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21.
Potentielle application de l’axe fibroblast growth factor 23-Klotho dans la maladie rénale chronique
《Néphrologie & thérapeutique》2020,16(2):83-92
Membrane Alpha Klotho (α-klotho) is expressed in the kidney and functions as a co-receptor of FGF receptors (FGFRs) to activate specific fibroblast growth factor 23 (FGF23) signal pathway. FGF23 is produced in bones and participates in mineral homeostasis. The extracellular domain of transmembrane αklotho can be cleaved by proteases and released into the circulation as soluble α-klotho. Klotho deficiency is a pathogenic factor for chronic kidney disease progression and cardiovascular diseases. The FGF23 excess may also contribute to cardiovascular diseases where its pathogenic effect acts via the FGFR4 and independently of α-klotho. The decline in serum α-klotho followed by a rise in serum FGF23 at an early stage of chronic kidney disease can serve as a robust predictor for risk of cardiovascular diseases and mortality in both CKD patients and the general population. The first randomized trials suggest the possibility to reduce FGF23 excess in chronic kidney disease by controlling the phosphate serum using phosphate binders and reducing PTH levels with calcimimetic drug. New strategies emerge, including the administration of α-klotho recombinant and the use of epidrugs in order to correct the klotho deficiency. The FGR4 inhibitors are promising to limit the development of left ventricular hypertrophy linked to FGF23 excess. Finally, a better understanding of the molecular mechanisms of FGF23/α-klotho axis will allow us to find new strategic approaches and improve the CKD patient's management and their outcomes. 相似文献
22.
《Néphrologie & thérapeutique》2014,10(6):441-450
The number of patients with chronic kidney disease (CKD) with its associated complications has increased dramatically worldwide in recent years. Therefore, many experimental and clinical studies have examined over the last decade the mechanisms involved, in order to explain the sharp increase in cardiovascular mortality. Hyperphosphatemia is a major problem in these patients especially at advanced stages of CKD, and it is associated with cardiovascular and mineral complications in these patients. Sevelamer is a phosphate binder that allows a better control of hyperphosphatemia, like other phosphate binder agents, but it has additional pleiotropic effects such as correcting certain abnormalities of lipid metabolism and clearance of several uremic toxins. These effects of sevelamer, restricted to the intestinal lumen, underline the importance of intestinal pathway in CKD and open the way to new therapeutic strategies for the management of the CKD and its complications. 相似文献
23.
An increased serum phosphate (P) level is common in acromegaly patients, however, the relationships among P, growth hormone (GH), insulin-like growth factor 1 (IGF-1) and disease status remain unknown. To reveal these relationships, we examined the association of P with comprehensive clinical data. We measured the serum P, calcium, GH, oral glucose tolerance test-GH (OGTT-GH), IGF-1, and insulin-like growth factor binding protein-3 (IGBP-3) levels in 103 acromegaly patients. SAGIT® was used to assess the disease status comprehensively. Spearman’s rank correlation coefficient was obtained to evaluate the associations among the above parameters. Stepwise multiple linear regression analysis was performed to investigate factors independently associated factors with the SAGIT scores. The area under the receiver operating characteristic curve (AUCROC) was used to evaluate the efficacy of the percentage change in the serum phosphate level in predicting remission in patients with postoperatively discordant GH and IGF-1 levels. Hyperphosphatemia was found in 68.9% of patients at baseline. The serum P level was higher in the non-remission group, but no correlation was found between hyperphosphatemia and remission. We revealed a significant correlation between the P level and SAGIT® score in patients both preoperatively (r = 0.659, p = 0.000) and 1-year postoperatively without remission patients (r = 0.534, p = 0.027). All biochemical levels decreased significantly postoperatively, and the GH and OGTT-GH levels achieved early stability (1 month); however, the P, IGF-1 and IGBP-3 levels showed a gradual decline. A percentage change in P of −8.12% is recommended as a cut-off value for predicting remission in patients with postoperatively discordant GH and IGF-1 levels. As a metabolic product which affected by the GH/IGF-1 axis, serum P appears to more closely reflect the comprehensive disease status in acromegaly. When the GH and IGF-1 levels are discordant during follow-up, perioperative change in the P level may be a potential predictor of remission. 相似文献
24.
Famke L. Schneiders Charlotte M. Huijts Martine Reijm Hetty J. Bontkes Henk M.W. Verheul Tanja D. de Gruijl Hans J. van der Vliet 《Immunobiology》2018,223(2):171-177
Aminobisphosphonates (NBP) are used for treatment of metastatic bone disease. Frequently, patients undergoing NBP-treatment experience side-effects, known as acute phase response (APR), resulting from cytokine production by Vγ9Vδ2-T cells. As opposed to NBP, statins reduce intracellular phosphoantigen levels and prevent NBP-induced Vγ9Vδ2-T cell activation in vitro. We conducted a pilot study in patients with (bone-)metastasized malignancies receiving NBP-treatment and evaluated the phenotype and function of circulating Vγ9Vδ2-T cells in vivo and the effects of statins on Vγ9Vδ2-T cell responses and the associated APR. We observed reduced expression of perforin, granzyme B and HLA-DR on Vγ9Vδ2-T cells in patients treated with NBP and statins. However, statins could not prevent NBP-induced changes in circulating Vγ9Vδ2-T cell numbers or production of IFNγ and TNFα. Consistent with this, simvastatin could not prevent the occurrence of APR upon NBP-infusion. These observations call for the exploration of alternative strategies to prevent collateral APR upon NBP treatment. 相似文献
25.
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27.
