Diagnostically significant differences septic and aseptic instability of endoprosthesis components during arthroplasty of large joints

The purpose of the work is to analyze the results of laboratory, microbiological and instrumental studies to search for screening criteria for the difference between aseptic and septic instability of endoprosthesis components after knee and hip joint arthroplasty. The materials contained 146 cases of revision arthroplasty of the knee and hip joints, performed under the conditions of Federal State Budgetary Institution Federal Center of Traumatology, Orthopedics and endoprosthesis replacement of Ministry of Health of the Russian Federation (Cheboksary) for a 3-year period, including cases of aseptic instability - 69, septic instability-77. By methods for laboratory diagnosis were used to evaluate the blood levels of leukocytes, stab neutrophils, ESR, C-reactive protein (CRP), presepsin, procalcitonin, D-dimer, interleukin-6. Using ultrasound (ultrasonic) examination of the periprosthetic zone, the presence of fluid, granulation tissue in the joint cavity, altered lymph nodes was determined. Before the operation, the level of cytosis and cellular composition were determined in the synovial fluid; tissue bioptates, removed components of implants (after ULTRASONIC treatment) with sowing on the microflora were studied intraoperatively. Intraoperative tissue biopsies were used to make smears-prints on the glass, with gram staining, estimating the number of leukocytes and neutrophils in the field of vision. Results. Determination of indicators of ESR, presepsin and interleukin-6, the level of which goes beyond the generally recognized normal values in the presence of infection, can be recommended as a screening test in the diagnosis of the infectious nature of instability of the components of the endoprosthesis of large joints. The second stage of differential diagnosis of septic and aseptic instability can be the detection of lymphadenopathy. The third (final) stage of determining the infectious nature of instability is an invasive technique to determine the level of cytosis with the calculation of neutrophils in the synovial fluid.Цель работы - анализ результатов лабораторных, микробиологических и инструментальных исследований для поиска скрининг-критериев отличия асептической и септической нестабильности компонентов эндопротеза после артропластики коленных и тазобедренных суставов. Материалами послужили 146 случаев ревизионной артропластики коленных и тазобедренных суставов, выполненной в условиях Федерального государственного бюджетного учреждения «Федеральный центр травматологии, ортопедии и эндопротезирования» Министерства здравоохранения российской Федерации (г. Чебоксары) за 3-летний период, из них случаев асептической нестабильности - 69, септической нестабильности - 77. Методами лабораторной диагностики проводилась оценка содержания в крови лейкоцитов, палочкоядерных нейтрофилов, СОЭ, С-реактивного белка (СРБ), пресепсина, прокальцитонина, Д-димера, интерлейкина-6. С помощью ультразвукового (УЗ) исследования перипротезной зоны определяли наличие жидкости, грануляционной ткани в полости сустава, измененных лимфатических узлов. до операции в синовиальной жидкости определяли уровень цитоза и клеточный состав; интраоперационно исследовались тканевые биоптаты, удаленные компоненты имплантов (после УЗ обработки) с посевом на микрофлору. Из интраоперационных тканевых биоптатов делали мазки-отпечатки на стекле, с окрашиванием по Граму, оценивая количество лейкоцитов и нейтрофилов в поле зрения. результаты. Определение показателей СОЭ, пресепсина и интерлейкина-6, уровень которых выходит за пределы общепризнанных нормальных значений при наличии инфекции, может быть рекомендовано в качестве скрининг-теста при диагностике инфекционной природы нестабильности компонентов эндопротеза крупных суставов. Вторым этапом дифференциальной диагностики септической и асептической нестабильности может служить выявление лимфоаденопатии. третьим (заключительным) этапом определения инфекционной природы нестабильности является инвазивная методика с определением уровня цитоза с подсчетом нейтрофилов в синовиальной жидкости

Evaluation of the effectiveness of the analgesic effect of selective and non-selective cyclooxygenase blockers in the composition of multimodal analgesia after knee joint endoprosthesis replacement

