Genital infection in women with spontaneous, timely and premature birth

In recent years, the influence of genital infection on pregnancy and perinatal outcomes has been actively studied. The question arises-why genital infection during pregnancy in some cases can cause premature birth, and in others practically does not affect its course is not fully understood. Objective: to assess the features of history, pregnancy, structure of infectious pathology and its treatment in women with timely and premature birth. 112 women with infectious diseases of the vagina and cervix were retrospectively analyzed. It was found that the structure of infectious pathology of the lower reproductive tract in women with spontaneous preterm labor was represented by: cervicitis-29.4%, vaginitis-21.6%, their combination (cervicovaginitis) -17.6%, bacterial vaginosis -15.7%, vaginal dysbiocenosis -15.7%. In very early and early preterm labor, the most common form of infectious pathology of the lower genitals was cervicovaginitis; in preterm labor - vaginitis. Structure of genital infections in patients with the timely childbirth: cervicitis is 27.9%, vaginitis - 26,2%, desbiens vagina -16,4% , bacterial vaginosis - 14.8%, cervicovaginitis is 14.8%. Conclusions: there were no differences in the structure of infectious pathology of the lower reproductive tract in women with spontaneous premature and timely delivery. In patients with genital infection, pregnancy in which ended spontaneous preterm birth significantly more often than in the comparison group there were: burdened obstetric and gynecological history, diseases of the urinary system, persistent threat of termination of pregnancy, placental insufficiency, iron deficiency anemia. In patients with spontaneous premature birth percentage of morphologically confirmed intrauterine infection was significantly higher than in women who gave birth at term and the set of morphological forms were distinguished by a higher degree of involvement of the tissues of the placenta in the inflammatory process (membranes, placenta).В последние годы активно изучается влияние генитальной инфекции на течение беременности и перинатальные исходы. Встает вопрос - почему генитальная инфекция во время беременности в одних случаях может стать причиной преждевременных родов, а в других практически не влияет на ее течение остается до конца не изученным. Цель работы: оценить особенности анамнеза, течения беременности, структуры инфекционной патологии и ее лечения у женщин со своевременными и преждевременными родами. Ретроспективно проанализировано 112 женщин с инфекционной патологией влагалища и шейки матки. Установлено, что структура инфекционной патологии нижнего отдела репродуктивного тракта у женщин со спонтанными преждевременными родами была представлена: цервицитом - 29,4%, вагинитом - 21,6%, их сочетанием (цервиковагинитом) -17,6%, бактериальным вагинозом -15,7%, дисбиоценозом влагалища -15,7%. При очень ранних и ранних преждевременных родах самой частой формой инфекционной патологии нижнего отдела гениталий являлся цервиковагинит; при преждевременных родах - вагинит. Структура генитальной инфекции у пациенток со своевременными родами: цервицит - 27,9%, вагинит - 26,2%, дисбиоценоз влагалища -16,4%, бактериальный вагиноз -14,8%, цервиковагинит - 14,8%. Выводы: У женщин со спонтанными преждевременными и своевременными родами не было выявлено отличий по структуре инфекционной патологии нижнего отдела репродуктивного тракта. У пациенток с генитальной инфекцией, беременность у которых закончилась спонтанными преждевременными родами достоверно чаще, чем в группе сравнения имели место: отягощенный акушерско-гинекологический анамнез, заболевания мочевыделительной системы, стойкая угроза прерывания беременности, плацентарная недостаточность, железодефицитная анемия. У пациенток со спонтанными преждевременными родами процент морфологически подтвержденной внутриматочной инфекции был достоверно выше, чем у женщин, родивших в срок и установленные морфологические формы отличались более высокой степенью вовлеченности тканей последа в воспалительный процесс (мембранит, плацентит)

Anti-cancer drug validation: the contribution of tissue engineered models

Abstract Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current Bstate of art^ on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their studyThis article is a result of the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This article was also supported by the EU Framework Programme for Research and Innovation HORIZON 2020 (H2020) under grant agreement n° 668983 — FoReCaST. FCT distinction attributed to Joaquim M. Oliveira (IF/00423/2012) and Vitor M. Correlo (IF/01214/2014) under the Investigator FCT program is also greatly acknowledged.info:eu-repo/semantics/publishedVersio

Staphylococcus aureus pathogenicity Factors and their Role in the Infection process and the induction of the postvaccination immunity

The rapid development of molecular-biological and genetic methods of research led to the broadening and deepening of knowledge of the pathogenesis of infection diseases, the structure of pathogenicity factors and their role in the development of the post-infection and post-vaccination immunity. In the review presented the literature data of this problem in relation to diseases, caused by S. aureus, which acquired great social and economic significance. Presented the list of numerous pathogenicity factors of S. aureus, their significance in the development of the infectious process and the results used to create vaccine preparations. Most of the vaccines in the construction of which used the capsular polysaccharides, toxins, protein antigens of the cell wall are in various stages of preclinical and clinical trials. Preliminary data indicate a need to use it to create protective immunity multiantigenic complex with focus on numerous factors of pathogenicity of S. aureus

Growth, characterization and biocompatibility of bone-like calcium phosphate layers biomimetically deposited on metallic substrata

Much research has been devoted to the coating of orthopedic and dental implants with porous ceramics, such as hydroxyapatite to increase hard tissue integration in vivo. Chemical immersion in simulated body fluids and supersaturated calcium-phosphate solutions (SCPS) have been shown to elicit apatite coatings on the order of 10-100 μm of thickness, which are very homogenous and would be more favorable to biological interaction than plasma-sprayed coatings. This study focuses on the growth, characterization and biocompatibility of bone-like apatite layers on metallic biomaterials produced through diminished time duration chemical immersion. The method presented here includes a pre-calcification step, in which samples were immersed in a boiling Ca(OH)2 solution to initiate and increase favorable ion exchange prior to immersion. Subsequent immersion in SCPS produced homogenous coatings of calcium phosphate with a thickness of 20-30 μm, 100% coverage and crystal sizes of 1-2 μm in 3 days. Coated samples were favored biologically over non-coated samples by osteoblast cells as indicated by alkaline phosphatase activity. This study suggests that an industrially viable method of chemical immersion in a SCPS, coupled with simple pre-treatments can produce calcium phosphate coatings that favor positive biological interactions, conducive to osseointegration. © 2005 Elsevier B.V. All rights reserved

The Study of Protective Extracellular Proteome Staphylococcus aureus № 6

In recent years, there is a persistent increase in the spread of community-acquired infections and medical care associated infections, the cause of which is S. aureus. Previously using liquid chromatography in combination with mass spectrometry (LC-MS) analysis, spectrum of having protective activity S. aureus № 6 proteins with a molecular weight of 30 - 50 kDa, secreted into the culture medium at the end of the exponential growth phase, was investigated. 11 proteins were identified from indicated peptides and preliminary results of the protective activity of the secreted protein-based substances (SPS), marked as «initial», were obtained. While its fractionation with ion exchange chromatography on DEAE-Sepharose, the protective fraction - II SPS - was obtained. Its hypodermic immunization leads to reduction of kidney inoculation, and to kidney abscess formation, compared to the control, during the generalized infection of mice BALB/c, developing as a result of retro-orbital injection of sublethal dose S. aureus. Aim. investigation the protective extracellular proteome II SPS S. aureus № 6. Material and methods. LC-MS analysis of the received data was carried out by comparing the detected mass-spectrum protein IISPS with the results of proteomic study of the virulent strain of S. aureus Newman widely used in researches. More than 100 interacting protein clusters were identified for certain using various databases. Results. During analysis main attention was paid to 46 identified proteins involved in various biological processes. Thus, the largest group (19 proteins) is composed of carbohydrate metabolism enzymes, eight of which are involved in key stages of glycolysis; 6 proteins are related to pathogenicity factors (including clamping factors A and B, gaptoglobin-adhesive surface protein) and 4 proteins are related to stress ones. The remaining 17 proteins represent a large group of proteins involved in various metabolic and biosynthetic processes. Conclusion. The received results confirmed the data of other researchers on the identification of a large number of secreted proteins of S. aureus and on their low coincidence with secreted from clinical isolates. This demonstrates the validity of the postulate of the plasticity of the S. aureus genome affecting the exoproteome profile that largely determines the difficulties in creation of effective anti-staphylococcal vaccines

IMMUNOGENIC PROPERTIES OF CELLULAR AND EXTRACELLULAR PROTEIN-CONTAINING ANTIGENS OF STAPHYLOCOCCUS AUREUS

Aim. Comparative study of immunobiological properties of cell wall surface antigens and extracellular protein-containing antigens of Staphylococcus aureus. Materials and methods. Preparations: surface antigens of the cell wall (peptidoglycan, teichoic acids, protein antigens) of the strains of S. aureus containing in the staphylococcal vaccine «Staphylovac» (SV) and extracellular protein-containing antigens of S. aureus (EPCA). The parameters of innate immunity were evaluated by the effect of preparations on the immunophenotype of mononuclear leukocytes (ML) of the spleen of mice, expression of Toll-like receptors (using flow cytometry), phagocytic activity of macrophages of peritoneal exudate of mice after the introduction of SV and EPCA; the protective activity of preparations was studied in experiments of active protection of BALB/c mice. Results. To isolate EPCA, we used the virulent strain of S. aureus №6, and for obtaining surface antigens of the cell wall, 4 strains were selected, the most immunogenic of which was the low virulent strain of S. aureus №1991. Both preparations increased the number of TLR2 and MHC II expressing cells; CV administration caused an increase in the number of cells with CD25 marker, reflecting the early activation of immunocompetent cells, and EPCA immunization — led to a shorter expression of this marker. On the other hand, an increased number of CD19 positive cells were detected for a longer period of time during EPCA immunization. The longest activation of phagocytosis under the action of SV was established. High protective activity of bo-th types of the studied preparations was noted. Conclusion. The antigens of the cell wall and extracellular protein-containing experimental drugs possessed comparable immunological  properties, however, the surface antigens to a greater extent activate innate immunity, and extracellular — adaptive immunity

Immunogenic Activity of Secreted Protein-Based Compounds Staphylococcus aureus № 6

Difficulties in the therapy of infection, caused by S. aureus, depends on the resistance of staphylococci to antibiotics, proceeding to chronicity of the diseases and the development on that background the depression of innate immunity functions and decreasing of the host resistance to the infection. In spite of tremendous efforts of researchers, up to date there are no commercial antistaphylococcal vaccine the efficacy of which would be proved in the completed clinical trials.Aim: obtaining secreted protein-based substances of the S. aureus № 6 and investigation their immunogenicity.Material and methods. Secreted protein-based substances (SPS) were obtain as: «initial» – from the filtrates of the culture fluid of the S. aureus № 6, grown to the end of the exponential phase according to the technology described previously [9], and I SPS and II SPS – after the ion-exchange chromatography of the «initial» SPS on the columns with Q-Sepharose and DEAE-Sepharose. The level of specific IgG antibodies in sera of immunized rabbits and mice determined in ELISA, the immunogenic activity evaluated in experiments of active and passive protection from the challenge performed on BALB/с mice and also by the determination of the bacterial content in organs and in the test of abscesses formation in kidneys. Results. Investigated SBS possessed the antigenic activity (the level of specific IgG antibodies in sera of immunized animals increased 2.2 – 7.5 times compared to the control groups), that is favor of the activation of the adaptive immunity system and significant protective activity revealed in experiments of active (index of efficacy 2.63 – 4.28) and passive protection. The immunization of mice with the «initial» and II SPS led to significant decrease of the number of colonyforming units of S. aureus and formation of abscesses in kidneys of mice. It is evidently, that investigated SPS, influence on the severity of staphylococcal infection and possesses the therapeutic effect.Conclusion. The preformed complex analysis at the current stage allowed to reveal perspectives of the further study of «initial» and II SPS in pre-clinical trials, as candidates, possessing the high protective facilities, for including them in the drug composition for immune prophylaxis and immunotherapy of diseases, caused by S. aureus

Synthesis and characterization of a new class of anti-angiogenic agents based on ruthenium clusters.

New triruthenium-carbonyl clusters derivatized with glucose-modified bicyclophosphite ligands have been synthesized. These compounds were found to have cytostatic and cytotoxic activity and depending on the number of bicyclophosphite ligands, and could be tuned for either anti-cancer or specific anti-angiogenic activity. While some compounds had a broad cellular toxicity profile in several cell types others showed endothelial cell specific dose-dependent anti-proliferative and anti-migratory efficacy. A profound inhibition of angiogenesis was also observed in the in vivo chicken chorioallantoic membrane (CAM) model, and consequently, these new compounds have considerable potential in drug design, e.g. for the treatment of cancer