High calcium bioglass enhances differentiation and survival of endothelial progenitor cells, inducing early vascularization in critical size bone defects

Early vascularization is a prerequisite for successful bone healing and endothelial progenitor cells (EPC), seeded on appropriate biomaterials, can improve vascularization. The type of biomaterial influences EPC function with bioglass evoking a vascularizing response. In this study the influence of a composite biomaterial based on polylactic acid (PLA) and either 20 or 40% bioglass, BG20 and BG40, respectively, on the differentiation and survival of EPCs in vitro was investigated. Subsequently, the effect of the composite material on early vascularization in a rat calvarial critical size defect model with or without EPCs was evaluated. Human EPCs were cultured with β-TCP, PLA, BG20 or BG40, and seeding efficacy, cell viability, cell morphology and apoptosis were analysed in vitro. BG40 released the most calcium, and improved endothelial differentiation and vitality best. This effect was mimicked by adding an equivalent amount of calcium to the medium and was diminished in the presence of the calcium chelator, EGTA. To analyze the effect of BG40 and EPCs in vivo, a 6-mm diameter critical size calvarial defect was created in rats (n = 12). Controls (n = 6) received BG40 and the treatment group (n = 6) received BG40 seeded with 5×105 rat EPCs. Vascularization after 1 week was significantly improved when EPCs were seeded onto BG40, compared to implanting BG40 alone. This indicates that Ca2+ release improves EPC differentiation and is useful for enhanced early vascularization in critical size bone defects

Forschen über die Pharmaindustrie: Ethische Positionierung in einem globalen Machtgeflecht

Unter Berücksichtigung globaler Machtverhältnisse in Bezug auf gesundheitliche Versorgung untersuchte ich im Rahmen einer medizinethnologischen Studie die Einführung eines neuen – inzwischen global führenden – Antimalaria-Medikaments in Tansania. Dabei wurde ich mit menschlichem Leid, der Erfahrung der Sterblichkeit (Malaria) und Konflikten auf eine Art und Weise konfrontiert, die ethische Fragen nach Verantwortung, Respekt und den eigenen Handlungsmöglichkeiten aufgeworfen hat. In diesem Artikel reflektiere ich meine Feldforschungserfahrungen im Hinblick auf ethische Positionierungen in einem Machtgeflecht, das unterschiedliche Rollen und (eigene bzw. Fremd-) Erwartungen in einem sensiblen, teils von Misstrauen geprägten Forschungsfeld beinhaltet. Vor diesem Hintergrund thematisiere ich forschungsethische Herausforderungen, Maßstäbe und Problemstellungen, die für qualitativ Forschende und insbesondere für die gegenwärtige (Medizin-) Ethnologie mit ihrer transkulturellen und transdisziplinären Problemstellung relevant sind. Der Fokus liegt zum einen auf Aspekten von Vertraulichkeit und Transparenz – Kernanliegen ethisch verantwortlichen Forschens – gegenüber InformantInnen und TeilnehmerInnen im Feld. Zum anderen greife ich die Frage auf, welchen Einfluss moralische (Selbst-) Zweifel bezüglich der eigenen Rolle als ForscherIn in besonderen Milieus (hier: Pharmaindustrie) auf die Datengewinnung und Analyse ausüben können

Fenretinide-induced caspase-8 activation and apoptosis in an established model of metastatic neuroblastoma

<p>Abstract</p> <p>Background</p> <p>Resistance of high-risk metastatic neuroblastoma (HR-NB) to high dose chemotherapy (HD-CT) raises a major therapeutic challenge in pediatric oncology. Patients are treated by maintenance CT. For some patients, an adjuvant retinoid therapy is proposed, such as the synthetic retinoid fenretinide (4-HPR), an apoptotic inducer. Recent studies demonstrated that NB metastasis process is enhanced by the loss of caspase-8 involved in the Integrin-Mediated Death (IMD) process. As the role of caspase-8 appears to be critical in preventing metastasis, we aimed at studying the effect of 4-HPR on caspase-8 expression in metastatic neuroblasts.</p> <p>Methods</p> <p>We used the human IGR-N-91 <it>MYCN</it>-amplified NB experimental model, able to disseminate <it>in vivo </it>from the primary nude mouse tumor xenograft (PTX) into myocardium (Myoc) and bone marrow (BM) of the animal. NB cell lines, <it>i.e.</it>, IGR-N-91 and SH-EP, were treated with various doses of Fenretinide (4-HPR), then cytotoxicity was analyzed by MTS proliferation assay, apoptosis by the propidium staining method, gene or protein expressions by RT-PCR and immunoblotting and caspases activity by colorimetric protease assays.</p> <p>Results</p> <p>The IGR-N-91 parental cells do not express detectable caspase-8. However the PTX cells established from the primary tumor in the mouse, are caspase-8 positive. In contrast, metastatic BM and Myoc cells show a clear down-regulation of the caspase-8 expression. In parallel, the caspases -3, -9, -10, Bcl-2, or Bax expressions were unchanged. Our data show that in BM, compared to PTX cells, 4-HPR up-regulates caspase-8 expression that parallels a higher sensitivity to apoptotic cell death. Stable caspase-8-silenced SH-EP cells appear more resistant to 4-HPR-induced cell death compared to control SH-EP cells. Moreover, 4-HPR synergizes with drugs since apoptosis is restored in VP16- or TRAIL-resistant-BM cells. These results demonstrate that 4-HPR in up-regulating caspase-8 expression, restores and induces apoptotic cell death in metastatic neuroblasts through caspase-8 activation.</p> <p>Conclusion</p> <p>This study provides basic clues for using fenretinide in clinical treatment of HR-NB patients. Moreover, since 4-HPR induces cell death in caspase-8 negative NB, it also challenges the concept of including 4-HPR in the induction of CT of these patients.</p

