Plasmatic concentration of organochlorine lindane acts as metabolic disruptors in HepG2 liver cell line by inducing mitochondrial disorder.

Lindane (LD) is a persistent environmental pollutant that has been the subject of several toxicological studies. However, concentrations used in most of the reported studies were relatively higher than those found in the blood of the contaminated area residents and effects of low concentrations remain poorly investigated. Moreover, effects on cell metabolism and mitochondrial function of exposure to LD have received little attention. This study was designed to explore the effects of low concentrations of LD on cellular metabolism and mitochondrial function, using the hepatocarcinoma cell line HepG2. Cells were exposed to LD for 24, 48 and 72 h and different parameters linked with mitochondrial regulation and energy metabolism were analyzed. Despite having any impact on cellular viability, exposure to LD at plasmatic concentrations led to an increase of maximal respiratory capacity, complex I activity, intracellular ATP and NO release but decreased uncoupled respiration to ATP synthesis and medium lactate levels. In addition, LD exposure resulted in the upregulation of mitochondrial biogenesis genes. We suggest that, at plasmatic concentrations, LD acts as a metabolic disruptor through impaired mitochondrial function and regulation with an impact on cellular energetic metabolism. In addition, we propose that a cellular assay based on the analysis of mitochondria function, such as described here for LD, may be applicable for larger studies on the effects of low concentrations of xenobiotics, because of the exquisite sensitivity of this organelle

A variant in XPNPEP2 is associated with angioedema induced by angiotensin I-converting enzyme inhibitors

Angiotensin I-converting enzyme inhibitors (ACEi), which are used to treat common cardiovascular diseases, are associated with a potentially life-threatening adverse reaction known as angioedema (AE-ACEi). We have previously documented a significant association between AE-ACEi and low plasma aminopeptidase P (APP) activity. With eight large pedigrees, we hereby demonstrate that this quantitative trait is partially regulated by genetic factors. We tested APP activity using a variance-component QTL analysis of a 10-cM genomewide microsatellite scan enriched with seven markers over two candidate regions. We found significant linkage (LOD = 3.75) to a locus that includes the YPNPEP2 candidate gene encoding membrane-bound APP. Mutation screening of this QTL identified a large coding deletion segregating in one pedigree and an upstream single-nucleotide polymorphism (C2399A SNP), which segregates in the remaining seven pedigrees. Measured genotype analysis strongly suggests that the linkage signal for APP activity at this locus is accounted for predominantly by the SNP association. In a separate case-control study (20 cases and 60 controls), we found significant association of this SNP to ACEi-induced AE (P =.0364). In conclusion, our findings provide supporting evidence that the C-2399A variant in YPNPEP2 is associated with reduced APP activity and a higher incidence of AE-ACEi

L’électromyostimulation pendant la dialyse a-t-elle sa place dans le réentraînement à l’effort des dialysés ?

National audienceIntroduction Les patients dialysés subissent une dysfonction musculaire progressive. Une part d’entre eux ne peut pas suivre de réentraînement classique. L’électromyostimulation (EMS) qui entraîne une contraction musculaire non volontaire par stimulation percutanée est utilisée avec succès chez les patients insuffisants cardiaques et respiratoires. L’étude EMS Dialyse est une étude randomisée, contrôlée évaluant l’efficacité d’un programme standardisé d’EMS des muscles quadriceps réalisé au cours des dialyses sur 3 mois. Patients et méthodes Soixante-six patients, avec un score faible d’activité (score de Voorips < 9,4) randomisés en 33 contrôlés (C), 33 entraînés (E) par EMS sur 39 séances, 30 min/dialyse, fréquence 35 Hz, intensité augmentée en fonction de la tolérance du patient par un STAPS ou une IDE du centre. Les critères d’évaluation à M0, M3 sont la distance lors du test de marche de 6 min (TM6), le volume du quadriceps, le test Time up and go (TUG), la qualité de vie (SF-36). Résultats Population : pas de différence entre (E) et (C) pour l’âge (70,9 ± 12,8, p = 0,2), le poids (69,2 ± 15,2, p = 0,9), l’IMC (25,5 ± 4,9, p = 0,8), l’albumine (38,5 ± 3,6, p = 0,8), les comorbidités (diabète 24 %, AVC 19 %, Angor 22 %, Artériopathie 43 %, Cancer 34 %, Dépression 12 %). Résultats : seuls 54 % des patients ont réalisé un nombre de séances > 35. TM6 : variation de distance entre M0 et M3 [M0 335, M3 345m (E) ; M0 334, M3 354m (C) ; p = 0,6]. TUG : variation entre M0 et M3 : [−0,1 % (E et C) ; p = 0,3]. Variation du volume musculaire : [+0,02 % (E)/−00,1(C) ; p = 0,03]. Aucune différence pour les scores SF-36. Discussion Aucun bénéfice n’est noté sur les tests fonctionnels mais seulement une variation faible du volume des quadriceps. Plusieurs facteurs d’échecs peuvent être discutés comme le mode intermittent des séances, la durée de séance et du réentraînement trop brève et surtout l’adhérence médiocre à la méthode due sans doute en partie à des sensations douloureuses. Celles-ci font discuter le rôle du soutien motivationnel dans l’acceptation de la méthode. Conclusion Cette étude pilote montre qu’un réentraînement de 3 mois basé sur des séances d’EMS lors des dialyses n’améliore pas la dysfonction musculaire des patients dialysés. Le biais le plus important semble la non adhérence au traitement pour un pourcentage élevé de patient

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed