Leukocyte-Endothelium Interaction in the Sublingual Microcirculation of Coronary Artery Bypass Grafting Patients

Objective: The aim of this study was to apply an innovative methodology to incident dark-field (IDF) imaging in coronary artery bypass grafting (CABG) patients for the identification and quantification of rolling leukocytes along the sublingual microcirculatory endothelium. Methods: This study was a post hoc analysis of a prospective study that evaluated the perioperative course of the sublingual microcirculation in CABG patients. Video images were captured using IDF imaging following the induction of anesthesia (T-0) and cardiopulmonary bypass (CPB) (T-1) in 10 patients. Rolling leukocytes were identified and quantified using frame averaging, which is a technique that was developed for correctly identifying leukocytes. Results: The number of rolling leukocytes increased significantly from T-0 (7.5 {[}6.4-9.1] leukocytes/capillary-postcapillary venule/4 s) to T-1 (14.8 {[}13.2-15.5] leukocytes/capillary-postcapillary venule/4 s) (p < 0.0001). A significant increase in systemic leukocyte count was also detected from 7.4 +/- 0.9 x 10(9)/L (preoperative) to 12.4 +/- 4.4 x 10(9)/L (postoperative) (p < 0.01). Conclusion: The ability to directly visualize leukocyte-endothelium interaction using IDF imaging facilitates the diagnosis of a systemic inflammatory response after CPB via the identification of rolling leukocytes. Integration of the frame averaging algorithm into the software of handheld vital microscopes may enable the use of microcirculatory leukocyte count as a real-time parameter at the bedside.1JAN8-155

Fluorescent Heterodoped Nanotetrapods as Synergistically Enhancing Positive and Negative Magnetic Resonance Imaging Contrast Agents

In this work, we report Mn-Fe heterodoped ZnSe tetrapod nanocrystals (NCs) synthesized to synergistically enhance contrast in both T1- and T2-weighted magnetic resonance imaging (MRI). The proposed NCs were prepared using a customized heteroarchitecture such that the manganese (Mn) is confined in the core and iron (Fe) in the branches of the tetrapods. The elemental composition and profile of these NCs were studied using X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy, and inductively coupled plasma mass spectroscopy. Photoluminescence quantum yield of these heterodoped NCs in water is ∼30%. Magnetic measurements reveal the simultaneous presence of superparamagnetic and paramagnetic behavior in these NCs because of the coexistence of Mn2+ and Fe2+ dopants. Their potential as simultaneous positive and negative MRI contrast agents was demonstrated by relaxivity measurements and in vivo MRI. From the in vivo studies, we also found that these NCs (with a hydrodynamic diameter of 20 nm) are excreted from the body within 24 h after the injection. Therefore, these heterodoped tetrapods NCs, while being fluorescent and safe, hold great future as a synergistically enhancing dual-modal MRI contrast agent. © 2016 American Chemical Society

Intrauterine growth restriction and placental angiogenesis

Background: Vascular endothelial growth factor (VEGF), basic-fibroblast growth factor (b-FGF), and endothelial nitric oxide synthase (eNOS) are factors that take part in placental angiogenesis. They are highly expressed during embryonic and fetal development, especially in the first trimester. In this study, we aimed to investigate the role of placental angiogenesis in the development of intrauterine growth restriction (IUGR) by comparing the levels of expression of VEGF-A, b-FGF, and eNOS in normal-term pregnancy and IUGR placentas.Methods: The expression of VEGF-A, b-FGF, and eNOS was studied using the avidin-biotin-peroxidase method in placental tissues diagnosed as normal (n = 55) and IUGR (n = 55). Results were evaluated in a semi-quantitative manner.Results: The expression of all the markers was significantly higher (p < 0.001) in cytotrophoblasts, syncytiotrophoblasts, extravillous trophoblasts, vascular smooth muscle cells, chorionic villous stromal cells, and villous vascular endothelial cells of the IUGR placentas when compared with those collected from normal-term pregnancies.Conclusion: Increased expression of VEGF-A, b-FGF, and eNOS may be the result of inadequate uteroplacental perfusion, supporting the proposal that abnormal angiogenesis plays a role in the pathophysiology of IUGR. © 2010 Barut et al; licensee BioMed Central Ltd

YK-4-279 Inhibits ERG and ETV1 Mediated Prostate Cancer Cell Invasion

Background: Genomic rearrangements involving the ETS family of transcription factors occur in 40–70 % of prostate cancer cases. ERG and ETV1 are the most common ETS members observed in these genetic alterations. The high prevalence of these rearrangements and their biological significance represents a novel therapeutic target for the treatment of prostate cancer. Methods and Findings: We recently reported the development of YK-4-279, a small molecule inhibitor of EWS-FLI1 oncoprotein in Ewing’s Sarcoma. Since ERG and ETV1 belong to the same class of ETS factors as FLI1, we tested the ability of YK-4-279 to inhibit biological functions of ERG and ETV1 proteins in prostate cancer. YK-4-279 inhibited ERG and ETV1 mediated transcriptional activity in a luciferase assay. YK-4-279 also decreased ERG and ETV1 downstream target mRNA and protein expression in ETV1-fusion positive LNCaP and ERG fusion positive VCaP cells. YK-4-279 reduced the motility of LNCaP cells in a scratch assay and the invasive phenotype of both LNCaP and VCaP cells in a HUVEC invasion assay. Fusion-negative PC3 cells were unresponsive to YK-4-279. SiRNA mediated ERG knockdown in VCaP cells resulted in a loss of drug responsiveness. Concurrently, transient ERG expression in PC-3 cells resulted in increased invasive potential, which was reduced by YK-4-279. Conclusion: These data demonstrate that YK-4-279 inhibits ERG and ETV1 biological activity in fusion-positive prostat

