84 research outputs found
Etude de la capacité d'inhibition de l'apolipoprotéine C1 sur l'activité de la protéine de transfert des esters de cholestérol chez des patients coronariens normolipidémiques et hyperlipidémiques et chez des patients diabétiques
High cholesteryl ester transfer protein (CETP) activity was found to accelerate the progression of atherosclerosis. Apolipoprotein C1 (apoC1) is a potent physiological inhibitor of CETP. ApoC1 operates as CETP inhibitor through its ability to modify the electrostatic charge at the lipoprotein surface. The inhibitory potential of apoC1 has never been studied in high risk patients or in patients with hyperlipidemia. Our aim was to address the functionality of apoC1 as CETP inhibitor in normo- and hyperlipidemic patients with documented coronary artery disease and in patients with type 1 and type 2 diabetes in comparison with normolipidemic-normoglycemic healthy subjects. We confirmed that apoC1 is a physiological inhibitor of CETP in normolipidemic subjects. We showed for the first time that this inhibitory potential is lost in hyperlipidemic patients with coronary artery disease and in patients with type 1 or type 2 diabetes. During hyperlipidemia, abundant triglyceride-rich lipoproteins, as preferential acceptors of HDL cholesteryl ester, probably drive the CETP-mediated cholesteryl ester transfer reaction. The modified distribution of apoC1 between HDL and VLDL might play a role in this loss of inhibitory property. During diabetes, especially in type 1, we showed that hyperglycemia, responsible for glycation, is involved, at least in part, in this loss of CETP inhibitory ability of apoC1. We also showed that in vitro glycation of apoC1 changed its electrostatic properties, which is recognized as a major determinant of its inhibitory ability.Une augmentation de lâactivitĂ© de la protĂ©ine de transfert des esters de cholestĂ©rol (CETP) est retrouvĂ©e associĂ©e Ă une Ă©lĂ©vation du dĂ©veloppement de lâathĂ©rosclĂ©rose. LâapolipoprotĂ©ine C1 est lâinhibiteur physiologique de la CETP. Ses propriĂ©tĂ©s Ă©lectrostatiques jouent un rĂŽle important dans sa capacitĂ© dâinhibition de lâactivitĂ© CETP. Aucune Ă©tude de ce potentiel inhibiteur de lâapoC1 nâa Ă©tĂ© rĂ©alisĂ©e chez des patients Ă haut risque cardio-vasculaire ou dyslipidĂ©miques. Nous avons souhaitĂ© Ă©tudier la fonctionnalitĂ© de lâapoC1 par rapport Ă la CETP chez des patients coronariens normolipidĂ©miques et hyperlipidĂ©miques dâune part et chez des patients diabĂ©tiques de type 1 et de type 2 en comparaison Ă des sujets sains normolipidĂ©miques dâautre part. Nous avons confirmĂ© que lâapoC1 Ă©tait un inhibiteur physiologique de la CETP chez lâhomme normolipidĂ©mique. Nous avons montrĂ© pour la premiĂšre fois la perte de cette capacitĂ© dâinhibition en cas dâhyperlipidĂ©mie chez des sujets coronariens et en cas de diabĂšte de type 1 ou de type 2.En cas dâhyperlipidĂ©mie, lâhypertriglycĂ©ridĂ©mie joue un rĂŽle important en stimulant la rĂ©action de transfert des esters de cholestĂ©rol. La possible modification de rĂ©partition de lâapoC1 entre HDL et VLDL secondaire Ă lâhyperlipidĂ©mie est probablement Ă©galement impliquĂ©e dans cette perte de fonctionnalitĂ©. Au cours du diabĂšte, notamment de type 1, nous avons dĂ©montrĂ© que lâhyperglycĂ©mie, Ă lâorigine du phĂ©nomĂšne de glycation, participe, au moins en partie, Ă cette perte de potentiel inhibiteur. Nous avons Ă©galement mis en Ă©vidence que la glycation in vitro de lâapoC1 modifiait sa charge Ă©lectrostatique, facteur dĂ©terminant de son potentiel inhibiteur
Intact Fish Skin Graft vs. Standard of Care in Patients with Neuroischaemic Diabetic Foot Ulcers (KereFish Study) : An International, Multicentre, Double-Blind, Randomised, Controlled Trial Study Design and Rationale
