New Approaches of Ovarian Tissue Cryopreservation from Domestic Animal Species

International audienc

High pressure and high temperature in situ X-ray diffraction studies in the Paris-Edinburgh cell using a laboratory X-ray source

International audienceWe have developed a new laboratory experimental set-up to study in situ the pressure-temperature phase diagram of a given pure element or compound, its associated phase transitions, or the chemical reactions involved at high pressure and high temperature (HP-HT) between different solids and liquids. This new tool allows laboratory studies before conducting further detailed experiments using more brilliant synchrotron X-ray sources or before kinetic studies. This device uses the diffraction of X-rays produced by a quasi-monochromatic micro-beam source operating at the silver radiation (λ(Ag)Kα1,2 ≈ 0.56Å). The experimental set-up is based on a VX Paris-Edinburgh cell equipped with tungsten carbide or sintered diamond anvils and uses standard B-epoxy 5 or 7mm gaskets. The diffracted signal coming from the compressed (and heated) sample is collected on an image plate. The pressure and temperature calibrations were performed by diffraction, using conventional calibrants (BN, NaCl and MgO) for determination of the pressure, and by crossing isochores of BN, NaCl, Cu or Au for the determination of the temperature. The first examples of studies performed with this new laboratory set-up are presented in the article: determination of the melting point of germanium and magnesium under HP-HT, synthesis of MgB2 or C-diamond and partial study of the P, T phase diagram of MgH2

Nestin-positive mesenchymal stem cells favour the astroglial lineage in neural progenitors and stem cells by releasing active BMP4

BACKGROUND: Spontaneous repair is limited after CNS injury or degeneration because neurogenesis and axonal regrowth rarely occur in the adult brain. As a result, cell transplantation has raised much interest as potential treatment for patients with CNS lesions. Several types of cells have been considered as candidates for such cell transplantation and replacement therapies. Foetal brain tissue has already been shown to have significant effects in patients with Parkinson's disease. Clinical use of the foetal brain tissue is, however, limited by ethical and technical problems as it requires high numbers of grafted foetal cells and immunosuppression. Alternatively, several reports suggested that mesenchymal stem cells, isolated from adult bone marrow, are multipotent cells and could be used in autograft approach for replacement therapies. RESULTS: In this study, we addressed the question of the possible influence of mesenchymal stem cells on neural stem cell fate. We have previously reported that adult rat mesenchymal stem cells are able to express nestin in defined culture conditions (in the absence of serum and after 25 cell population doublings) and we report here that nestin-positive (but not nestin-negative) mesenchymal stem cells are able to favour the astroglial lineage in neural progenitors and stem cells cultivated from embryonic striatum. The increase of the number of GFAP-positive cells is associated with a significant decrease of the number of Tuj1- and O4-positive cells. Using quantitative RT-PCR, we demonstrate that mesenchymal stem cells express LIF, CNTF, BMP2 and BMP4 mRNAs, four cytokines known to play a role in astroglial fate decision. In this model, BMP4 is responsible for the astroglial stimulation and oligodendroglial inhibition, as 1) this cytokine is present in a biologically-active form only in nestin-positive mesenchymal stem cells conditioned medium and 2) anti-BMP4 antibodies inhibit the nestin-positive mesenchymal stem cells conditioned medium inducing effect on astrogliogenesis. CONCLUSIONS: When thinking carefully about mesenchymal stem cells as candidates for cellular therapy in neurological diseases, their effects on resident neural cell fate have to be considered

The Use of Chitooligosaccharides in Cryopreservation: Discussion of Concept and First Answers from DSC Thermal Analysis

The use of dimethyl sulfoxide (Me2SO) as a cryoprotectant agent (CPA) is controversial. Indeed, this cryoprotectant agent (CPA) is cytotoxic and potentially mutagenic. Therefore, other cryoprotectants must be used to reduce the proportion of Me2SO in slow-freezing solutions. In this chapter, we propose to present the first evaluation of new non-penetrating cryoprotectants: the chitooligosaccharides (COS). These molecules are chitosan oligomers, which are biocompatible, antioxidant, and bacteriostatic. We first review the use of saccharides through cryopreservation processes. We question the possibility to reduce penetrating CPA during slow-freezing procedures. We propose to use COS as extracellular CPA to reduce the use of Me2SO. We question the biocompatibility of COS on mouse embryos through the analysis of the cells’ development. Next, we evaluate these molecules in slow-freezing solutions with a reduced quantity of Me2SO. Our experimental approach is a physical method often used to characterize slow-freezing solutions. Differential scanning calorimetry (DSC) allows to evaluate the crystallization and melting processes, the amount of crystallized water, and the equilibrium temperature and consequently to evaluate the impact of different cryoprotectants. This study gives a better understanding on how slow-freezing protocols could be improved with extracellular CPA

Experimental Approach of Quadriceps Strength Measurement: Implications for Assessments in Critically Ill Survivors.

