChl B(B). Contrary to expectations, the double mutation I(L177)H+H(L173)L does not bring about a heterodimer RC but causes a 46nm blue shift of the long-wavelength P absorbance band. The histidine L177 or a water molecule were suggested as putative ligands for P(A) in the RC I(L177)H+H(L173)L although this would imply a reorientation of the His backbone and additional rearrangements in the primary donor environment or even a repositioning of the BChl dimer. The crystal structure of the mutant I(L177)H reaction center determined to a resolution of 2.9Å shows changes at the interface region between the BChl P(A) and the monomeric BChl B(B). Spectral and pigment analysis provided evidence for ß-coordination of the BChl B(B) in the double mutant RC I(L177)H+H(M182)L and for its hexacoordination in the mutant reaction center I(L177)H. Computer modeling suggests involvement of two water molecules in the ß-coordination of the BChl B(B). Possible structural consequences of the L177 mutation affecting the coordination of the two BChls P(A) and B(B) are discussed. This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: from Natural to Artificial.

Pressurized H2 RF cavities in ionizing beams and magnetic fields.

A major technological challenge in building a muon cooling channel is operating rf cavities in multitesla external magnetic fields. We report the first proof-of-principle experiment of a high pressure gas-filled rf cavity for use with intense ionizing beams and strong external magnetic fields. rf power consumption by beam-induced plasma is investigated with hydrogen and deuterium gases with pressures between 20 and 100 atm and peak rf gradients between 5 and 50 MV/m. The low pressure case agrees well with an analytical model based on electron and ion mobilities. Varying concentrations of oxygen gas are investigated to remove free electrons from the cavity and reduce the rf power consumption. Measurements of the electron attachment time to oxygen and rate of ion-ion recombination are also made. Additionally, we demonstrate the operation of the gas-filled rf cavity in a solenoidal field of up to 3 T, finding no major magnetic field dependence. All these results indicate that a high pressure gas-filled cavity is a viable technology for muon ionization cooling.

Charge separation in Rhodobacter sphaeroides mutant reaction centers with increased midpoint potential of the primary electron donor.

Primary charge separation dynamics in four mutant reaction centers (RCs) of the purple bacterium Rhodobacter sphaeroides with increased midpoint potential of the primary electron donor P (M160LH, L131LH, M197FH, and M160LH + L131LH + M197FH) have been studied by femtosecond transient absorption spectroscopy at room temperature. The decay of the excited singlet state in the wild-type and mutant RCs is complex and has two main exponential components, which indicates heterogeneity of electron transfer rates or the presence of reverse electron transfer reactions. The radical anion band of monomeric bacteriochlorophyll B(A) at 1020 nm was first observed in transient absorbance difference spectra of single mutants. This band remains visible, although with somewhat reduced amplitude, even at delays up to tens of picoseconds when stimulated emission is absent and the reaction centers are in the P(+)H(A)(-) state. The presence of this band in this time period indicates the existence of thermodynamic equilibrium between the P(+)B(A)(-)H(A) and P(+)B(A)H(A)(-) states. The data give grounds for assuming that the value of the energy difference between the states P*, P(+)B(A)(-)H(A), and P(+)B(A)H(A)(-) at early times is of the same order of magnitude as the energy kT at room temperature. Besides, monomeric bacteriochlorophyll B(A) is found to be an immediate electron acceptor in the single mutant RCs, where electron transfer is hampered due to increased energy of the P(+)B(A)(-) state with respect to P*.

Higher order spin resonances in a 2.1-GeV/c polarized proton beam.

Spin resonances can depolarize or spin flip a polarized beam. We studied 1st and higher order spin resonances with stored 2.1 GeV/c vertically polarized protons. The 1st order vertical (ν(y)) resonance caused almost full spin flip, while some higher order ν(y) resonances caused partial depolarization. The 1st order horizontal (ν(x)) resonance caused almost full depolarization, while some higher order ν(x) resonances again caused partial depolarization. Moreover, a 2nd order ν(x) resonance is about as strong as some 3rd order ν(x) resonances, while some 3rd order ν(y) resonances are much stronger than a 2nd order ν(y) resonance. One thought that ν(y) spin resonances are far stronger than ν(x), and that lower order resonances are stronger than higher order; the data do not support this.

Structure-function investigations of bacterial photosynthetic reaction centers.