Publisher Copyright: © 2022 by the authors.Background: Cell and/or tissue-based wound care products have slowly advanced in the treatment of non-healing ulcers, however, few studies have evaluated the effectiveness of these devices in the management of severe diabetic foot ulcers. Method: This study (KereFish) is part of a multi-national, multi-centre, randomised, controlled clinical investigation (Odin) with patients suffering from deep diabetic wounds, allowing peripheral artery disease as evaluated by an ankle brachial index equal or higher than 0.6. The study has parallel treatment groups: Group 1 treatment with KerecisŸ Omega3 Wound⹠versus Group 2 treatment with standard of care. The primary objective is to test the hypothesis that a larger number of severe diabetic ulcers and amputation wounds, including those with moderate arterial disease, will heal in 16 weeks when treated with KerecisŸ Omega3 Wound⹠than with standard of care. Conclusion: This study has received the ethics committee approval of each participating country. Inclusion of participants began in March 2020 and ended in July 2022. The first results will be presented in March 2023. The study is registered in ClinicalTrials.gov as Identifier: NCT04537520.Peer reviewe
Functional Role of Kallikrein 6 in Regulating Immune Cell Survival
Kallikrein 6 (KLK6) is a newly identified member of the kallikrein family of secreted serine proteases that prior studies indicate is elevated at sites of central nervous system (CNS) inflammation and which shows regulated expression with T cell activation. Notably, KLK6 is also elevated in the serum of multiple sclerosis (MS) patients however its potential roles in immune function are unknown. Herein we specifically examine whether KLK6 alters immune cell survival and the possible mechanism by which this may occur.Using murine whole splenocyte preparations and the human Jurkat T cell line we demonstrate that KLK6 robustly supports cell survival across a range of cell death paradigms. Recombinant KLK6 was shown to significantly reduce cell death under resting conditions and in response to camptothecin, dexamethasone, staurosporine and Fas-ligand. Moreover, KLK6-over expression in Jurkat T cells was shown to generate parallel pro-survival effects. In mixed splenocyte populations the vigorous immune cell survival promoting effects of KLK6 were shown to include both T and B lymphocytes, to occur with as little as 5 minutes of treatment, and to involve up regulation of the pro-survival protein B-cell lymphoma-extra large (Bcl-XL), and inhibition of the pro-apoptotic protein Bcl-2-interacting mediator of cell death (Bim). The ability of KLK6 to promote survival of splenic T cells was also shown to be absent in cell preparations derived from PAR1 deficient mice.KLK6 promotes lymphocyte survival by a mechanism that depends in part on activation of PAR1. These findings point to a novel molecular mechanism regulating lymphocyte survival that is likely to have relevance to a range of immunological responses that depend on apoptosis for immune clearance and maintenance of homeostasis
Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets
Deletion of Bak and Bax, the effectors of mitochondrial apoptosis, does not affect platelet production, however, loss of prosurvival Bcl-xL results in megakaryocyte apoptosis and failure of platelet shedding
Soil macrofauna communities in Brazilian land-use systems
Soil animal communities include more than 40 higher-order taxa, representing over 23% of all described species. These animals have a wide range of feeding sources and contribute to several important soil functions and ecosystem services. Although many studies have assessed macroinvertebrate communities in Brazil, few of them have been published in journals and even fewer have made the data openly available for consultation and further use. As part of ongoing efforts to synthesise the global soil macrofauna communities and to increase the amount of openly-accessible data in GBIF and other repositories related to soil biodiversity, the present paper provides links to 29 soil macroinvertebrate