The purpose of the work is to compare the effectiveness of anesthesia with the use of a highly specific blocker COX-2 and a dedicated cyclo-oxygenase blocker COX-1 and COX-2 lornoxicam as part of multimodal analgesia in patients after primary knee replacement. The material was the cases of knee prosthesis (N=196) using multimodal analgesia; patients were divided into two groups, depending on the type of anesthesia, in accordance with the developed scheme of pharmacotherapy: I – receiving celecoxib (n=98) and II - lornoxicam (n=98). Methods for evaluating the effectiveness of anesthesia were the visual analogue scale (VAS), the KSS knee joint function evaluation scale before surgery and on the 5th day after it; analysis of the features of early verticalization, the patient's need for additional pain relief after surgery; costs of drug therapy are calculated. Results. Patients of both groups were comparable in age and average duration of hospitalization. The pain syndrome assessment on the VAS scale showed a higher efficacy of pain relief on days 1 and 5 in group II (4.1 ± 0.1 versus 3.5 ± 0.1 and 1.9 ± 0.04 versus 1.6 ± 0.1 points respectively) (p≤0.05). Evaluation of the functional activity of the prosthetic knee joint on the KSS scale did not reveal any differences between the groups. Of the features of early verticalization on the first day after surgery, a higher percentage of weakness in the legs (79.6%) and nausea (70.4%) was noted in group I, and a higher percentage of dizziness (15.3%) and hemodynamic disorders (6.1% of cases). The cost of providing basic pain therapy in group I was 2.4 times higher than in group II, with the same costs for additional anesthesia with solutions of paracetamol and narcotic analgesics. Conclusions. As part of multimodal analgesia, Lornoxicam showed a higher efficacy in relieving pain syndrome at a low cost of a course of treatment compared with celecoxib.Цель работы - сравнение эффективности обезболивания при использовании высокоспецифичного блокатора ЦОГ-2 целекоксиба и неспецифичного блокатора циклооксигеназы ЦОГ-1 и ЦОГ-2 лорноксикама в составе мультимодальной анальгезии у пациентов после первичного эндопротезирования коленного сустава. Материалом послужили случаи протезирования коленных суставов (N=196) с использованием мультимодальной анальгезии; в зависимости от типа обезболивания, в соответствии с разработанной схемой фармакотерапии, пациенты разделены на две группы: I - получающие целекоксиб (n=98) и II - лорноксикам (n=98). Методами оценки эффективности обезболивания являлись визуально-аналоговая шкала (ВАШ), шкала оценки функции коленного сустава KSS до операции и на 5 сутки после неё; анализ особенностей ранней вертикализации, потребности пациента в дополнительном обезболивании после операции; рассчитаны затраты на медикаментозную терапию. результаты. Пациенты обеих групп были сопоставимы по возрасту и средней длительности госпитализации. оценка болевого синдрома по шкале ВАШ показала более высокую эффективность купирования болевого синдрома на 1 и 5 сутки во II группе (4,1±0,1 против 3,5±0,1 и 1,9±0,04 против 1,6±0,1 балла соответственно) (p≤0,05). оценка функциональной активности протезированного коленного сустава по шкале KSS не выявила различий между группами. особенности ранней вертикализации в 1 сутки после операции: в I группе - более высокий процент слабости в ногах (79,6%) и тошноты (70,4%), во II - выше процент головокружения (15,3%) и нарушений гемодинамики (6,1% случаев). Затраты на обеспечение базовой обезболивающей терапии в I группе в 2,4 раза превысили показатель II группы, при равных затратах на дополнительное обезболивание растворами парацетамола и наркотических анальгетиков. Выводы. Лорноксикам в составе мультимодальной анальгезии показал более высокую эффективность купирования болевого синдрома при низкой стоимости курсового лечения по сравнению с целекоксибом