During photosynthesis light energy is converted into energy of chemical bonds through a series of electron and proton transfer reactions. Over the first ultrafast steps of photosynthesis that take place in the reaction center (RC) the quantum efficiency of the light energy transduction is nearly 100%. Compared to the plant and cyanobacterial photosystems, bacterial RCs are well studied and have relatively simple structure. Therefore they represent a useful model system both for manipulating of the electron transfer parameters to study detailed mechanisms of its separate steps as well as to investigate the common principles of the photosynthetic RC structure, function, and evolution. This review is focused on the research papers devoted to chemical and genetic modifications of the RCs of purple bacteria in order to study principles and mechanisms of their functioning. Investigations of the last two decades show that the maximal rates of the electron transfer reactions in the RC depend on a number of parameters. Chemical structure of the cofactors, distances between them, their relative orientation, and interactions to each other are of great importance for this process. By means of genetic and spectral methods, it was demonstrated that RC protein is also an essential factor affecting the efficiency of the photochemical charge separation. Finally, some of conservative water molecules found in RC not only contribute to stability of the protein structure, but are directly involved in the functioning of the complex.

[Evolution of oral drug forms of metoprolol: advantages of long acting modified release forms with modified release].

Review oral modified release drug forms of beta-adrenoblocker metoprolol which is used in arterial hypertension and ischemic heart disease is presented. Metoprolol has salts such as tartrate which is used for production of immediate release (IR) and sustained release (SR) forms and succinate used for production of controlled release form (CR/XL). Metoprolol SR has monolith matrix type, metoprolol CR/XL-system of multiple pellets. Effect of metoprolol tartrate (IR) on mortality was demonstrated in a number of studies in patients with arterial hypertension (AH) (MAPHY), myocardial infarction (SMT, GMT, MIAMI), dilated cardiomyopathy and heart failure (MDC). Studies of efficacy of metoprolol SR are scarce. Antihypertensive efficacy of metoprolol SR in patients with AH did not exceed that of a metoprolol IR or CR/XL. First retrospective analysis of efficacy of metoprolol tartrate and succinate (CR/XL) in patients after myocardial infarction allowed to obtain comparable results of 34% mortality lowering. In a prospective study in patients with chronic heart failure (COMET) metoprolol tartrate IR was not superior to carvedilol when mortality lowering was concerned. At the same time administration of controlled release metoprolol (CR/XL) in 2 large clinical trials (RESOLVD, MERITAHF) was advantageous in patients with chronic heart failure relative to lowering of mortality and rate of hospitalizations. A novel controlled release form of metoprolol has been created as a tartrate salt on the basis of pellet technology (CD/ERT) and its bioequivalence to metoprolol CR/XL has been proved.

Narrow spin resonance width and spin flip with an rf-bunched deuteron beam.

We used an rf solenoid to study the widths of rf spin resonances with both bunched and unbunched beams of 1.85 GeV/c polarized deuterons stored in the COSY synchrotron. With the unbunched beam at different fixed rf-solenoid frequencies, we observed only partial depolarization near the resonance. However, the bunched beam's polarization was almost fully flipped; moreover, its resonance was much narrower. We then used Chao's recent equations to explain this behavior and to calculate the polarization's dependence on various rf-solenoid and beam parameters. Our data and calculations indicate that a bunched deuteron beam's polarization can behave as if the beam has zero momentum spread.

Properties of mutant reaction centers of Rhodobacter sphaeroides with substitutions of histidine L153, the axial Mg2+ ligand of bacteriochlorophyll B(A).

Mutant reaction centers (RC) from Rhodobacter sphaeroides have been studied in which histidine L153, the axial ligand of the central Mg atom of bacteriochlorophyll B(A) molecule, was substituted by cysteine, methionine, tyrosine, or leucine. None of the mutations resulted in conversion of the bacteriochlorophyll B(A) to a bacteriopheophytin molecule. Isolated H(L153)C and H(L153)M RCs demonstrated spectral properties similar to those of the wild-type RC, indicating the ability of cysteine and methionine to serve as stable axial ligands of the Mg atom of bacteriochlorophyll B(A). Because of instability of mutant H(L153)L and H(L153)Y RCs, their properties were studied without isolation of these complexes from the photosynthetic membranes. The most prominent effect of the mutations was observed with substitution of histidine by tyrosine. According to the spectral data and the results of pigment analysis, the B(A) molecule is missing in the H(L153)Y RC. Nevertheless, being associated with the photosynthetic membrane, this RC can accomplish photochemical charge separation with quantum yield of approximately 7% of that characteristic of the wild-type RC. Possible pathways of the primary electron transport in the H(L153)Y RC in absence of photochemically active chromophore are discussed.

