Bull Acad Natl Med
· 2020 Dec · PMID 33012790
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Ex vivo production of human platelets have been pursued as an alternative measure to resolve limitations in the supply and safety of current platelet transfusion products. To this end, induced pluripotent stem cells (iPS...Ex vivo production of human platelets have been pursued as an alternative measure to resolve limitations in the supply and safety of current platelet transfusion products. To this end, induced pluripotent stem cells (iPSCs) are considered an ideal global source, since they are not only pluripotent and self-renewing, but also are available from basically any person, have relatively few ethical issues, and are easy to manipulate. From human iPSCs, megakaryocyte (MK) lines with robust proliferation capacity have been established by the introduction of specified sets of genes. These expandable MKs are also cryopreservable and thus would be suitable as master cells for good manufacturing practice (GMP) grade production of platelets, assuring availability on demand and safety against blood-borne infections. Meanwhile, developments in bioreactors that physically mimic the in vivo environment and discovery of substances that promote thrombopoiesis have yielded competent platelets with improved efficiency. The derivation of platelets from iPSCs could further resolve transfusion-related alloimmune complications through the manufacturing of autologous products and human leukocyte antigen (HLA)-compatible platelets by manipulation of HLAs and human platelet antigens (HPAs). Considering these key advances in the field, HLA-deleted platelets could become a universal product that is manufactured at industrial level to safely fulfill almost all demands. In this review, we overview the ex vivo production of iPSC-derived platelets towards clinical applications, a production that would revolutionize the blood transfusion system.
Bull Acad Natl Med
· 2020 Dec · PMID 33012789
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Full text
The increase in international trade over the last thirty years, climate change owing to the industrial revolution, disruption of ecosystems, etc. are some of the factors that may explain the dynamics of disease emergence...The increase in international trade over the last thirty years, climate change owing to the industrial revolution, disruption of ecosystems, etc. are some of the factors that may explain the dynamics of disease emergence in regions of the world where they were not present. Thus in 1999, West Nile virus was introduced on the American continent where it spread at high speed. More than 2300 deaths and more than 25,000 neuroinvasive forms were recorded in humans from 1999 to 2019 in the United States of America. In the field of animal diseases, two viruses have made headlines in Europe: bluetongue virus (BTV) and Schmallenberg virus (SBV). The bluetongue virus, previously absent from Europe, was introduced in 1999. Numerous serotypes (1, 2, 4, 6, 8, 9, 25, 27) have since been identified in the European Union. Schmallenberg virus was identified in 2011 in Northern Germany and rapidly spread to other European countries. This virus had never been identified in the world before. These three viruses (WNV, BTV and SBV) are transmitted by arthropod vectors (mosquitoes and Culicoïdes). These emergences are a good illustration of the challenges that our countries will face in the coming years, in public, human and veterinary health.
Bull Acad Natl Med
· 2020 Dec · PMID 32981935
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Rabies still causes about 60,000 human deaths per year, mainly in poor populations in Africa and Asia. However, since Louis Pasteur developed the first vaccine 130 years ago, prophylactic measures have been considerably...Rabies still causes about 60,000 human deaths per year, mainly in poor populations in Africa and Asia. However, since Louis Pasteur developed the first vaccine 130 years ago, prophylactic measures have been considerably improved and simplified. They now consist of the vaccine combined with purified rabies immunoglobulins of equine or human origin. In general, however, post-exposure prophylaxis protocols are long and expensive. Furthermore, the immunoglobulins used for associated serotherapy are costly and not widely available in developing countries. Approaches have been developed to deal with these two issues that offer hope for a paradigm shift for the benefit of exposed populations. Finally, mass rabies vaccination in dogs, which are the most cost-effective measure for preventing rabies in humans, are difficult to implement and sometimes have moderate effectiveness. The identification and analysis of the epidemiological drivers conditioning the circulation of the virus in dog populations allow a better understanding of the key control points that need to be associated with these campaigns for a better efficacy.
Carrillo P, Petit AC, Gaillard R
… +1 more, Vinckier F
Bull Acad Natl Med
· 2020 Dec · PMID 32963409
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Since the 1950s, the therapeutic arsenal against depression has grown considerably. From the discovery of monoamine oxidase inhibitors (MAOI) to the antidepressant effect of ketamine, these pharmacological breakthroughs...Since the 1950s, the therapeutic arsenal against depression has grown considerably. From the discovery of monoamine oxidase inhibitors (MAOI) to the antidepressant effect of ketamine, these pharmacological breakthroughs made the history of psychiatry. They also guided the research about the pathophysiology of depression, one of the most devasting diseases, which affects between 10 and 20 % of general population. In this article, we offer a short historical review of the various therapeutic options developed over the past century and the consequences of these innovations. We then review the most recent one, ketamine (and its enantiomer S, esketamine). Ketamine's effects are spectacular both in terms of their very short onset time, and because they are observed even in treatment-resistant depression. Just as MAOIs and tricyclic antidepressants allowed the "monoaminergic hypothesis of depression" to emerge, to unravel the mechanisms of ketamine's antidepressant effects should allow the understanding of the role of glutamatergic system, or that of neuro-inflammation, in the neurobiology of depression. Ketamine might also help to refine our understanding of the cognitive pathophysiology of depression, or even to deeply transform the clinical representations about what depression is.