Investigation of the erosive potential of sour novelty sweets

Provides a background about the link between acidic beverages and dental erosion. Discusses the potential risk of developing dental erosion upon the frequent consumption of novelty sweets. Provides information which could be used by dental personnel in counselling patients who consume novelty sweets or at risk of developing dental erosion. Abstract Background The expansion of the novelty sweets market in the UK has major potential public health implications in children and young adults as they may cause dental erosion. Objective To investigate the erosive potential of the novelty sweets in term of their physiochemical properties and amount of enamel loss. Subjects and methods The pH of a variety of novelty sweets was tested in vitro using a pH meter and the neutralisable acidity was assessed by titrating the sweets against 0.1M NaOH. The viscosity of the novelty sweets was measured using a rotational viscometer. The wettability of enamel by each sweet was measured using dynamic contact angle analyser. Enamel loss was assessed using contact profilometry. Results The pH ranged from 1.8–3.2, the neutralisable acidity ranged from 9–201 ml of 0.1 NaOH. The viscosity of the novelty sweets that come in liquid form ranged from 2–594 mPa s. The surface enamel erosion ranged from 1.95–15.77 μm and from 2.5–17.6 μm with and without immersing in saliva for 1 hour before immersing in acidic solution respectively. The amount of subsurface enamel loss was ranged from 0.75 to 2.3 μm following ultrasonication at 0 min of acidic attack and from 0.23 to 0.85 μm at 60 minutes of acidic attack while immersed in saliva. The contact angle between enamel surface and four sweet was less than the angle formed between the orange juice and the enamel which caused more wettability of enamel. Conclusion The pH is lower than the critical value for enamel erosion (5.5), high neutralisable acidity and high sugar content strongly suggest that these sweets may cause significant amount of dental erosion clinically. In addition, the degree of wettability of enamel by solution is an important factor to consider in determining the enamel loss caused by acidic solution. Immediate tooth brushing would cause further enamel loss as a result of the mechanical removal of softened enamel. However, it has been suggested that postponing brushing after erosive attack should be reconsidered

Co-circulation of West Nile virus and distinct insect-specific flaviviruses in Turkey

Background: Active vector surveillance provides an efficient tool for monitoring the presence or spread of emerging or re-emerging vector-borne viruses. This study was undertaken to investigate the circulation of flaviviruses. Mosquitoes were collected from 58 locations in 10 provinces across the Aegean, Thrace and Mediterranean Anatolian regions of Turkey in 2014 and 2015. Following morphological identification, mosquitoes were pooled and screened by nested and real-time PCR assays. Detected viruses were further characterised by sequencing. Positive pools were inoculated onto cell lines for virus isolation. Next generation sequencing was employed for genomic characterisation of the isolates. Results: A total of 12,711 mosquito specimens representing 15 species were screened in 594 pools. Eleven pools (2%) were reactive in the virus screening assays. Sequencing revealed West Nile virus (WNV) in one Culex pipiens (s.l.) pool from Thrace. WNV sequence corresponded to lineage one clade 1a but clustered distinctly from the Turkish prototype isolate. In 10 pools, insect-specific flaviviruses were characterised as Culex theileri flavivirus in 5 pools of Culex theileri and one pool of Cx. pipiens (s.l.), Ochlerotatus caspius flavivirus in two pools of Aedes (Ochlerotatus) caspius, Flavivirus AV-2011 in one pool of Culiseta annulata, and an undetermined flavivirus in one pool of Uranotaenia unguiculata from the Aegean and Thrace regions. DNA forms or integration of the detected insect-specific flaviviruses were not observed. A virus strain, tentatively named as “Ochlerotatus caspius flavivirus Turkey”, was isolated from an Ae. caspius pool in C6/36 cells. The viral genome comprised 10,370 nucleotides with a putative polyprotein of 3,385 amino acids that follows the canonical flavivirus polyprotein organisation. Sequence comparisons and phylogenetic analyses revealed the close relationship of this strain with Ochlerotatus caspius flavivirus from Portugal and Hanko virus from Finland. Several conserved structural and amino acid motifs were identified. Conclusions: We identified WNV and several distinct insect-specific flaviviruses during an extensive biosurveillance study of mosquitoes in various regions of Turkey in 2014 and 2015. Ongoing circulation of WNV is revealed, with an unprecedented genetic diversity. A probable replicating form of an insect flavivirus identified only in DNA form was detected