Regulation of the urokinase-type plasminogen activator gene by the oncogene Tpr-Met involves GRB2

The oncogene Tpr-Met is a constitutively active form of the hepatocyte growth factor/scatter factor (HGF/SF) receptor Met. It comprises the intracellular moiety of Met linked to the dimerization domain of the nuclear envelope protein Tpr, thus functioning as a constitutively activated Met. HGF/SF is responsible for various biological processes including angiogenesis and wound healing, in which secreted serine protease urokinase-type plasminogen activator (uPA) is implicated. The action of HGF/SF on cells is mediated by the autophosphorylation of Met on two carboxyterminal tyrosine residues, Y1349VHVNATVY1356VNV. The two tyrosine residues provide docking sites for various effector molecules, suggesting that multiple signaling pathways are activated to exert biological effects of HGF/SF [Ponzetto et al., Cell (1994) 77: 261]. We found that Tpr-Met efficiently activates the uPA gene via a SOS/Ras/extracellular signal regulated kinase (ERK)-dependent signaling pathway. Mutation of Y1356, which abrogates GRB2 binding, reduced the induction to half of the control level, while mutation of Y1349 showed little effect on uPA induction, suggesting an important but partly replaceable role for GRB2 in Met-dependent uPA gene induction. Mutation of both Y1349VHV and Y1356VNV into optimal PI 3-kinase sites resulted in a residual induction of about one quarter of the control level, suggesting a potential role for PI 3-kinase. Dose-response analysis of the Tpr-Met showed a biphasic curve. These results suggest that the interplay among different signaling molecules on the receptor is important for full induction of the pathway leading to the activation of the uPA gene

Nuclear phospholipid signaling: phosphatidylinositol-specific phospholipase C and phosphoinositide 3-kinase

Over the last 20 years, numerous studies have demonstrated the existence of nuclear phosphoinositide signaling distinct from the one at the plasma membrane. The activation of phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphoinositide 3-kinase (PI3K), the generation of diacylglycerol, and the accumulation of the 3-phosphorylated phosphoinositides have been documented in the nuclei of different cell types. In this review, we summarize some recent studies of the subnuclear localization, mechanisms of activation, and the possible physiological roles of the nuclear PI-PLC and PI-3 kinases in the regulation of cell cycle, survival, and differentiation

IL-4 enhances survival of in vitro-differentiated mouse basophils through transcription-independent signaling downstream of PI3K

Interleukin 4 (IL-4) is a critical cytokine implicated with T2 immune reactions, which are linked to pathologic conditions of allergic diseases. In that context, the initiation of T2 responses can critically depend on early basophil-derived IL-4 to activate T-cell responses, which then amplify IL-4 secretion. As a pleiotropic cytokine, IL-4 acts on a broad variety of hematopoietic and non-hematopoietic cells. However, the effect of IL-4 on basophils themselves, which are emerging as relevant players in allergic as well as autoimmune diseases, was only scarcely addressed so far. Here we used in vitro-differentiated mouse basophils to investigate the direct effects of IL-4 on cellular viability and surface expression of the high-affinity receptor for IgE, FcεRI. We observed that IL-4 elicits pronounced pro-survival signaling in basophils, delaying spontaneous apoptosis in vitro to a degree comparable to the known pro-survival effects of IL-3. Our data indicate that IL-4-mediated survival depends on PI3K/AKT signaling and-in contrast to IL-3-seems to be largely independent of transcriptional changes but effectuated by post-translational mechanisms affecting BCL-2 family members among others. Additionally, we found that IL-4 signaling has a stabilizing effect on the surface expression levels of the critical basophil activation receptor FcεRI. In summary, our findings indicate an important regulatory role of IL-4 on in vitro-differentiated mouse basophils enhancing their survival and stabilizing FcεRI receptor expression through PI3K-dependent signaling. A better understanding of the regulation of basophil survival will help to define promising targets and consequently treatment strategies in basophil-driven diseases