datasets covering 42 soil fauna taxa, collected in various land-use systems in Brazil. A total of 83,085 georeferenced occurrences of these taxa are presented, based on quantitative estimates performed using a standardised sampling method commonly adopted worldwide to collect soil macrofauna populations, i.e. the TSBF (Tropical Soil Biology and Fertility Programme) protocol. This consists of digging soil monoliths of 25 x 25 cm area, with handsorting of the macroinvertebrates visible to the naked eye from the surface litter and from within the soil, typically in the upper 0-20 cm layer (but sometimes shallower, i.e. top 0-10 cm or deeper to 0-40 cm, depending on the site). The land-use systems included anthropogenic sites managed with agricultural systems (e.g. pastures, annual and perennial crops, agroforestry), as well as planted forests and native vegetation located mostly in the southern Brazilian State of ParanĂĄ (96 sites), with a few additional sites in the neighbouring states of SĂŁo Paulo (21 sites) and Santa Catarina (five sites). Important metadata on soil properties, particularly soil chemical parameters (mainly pH, C, P, Ca, K, Mg, Al contents, exchangeable acidity, Cation Exchange Capacity, Base Saturation and, infrequently, total N), particle size distribution (mainly % sand, silt and clay) and, infrequently, soil moisture and bulk density, as well as on human management practices (land use and vegetation cover) are provided. These data will be particularly useful for those interested in estimating land-use change impacts on soil biodiversity and its implications for below-ground foodwebs, ecosystem functioning and ecosystem service delivery.Quantitative estimates are provided for 42 soil animal taxa, for two biodiversity hotspots: the Brazilian Atlantic Forest and Cerrado biomes. Data are provided at the individual monolith level, representing sampling events ranging from February 2001 up to September 2016 in 122 sampling sites and over 1800 samples, for a total of 83,085 ocurrences
COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study
Background:
The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms.
Methods:
International, prospective observational study of 60â109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms.
Results:
âTypicalâ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (â€â18 years: 69, 48, 23; 85%), older adults (â„â70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each Pâ<â0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country.
Interpretation:
This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men
Study of the ability of apolipoprotein C1 to inhibit cholesteryl ester transfer protein activity in normolipidemic and hyperlipidemic patients with coronary artery disease and in patients with diabetes
Une augmentation de lâactivitĂ© de la protĂ©ine de transfert des esters de cholestĂ©rol (CETP) est retrouvĂ©e associĂ©e Ă une Ă©lĂ©vation du dĂ©veloppement de lâathĂ©rosclĂ©rose. LâapolipoprotĂ©ine C1 est lâinhibiteur physiologique de la CETP. Ses propriĂ©tĂ©s Ă©lectrostatiques jouent un rĂŽle important dans sa capacitĂ© dâinhibition de lâactivitĂ© CETP. Aucune Ă©tude de ce potentiel inhibiteur de lâapoC1 nâa Ă©tĂ© rĂ©alisĂ©e chez des patients Ă haut risque cardio-vasculaire ou dyslipidĂ©miques. Nous avons souhaitĂ© Ă©tudier la fonctionnalitĂ© de lâapoC1 par rapport Ă la CETP chez des patients coronariens normolipidĂ©miques et hyperlipidĂ©miques dâune part et chez des patients diabĂ©tiques de type 1 et de type 2 en comparaison Ă des sujets sains normolipidĂ©miques dâautre part. Nous avons confirmĂ© que lâapoC1 Ă©tait un inhibiteur physiologique de la CETP chez lâhomme normolipidĂ©mique. Nous avons montrĂ© pour la premiĂšre fois la perte de cette capacitĂ© dâinhibition en cas dâhyperlipidĂ©mie chez des sujets coronariens et en cas de diabĂšte de type 1 ou de type 2.En cas dâhyperlipidĂ©mie, lâhypertriglycĂ©ridĂ©mie joue un rĂŽle