Multiple Beneficial Health Effects of Natural Alkylglycerols from Shark Liver Oil

Alkylglycerols (alkyl-Gro) are ether lipids abundant in the liver of some elasmobranch fish species such as ratfishes and some sharks. Shark liver oil from Centrophorus squamosus (SLO), or alkyl-Gro mix from this source, have several in vivo biological activities including stimulation of hematopoiesis and immunological defences, sperm quality improvement, or anti-tumor and anti-metastasis activities. Several mechanisms are suggested for these multiple activities, resulting from incorporation of alkyl-Gro into membrane phospholipids, and lipid signaling interactions. Natural alkyl-Gro mix from SLO contains several alkyl-Gro, varying by chain length and unsaturation. Six prominent constituents of natural alkyl-Gro mix, namely 12:0, 14:0, 16:0, 18:0, 16:1 n-7, and 18:1 n-9 alkyl-Gro, were synthesized and tested for anti-tumor and anti-metastatic activities on a model of grafted tumor in mice (3LL cells). 16:1 and 18:1 alkyl-Gro showed strong activity in reducing lung metastasis number, while saturated alkyl- Gro had weaker (16:0) or no (12:0, 14:0, 18:0) effect. Multiple compounds and mechanisms are probably involved in the multiple activities of natural alkyl-Gro

Place du pharmacien dans la prévention et la prise en charge des chutes chez les personnes âgées

Du fait de l allongement de l espérance de vie, nos aînés représentent une part importante de la population. Cette tranche d âge est cependant touchée par le vieillissement physiologique de l organisme, ciblant la plupart des sens et organes. De plus, l apparition de différentes maladies rend les personnes âgées plus fragiles. Elles sont donc malheureusement plus sujettes aux chutes. Les conséquences peuvent être dramatiques, parfois fatales. Cette prévention et prise en charge représente un enjeu important, humainement parlant, mais aussi d un point de vue économique. La prise en charge doit faire appel à plusieurs professionnels de santé. Le pharmacien a toute sa place au cœur de cette équipe pluridisciplinaire. En effet, ses connaissances sur le médicament, les dispositifs médicaux, ainsi que son sens de l écoute permettent de délivrer de précieux conseils afin d éviter les chutes. Ceci fait de la pharmacie un lieu propice pour échanger sur ce problème important de santé publique.Due to the increase of life expectancy, our elders represent an important part of the population. However, this age class is affected by the physiological aging of the body, targeting the majority of senses and organs. Moreover, the occurrence of various diseases makes the frail elderly, susceptible. They are unfortunately subject to falls. The consequences can be devastating, even fatal. Prevention and management constitute an important issue, humanly speaking, but also from an economic point of view. The management should involve several health professionals. It s the place of the pharmacist to be at the heart of this multidisciplinary team. Indeed, with the knowledge of the drugs, medical devices, as well as his sense of hearing, he can deliver valuable tips to prevent falls. All thse reasons prove that pharmacy is the good place to discuss this important public health problem.LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Critères de choix des antithyroïdiens de synthèse en obstétrique et traitements adjuvants

Une hyperthyroïdie liée à la maladie de Basedow pendant la grossesse peut nécessiter l'utilisation des antithyroïdiens de synthèse. Quelle molécule choisir? Les différents critères de choix des antithyroïdiens de synthèse utilisables en obstétrique ont été répertoriés. L'objectif est de permettre au prescripteur de choisir le médicament ayant le meilleur rapport bénéfice-risque pour la future mère et le fœtus. Il s'avère que les données sur la tératogénicité du propylthiouracile et du carbimazole sont insuffisantes. De nouvelles études sont nécessaires pour confirmer ou infirmer l'apparition de malformations congénitales liées à ces molécules. En attendant de nouvelles données, une prise en charge pluridisciplinaire et rigoureuse de l'hyperthyroïdie en obstétrique apparaît primordiale pour le bon déroulement de la grossesse.An hyperthyroidism caused by Graves' disease during pregnancy may make the use of antithyroid drugs necessary. Which molecule should be chosen? Different selection criteria of antithyroid drugs used in obstetrics have been listed. The objective is to enable the prescriber to choose, between the different possible drugs, the one which has the bes benefit-risk ration for both the mother and the fœtus. Nonetheless, scientific data on the propylthiouracil and the carbimazole teratogenicity are lacunar. Further studies are needed to confirm or refute the occurrence of congenital malformations associated with these molecules. Pending new data are available, a multidisciplinary and rigourous support of hyperthyroidism n obstetrics appears essential in order to ensure a good evolution of pregancy.RENNES1-BU Santé (352382103) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

Antidiabétiques oraux et grossesse

RENNES1-BU Santé (352382103) / SudocSudocFranceF

Situation du Lénalidomide dans la classe des antiangiogéniques antitumoraux

Langiogénèse tumorale a été décrite dès 1971 par Judah Folkman comme un processus conduisant à l'augmentation de la vascularisation de la tumeur. La compréhension du mécanisme de l'angiogenèse tumorale a permis l'élaboration de nouvelles molécules antiangiogéniques. Le Lénalidomide, un immunomodulateur dérivé du Thalidomide, a de nombreux effets dont un effet antiangiogénique démontré in vitro. Il s'agit d'une nouvelle molécule qui vient d'avoir une autorisation de mise sur le marché en 2007 dans l'indication du traitement du myélome multiple réfractaire ou en rechute. Ses propriétés le rendent intéressant dans le traitement de cancers ayant une composante angiogénique. C'est pourquoi il s'agit d'une molécule en plein essor dont l'activité et la tolérance sont à situer dans la nouvelle classe des antiangiogéniques antitumoraux.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Which alkylglycerols from shark liver oil have anti-tumour activities?

International audienc

Activités antitumorale et antimétastasique des alkylglycérols naturels : relation structure-activité

Oral alkylglycerols (AKG) from shark liver oil (SLO) have multiple biological activities including immuno-stimulation and anti-tumour properties. In several cell types they are incorporated into phospholipids and therefore they may produce modified messengers and mediators following cellular activation of the phospholipase pathway. Structure of naturally occurring AKG vary depending on length and unsaturation of the alkyl chain. We synthesized six of the major natural constituants of AKG from SLO and tested their anti-tumour and anti-metastasis activities on a model of solid tumour grafted in mice. We found that unsaturated compounds were the most active for reducing tumour volume, lung metastasis number, and splenomegaly. Saturated compounds had weaker, no, or deleterious activities on this model. These data suggest that the selective use of unsaturated natural AKG would improve anti-tumour activities as compared to natural mix of AKG

Type 1 Diabetes in People Hospitalized for COVID-19: New Insights From the CORONADO Study

International audienc

The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19)

International audienceAbstract Background It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. Methods We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020—October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. Results Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83–2.45 with an I 2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29–1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31–0.75], I 2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40–0.68], I 2 37%) were significantly lower for people with previous macrovascular disease. Conclusions This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old