INTERRELATION BETWEEN LUNGS FUNCTiONAL PARAMETERS AND CONDiTiON OF BONE TISSUE AT THE TERMINAL PULMONARY PATHOLOGY

The aim of this study was to evaluate the condition of mineral density of bone tissue at the terminal pulmonary pathology, to determine correlations between lungs functional parameters and. pre-transplantation bone mass. Materials and methods: we realized retrospective analysis of 74 case histories of patients with terminal pulmonary pathology, waiting for lung transplantation. MDBT in lumbar segment of spine (L2—L4) and. femoral neck (FN) was evaluated, with help of double-energy X-ray absorptiometry (Hologic). Function of external respiration was researched, gasometry and 6-minutes walking test were realized, in all the patients. Results: osteopenic syndrome in any zone of interest was registered in 69 % of patients. Normal indices of MDBT both in L2—L4 and. in FN were registered only in 11 % of patients. On our data the indices of T-criterion (both, in L2—L4 and. in FN) had. direct relation with, body weight index (BWI) and. total fatty mass. Direct correlation between MDBT, volume of forced expiration for 1 second. (FEV) (r = 0,49, p < 0,05 in L2—L4 and. r = 0,52, p < 0,05 in FN) and. indirect correlation with, total lungs capacity (TLC) (r = —0,53, p < 0,01) with residual lungs volume (RV) (r = —0,48, p < 0,05) only in FN. We revealed, reliable negative interrelation, of MDBT only with pCO2 of arterial blood (r = —0,54, p < 0,01 in L2—L4 and r = —0,48, p < 0,05 in FN). There were no reliable correlation between DLCO, 6-minutes walking test and. MDBT both in L2—L4 and. in FN. 11% of patients had. atraumatic fractures of different localization. Conclusion: thus, osteoporosis is sufficiently frequent system, manifestation, in patients with, different terminal pulmonary pathology in pre-transplantation period. Worsening of lungs functional parameters, low BWI and. decrease of total fatty mass can be strong predictors of osteoporosis at the serious respiratory pathology

Fortification of food with micronutrients: development of methodological and regulatory framework in the Russian Federation

The available scientific literature, domestic and international regulatory codes of normative documents concerning the fortification of various types of food products have been analyzed. The groups of food products of conventional and regular consumption included into the diets of all categories of consumers, recommended for fortification with essential micronutrients, have been determined: wheat and cereal flour (spelt wheat, buckwheat, oat, corn flour, etc.); pastry; milk and dairy products, including ice cream; non-alcoholic soft drinks; mineralized drinking water; fruit and vegetable juices; fat and oil products (vegetable oils, margarines, spreads, mayonnaise); confectionery and sweets (pastry, sugar, chocolate); cereals (breakfast cereals, muesli, ready-to-eat extruded cereals, instant pasta and cereals, mixtures for bakery, flour for sweet pastry); food concentrates (jelly, instant drinks, concentrates of sweet foods, instant food, instant cereal concentrates); table salt. The groups of food products assigned for certain categories of population are used as part of therapeutic diets for patients with various diseases (metabolic disorder syndrome, cardio-vascular system pathology with atherosclerotic vascular injury, type 2 diabetes mellitus, gastrointestinal tract diseases, non-alcoholic fatty liver disease, diabetic nephropathy, etc.), as well as assigned to reduce the risk of diseases developing, the nutrients are recommended for targeted fortification of certain types of food. Examples of micronutrients fortification of sausages and minced meat semifinished products are given below. Requirements for fortification of mass consumption food products and for fortification of foods for special dietary uses are formulated in this article, the amount of fortifying components in the various groups of food products are justified, ensuring their efficiency for improving the micronutrient status and safety of its consumption. Based on the analysis of the available scientific literature, domestic and international regulatory framework of normative documents on fortification of various types of food products, recommendations have been developed for fortification of food with micronutrients

A Case of Medullary Carcinoma of the Jejunum Combined with the Intestinal Lymphangiectasia Accompanied by the Malabsorption Syndrome