[Comparative efficacy and safety of contemporary Angiotensin converting enzyme inhibitors moexipril and spirapril in women with postmenopausal metabolic syndrome].

Moexipril (7.4-15 mg/day) was given to 34, spirapril (3-6 mg/day) -- to 18 postmenopausal women with hypertension and metabolic syndrome for 16 weeks. Hydrochlorthiazide was added when therapy was not sufficiently effective. Both angiotensin converting enzyme inhibitors had similar hypotensive activity: blood pressure normalized in 71 and 61% of moexipril and spirapril treated women, respectively. Both drugs promoted normalization of metabolism of lipid (lowering of levels of cholesterol, atherogenic lipoproteins and triglycerides) and carbohydrates (lowering of hyperinsulinemia). Patients with postmenopausal metabolic syndrome had elevation of leptin level up to 27.5+/-5.5 pg/ml. Moexipril and spirapril caused lowering of elevated levels of leptin. These drugs did not affect levels of sex hormones. They exerted vasoprotective (normalization of endothelium dependent and independent vasodilatation) and nephroprotective (attenuation and normalization of microalbuminuria) effects. Thus spirapril and moexipril are effective in treatment of hypertension in patients with postmenopausal metabolic syndrome.

[Hypotensive, organoprotective, and metabolic effects of Angiotensin converting enzyme inhibitor moexipril in women with postmenopausal syndrome].

Hypotensive, organoprotective, and metabolic effects of angiotensin converting enzyme inhibitor moexipril (7.5-15 mg/day for 16 weeks) with or without combination with hydrochlorothiazide was studied in 34 women (mean age 59.6+/-1.6 years) with postmenopausal metabolic syndrome and hypertension. Thirty four women had dyslipidemia, 22 -- disturbances of carbohydrate metabolism, 18 -- obesity (mean body mass index 31.1+/-0.8 kg/m(2)). Treatment was associated with lowering of office systolic(-20.1%) and diastolic (-17.4%) blood pressure (BP). Target BP (140/90 mm Hg) was achieved in 27 patients. There also occurred significant lowering of mean 24 hour, diurnal, and nocturnal systolic and diastolic BP (p<0.05), significant changes of values of systolic and diastolic BP time indexes, normalization of which was observed both during day and night hours. Significant lowering of total cholesterol (-11.6%, p<0.05), low density lipoprotein cholesterol (-16.3%, p<0.02), and in patients with obesity of triglycerides (-27%, p<0.02) was revealed at the background of treatment with moexipril. In a group as a whole we observed significant lowering of excretion of albumins and b2-microglobulin; most pronounced antiproteinuretic effect was noted in patients with high microproteinuria and obesity. Vasodilating function of vessels improved in all patients with postmenopausal metabolic syndrome, mainly at the account of increment of endothelium dependent vasodilation and normalization of index of vasodilatation.

[THE DEPENDENCE OF THE DYNAMICS IN THE BAND OF THETA ON THE TIME DELAY AND LEVEL OF CONSISTENCY IN THE PRESENTATION OF THE ACOUSTIC IMAGE OWN EEG].

Dynamics of activity in the frequency band of theta waves during of procedures, listening of the acoustic image of the own EEG was investigated. The formation of the acoustic image EEG was performed with a significant reduction of musical properties. It is shown that the increase in activity in the theta range depends on the level of synchronization and consistency of the presentation of the acoustic image own EEG relative to the current bioelectrical activity of the brain. The maximum increase in activity in the theta range was observed with minimum time delay and maximum consistency requirements of sounds with the current EEG. It is concluded that the increase in activity in the range of theta waves in the listening environment acoustic image own EEG is determined by the correlation of sounds with the current bioelectric activity of the brain.

Vector and tensor polarization lifetimes for a stored deuteron beam.

The time dependence of the vector and tensor polarization of a 270 MeV stored deuteron beam was measured near a depolarizing resonance, which was induced by an oscillating, longitudinal magnetic field. The distance to the resonance was varied by changing the oscillation frequency. The measured ratio of the polarization lifetimes is tau(vector)/tau(tensor)=1.9+/-0.2. Assuming that the effect of the resonance is to induce transitions between magnetic substates m(I), we find that the transition rate between neighboring states (+1 and 0 or -1 and 0) is four times higher than between the states with m(I)=+1 and -1.

[Results of pharmacoepidemiological study of arterial hypertension in Russia (PIFAGOR)]. / Rezul'taty farmakoépidemiologicheskogo issledovaniia arterial'noi gipertonii v Rossii (PIFAGOR).

