Synthesis and biological evaluation of oxindoles and benzimidazolines derivatives

The synthesis of new oxindoles and benzimidazolinones derivatives bearing a sugar residue on the aromatic nitrogen is described. The presence of the glycoside moiety should enhance the solubility of these heterocyclic compounds and/or improve the interaction with the active site of the biological targets. The inhibitory activities of these new compounds toward five kinases were examined: KDR (VEGFR-2), FGFR-1, PDGFR-β, EGFR and Tie 2. Furthermore, the antibacterial activities of the prepared compounds were tested against two Gram-positive bacteria Bacillus cereus and Streptomyces chartreusis, a Gram-negative bacterium Escherichia coli and a yeast Candida albican

Synthesis and biological evaluation of oxindoles and benzimidazolinones derivatives

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Ultrasound in Total Hip Replacement Value of Anterior Acetabular Cup Visibility and Contact With the Iliopsoas Tendon

International audienceObjectives - To assess visibility of the acetabular cup in total hip replacement and to determine the value of direct and indirect signs of iliopsoas impingement syndrome with ultrasound. Methods - Ultrasound examinations were performed by a single operator in 17 patients with iliopsoas impingement syndrome and 48 control patients. Cup visibility, contact between the cup and psoas tendon, and the presence of indirect signs of iliopsoas impingement syndrome were investigated in all patients. When the acetabular cup was visible, its size and position in relation to the psoas tendon were recorded. Results - Anterior cup visibility (P = .03), contact with the psoas tendon (P < .001), psoas tendinopathy (P = .02), and iliopsoas bursitis (P < .001) were significantly associated with iliopsoas impingement syndrome, the latter reported with specificity of 100%. In the sagittal plane at the level of the psoas tendon, a maximum sagittal length of greater than 5 mm and a posteroanterior cup shift of 3 mm or greater yielded respective sensitivities of 82% and 59% and specificities of 81% and 100%. Conclusions - When iliopsoas impingement syndrome is clinically suspected, the presence of iliopsoas bursitis or a posteroanterior cup shift of greater than 3 mm under the psoas tendon serve to confirm the diagnosis. In the absence of these conditions, a therapeutic test may be necessary because of the incomplete, albeit high, specificity of other signs

Dose-Ranging Study of the Performance of the Natural Oxygen Transporter HEMO 2 Life in Organ Preservation

International audienceThe intensity of ischemia-reperfusion injury of the donor organ during the preservation phase and after anastomosis is acknowledged as being a key factor for long-term graft outcome. We previously showed that the addition of 5 g/L of the natural oxygen carrier HEMO(2)Life was beneficial for the cold static preservation of kidney grafts in both University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate solutions. Herein, we refined these findings by evaluating HEMO(2)Life at various dose levels in UW, both in vitro with endothelial cells and in vivo in a pig kidney autotransplantation preclinical model. We showed in vitro that cells were significantly better preserved with HEMO(2)Life in a dose-dependent manner, with benefits in terms of survival, metabolic activity, and cellular integrity. In vivo, serum creatinine measurements at reperfusion confirmed the important benefits of HEMO(2)Life treatment on function recovery at the dose levels of 1, 2, and 5 g/L. Likewise, histological analysis of kidney parenchyma biopsies from day 7 confirmed the superiority of HEMO(2)Life-supplemented UW over UW alone, and there was no difference between the doses. Three months' follow-up confirmed the trend of the first 2 weeks, with creatinine and fibrosis levels similar to those in pretransplant kidneys