(1) Background: The supine testing position is suitable for early quadriceps strength (QS) assessment in intensive care unit, while a seated position is more appropriate for survivors who have regained mobility. Acquiring consistent measurements is essential for longitudinal follow-up. We compared the QS generated in different settings in healthy volunteers. (2) Methods: Isometric QS was assessed using a MicroFet2 and standardised protocols comparing different modalities. Hip and knee flexion angles were, respectively, 45° and 40° (H45-K40) in the supine position, and both at 90° (H90-K90) in the seated position. Dynamometer was either handheld (non-fixed configuration, NFC), or fixed (FC) in a cubicle. (3) Results: QS in H90–K90 and H45-K40 positions were strongly correlated, but QS was higher in the later position regardless of the configuration. Compared to H45-K40, biases of 108.2N (or 28.05%) and 110.3N (27.13%) were observed in H90-K90 position, respectively, in the NFC and FC. These biases were independently and positively associated with QS (p < 0.001). For both position, there were no significant differences between QS measured in NFC or FC. (4) Conclusions: The quadriceps was less efficient in the seated position, compared to the supine position, in healthy volunteers. These findings have practical implications for further assessments and research in critically ill patients

A FRAX model for the assessment of fracture probability in Belgium

peer reviewedRESUME : Cette étude a pour but d’adapter à la population belge l’algorithme FRAX® récemment publié par l’Organisation Mondiale de la Santé (OMS) et permettant de calculer, dans les deux sexes, le risque absolu de fractures ostéoporotiques, à 10 ans. Nous nous sommes attachés à quantifier le risque fracturaire correspondant aux critères actuellement appliqués, en Belgique, pour le remboursement des médicaments de l’ostéoporose et à identifier les situations cliniques correspondant à une probabilité équivalente de fracture. Les probabilités fracturaires ont été calculées, à partir des incidences de fractures et de décès publiées, pour la population belge. Ces probabilités prennent en considération l’âge, le sexe, l’existence de facteurs cliniques de risque (FCR) et la densité minérale osseuse (DMO), mesurée au niveau de la zone propre du col fémoral. L’algorithme FRAX® permet d’identifier différents scénarios d’intervention, en Belgique, correspondant à un risque fracturaire identique ou supérieur à celui servant de base aux critères actuels de remboursement des médicaments. Il est donc possible de recommander une modification des attitudes actuelles, délaissant une stratégie basée sur une évaluation dichotomique de la DMO, au profit d’une intégration progressive des FCR qui permettra, in fine, une meilleure identification des patients à risque accru de fracture. Cette approche devra être substantiée par des analyses pharmaco-économiques appropriées

