Background The circadian variation of clinical symptoms and the underlying variation of cytokine and hormone levels in rheumatoid arthritis (RA) are well described and have already led to the successful application of chronotherapy with prednisone (Buttgereit et al., Lancet, 2008). Much less is known about the circadian rhythms of different immune cell populations in RA. Objectives In this pilot study we investigated molecular, cellular and humoral circadian parameters in postmenopausal female RA patients in comparison to healthy control subjects. Methods Blood samples from postmenopausal female patients with active RA (DAS 28 ≥4.2) (n=5) and postmenopausal female healthy controls (n=5) were collected every 2 hours for 24 hours and analysed by flow cytometry and multiplex suspension array of 28 cytokines. Clock gene expression of isolated CD14+ monocytes was analysed by quantitative RT-PCR. Endogenous circadian rhythm dynamics of macrophages were determined by means of a Bmal1-promotor driven luciferase reporter construct. COSINOR analysis was used for statistical analysis of the groups. Results Expression of the clock gene RevErbα in CD14+ monocytes showed a significant circadian expression pattern in both RA patients and healthy controls subjects, whereas the clock genes Per2 and Per3 were not expressed in a circadian manner in RA patients but in healthy controls only. The amplitude of the endogenous circadian rhythm of macrophages tended to be lower in RA patients than in healthy controls, whereas period length was not altered. In flow cytometric analysis of surface marker expression of blood cells we found a significant circadian rhythm in RA patients and healthy subjects for the frequency of CD3-CD56+ natural killer (NK) cells, Interleukin-8 Receptor (IL-8R) expressing CD4+ T helper and CD8+ cytotoxic T cells, and CXCR4 expressing CD4+ T helper and CD8+ cytotoxic cells. A significant circadian rhythm was not detectable in RA patients but in healthy controls only for CD3+CD56+ NK T cells. In contrast, a significant circadian expression of IL-8R+ monocytes was found in RA patients only but not in healthy subjects. Of note, CCR7 did not at all show a circadian expression. A significant circadian cytokine expression was detected only for MCP-1 in healthy controls. Conclusions This is the first indication of alterations of clock gene expression and endogenous circadian rhythms in immune cells of RA patients. Traffic of peripheral blood cells shows circadian variation in RA patients and healthy controls with characteristic peak phases, especially in NK cells and chemokine receptor expressing cells. NKT and other cells may lose their normal circadian rhythm in RA, whereas IL-8R expression on monocytes may be established as new “inflammatory” circadian rhythm in RA patients. These findings provide new aspects of RA chronobiology and may have therapeutic implications. Disclosure of Interest C. Spies: None Declared, T. Gaber: None Declared, P. Hoff: None Declared, J. Mazuch: None Declared, B. Maier: None Declared,...
ФГБУ «Национальный медицинский исследовательский центр сердечно-сосудистой хирургии имени А.Н. Бакулева» Минздрава России, Москва, Российская Федерация Несоответствие между протезом и пациентом (PPM) возникает, когда протез клапана, имплантированный во время операции, слишком мал по отношению к размеру тела пациента, что вызывает высокие трансвальвулярные градиенты. Мы исследовали непосредственные результаты и зависимость трансвальвулярных градиентов от индекса массы тела и площади поверхности пациента после протезирования аортального клапана протезом «БиоЛАБ» с маленькими размерами. Материал и методы.
Nitric oxide (NO) is a universal regulator of different processes, including vascular tone, hemostasis ?nd apoptosis. One of the important functions of NO as a signaling molecule is determined by a high capacity for diffusion through the cell membrane to synthesize it and penetrate into target cells by controlling their metabolism ?nd realizing intercellular interactions. For the purpose of estimation in elderly persons due to for determine the effect of nitric oxide and its products on the process of subclinical inflammation and apoptosis of endothelial cells in the development of endothelial dysfunction as a target organ in arterial hypertension 66 patients of elderly age with arterial hypertension (AH) of II stage and 24 persons of similar age without cardiovascular diseases were examined. The degree of endothelial dysfunction was examined by dopplerography of brachial artery, the endotheliocytemia level was estimated by the Hladovec and Rossmann method, the concentration of nitric oxide - in the Griess reaction, the levels of C-reactive protein, primary inflammatory mediator of TNF-a, apoptosis markers and nitrotyrosine - were determined by the immune enzyme method. It has been established that the synthesis of basal nitric oxide depends on the activity of endothelial constitutive NO - synthase and maintains the tone of the vessel in a state of light relaxation. In the progression of endothelial dysfunction (ED) a number of phases were identified: a compensation phase with increased secretory activity of endothelial cells, an intermediate phase when the balance is disrupted due to changes in the secretion process of production and inactivation of endothelial factors and a decompensation phase as a result of structural and metabolic disorders of endothelium resulting in its functional failure, death and desquamation. Regulatory effect of NO on subclinical inflammation and apoptosis intensity was confirmed by its strong inverse correlation with the level of TNF-a and caspase-3. It proved the change in the NO concentration, its auto- and paracrine effect on the formation of involutive changes in the vascular wall, its regulatory effect on the processes of subclinical inflammation and apoptosis of endothelial cells in the formation of hypertension, as well as its progression during aging.
Background. The use of radiation therapy for the treatment of tumors of the chest сan lead to the development of cardiac pathology, including that of the valves and coronary arteries. Study aim: to analyze the specifics of post-radiation lesions of the valvular apparatus and coronary arteries, and to assess the immediate results and risks of surgical correction of detected defects. Materials and methods. In the Emergency department of surgery of acquired heart disease of A. N. Bakulev National Medical Research Center of Cardiovascular Surgery in the period from 2004 to 2017 were examined and operated 46 patients aged 35–81 years (mean age 56±12.4 years, 80 % women). The period from primary irradiation of the chest to surgical treatment of valvular pathology ranged from 4 to 40 years. Indications for thoracic radiotherapy were Hodgkin’s lymphoma in 23 patients (50 %), breast cancer – in 20 (43 %). Results. Stenosis of the aortic valve was the leading defect in 42 patients (91 %). According to coronary angiography, coronary artery disease was diagnosed in 31 patients (67 %). Isolated aortic valve prosthesis was performed in 14 (30 %) patients, other operations were combined. Hospital mortality was 11 % (5 patients). There were no deaths among patients who underwent radiation therapy after mastectomy. Main nonlethal complications were: pericardial effusion in 6 patients (13 %), hydrothorax requiring repeated pleural punctures in 5 patients (11 %). Conclusion. The variety of clinical manifestations of radiation heart disease and its progressive nature emphasize the need for long-term dynamic observation of patients after thoracic irradiation in order to timely identify the pathology and eliminate the risk of sudden cardiac complications and the development of severe heart failure decompensation.
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