[Bioactive compounds in the nutrition of peri- and postmenopausal women within the concept of 4P-medicine].

An updated consensus statement from the European Menopause and Andropause Society noted that a woman's quality of life may decline during peri- and post-menopause as a result of various menopausal symptoms and age-related comorbidities. The purpose of the work was to assess the possibility of using bioactive compounds in periand postmenopausal women to prevent the development of menopausal complications and chronic diseases associated with aging. Material and methods. Literature search was carried out using PubMed, Google Scholar, ResearchGate, RSCI databases mainly over the past 10 years, with the exception of works of fundamental importance, according to the keywords "perimenopause", "postmenopause", "Affron® saffron extract", "special extract ERr 731". Results. The use of diet, dietary supplements including those containing extracts of saffron (Affron®) and Siberian rhubarb (ERr 731) and their biologically active substances, has a versatile effect on the correction of menopausal disorders due to the impact on various pathogenetic pathways of their development and can be used in women in this period as a phytonutrient support. Conclusion. The combined use of saffron and Siberian rhubarb extracts is promising from the point of view of correcting the female state during peri- and postmenopause, taking into account the pathogenetic moments of the development of menopausal complications and chronic diseases associated with aging.

[Clinical efficacy of electric stimulation of crural muscles in comprehensive treatment of post-thrombotic disease]. / Klinicheskaia éffektivnost' élektricheskoi stimuliatsii myshts goleni v kompleksnom lechenii posttromboticheskoi bolezni.

The purpose of the study was to evaluate clinical efficacy of electromyostimulation (EMS) of the crural muscles as part of comprehensive therapy for post-thrombotic disease in patients with residual venous obstruction in the femoropopliteal segment. We carried out a prospective comparative clinical study enrolling patients having endured a fist episode of clinically unprovoked venous thrombosis of the femoropopliteal segment and completed the standard 6-month course of anticoagulant therapy and presenting with ultrasonographic signs of complete recanalization of the proximal venous segments (stenosis of 20% and more from the vessel's initial diameter), as well as scoring 5 points and more by the Villalta scale. The study included a total of 60 patients (38 men and 22 women, mean age 58.5±11.4 years) subdivided into two groups consisting of 30 patients each. Patients of both the Study and Control Groups underwent comprehensive therapy including wearing a compression knee sock (23-32 mmHg), a course phlebotrophic drugs, and dosed walking (not less than 5,000 steps a day). The Study Group patients were additionally subjected to daily electrical stimulation of the crural muscles with the "Veinoplus VI" unit (three 30-minute sessions a day). The duration of the follow up amounted to 12 months. The criteria for assessing therapeutic efficacy were as follows: severity of the disease by the VCSS and Villalta scales, quality of life as assessed by the CIVIQ-20 questionnaire, and lack of relapses of the venous thrombus. Clinical and instrumental assessment of the patients' condition was carried out monthly, with the disease's severity and quality of life assesses each 6 months. Relapses of venous thrombosis were registered in 7 (23.3%) patients from the Control Group and were not observed in patients undergoing EMS (p=0.011). In 5 cases, thrombosis was asymptomatic and in 4 cases it was presented by reocclusion of the involved venous segments. Patients of the Study Group were found to have a decrease in the disease's severity, reflected in points: VCSS (9.9±1.6 - 7.8 ± 1.6 - 6.1±1.5 (p <0.0001)); Villalta scale (18.9±3.9 - 12.8±4.0 - 8.3±2.7 (p<0.0001)); CIVIQ-20 score (67.8±8.4 - 51.3±8.4 - 40.0±10.5 (p<0.001)). The Control Group patients showed a similar tendency for the disease's severity: 8.1±2.8 - 7.3±2.1 - 7.2±2.1 points by the VCSS (p=0.014); 12.7±6.7 - 10.9±5.6 - 10.2±5.4 points by the Villalta scale (p=0.002), but not for quality of life: 48.2±19.3 - 46.7±17.3 - 47.4±16.2 points by the CIVIQ-20 (p>0.05). On the background of using EMS, the alterations in the studied parameters were characterized by higher velocity and intensity (p<0.05). The use of electromyostimulation as part of comprehensive treatment for post-thrombotic disease makes it possible to efficiently eliminate both subjective and objective signs of venous insufficiency, improve patients' quality of life and decrease the risk for the development of relapsing venous thrombosis.

[Trisomy of chromosome 8 in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia treated with inhibitors of BCR-ABL tyrosine kinases].