Aim: to present a clinical and morphological observation of an extremely rare combination of medullary carcinoma of the jejunum and intestinal lymphangiectasia in a 33-year-old patient with clinical features of malabsorption syndrome over the 10 years.Key points. An autopsy revealed a tumor formation spreading from the wall of the jejunum to the mesentery, with metastases to the mesenteric lymph nodes. The medullary carcinoma with positive expression of СD117, DOG1, EMA, PanCK, PDL-1, vimentin, mosaic non-intense expression of CA19-9, calretinin, CD10, CDX2, CEA, MUC-5AC, SATB2, and negative reaction to ALK, CD3, CD8, CD20, CD30, CD31, CD34, CD45, CD56, chromogranin, CK7, CK20, desmin. The proliferative index was high: Ki-67 &gt; 80 %. Moreover, during the histological examination of the intestinal wall, intestinal lymphangiectasia complicated by the malabsorption syndrome was revealed.Conclusion. The uniqueness of this clinical and morphological case is in the combination of medullary carcinoma of the jejunum metastasized to the mesenteric lymph nodes with the underlying intestinal lymphangiectasia accompanied by the development of malabsorption syndrome

p53 Target Gene SMAR1 Is Dysregulated in Breast Cancer: Its Role in Cancer Cell Migration and Invasion

Tumor suppressor SMAR1 interacts and stabilizes p53 through phosphorylation at its serine-15 residue. We show that SMAR1 transcription is regulated by p53 through its response element present in the SMAR1 promoter. Upon Doxorubicin induced DNA damage, acetylated p53 is recruited on SMAR1 promoter that allows activation of its transcription. Once SMAR1 is induced, cell cycle arrest is observed that is correlated to increased phospho-ser-15-p53 and decreased p53 acetylation. Further we demonstrate that SMAR1 expression is drastically reduced during advancement of human breast cancer. This was correlated with defective p53 expression in breast cancer where acetylated p53 is sequestered into the heterochromatin region and become inaccessible to activate SMAR1 promoter. In a recent report we have shown that SMAR1 represses Cyclin D1 transcription through recruitment of HDAC1 dependent repressor complex at the MAR site of Cyclin D1 promoter. Here we show that downmodulation of SMAR1 in high grade breast carcinoma is correlated with upregulated Cyclin D1 expression. We also established that SMAR1 inhibits tumor cell migration and metastases through inhibition of TGFβ signaling and its downstream target genes including cutl1 and various focal adhesion molecules. Thus, we report that SMAR1 plays a central role in coordinating p53 and TGFβ pathways in human breast cancer

CXCR4/CXCL12 Participate in Extravasation of Metastasizing Breast Cancer Cells within the Liver in a Rat Model

INTRODUCTION: Organ-specific composition of extracellular matrix proteins (ECM) is a determinant of metastatic host organ involvement. The chemokine CXCL12 and its receptor CXCR4 play important roles in the colonization of human breast cancer cells to their metastatic target organs. In this study, we investigated the effects of chemokine stimulation on adhesion and migration of different human breast cancer cell lines in vivo and in vitro with particular focus on the liver as a major metastatic site in breast cancer. METHODS: Time lapse microscopy, in vitro adhesion and migration assays were performed under CXCL12 stimulation. Activation of small GTPases showed chemokine receptor signalling dependence from ECM components. The initial events of hepatic colonisation of MDA-MB-231 and MDA-MB-468 cells were investigated by intravital microscopy of the liver in a rat model and under shRNA inhibition of CXCR4. RESULTS: In vitro, stimulation with CXCL12 induced increased chemotactic cell motility (p,0.05). This effect was dependent on adhesive substrates (type I collagen, fibronectin and laminin) and induced different responses in small GTPases, such as RhoA and Rac-1 activation, and changes in cell morphology. In addition, binding to various ECM components caused redistribution of chemokine receptors at tumour cell surfaces. In vivo, blocking CXCR4 decreased extravasation of highly metastatic MDA-MB-231 cells (p < 0.05), but initial cell adhesion within the liver sinusoids was not affected. In contrast, the less metastatic MDA-MB-468 cells showed reduced cell adhesion but similar migration within the hepatic microcirculation. CONCLUSION: Chemokine-induced extravasation of breast cancer cells along specific ECM components appears to be an important regulator but not a rate-limiting factor of their metastatic organ colonization.Claudia Wendel, André Hemping-Bovenkerk, Julia Krasnyanska, Sören Torge Mees, Marina Kochetkova, Sandra Stoeppeler and Jörg Haie

