404 research outputs found
Extended Czjzek model applied to NMR parameter distributions in sodium metaphosphate glass
The Extended Czjzek Model (ECM) is applied to the distribution of NMR
parameters of a simple glass model (sodium metaphosphate, )
obtained by Molecular Dynamics (MD) simulations. Accurate NMR tensors, Electric
Field Gradient (EFG) and Chemical Shift Anisotropy (CSA), are calculated from
Density Functional Theory (DFT) within the well-established PAW/GIPAW
framework. Theoretical results are compared to experimental high-resolution
solid-state NMR data and are used to validate the considered structural model.
The distributions of the calculated coupling constant and
of the asymmetry parameter that characterize the quadrupolar
interaction are discussed in terms of structural considerations with the help
of a simple point charge model. Finally, the ECM analysis is shown to be
relevant for studying the distribution of CSA tensor parameters and gives new
insight into the structural characterization of disordered systems by
solid-state NMR.Comment: 17 pages, 12 figures to be published in J. Phys.: Condens. Matte
Oxidative stress in hemodialysis patients: Is NADPH oxidase complex the culprit?
Oxidative stress in hemodialysis patients: Is NADPH oxidase complex the culprit?Oxidative stress results from an imbalance between oxidant production, including reactive oxygen species (ROS), reactive nitrogen species (RNS), chlorinated compounds, and antioxidant defense mechanisms. Most reports prove that oxidative stress is present in ESRD patients. Several studies tend to accreditate the hypothesis by which oxidative stress is a strong co-factor for the development of complications related to long-term HD such as atherosclerosis, amyloidosis, malnutrition, anemia, and infection.In order to evaluate the rationale for curative action against oxidative damage in chronic renal failure patients, we reviewed the putative factors involved in this process. Antioxidant systems are severely impaired in uremic patients and gradually altered with the degree of renal failure. Moreover, the inflammatory state caused by the hemoincompatibility of the dialysis system plays a critical role in the activation of NADPH oxidase, aggravating the pro-oxidant status of uremic patients.Prevention of ROS overproduction by improvement of dialysis biocompatibility, an important component of adequate dialysis, might be completed by antioxidant supplementation
NADPH oxidase activity is associated with cardiac osteopontin and pro-collagen type I expression in uremia.
International audienceCardiovascular disease is a frequent complication inducing mortality in chronic kidney disease (CKD) patients, which can be determined by both traditional risk factors and non-traditional risk factors such as malnutrition and oxidative stress. This study aimed to investigate the role of oxidative stress in uremia-induced cardiopathy in an experimental CKD model. CKD was induced in Sprague-Dawley rats by a 4-week diet supplemented in adenine, calcium and phosphorous and depleted in proteins. CKD was associated with a 3-fold increase in superoxide anion production from the NADPH oxidase in the left ventricle, but the maximal activity of mitochondrial respiratory chain complexes was not different. Although manganese mitochondrial SOD activity decreased, total SOD activity was not affected and catalase or GPx activities were increased, strengthening the major role of NADPH oxidase in superoxide anion output. Superoxide anion output was associated with enhanced expression of osteopontin (Ă7.7) and accumulation of pro-collagen type I (Ă3.7). To conclude, the increased activity of NADPH oxidase during CKD is associated with protein modifications which could activate a pathway leading to cardiac remodelling
Triglycerides and glycated hemoglobin for screening insulin resistance in obese patients