AIM: To assess physicians preferences concerning the use of various groups of antihypertensive drugs in Russia. METHODS: Special questionnaires containing 8 questions related to preferential adherence to representatives of various groups of antihypertensive drugs were distributed among practicing physicians who routinely treated patients with hypertension. RESULTS: Of questionnaires returned between January and July of 2002 from 34 towns 530 were considered valid for analysis. Half of responses (50.4%) were from hospital physicians, 40.5% - from physicians of policlinics (outpatient clinics), 9.1% - from physicians working in other health care facilities. Most of respondents were internists (60.8%) and cardiologists (32.7%). Preferences concerning prescription of antihypertensive drugs were distributed in the following way: angiotensin converting enzyme inhibitors - 32% (50% captopril and enalapril); beta-adrenoblockers - 27% (77% atenolol, metoprolol and propranolol); diuretics (hydrochlorothiazide and indapamide) - 22%; calcium antagonists - 15% (81% verapamil, nifedipine, diltiazem, 64% - long acting preparations); angiotensin receptor blockers - 1.7%; centrally acting drugs - 1.5%; alpha-adrenoblockers - 0.8%. CONCLUSION: Tendencies in real life treatment of patients with hypertension in Russia should be considered positive. Basic antihypertensive therapy included agents (mostly long-acting) from 4 main classes and the use of outdated drugs such as clonidine and reserpine was low.

[Various aspects of the anti-aggregatory action of diltiazem and cordaphene in patients with ischemic heart disease]. / Nekotorye aspekty antiagregantnogo deistviia dilzema i kordafena u bol'nykh ishemicheskoi bolezn'iu serdtsa.

Some aspects of the antiaggregatory action of calcium antagonists were studied in 50 patients with stable angina pectoris. Dilzem (diltiazem) and cordaphene (nifedipine) were tested for their effects on the erythrocytic component of hemostasis, taking into account their capability of suppressing hemolysis, which made ADP, an important thrombocytic activator, enter the blood flow. The two agents significantly reduce the concentration of plasma ADP, free hemoglobin, diminish mechanical erythrocytic resistance, and block platelet aggregation to a varying degree. A relationship was established between the levels of blood nifedipine and the magnitude of rheological effects. With this, the patients with coronary heart disease showed a good antianginal effect.

[Effect of diltiazem on the functional activity of erythrocytes and thrombocytes in patients with ischemic heart disease]. / Vliianie diltiazema na funktsiona'lnuiu aktivnos't éritrotsitov i trombotsitov u bo'lnykh ishemicheskoi bolez'niu serdtsa.

The functional activity of erythrocytes and platelets was studied in 50 patients with various types of coronary heart disease. The patients' plasma exhibited higher ADP levels due to erythrocyte microhemolysis and higher platelet malonic dialdehyde and intracellular calcium, which led to enhanced platelet functional activity. Treating the patients with the calcium antagonist diltiazem was found to result in lower ADP and platelet calcium levels whereas the concentrations of malonic dialdehyde remained unchanged.

[Selective microproteinuria as a marker of incipient renal impairment in patients with hypertension]. / Selektivnaia mikroproteinuriia kak marker nachal'nogo porazheniia pochek u bol'nykh s arterial'noi gipertenziei.

Incidence of chronic renal failure has a worldwide tendency to growth. Hypertension occupies an important place among causes of this upward trend. That is why in patients with hypertension and incipient changes of the kidneys it seems most appropriate to use antihypertensive drugs with renoprotective properties. Early treatment with these drugs enables most effective lowering of risk of renal failure development and thus has a potential to prolong life of a patient. Selective microproteinuria is considered to be a marker of incipient renal impairement. Among groups of antihypertensive agents angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium antagonists, beta-blockers, and diuretics have proven renoprotective properties.

[The evaluation of cilazapril efficacy in patients with stable arterial hypertension (a randomized study)]. / Otsenka éffektivnosti tsilazaprila u bol'nykh stabil'noi arterial'noi gipertoniei (randomizirovannoe issledovanie).

34 patients with stable arterial hypertension (AH) were randomized by mean arterial pressure (MAP), end-diastolic LV volume and cardiac output in a study of cilazapril efficacy in a dose 2.5 and 5 mg/day. Antihypertensive effect in the majority of patients with MAP 120-135 and 136-150 mm Hg was insufficient (diastolic pressure > 94 mm Hg). Dose-effect action on hemodynamics was absent. Hemodynamic benefits were noted in patients with end diastolic LV volume > 5.0-5.7 cm.