García-Escudero V García-Gómez A Langa E Martín-Bermejo MJ Ramírez-Camacho R García-Berrocal JR Moreno-Flores MT Avila J Lim F 《Neuroscience letters》2012,507(1):27-32
Ether-a-go-go (ERG) K+ channel is a channel of potassium inward rectification. ERG channelopathy may be a cause of sudden unwanted death. The purpose of our study is to assess the effect of antiepileptic drugs on the expression of ERG K+ channel in the hippocampus using seizure resistant (SR) and seizure sensitive (SS) gerbils. As compared to controls, in principal neuron of hippocampus ERG immunoreactivity was significantly decreased after administration of AEDs in SS and SR gerbils. In addition, population spike in response to the second stimulus disappeared, thus population spike amplitude ratio was significantly reduced to zero. These findings indicate that AEDs reduce the expression of ERG channel in the hippocampus of the SR and SS gerbils accompanied by the enhancement of paired-pulse inhibition. In addition, the influence of AEDs on ERG expression in the brain may not be relevant to sudden unexpected death in epilepsy. 相似文献
28.
Prabhu R Horstemeyer MF Tucker MT Marin EB Bouvard JL Sherburn JA Liao J Williams LN 《Journal of the Mechanical Behavior of Biomedical Materials》2011,4(7):1067-1080
This paper presents a coupled experimental/modeling study of the mechanical response of porcine brain under high strain rate loading conditions. Essentially, the stress wave propagation through the brain tissue is quantified. A Split-Hopkinson Pressure Bar (SPHB) apparatus, using a polycarbonate (viscoelastic) striker bar was employed for inducing compression waves for strain rates ranging from 50 to 750 s−1. The experimental responses along with high speed video showed that the brain tissue’s response was nonlinear and inelastic. Also, Finite Element Analysis (FEA) of the SHPB tests revealed that the tissue underwent a non-uniform stress state during testing when glue is used to secure the specimen with the test fixture. This result renders erroneous the assumption of uniaxial loading. In this study, the uniaxial volume averaged stress–strain behavior was extracted from the FEA to help calibrate inelastic constitutive equations. 相似文献
29.
Lucía Pérez-Costillas M. Rosa Montes José M. Martínez-Ortega María Dolores Carretero Luis Gutiérrez-Rojas Manuel Gurpegui 《Journal of psychiatric research》2013
Objective
Low serum phosphate level is considered one of the metabolic adaptations to the respiratory alkalosis induced by hyperventilation associated with panic disorder. The aim of this study was to assess phosphatemia as a possible state marker for panic disorder.Methods
Sixteen panic disorder patients underwent clinical assessment with a semi-structured interview, a set of rating scales and the self-rated State and Trait Anxiety Inventory (STAI), as well as extraction of venous blood samples at baseline and after 12 weeks of pharmacological treatment. Ten healthy volunteers of similar sex, age and educational level filled out the STAI and gave blood samples at baseline and 12 weeks later.Results
The median (25th–75th percentiles) of phosphate levels (mg/dl) was 2.68 (2.22–3.18) among patients and 4.13 (3.74–4.70) among healthy volunteers respectively (P < 0.001). Seven (44%) patients and no healthy volunteers presented low serum phosphate (<2.50 mg/dl) at baseline; this patient abnormality was corrected in all cases after successful treatment. At baseline, the age-adjusted correlation between phosphate levels and state-anxiety was −0.66 (P < 0.001) among all 26 participants and −0.51 (P = 0.05) among the 16 panic disorder patients.Conclusions
Measurement of phosphate levels could be easily introduced into clinical practice as a possible marker for chronic hyperventilation in panic disorder, although further investigations with larger sample sizes are necessary to characterize panic disorder patients with low versus normal phosphate levels. 相似文献30.
Phosphate Kinetics During Weekly Cycle of Hemodialysis Sessions: Application of Mathematical Modeling 下载免费PDF全文
Malgorzata Debowska Jan Poleszczuk Alicja Wojcik‐Zaluska Andrzej Ksiazek Wojciech Zaluska 《Artificial organs》2015,39(12):1005-1014
Both hyperphosphatemia and hypophosphatemia are associated with increased morbidity and mortality among patients on dialysis. The control of serum phosphate concentration is a considerable clinical problem. Our study aimed to improve understanding of phosphate kinetics in patients on dialysis using mathematical modeling. Three consecutive hemodialysis sessions with breaks of 2–2–3 days were monitored in 25 patients. Phosphate concentration was measured every hour and 45 min after the end of dialysis in blood serum and every 30 min in dialysate during each session. Volume of fluid compartments and body composition were assessed by bioimpedance. The pseudo one‐compartment model was applied to describe the profile of phosphate in blood serum during intra‐ and interdialytic periods of 1‐week cycle of three hemodialysis sessions. Model parameters, such as phosphate internal clearance (KM) and the rate of phosphate mobilization (RM), were correlated with the reduction of serum phosphate concentration during dialysis (Cpost/Cpre) and with equivalent continuous clearance (ECC) for phosphate. KM correlated negatively with predialysis serum phosphate concentration. There was significant positive correlation between RM and age. Postdialysis volume of phosphate central compartment was lower than, but correlated to, extracellular water volume. Parameters of the pseudo one‐compartment model, phosphate internal clearance, and the rate of phosphate inflow to the central compartment (the one accessible for dialysis) from other phosphate body reservoirs correlated with the indices of dialysis adequacy, such as reduction of serum phosphate and ECC. The pseudo one‐compartment model can be successfully extended from a single hemodialysis to the standard weekly cycle of sessions and the model parameters strongly correlate with the adequacy parameters of dialytic removal of phosphate. 相似文献