International audienceOBJECTIVE: Assessment of insulin resistance (IR) is essential in non-diabetic patients with obesity. Thus study aims to identify the best determinants of IR and to propose an original approach for routine assessment of IR in obesity. DESIGN AND PATIENTS: All adult with obesity defined by a body mass index >=30kg/m2, evaluated in the Nutrition Department between January 2010 and January 2015 were included in this cross-sectional study. Patients with diabetes were excluded. IR was diagnosed according to the HOMA-IR. Based on a logistic regression, we determined a composite score of IR. We then tested the variables with a principal component analysis and a hierarchical clustering analysis. RESULTS: A total of 498 patients with obesity were included. IR was associated with grade III obesity (OR=2.6[1.6-4.4], p\textless0.001), HbA1c>=5.7% (OR=2.6[1.7-4.0], p\textless0.001), hypertriglyceridemia \textgreater1.7mmol/l (OR=3.0[2.0-4.5], p\textless0.001) and age (OR=0.98[0.96-0.99], p=0.002). Exploratory visual analysis using factor map and clustering analysis revealed that lipid and carbohydrates metabolism abnormalities were correlated with insulin resistance but not with excessive fat accumulation and low-grade inflammation. CONCLUSIONS: Our results highlight the interest of simple blood tests such as HbA1c and triglyceride determination, which associated with BMI, may be widely available tools for screening IR in obese patients
Enzymatic creatinine assays allowestimation of glomerular filtration rate in stages 1 and 2 chronic kidney disease using CKD-EPI equation
The National Kidney Disease Education Program group demonstrated that MDRD equation is sensitive to creatinine measurement error, particularly at higher glomerular filtration rates. Thus, MDRD-based eGFR above 60 mL/min/1.73 m2 should not be reported numerically. However, little is known about the impact of analytical error on CKD-EPI-based estimates. This study aimed at assessing the impact of analytical characteristics (bias and imprecision) of 12 enzymatic and 4 compensated Jaffe previously characterized creatinine assays
on MDRD and CKD-EPI eGFR. In a simulation study, the impact of analytical error was assessed on a hospital population of 24 084 patients. Ability using each assay to correctly classify patients according to chronic kidney disease (CKD) stages was evaluated.
For eGFR between 60 and 90 mL/min/1.73 m2, both equations were sensitive to analytical error. Compensated Jaffe assays displayed high bias in this range and led to poorer sensitivity/specificity for classification according to CKD stages than enzymatic assays. As compared to MDRD equation, CKD-EPI equation decreases impact of analytical error in creatinine measurement above 90 mL/min/1.73 m2.
Compensated Jaffe creatinine assays lead to important errors in eGFR and should be avoided. Accurate enzymatic assays allow estimation of eGFR until 90 mL/min/1.73 m2 with MDRD and 120 mL/min/1.73 m2 with CKD-EPI equation.Peer reviewe
Etude de lâeffet dâun rĂ©gime riche en huile de palme sur lâexpression gĂ©nĂ©tique des facteurs myogĂ©niques
Un niveau Ă©levĂ© d'acides gras saturĂ©s (AGS) dans le sang a un effet dĂ©lĂ©tĂšre sur les muscles squelettiques en inhibant Ă la fois la rĂ©gĂ©nĂ©ration des fibres musculaires et la synthĂšse des protĂ©ines musculaires. Du fait de sa richesse en AGS, lâhuile de palme est controversĂ©e. Cette Ă©tude avait pour objectif dâĂ©tudier lâeffet dâun rĂ©gime riche en huile de palme (brute et raffinĂ©e) sur lâexpression des facteurs myogĂ©niques dans le muscle de rats sĂ©dentaires et le comparer avec un rĂ©gime riche en huile dâolive et en Lard. Quarante rats mĂąles Wistar ont Ă©tĂ© rĂ©partis en 5 groupes de 8 rats chacun : 1 groupe tĂ©moin et 4 groupes nourris par des rĂ©gimes riches en graisse (HFD) contenant respectivement de lâhuile de palme brute, de lâhuile de palme raffinĂ©e, de lâhuile dâolive et du lard. AprĂšs 12 semaines de rĂ©gime, les rats ont Ă©tĂ© sacrifiĂ©s et les tissus prĂ©levĂ©s L'expression de Pax7, Myf5, MyoD et MyoG a Ă©tĂ© Ă©valuĂ©e par RT-qPCR dans les muscles gastrocnĂ©miens. Aucune diffĂ©rence significative nâa Ă©tĂ© observĂ©e entre rĂ©gime tĂ©moin et HFD concernant les expressions de Pax7, Myf5 et MyoG. Lâexpression de MyoD sâest avĂ©rĂ©e significativement plus Ă©levĂ©e dans les animaux HFD (p=0,0004) par rapport au tĂ©moin ; en particulier dans le rĂ©gime riche en huile dâolive par rapport aux autres rĂ©gimes HFD (p=0,05). Aucune altĂ©ration significative de lâexpression des gĂšnes des facteurs de rĂ©gulation myogĂ©nique nâa Ă©tĂ© observĂ©e avec lâhuile de palme sous ses 2 formes, brute et raffinĂ©e. En conclusion, lâhuile de palme, malgrĂ© sa richesse en AGS, nâa pas dâeffet dĂ©lĂ©tĂšre sur la rĂ©gĂ©nĂ©ration du muscle squelettique.Mots clĂ©s : RĂ©gime riche graisses, muscle squelettique, Pax7, Myf5, MyoD, MyoG