A Need to Meet Patient Expectations

Funding Information: Open access funding provided by Università degli Studi di Palermo within the Nicola Veronese reports personal fees from IBSA, Mylan, and Fidia outside of the submitted work. Cyrus Cooper reports personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda, and UCB outside of the submitted work. Jean-Yves Reginster reports CRUI-CARE Agreement. Funding Information:grants from IBSA-Genevrier, Mylan, CNIEL, and Radius Health (through his institution); consulting fees from IBSA-Genevrier, Mylan, CNIEL, Radius Health, and Pierre Fabre; fees for participation in review activities from IBSA-Genevrier, Mylan, CNIEL, Radius Health, and Teva; and payment for lectures from Ag-Novos, CERIN, CNIEL, Dairy Research Council (DRC), Echolight, IBSA-Genevrier, Mylan, Pfizer Consumer Health, Teva, and Theramex outside of the submitted work. Olivier Bruyère reports grants or lecture fees from Amgen, Aptissen, Biophytis, IBSA, MEDA, Mylan, Novartis, Sanofi, Servier, SMB, TRB Chemedica, UCB, and Viatris outside of the submitted work. Ali Mobasheri declares personal fees from Abbott, Abbvie, Achē Laboratórios Farmacêuticos, Galapagos, GSK Consumer Healthcare, Kolon TissueGene, Laboratoires Expansciences, Merck, Pacira Biosciences, Pfizer, Sanofi, and Servier. François Rannou reports grants or lecture fees from Pierre Fabre, Mylan, MSD, Thuasne, IBSA, Pfizer, Genévrier, Expanscience, Scarcell, Skindermic, and Peptinov. Ida K. Haugen reports grants from Pfizer and is a consultant for Novartis outside of the submitted work. Elaine M. Dennison declares grants/fees from Pfizer, Lilly, UCB, and Viatris. Philip G. Conaghan is supported in part by the National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre (the views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health), and reports consultancies or lecture fees from AbbVie, Amgen, AstraZeneca, Eli Lilly, Galapagos, GSK, Grunenthal, Pfizer, Novartis, and UCB. Nasser M. Al-Daaghri, Antonella Fioravanti, Sara Cheleschi, Jean-Pierre Pelletier, Maarten de Wit, Etienne Cavalier, Radmila Matijevic, Germain Honvo, Régis Pierre Radermecker, René Rizzoli, Jaime Branco, Andrea Laslop, María Concepción Prieto Yerro, Alberto Migliore, Gabriel Herrero-Beaumont, and Nicholas R. Fuggle declare that they have no conflicts of interest. Publisher Copyright: © 2022, The Author(s).Knee osteoarthritis (OA) is one of the most common and disabling medical conditions. In the case of moderate to severe pain, a single intervention may not be sufficient to allay symptoms and improve quality of life. Examples include first-line, background therapy with symptomatic slow-acting drugs for OA (SYSADOAs) or non-steroidal anti-inflammatory drugs (NSAIDs). Therefore, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) performed a review of a multimodal/multicomponent approach for knee OA therapy. This strategy is a particularly appropriate solution for the management of patients affected by knee OA, including those with pain and dysfunction reaching various thresholds at the different joints. The multimodal/multicomponent approach should be based, firstly, on different combinations of non-pharmacological and pharmacological interventions. Potential pharmacological combinations include SYSADOAs and NSAIDs, NSAIDs and weak opioids, and intra-articular treatments with SYSADOAs/NSAIDs. Based on the available evidence, most combined treatments provide benefit beyond single agents for the improvement of pain and other symptoms typical of knee OA, although further high-quality studies are required. In this work, we have therefore provided new, patient-centered perspectives for the management of knee OA, based on the concept that a multimodal, multicomponent, multidisciplinary approach, applied not only to non-pharmacological treatments but also to a combination of the currently available pharmacological options, will better meet the needs and expectations of patients with knee OA, who may present with various phenotypes and trajectories.publishersversionpublishe

Value of biomarkers in osteoarthritis: Current status and perspectives

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the ‘omics’ (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial

Novel formulations of oral bisphosphonates in the treatment of osteoporosis.

Oral bisphosphonates are a key intervention in the treatment of osteoporosis and in reducing the risk of fragility fractures. Their use is supported by over 3 decades of evidence; however, patient adherence to oral bisphosphonates remains poor in part due to complex dosing instructions and adverse events, including upper gastrointestinal symptoms. This problem has led to the development of novel oral bisphosphonate formulations. Buffered, effervescent alendronate is dissolved in water and so seeks to reduce upper gastro-intestinal adverse events, and gastro-resistant risedronate aims to reduce the complexity of dosing procedure (e.g. fasting prior to consumption) whilst still maintaining the efficacy of fracture risk reduction. Clinical trials and real-world data have been employed to demonstrate some benefits in terms of reduced upper gastro-intestinal adverse events, adherence, persistence and health economic outcomes. This report describes the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores where oral bisphosphonates sit in current clinical practice guidelines, review their risk-benefit profile and the consequences of poor adherence before exploring novel oral bisphosphonate formulations and their potential clinical and health economic impact. Further research is required but there are signs that these novel, oral bisphosphonate formulations may lead to improved tolerance of oral bisphosphonates and thus, improved adherence and fracture outcomes