Evaluation of real-time PCR endogenous control genes for analysis of gene expression in bovine endometrium

Background: Quantitative real-time PCR gene expression results are generally normalised using endogenous control genes. These reference genes should be expressed at a constant level across all sample groups in a study, and should not be influenced by study treatments or conditions. There has been no systematic investigation of endogenous control genes for bovine endometrium to date. The suitability of both commonly used and novel endogenous control genes was evaluated in this study, with the latter being selected from stably expressed transcripts identified through microarray analysis of bovine endometrium. Fifteen candidate endogenous control genes were assessed across different tissue subtypes in pregnant and cycling Holstein-Friesian dairy cows from two divergent genetic backgrounds

Dyadic Coping Among Couples with COPD: A Pilot Study

COPD (chronic obstructive pulmonary disease) is associated with psychological distress for patients as well as their partners. Dyadic coping can be negatively impacted by stressors. This study's objective was to compare the dyadic coping of couples in which one partner suffered from COPD with healthy couples of the same age. A total of 43 complete couples with COPD and 138 healthy couples participated in this pilot study. The surveys were sent by mail. The response rate of the COPD sample was 24.3%. In order to analyze the effect of gender and role (patient vs. partner) on dyadic coping, linear mixed models were calculated. To analyze the effect of gender and group (COPD group vs. normative comparison group) on dyadic coping, two-way analyses of variance were calculated for independent samples. COPD patients and their partners indicated that the patients received more support and were less able to provide support to their partners. This difference was also evident in comparison with the normative comparison group. In addition, couples with COPD perceived higher levels of negative coping and provided a considerably lower assessment of their positive dyadic coping. The dyadic coping of couples with COPD is unbalanced and more negative when compared to that of healthy couples. Interventions aimed at supporting COPD couples should seek to improve couples' dyadic coping in addition to individual coping strategie

Modulation of the maternal immune system by the pre-implantation embryo

Background: A large proportion of pregnancy losses occur during the pre-implantation period, when the developing embryo is elongating rapidly and signalling its presence to the maternal system. The molecular mechanisms that prevent luteolysis and support embryo survival within the maternal environment are not well understood. To gain a more complete picture of these molecular events, genome-wide transcriptional profiles of reproductive day 17 endometrial tissue were determined in pregnant and cyclic Holstein-Friesian dairy cattle

The Small Whiskbroom Imager for atmospheric compositioN monitorinG (SWING) and its operations from an unmanned aerial vehicle (UAV) during the AROMAT campaign

The Small Whiskbroom Imager for atmospheric compositioN monitorinG (SWING) is a compact remote sensing instrument dedicated to mapping trace gases from an unmanned aerial vehicle (UAV). SWING is based on a compact visible spectrometer and a scanning mirror to collect scattered sunlight. Its weight, size, and power consumption are respectively 920g, 27cm × 12cm × 8cm, and 6W. SWING was developed in parallel with a 2.5m flying-wing UAV. This unmanned aircraft is electrically powered, has a typical airspeed of 100km h−1, and can operate at a maximum altitude of 3km. We present SWING-UAV experiments performed in Romania on 11 September 2014 during the Airborne ROmanian Measurements of Aerosols and Trace gases (AROMAT) campaign, which was dedicated to test newly developed instruments in the context of air quality satellite validation. The UAV was operated up to 700m above ground, in the vicinity of the large power plant of Turceni (44.67°N, 23.41°E; 116m a. s. l. ). These SWING-UAV flights were coincident with another airborne experiment using the Airborne imaging differential optical absorption spectroscopy (DOAS) instrument for Measurements of Atmospheric Pollution (AirMAP), and with ground-based DOAS, lidar, and balloon-borne in situ observations. The spectra recorded during the SWING-UAV flights are analysed with the DOAS technique. This analysis reveals NO2 differential slant column densities (DSCDs) up to 13±0.6×1016molec cm−2. These NO2 DSCDs are converted to vertical column densities (VCDs) by estimating air mass factors. The resulting NO2 VCDs are up to 4.7±0.4×1016molec cm−2. The water vapour DSCD measurements, up to 8±0.15×1022molec cm−2, are used to estimate a volume mixing ratio of water vapour in the boundary layer of 0.013±0.002mol mol−1. These geophysical quantities are validated with the coincident measurements