Efficacy of broccoli and glucoraphanin in COVID-19: From hypothesis to proof-of-concept with three experimental clinical cases
COVID-19 is described in a clinical case involving a patient who proposed the hypothesis that Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-interacting nutrients may help to prevent severe COVID-19 symptoms. Capsules of broccoli seeds containing glucoraphanin were being taken before the onset of SARS-CoV-2 infection and were continued daily for over a month after the first COVID-19 symptoms. They were found to reduce many of the symptoms rapidly and for a duration of 6-12 h by repeated dosing. When the patient was stable but still suffering from cough and nasal obstruction when not taking the broccoli capsules, a double-blind induced cough challenge confirmed the speed of onset of the capsules (less than 10 min). A second clinical case with lower broccoli doses carried out during the cytokine storm confirmed the clinical benefits already observed. A third clinical case showed similar effects at the onset of symptoms. In the first clinical trial, we used a dose of under 600 mmol per day of glucoraphanin. However, such a high dose may induce pharmacologic effects that require careful examination before the performance of any study. It is likely that the fast onset of action is mediated through the TRPA1 channel. These experimental clinical cases represent a proof-of-concept confirming the hypothesis that Nrf2interacting nutrients are effective in COVID-19. However, this cannot be used in practice before the availability of further safety data, and confirmation is necessary through proper trials on efficacy and safety.Peer reviewe
Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARÎł:Peroxisome proliferator-activated receptor, NFÎșB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity
Bone Biomarkers Help Grading Severity of Coronary Calcifications in Non Dialysis Chronic Kidney Disease Patients
BACKGROUND: Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF23) are recognized as strong risk factors of vascular calcifications in non dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between FGF23, OPG, and coronary artery calcifications (CAC) in this population and to attempt identification of the most powerful biomarker of CAC: FGF23? OPG? METHODOLOGY/PRINCIPAL FINDINGS: 195 ND-CKD patients (112 males/83 females, 70.8 [27.4-94.6] years) were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. Vascular risk markers including FGF23 and OPG were measured. Logistic regression analyses were used to study the potential relationships between CAC and these markers. The fully adjusted-univariate analysis clearly showed high OPG (â„10.71 pmol/L) as the only variable significantly associated with moderate CAC ([100-400[) (ORâ=â2.73 [1.03;7.26]; pâ=â0.04). Such association failed to persist for CAC scoring higher than 400. Indeed, severe CAC was only associated with high phosphate fractional excretion (FEPO(4)) (â„38.71%) (ORâ=â5.47 [1.76;17.0]; pâ=â0.003) and high FGF23 (â„173.30 RU/mL) (ORâ=â5.40 [1.91;15.3]; pâ=â0.002). In addition, the risk to present severe CAC when FGF23 level was high was not significantly different when OPG was normal or high. Conversely, the risk to present moderate CAC when OPG level was high was not significantly different when FGF23 was normal or high. CONCLUSIONS: Our results strongly suggest that OPG is associated to moderate CAC while FGF23 rather represents a biomarker of severe CAC in ND-CKD patients
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