РЕЗУЛЬТАТЫ ПРИМЕНЕНИЯ ФОСФОМИЦИНА ДЛЯ ИМПРЕГНАЦИИ ОСТЕОЗАМЕЩАЮЩИХ МАТЕРИАЛОВ ПРИ ЛЕЧЕНИИ ХРОНИЧЕСКОГО ОСТЕОМИЕЛИТА

Aim – to evaluate in the experimental study in vitro the duration of antimicrobial activity of fosfomycin-impregnated bone cement and to study the dynamics of radiological and morphological changes depending on the local antibiotic therapy in two-stage treatment of chronic osteomyelitis in rabbits.Materials and methods. Duration of antimicrobial activity of bone cement (depuy cmw1 gentamicin) with fosfomycin in vitro was studied in comparison to cements with vancomycin and controls without additional antibiotics. Presence of the lysis zone of bacterial cultures was evaluated (Staphylococcus aureus ATCC6538 and ATCC33591, Klebsiella pneumoniae ATCC33495 and Escherichia coli ATCC25922) after application of 10 μl of the solution, collected from the cement samples after incubation for 24 hours. For the in vivo experiment, Chinchilla rabbits (n = 20) with local osteomyelitis of the tibia underwent two-stage treatment where substitution of the bone defect at stage I was performed with PMMA and stage II – with the bioresorbable material based on hydroxyapatite and triclacium phosphate (ReproBone). In an experience group (n = 10) before setting osteoreplacement materials with fosfomycin (group FOSFO), and by control (n = 10) – vancomycin (group VANCO). X-ray imaging was performed on the 1st and 21st day after installation of the cement spacer, and 45th day after substitution of the spacer with the bioresorbable material. Microbiological analysis of the samples was performed intraoperatively and on the 7th, 14th day after each stage. Histological study was conducted in both groups on the 14th, 21th day after stage I and 45th day after stage II of the treatment.Results. Maximal duration of antimicrobial activity in vitro was observed in samples of PMMA with fosfomycin whereas minimal – in control samples of gentamicin-based bone cement. Relief of the infection was attained in all animals while application of fosfomycin resulted in a more rapid elimination of the bacteria. Reaction of the adjacent tissue to the implanted material and results of X-ray imaging in both groups did not differ significantly. Long duration of the broad-spectrum antimicrobial activity of the bone cement with fosfomycin with the comparable perifocal reaction in vivo necessitates further study of the use of this antibiotic in bioresorbable materials for the treatment of osteomyelitis in clinical practice.Цель – оценить в эксперименте in vitro длительность антимикробной активности образцов импрегнированного фосфомицином костного цемента и изучить динамику рентгенологической и морфологической картины в зависимости от локальной антибактериальной терапии при двухэтапном лечении хронического остеомиелита у кроликов.Материал и методы. Изучали in vitro длительность антимикробной активности образцов импрегнированного фосфомицином костного цемента (depuy cmw1 gentamicin) в сравнении с импрегнацией ванкомицином и контрольными образцами без внесения дополнительного антибиотика. Оценивали наличие зоны лизиса бактериальной культуры (Staphylococcus aureus ATCC6538 и ATCC33591, Klebsiella pneumoniae ATCC33495 и Escherichia coli ATCC25922) в области нанесения 10 мкл инкубационного раствора после инкубации образца в течение 24 час. В эксперименте in vivo 20 кроликам породы Шиншилла c локальным очагом остеомиелита большеберцовой кости проводили двухэтапное лечение. На первом этапе костный дефект замещали костным цементом на основе полиметилметакрилата (ПММА), на втором этапе – биорезорбируемым материалом на основе гидроксиапатита и трикальцийфосфата (ReproBone). В опытной группе (n = 10) перед установкой остеозамещающие материалы импрегнировали фосфомицином (группа ФОСФО), а в контрольной группе (n = 10) – ванкомицином (группа ВАНКО). Рентгенологические исследования выполняли в первые и 21-е сутки после установки цементного спейсера, на 45-е сутки после удаления цементного спейсера и укладки биорезорбируемого материала. Бактериологические исследования выполняли интраоперационно, на 7-е и 14-е сутки после каждого этапа. Морфологические исследования выполняли в обеих группах на 14-е и 21-е сутки после первого этапа и на 45-е сутки после второго этапа лечения.Результаты. Максимальная продолжительность антимикробной активности in vitro установлена при использовании ПММА с фосфомицином, минимальная – для контрольных образцов из официнального гентамицин-содержащего цемента. В эксперименте in vivo у всех животных было достигнуто купирование инфекционного процесса, однако применение фосфомицина приводило к более быстрой эрадикации возбудителя. Реакции тканей, окружающих имплантированный материал, в обеих группах экспериментальных животных различались незначительно, рентгенологическая картина была схожей. Большая длительность антимикробного действия образцов костного цемента с фосфомицином в отношении широкого спектра возбудителей при сопоставимых перифокальных реакциях в эксперименте in vivo делает перспективным дальнейшее изучение данного антибиотика в составе остеозамещающих материалов при лечении остеомиелита в клинической практике

The spectrum features of UHECRs below and surrounding GZK

The energy spectrum of UHECRs is discussed on the basis of the Yakutsk array database analysis. In the region E=0.1 to 30 EeV the showers are detected under trigger-500, while at energies above 30 EeV the whole acceptance area for trigger-1000 is used in order to utilize all the data available in the region of GZK cutoff.Comment: Invited talk at CRIS2004: GZK and surroundings, Catania, Italy, 31.05.04. To appear in Nucl. Phys. B Proc. Supp

The γγ→J/ψJ/ψ\gamma \gamma \to J/\psi J/\psi reaction and the J/ψJ/ψJ/\psi J/\psi pair production in exclusive ultraperipheral ultrarelativistic heavy ion collisions

We calculate the cross section for the $\gamma \gamma \to J/\psi J/\psi$ process. Two mechanisms are considered: box (two-loop) diagrams of the order of $O(\alpha_{em}^2 \alpha_s^2)$ and two-gluon exchange of the order of $O(\alpha_{em}^2 \alpha_s^4)$. The first mechanism is calculated in the heavy-quark non-relativistic approximation while the second case we also include the effects of quantum motion of quarks in the bound state. The box contribution dominates at energies close to the threshold ($W <$ 15 GeV) while the two-gluon mechanism takes over at $W >$ 15 GeV. Including the bound-state wave function effects for the two-gluon exchange mechanism gives a cross section 0.1 - 0.4 pb, substantially smaller than that in the non-relativistic limit (0.4 - 1.6 pb). We also find a strong infrared sensitivity which manifests itself in a rather strong dependence on the mass for the $t$-channel gluons. The elementary cross section is then used in the Equivalent Photon Approximation (EPA) in the impact parameter space to calculate the cross section for $^{208}Pb+^{208}Pb \to ^{208}Pb + J/\psi J/\psi + ^{208}Pb$ reaction. Distributions in rapidity of the $J/\psi J/\psi$ pair and invariant mass of the pair are shown.Comment: 15 pages, 11 figure

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair