Mono-2-ethylhexyl Phthalate Stimulates Parturition-Related Responses in Human Gestational Tissues and Cells.

Diethyhexyl phthalate (DEHP) is an environmental pollutant used universally as a plasticizer in polyvinyl consumer products. Exposure to DEHP increases risk of adverse pregnancy outcomes in humans, including decreased gestation length, preterm birth, low birth weight, and early pregnancy loss. Moreover, monoethylhexyl phthalate (MEHP), the active metabolite of DEHP increases oxidative stress and inflammatory responses in vitro. Because oxidative stress and inflammatory responses are linked to the pathogenesis of preterm birth, we investigated MEHP stimulated oxidative stress and inflammatory responses in human gestational cells and tissues as mechanisms by which MEHP exposure may contribute to preterm birth. To identify whether MEHP exposure induces oxidative stress responses in the gestational compartment, we treated human placental cells (HTR-8/SVneo) with MEHP and measured reactive oxygen species (ROS) generation using the dichlorofluorescein (DCF) assay, oxidized thymine (oT) with mass-spectrometry, redox-sensitive gene expression with RT-PCR, and activation of caspase 3/7 using a luminescence assay. We found that MEHP increased ROS generation, oxidative DNA damage, and apoptosis, and modified redox-sensitive gene expression. Notably, MEHP significantly induced mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2), the gene for COX-2, an enzyme important for prostaglandin synthesis. To assess whether MEHP may stimulate inflammatory responses in the gestational compartment, we treated human primary placental macrophages, primary decidual macrophages, gestational membrane explants, and HTR-8 cells with MEHP and measured prostaglandin and cytokine release using enzyme-linked immunosorbent assays (ELISA) and PTGS2 mRNA expression using RT-PCR. Our results demonstrate that MEHP treatment significantly increased total prostaglandin, PGF2α, and PGE2 release in human primary placental macrophage Hofbauer cells, and induced PTGS2 mRNA expression in the HTR-8 human trophoblast cell line. MEHP treatment showed no effect on pro-inflammatory cytokine release. The results from the present study are consistent with the hypothesis that MEHP stimulates oxidative stress and prostaglandin synthesis in gestational tissues and cells. The findings from the current study warrant future epidemiological studies of oxidative stress and prostaglandin synthesis as mechanisms by which MEHP may contribute to preterm birth and other adverse pregnancy outcomes.PHDToxicologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/94101/1/ltetz_1.pd

Микробиота и онкологические заболевания (обзор литературы)

Article presents current data on the contribution of the human microbiota to the development of oncological conditions, microbial impact on cell transformation, influence on chemotherapy outcome. Brief description of the methods used for studying microbiota in carcinogenesis as well as prospects of creating non-invasive diagnostic tools is given.Представлены современные данные о вкладе микробиоты человека в развитие неопластических заболеваний, механизмы клеточной трансформации и эффективность химиотерапии. Описаны методы изучения микробиоты при опухолевых заболеваниях, перспективы создания неинвазивных методов диагностики неоплазий

A freely accessible, evidence based, objective system of analysis of posterior capsular opacification ; Evidence for its validity and reliability

BACKGROUND: The aim of this study was to develop a system of computerised analysis of digital images of posterior capsule opacification (PCO) that is evidence based, objective and freely available. The paper will present evidence for the reliability and validity of the developed system. METHODS: The system of PCO analysis was developed considering current published evidence on visual significance of PCO and additional investigative analysis of PCO images. Details of the image processing and analysis steps are discussed and a final system that measures an entropy score weighted toward proximity to central areas is described. In order to assess validity, the systems ability to measure PCO progression is assessed along with the visual significance of its final computerised scores. Reliability of the system is also assessed. RESULTS: The final system runs successfully and is simple to use. Analyses of PCO by the system show an ability to detect early progression of PCO as well as detection of visually significant PCO. Images with no clinical PCO produce very low scores in the analysis. Reliability of the system of analysis is shown to be satisfactory. CONCLUSION: This paper presents a system of PCO analysis that is evidence based, objective and clinically useful. Substantial evidence is provided for its validity and reliability

OSCA: a comprehensive open-access system of analysis of posterior capsular opacification

BACKGROUND: This paper presents and tests a comprehensive computerised system of analysis of digital images of posterior capsule opacification (PCO). It updates and expands significantly on a previous presentation to include facilities for selecting user defined central areas and for registering and subsequent merging of images for artefact removal. Also, the program is compiled and thus eliminates the need for specialised additional software. The system is referred to in this paper as the open-access systematic capsule assessment (OSCA). The system is designed to be evidence based, objective and openly available, improving on current systems of analysis. METHODS: Principal features of the OSCA system of analysis are discussed. Flash artefacts are automatically located in two PCO images and the images merged to produce a composite free from these artefacts. For this to be possible the second image has to be manipulated with a registration technique to bring it into alignment with the first. Further image processing and analysis steps use a location-sensitive entropy based texture analysis of PCO. Validity of measuring PCO progression of the whole new system is assessed along with visual significance of scores. Reliability of the system is assessed. RESULTS: Analysis of PCO by the system shows ability to detect early progression of PCO, as well as detection of more visually significant PCO. Images with no clinical PCO produce very low scores in the analysis. Reliability of the system of analysis is demonstrated. CONCLUSION: This system of PCO analysis is evidence-based, objective and clinically useful. It incorporates flash detection and removal as well as location sensitive texture analysis. It provides features and benefits not previously available to most researchers or clinicians. Substantial evidence is provided for this system's validity and reliability

Presence of extracellular DNA in the Candida albicans biofilm matrix and its contribution to biofilms

DNA has been described as a structural component of the extracellular matrix (ECM) in bacterial biofilms. In Candida albicans, there is a scarce knowledge concerning the contribution of extracellular DNA (eDNA) to biofilm matrix and overall structure. This work examined the presence and quantified the amount of eDNA in C. albicans biofilm ECM and the effect of DNase treatment and the addition of exogenous DNA on C. albicans biofilm development as indicators of a role for eDNA in biofilm development. We were able to detect the accumulation of eDNA in biofilm ECM extracted from C. albicans biofilms formed under conditions of flow, although the quantity of eDNA detected differed according to growth conditions, in particular with regards to the medium used to grow the biofilms. Experiments with C. albicans biofilms formed statically using a microtiter plate model indicated that the addition of exogenous DNA (>160 ng/ml) increases biofilm biomass and, conversely, DNase treatment (>0.03 mg/ml) decreases biofilm biomass at later time points of biofilm development. We present evidence for the role of eDNA in C. albicans biofilm structure and formation, consistent with eDNA being a key element of the ECM in mature C. albicans biofilms and playing a predominant role in biofilm structural integrity and maintenance.National Institute of Dental & Craniofacial ResearchFundação para a Ciência e Tecnologia (FCT) - SFRH/BD/28222/2006National Institute of Allergy and Infectious Disease

In vitro activity of daptomycin, linezolid and rifampicin on Staphylococcus epidermidis biofilms

Owing to their massive use, Staphylococcus epidermidis has recently developed significant resistance to several antibiotics, and became one of the leading causes of hospital-acquired infections. Current antibiotics are typically ineffective in the eradication of bacteria in biofilmassociated persistent infections. Accordingly, the paucity of effective treatment against cells in this mode of growth is a key factor that potentiates the need for new agents active in the prevention or eradication of biofilms. Daptomycin and linezolid belong to the novel antibiotic therapies that are active against gram-positive cocci. On the other hand, rifampicin has been shown to be one of the most potent, prevalent antibiotics against S. epidermidis biofilms. Therefore, the main aim of this study was to study the susceptibility of S. epidermidis biofilm cells to the two newer antimicrobial agents previously mentioned, and compare the results obtained with the antimicrobial effect of rifampicin, widely used in the prevention/treatment of indwelling medical device infections. To this end the in vitro activities of daptomycin, linezolid, and rifampicin on S. epidermidis biofilms were accessed, using these antibiotics at MIC and peak serum concentrations. The results demonstrated that at MIC concentration, rifampicin was the most effective antibiotic tested. At peak serum concentration, both strains demonstrated similar susceptibility to rifampicin and daptomycin, with colony-forming units (CFUs) reductions of approximately 3–4 log10, with a slightly lower response to linezolid, which was also more strain dependent. However, considering all the parameters studied, daptomycin was considered the most effective antibiotic tested, demonstrating an excellent in vitro activity against S. epidermidis biofilm cells. In conclusion, this antibiotic can be strongly considered as an acceptable therapeutic option for S. epidermidis biofilm-associated infections and can represent a potential alternative to rifampicin in serious infections where rifampicin resistance becomes prevalent.Bruna Leite acknowledges the financial support from ISAC/Program Erasmus Munds External Cooperation and the IBB-Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, University of Minho, Campus of Gualtar. Fernanda Gomes and Pilar Teixeira fully acknowledge the financial support from Fundacao para a Ciencia e Tecnologia (FCT) through the grants SFRH/BD/32126/2006 and SFRH/BPD/26803/2006, respectively

Viscoat versus Visthesia during phacoemulsification cataract surgery: corneal and foveal changes