important en stimulant la rĂ©action de transfert des esters de cholestĂ©rol. La possible modification de rĂ©partition de lâapoC1 entre HDL et VLDL secondaire Ă lâhyperlipidĂ©mie est probablement Ă©galement impliquĂ©e dans cette perte de fonctionnalitĂ©. Au cours du diabĂšte, notamment de type 1, nous avons dĂ©montrĂ© que lâhyperglycĂ©mie, Ă lâorigine du phĂ©nomĂšne de glycation, participe, au moins en partie, Ă cette perte de potentiel inhibiteur. Nous avons Ă©galement mis en Ă©vidence que la glycation in vitro de lâapoC1 modifiait sa charge Ă©lectrostatique, facteur dĂ©terminant de son potentiel inhibiteur.High cholesteryl ester transfer protein (CETP) activity was found to accelerate the progression of atherosclerosis. Apolipoprotein C1 (apoC1) is a potent physiological inhibitor of CETP. ApoC1 operates as CETP inhibitor through its ability to modify the electrostatic charge at the lipoprotein surface. The inhibitory potential of apoC1 has never been studied in high risk patients or in patients with hyperlipidemia. Our aim was to address the functionality of apoC1 as CETP inhibitor in normo- and hyperlipidemic patients with documented coronary artery disease and in patients with type 1 and type 2 diabetes in comparison with normolipidemic-normoglycemic healthy subjects. We confirmed that apoC1 is a physiological inhibitor of CETP in normolipidemic subjects. We showed for the first time that this inhibitory potential is lost in hyperlipidemic patients with coronary artery disease and in patients with type 1 or type 2 diabetes. During hyperlipidemia, abundant triglyceride-rich lipoproteins, as preferential acceptors of HDL cholesteryl ester, probably drive the CETP-mediated cholesteryl ester transfer reaction. The modified distribution of apoC1 between HDL and VLDL might play a role in this loss of inhibitory property. During diabetes, especially in type 1, we showed that hyperglycemia, responsible for glycation, is involved, at least in part, in this loss of CETP inhibitory ability of apoC1. We also showed that in vitro glycation of apoC1 changed its electrostatic properties, which is recognized as a major determinant of its inhibitory ability
Etude de la capacité d'inhibition de l'apolipoprotéine C1 sur l'activité de la protéine de transfert des esters de cholestérol chez des patients coronariens normolipidémiques et hyperlipidémiques et chez des patients diabétiques
High cholesteryl ester transfer protein (CETP) activity was found to accelerate the progression of atherosclerosis. Apolipoprotein C1 (apoC1) is a potent physiological inhibitor of CETP. ApoC1 operates as CETP inhibitor through its ability to modify the electrostatic charge at the lipoprotein surface. The inhibitory potential of apoC1 has never been studied in high risk patients or in patients with hyperlipidemia. Our aim was to address the functionality of apoC1 as CETP inhibitor in normo- and hyperlipidemic patients with documented coronary artery disease and in patients with type 1 and type 2 diabetes in comparison with normolipidemic-normoglycemic healthy subjects. We confirmed that apoC1 is a physiological inhibitor of CETP in normolipidemic subjects. We showed for the first time that this inhibitory potential is lost in hyperlipidemic patients with coronary artery disease and in patients with type 1 or type 2 diabetes. During hyperlipidemia, abundant triglyceride-rich lipoproteins, as preferential acceptors of HDL cholesteryl ester, probably drive the CETP-mediated cholesteryl ester transfer reaction. The modified distribution of apoC1 between HDL and VLDL might play a role in this loss of inhibitory property. During diabetes, especially in type 1, we showed that hyperglycemia, responsible for glycation, is involved, at least in part, in this loss of CETP inhibitory ability of apoC1. We also showed that in vitro glycation of apoC1 changed its electrostatic properties, which is recognized as a major determinant of its inhibitory