AIM: To analyse clinical implications of chromosome 8 trisomy in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia (CML) treated with inhibitors of tyrosinkinases (ITK). MATERIAL AND METHODS: A total of 386 patients with CML (chronic phase--288, acceleration phase--77) received imatinib (400-800 mg/day). Because of resistance and/or intolerance some patients were switched to ITK II (nilotinib, dasatinib, bozutinib). This study included 8 CML patients (7 in a chronic phase, 1 in acceleration phase) treated with BCR-ABL ITK inhibitors of the first (imatinib) and the second line (ITK-II). The standard cytogenetic examination, on demand--investigation of the interphase nuclei with FISH, in some cases morphological, cytochemical and histological examinations of the bone marrow were made. RESULTS: The existence of a Ph-negative clone with trisomy of chromosome 8 had no negative effect on the course of the disease. The patients showed a stable hematological and cytogenetic response and no need in changing treatment policy. In long-term follow-up Ph-negative clone with trisomy of the chromosome 8 persisted without a clear trend to rise in most patients. CONCLUSION: Detection of a Ph-negative clone with chromosome 8 trisomy at early stages suggests parallel existence of Ph-positive and Ph-negative clones. None of the patients had myelodisplasia.

[Dasatinib treatment of imatinib-resistant and imatinib-intolerant patients with chronic myeloid leukemia in a chronic phase].

AIM: To analyse resistance to imatinib therapy, efficacy and safety of dasatinib. MATERIAL AND METHODS: A total of 18 patients with chronic myeloid leukemia (CML) in a chronic stage received dasatinib for 9-30 months (median 30 months) to September 2008. RESULTS: Lethal outcomes during dasatinib treatment were absent. To September 2008, 16 (89%) patients were alive, 2 (11%) patients died of the disease progression after dasatinib discontinuation. A complete clinicohematological response was observed in all the patients. Major cytogenetic, complete cytogenetic, major molecular, complete molecular responses were achieved in 12 (67%), 10 (55%), 7 (39%) and 5 (28%) patients, respectively. Hematological and non-hematological toxicity occurred in 9 (50%) patients. Now 12 (67%) patients continue dasatinib treatment, in 6 (33%) patients the drug was discontinued. CONCLUSION: The results from trials in Russian Hematological Research Center are the same as in the international study. Dasatinib is effective and well tolerated therapeutic option for imatinib-resistant patients with a chronic phase of CML.

Cell Regulation of Proliferation and Differentiation ex vivo for Cells Containing Ph Chromosome in Chronic Myeloid Leukemia.

Cell regulation of Ph(+)cell proliferation and differentiation has been studied ex vivo in various chronic myeloid leukemia (CML) patients. The regulation is provided by alternation of effective stages of proliferation and maturation with inhibition of Ph(+) cell proliferation by accumulating neutrophils under apoptosis blockage. The alternation of stages consists of switching stage 1 (effective proliferation) to stage 2 (effective maturation) and proceeds according to the 1/2 -1/2/1 or 2/1-2/1/2/1 schemes. The kinetic plots of alternations pass through control points of crossing plots, where the parameters of proliferation and maturation are equal. The indices of P/D efficiency (ratio of proliferation and maturation rates) are 1.06±0.23 and don't depend on time, alternation order, or sources of Ph(+) cells - CML patients. During stages alternation, conversely, the parameters of Ph+ cell proliferation and maturation vary. The proliferation stages are characterized by increased proliferating cells content, a decreased number of neutrophils, and apoptosis induction. At the maturation stages, conversely, apoptosis is inhibited, the number of mature neutrophils increases, while immature Ph(+) cells decrease. High content neutrophils inhibit the proliferation of Ph(+) cells and impair their own maturation by inversion of maturation order, probably through a feedback mechanism. The regulation differences ex vivo reveal three types of Ph(+) cells from various individual CML patients, distinguished by the number and duration of alternating stages of proliferation and maturation. Ph(+) cells types 1 and 2 have one prolonged stage of effective proliferation or effective maturation with efficiency indices P/D(1) = 1-20 or P/D(2) ⇐ 1. At the same time period, the proliferation and differentiation of the Ph(+) cells type 3 proceeds with repeated alternations of stages with P/D(1) = 1-4 or P/D(2) ⇐ 1. Type 1 Ph(+) cells (~20%) were isolated from patients in advanced stages of CML, while Ph(+) cells types 2 and 3 (30 and 50% correspondingly) were isolated from CML chronic phase patients sensitive to chemotherapy.

[Gradual tensometric load in rehabilitation of patients with diaphysial fractures of shin bones]. / Dozirovannaia nagruzka v vosstanovitel'nom lechenii bol'nykh s diafizarnymi perelomami kostei goleni.

The regime of gradual early tensometric load (GETL) was used in rehabilitation of patients with diaphysial fractures of crural bones (DFCB). The results of such rehabilitation were compared to those of rehabilitation without GETL. A total of 198 patients were studied. The GETL technique uses ground-type scales and step-by-step load intensification. Principles of pre- and postoperative rehabilitation are provided. The results of the study show that GETL allows control and correction of the fracture consolidation, improves microcirculation, prevents local osteoporosis and contractures of near-by joints, shortens duration of disability.