COVID-19 vaccine hesitancy among healthcare workers

International audienceObjective: To characterize healthcare workers' (HCWs) intention to receive the COVID-19 vaccine by thebeginning of the vaccine campaign in France. Methods: Data were collected on a self-administered questionnaire through the website of a tertiary carecenter (February 9-18, 2021). Results: Among 1,965 respondents, 1,436 (73.1%), 453 (23.1%), and 76 (3.9%) declared themselves infavor, hesitant, or against the COVID-19 vaccine: &lt; 60% of auxiliary nurses and technicians intended to bevaccinated, as compared to 60-79% of nurses and support staff, and &gt; 80% of medical staff. On multivariateanalysis, age, occupation, flu vaccine history, and controversy over the AstraZeneca vaccine tolerabilitywere independently associated with COVID-19 vaccine intention. Conclusions: Patterns of vaccine hesitancy related to the COVID-19 and influenza vaccines are similaramong HCWs. Media communication on vaccine side effects have a dramatic effect on vaccine hesitancy. Efforts are requested to inform HCWs about the risk/benefit balance of COVID-19 vaccines

Assessment of cellular actin dynamics by measurement of fluorescence anisotropy.

To study cellular actin dynamics, a cell-free assay based on fluorescence anisotropy was developed. Using G-actin-Alexa as a probe, we found that anisotropy enhancement reflects F-actin elongation. Anisotropy enhancement varies with the concentration of magnesium and calcium cations and with ethylenediaminetetraacetate or well-known effectors of the polymerization. This assay gives the overall status of actin dynamics in cell extracts which are the closest conditions to in vivo, implying most of the regulating proteins that are missing in purified actin measurements. It can be used in a large-scale screening for chemical compounds which modulate actin polymerization.status: publishe

In vivo biodistribution and oxygenation potential of a new generation of oxygen carrier.

International audienceNatural giant extracellular hemoglobins (Hbs) from polychaete annelids are currently actively investigated as promising oxygen carriers. Their powerful oxygenating ability and their safety have been demonstrated in preclinical studies, motivating their development for therapeutic and industrial applications. HEMARINA-M101 (M101) is derived from the marine invertebrate Arenicola marina. It is formulated as a manufactured product designated HEMOXYCarrier(®) (HEMARINA SA, France). The aim of the present study was to unveil the fate of M101 after a single intravenous (i.v.) injection in mice. For this purpose, M101 was tagged with a far-red fluorescent dye. Repeated non-invasive fluorescent imaging revealed a rapid diffusion of M101 in the whole body of animals, reaching all the examined organs such as brain, liver, lungs and ovaries. Functional M101 was circulating in bloodstream for several hours, without inducing any obvious side-effects. Last, a single i.v. injection of M101 in mice bearing human-derived subcutaneous tumors demonstrated the ability of this Hb to reduce hypoxia in poorly vascularized tissues, thus supporting the biological relevance of M101 oxygen release to vertebrate tissues. Altogether, these results further encourage the development of M101 as an oxygen carrying therapeutic

Adhesion, proliferation and osteogenic differentiation of human MSCs cultured under perfusion with a marine oxygen carrier on an allogenic bone substitute

International audienceTissue engineering strategies have been developed to optimize osseointegration in dental implant surgery. One of the major problems is the non-homogeneous spatial cell distribution in the scaffold, as well as subsequent matrix production. Insufficient nutrient and oxygen supplies inside the scaffold are factors in this phenomenon. To mediate this gradient formation, we have implemented a perfusion culture method to seed human bone marrow mesenchymal stem cells (MSCs) into three-dimensional (3-D)-allogenic bone scaffolds in combination with a marine haemoglobin, HEMOXCell®, for oxygen delivery. Cell culture was performed under static and perfusion conditions, with standard and osteogenic media, with and without HEMOXCell®. The cell seeding efficiency, as well as MSC/scaffold cytocompatibly were assessed using viability and proliferation assays. Scaffolds' cellularization and extracellular matrix (ECM) formation were analyzed using scanning electron microscopy and histological staining. Cell differentiation was investigated with osteogenic biomarkers gene expression analysis. The perfusion culture was observed to significantly promote MSC proliferation and differentiation throughout the scaffolds, especially when using the induction medium w/HEMOXCell®. Our data suggest that perfusion culture of MSC into allogenic bone substitute with HEMOXCell® as a natural oxygen carrier is promising for tissue engineering applications to oxygenate hypoxic areas and to promote cellular proliferation