ability.Une augmentation de lâactivitĂ© de la protĂ©ine de transfert des esters de cholestĂ©rol (CETP) est retrouvĂ©e associĂ©e Ă une Ă©lĂ©vation du dĂ©veloppement de lâathĂ©rosclĂ©rose. LâapolipoprotĂ©ine C1 est lâinhibiteur physiologique de la CETP. Ses propriĂ©tĂ©s Ă©lectrostatiques jouent un rĂŽle important dans sa capacitĂ© dâinhibition de lâactivitĂ© CETP. Aucune Ă©tude de ce potentiel inhibiteur de lâapoC1 nâa Ă©tĂ© rĂ©alisĂ©e chez des patients Ă haut risque cardio-vasculaire ou dyslipidĂ©miques. Nous avons souhaitĂ© Ă©tudier la fonctionnalitĂ© de lâapoC1 par rapport Ă la CETP chez des patients coronariens normolipidĂ©miques et hyperlipidĂ©miques dâune part et chez des patients diabĂ©tiques de type 1 et de type 2 en comparaison Ă des sujets sains normolipidĂ©miques dâautre part. Nous avons confirmĂ© que lâapoC1 Ă©tait un inhibiteur physiologique de la CETP chez lâhomme normolipidĂ©mique. Nous avons montrĂ© pour la premiĂšre fois la perte de cette capacitĂ© dâinhibition en cas dâhyperlipidĂ©mie chez des sujets coronariens et en cas de diabĂšte de type 1 ou de type 2.En cas dâhyperlipidĂ©mie, lâhypertriglycĂ©ridĂ©mie joue un rĂŽle important en stimulant la rĂ©action de transfert des esters de cholestĂ©rol. La possible modification de rĂ©partition de lâapoC1 entre HDL et VLDL secondaire Ă lâhyperlipidĂ©mie est probablement Ă©galement impliquĂ©e dans cette perte de fonctionnalitĂ©. Au cours du diabĂšte, notamment de type 1, nous avons dĂ©montrĂ© que lâhyperglycĂ©mie, Ă lâorigine du phĂ©nomĂšne de glycation, participe, au moins en partie, Ă cette perte de potentiel inhibiteur. Nous avons Ă©galement mis en Ă©vidence que la glycation in vitro de lâapoC1 modifiait sa charge Ă©lectrostatique, facteur dĂ©terminant de son potentiel inhibiteur
Prévalence et prise en charge du diabÚte du sujet ùgé dans 7 EHPAD de la Haute CÎte d'Or
DIJON-BU MĂ©decine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Les luxations péri-lunaires du carpe (à propos de 38 cas)
Les luxations périlunaires du carpe sont des lésions rares qui représentent 5 à 10% des lésions du carpe et laissent fréquemment des séquelles. Le but de cette étude est d'évaluer les résultats cliniques et radiologiques d'une série de patients opérés et revus à long terme. 18 patients ont répondu aux reconvocations des cas opérés entre 2001 et 2009. La force et les amplitudes articulaires du poignet ont été comparées au poignet controlatéral. Les radiographies pré et post-opératoire ont été relues et des groupes ont été identifiés en utilisant la classification de Herzberg. La technique chirurgicale utilisée est précisée. La reprise d'une activité a été notée, ainsi que le recours aux antalgiques. Les patients ont été évalué frùce au score de Green et O'Brien modifié, au quick DASH et à un score de satisfaction subjective. Il s'agit d'hommes ùgés en moyenne de 36,2 ans, 61% atteints sur le coté dominant. Le recul à la révision est de 41,7 mois. Tous les déplacements sont postérieurs. On retrouve 10 luxations périlunaires pures et 8 fractures luxation périlunaires (toute trans-scaphoïdienne). Tous les patients ont bénéficié d'un geste initial conservateur. Le résultat moyen au score de Green et O'Brien est de 70 et de 27 au quick DASH. On retrouve 33,3% de résultats fonctionnels satisfaisants, 44,4% de moyen. Les résultats radiologiques retrouvent 45,5% de résultats satisfaisants et une évolution arthrosique dans 55% des cas. Cependant 66,5% des patients sont satisfaits. Les luxations périlunaires sont des urgences chirurgicales dont les lésions initiales doivent bénéficier d'un traitement précoce et exhaustif à ciel ouvert afin d'obtenir le meilleur résultat fonctionnel à distance. Quelle que soit la qualité de la réduction initiale, l'évolution arthrosique reste fréquente. Les résultats cliniques restent cependant bons durant plusieurs années.CLERMONT FD-BCIU-Santé (631132104) / SudocSudocFranceF
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