<p>Abstract</p> <p>Background</p> <p>Ophthalmic viscosurgical devices (OVDs) are widely used in phacoemulsification cataract surgery to maintain adequate intraocular space, stabilize ocular tissue during the operation and decrease the possible damage of the corneal endothelium. Our study has the purpose to compare the corneal and foveal changes of Viscoat and Visthesia in patients undergoing uneventful phacoemulsification cataract surgery.</p> <p>Methods</p> <p>Participants in our study were 77 consecutive patients, who were randomized into two groups based on type of OVD used during phacoemulsification: Viscoat or Visthesia. All patients underwent a complete ophthalmological examination i.e., measurement of best corrected visual acuity (BCVA) by means of Snellen charts, intraocular pressure examination by Goldmann tonometry, slit lamp examination, fundus examination, optical coherence tomography, specular microscopy and ultrasound pachymetry preoperatively and at three time points postoperatively (day 3, 15, 28 postoperatively). The differences in baseline characteristics, as well as in outcomes between the two groups were compared by Mann-Whitney-Wilcoxon test and Student's t-test, as appropriate.</p> <p>Results</p> <p>Intraoperatively, there was no statistically significant difference in the duration of the ultrasound application between the two groups, while Viscoat group needed more time for the operation performance. It is also worthy to mention that Visthesia group exhibited less intense pain than patients in Viscoat group. Postoperatively, there was a statistically significant difference in central corneal thickness, endothelial cell count and macular thickness between the two groups, but BCVA (logMAR) did not differ between the two groups.</p> <p>Conclusions</p> <p>Our study suggests that Viscoat is more safe and protective for the corneal endothelium during uneventful phacoemulsification cataract surgery, while Visthesia is in superior position regarding intraoperative pain. Patients of both groups acquired excellent visual acuity postoperative. Finally, this is the first study comparing OVDs in terms of macular thickness, finding that Visthesia cause a greater increase in macular thickness postoperatively than Viscoat, although it reaches normal ranges in both groups.</p

Bioconjugation Strategies for Microtoroidal Optical Resonators

The development of label-free biosensors with high sensitivity and specificity is of significant interest for medical diagnostics and environmental monitoring, where rapid and real-time detection of antigens, bacteria, viruses, etc., is necessary. Optical resonant devices, which have very high sensitivity resulting from their low optical loss, are uniquely suited to sensing applications. However, previous research efforts in this area have focused on the development of the sensor itself. While device sensitivity is an important feature of a sensor, specificity is an equally, if not more, important performance parameter. Therefore, it is crucial to develop a covalent surface functionalization process, which also maintains the device’s sensing capabilities or optical qualities. Here, we demonstrate a facile method to impart specificity to optical microcavities, without adversely impacting their optical performance. In this approach, we selectively functionalize the surface of the silica microtoroids with biotin, using amine-terminated silane coupling agents as linkers. The surface chemistry of these devices is demonstrated using X-ray photoelectron spectroscopy, and fluorescent and optical microscopy. The quality factors of the surface functionalized devices are also characterized to determine the impact of the chemistry methods on the device sensitivity. The resulting devices show uniform surface coverage, with no microstructural damage. This work represents one of the first examples of non-physisorption-based bioconjugation of microtoroidal optical resonators

МАЛОИЗВЕСТНЫЕ БАКТЕРИИ, ВЫДЕЛЕННЫЕ ПРИ ЗАБОЛЕВАНИЯХ ЧЕЛОВЕКА

The paper is devoted to the study of little-known and previously unknown bacteria isolated from patients with various diseases. Here we present the data on 22 strains that are little-known or previously unknown as human pathogens and isolated from patients with various diseases. Most of the isolates were found to have multiple antibiotic resistances. Moreover, in many conditions potentially pathogenic spore-forming bacteria were identified. Spore formation provides bacteria for survival in the environment and promotes high resistance to antiseptics and disinfectants. Spore-forming bacteria are high survival and especially dangerous as potential hospital-acquired infections because of its antibiotic resistance but the activity of this antibiotic therapy doesn’t concern microbial spores.Работа посвящена изучению малоизвестных и ранее не известных бактерий, изолированных у больных с патологиями различной локализации. Выделенные и изученные 22 штамма малоизвестных бактерий или вообще не описаны ранее как возбудители заболеваний человека, или обнаружены при патологии другой локализации. Большинство полученных бактерий обладает множественной  устойчивостью к различным  антибиотикам. При  разных  заболеваниях в материале обнаружено много потенциально-патогенных спорообразующих   бактерий. Спорообразование   обеспечивает бактериям  сохранение  жизнеспособности в окружающей среде и повышенную устойчивость к антисептикам и дезинфектантам. Спорообразующие бактерии хорошо   сохраняются   и особенно  опасны  в качестве потенциальных  возбудителей внутрибольничных   инфекций,   поскольку резистентны к антибиотикотерапии, активность которой не распространяется на микробные споры