Spin period evolution of GX 1+4

We aim both to complement the existing data on the spin history of the peculiar accreting X-ray pulsar GX 1+4 with more past and current data from BeppoSAX, INTEGRAL, and Fermi and to interpret the evolution in the framework of accretion theory. We used source light curves obtained from BeppoSAX/WFC and INTEGRAL/ISGRI to derive pulse periods using an epoch-folding analysis. Fermi/GBM data were analyzed by fitting a constant plus a Fourier expansion to background-subtracted rates, and maximizing the Y2 statistic. We completed the sample with hard X-ray light curves from Swift/BAT. The data were checked for correlations between flux and changes of the pulsar spin on different timescales. The spin-down of the pulsar continues with a constant change in frequency, i.e., an apparently accelerating change in the period. Over the past three decades, the pulse period has increased by about ~50%. Short-term fluctuations on top of this long-term trend do show anti-correlation with the source flux. Possible explanations of the observed long-term frequency and its dependence on flux are discussed.Comment: Accepted for publication in A&

CCL21/CCR7 Prevents Apoptosis via the ERK Pathway in Human Non-Small Cell Lung Cancer Cells

Previously, we confirmed that C-C chemokine receptor 7 (CCR7) promotes cell proliferation via the extracellular signal-regulated kinase (ERK) pathway, but its role in apoptosis of non-small cell lung cancer (NSCLC) cell lines remains unknown. A549 and H460 cells of NSCLC were used to examine the effect of CCL21/CCR7 on apoptosis using flow cytometry. The results showed that activation of CCR7 by its specific ligand, exogenous chemokine ligand 21 (CCL21), was associated with a significant decline in the percent of apoptosis. Western blot and real-time PCR assays indicated that activation of CCR7 significantly caused upregulation of anti-apoptotic bcl-2 and downregulation of pro-apoptotic bax and caspase-3, but not p53, at both protein and mRNA levels. CCR7 small interfering RNA significantly attenuated these effects of exogenous CCL21. Besides, PD98059, a selective inhibitor of MEK that disrupts the activation of downstream ERK, significantly abolished these effects of CCL21/CCR7. Coimmunoprecipitation further confirmed that there was an interaction between p-ERK and bcl-2, bax, or caspase-3, particularly in the presence of CCL21. These results strongly suggest that CCL21/CCR7 prevents apoptosis by upregulating the expression of bcl-2 and by downregulating the expression of bax and caspase-3 potentially via the ERK pathway in A549 and H460 cells of NSCLC

Эффективность и безопасность джозамицина при лечении нетяжелой внебольничной пневмонии в рутинной клинической практике: результаты проспективной многоцентровой наблюдательной программы

Aim. A goal of this noninterventional prospective multicenter observational program was to evaluate efficacy and safety of josamycin in patients with nonsevere communityacquired pneumonia (CAP) in routine clinical practice.Methods. Patients (n = 104) with radiological signs of pneumonia were treated with josamycin (Wilprafen® Solutab®, dispersible tablets 1 000 mg). Complete resolution of CAP was achieved in 95.6 % of patients, a clinically significant improvement was seen in 3.3 % of patients and a lack of effect was seen in 1 (1.1 %) patient. Radiological followup did not reveal worsening in any patients.The results of this study have demonstrated that josamycin was highly effective (&gt; 95 %) and had a good safety profile in outpatients with nonsevere CAP.С целью изучения эффективности и безопасности препарата джозамицин при лечении пациентов с нетяжелой внебольничной пневмонией (ВП) в рутинной клинической практике реализована неинтервенционная проспективная многоцентровая наблюдательная программа. Пациентам (n = 104) с рентгенологически подтвержденным диагнозом ВП в качестве антибактериального препарата назначался джозамицин (Вильпрафен® Солютаб®, таблетки диспергируемые 1 000 мг). По данным оценки клинической эффективности терапии у 95,6 % пациентов отмечалось полное выздоровление, у 3,3 % – клинически значимое улучшение, отсутствие эффекта от проводимой терапии – лишь в 1 (1,1 %) случае. При контрольном рентгенологическом обследовании отрицательной динамики не выявлено ни у одного пациента. По результатам наблюдательной программы при лечении пациентов с нетяжелой ВП в амбулаторных условиях показаны высокая эффективность (&gt; 95 %) и хороший профиль безопасности препарата