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

Determination of protein composition in milk by mid-infrared spectrometry

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Standardized Method to Measure Muscle Force at the Bedside in Hemodialysis Patients

International audienceIn hemodialysis, diminution of muscle strength constitutes a major prognostic factor of mortality. Currently, measurement of quadriceps isometric maximal voluntary force (MVF) represents the reference method to investigate muscle strength. However, reduction of MVF is rarely detected in these patients due to the absence of portative bedside tools in clinical practice. The purposes of this study were therefore to assess the agreement of a belt-stabilized handheld dynamometer (HHD) with the dynamometer chair (reference method) and to determine intratester and intertester reliability of the quadriceps MVF measurements using belt-stabilized HHD in healthy subjects and in hemodialysis patients.Not applicable

Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors

International audienceFactors released by surrounding cells such as cancer-associated mesenchymal stromal cells (CA-MSCs) are involved in tumor progression and chemoresistance. In this study, we characterize the mechanisms by which naïve mesenchymal stromal cells (MSCs) can acquire a CA-MSCs phenotype. Ovarian tumor cells trigger the transformation of MSCs to CA-MSCs by expressing pro-tumoral genes implicated in the chemoresistance of cancer cells, resulting in the secretion of high levels of CXC chemokine receptors 1 and 2 (CXCR1/2) ligands such as chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, and interleukin 8 (IL-8). CXCR1/2 ligands can also inhibit the immune response against ovarian tumor cells. Indeed, through their released factors, CA-MSCs promote the differentiation of monocytes towards M2 macrophages, which favors tumor progression. When CXCR1/2 receptors are inhibited, these CA-MSC-activated macrophages lose their M2 properties and acquire an anti-tumoral phenotype. Both ex vivo and in vivo, we used a CXCR1/2 inhibitor to sensitize ovarian tumor cells to carboplatin and circumvent the pro-tumoral effects of CA-MSCs. Since high concentrations of CXCR1/2 ligands in patients' blood are associated with chemoresistance, CXCR1/2 inhibition could be a potential therapeutic strategy to revert carboplatin resistance

Comparison of Two Methods for Estimating MS-Related Mortality: The Excess Mortality vs. the Cause-Specific Frameworks

Background and objective: Determining whether multiple sclerosis (MS) causes death is challenging. Our objective was to contrast two frameworks to estimate probabilities of death attributed to MS (PMS) and to other causes (POther): the cause-specific framework (CSF) which requires the causes of death and the excess mortality framework (EMF) which does not.Methods: We used data from the Observatoire Français de la Sclérose en Plaques (OFSEP, n=37,524) and from a comparative subset where causes of death was available (4,004 women with relapsing onset (R-MS)). In CSF, the probabilities were estimated using Aalen-Johansen method. In EMF, they were estimated from the excess mortality hazard, which is the additional mortality among MS patients as compared to the expected mortality in the matched general population. PMS were estimated at 30 years of follow-up, i) with both frameworks in the comparative subset, by age group at onset, and ii) with EMF only in the OFSEP population, by initial phenotype, sex and age at onset.Results: In the comparative subset, the estimated 30-year PMS were greater using EMF than CSF: respectively 10.9% [95%CI 8.3-13.6] vs 8.7% [6.4-11.8] among the youngest, and 20.4% [11.3-29.5] vs 16.2% [8.7-30.2] for the oldest groups. In the CSF, probabilities of death from unknown causes ranged from 1.5% [0.7-3.0] to 6.4% [2.5-16.4], and even after their reallocation, PMS remained lower with CSF than with EMF. The estimated probabilities of being alive were close using the two frameworks and the estimated POther (EMF vs CSF) were 2.6% [2.5-2.6] vs 2.1% [1.2-3.9] and 18.1% [16.9-19.3] vs 26.4% [16.5-42.2] respectively for the youngest and oldest groups. In the OFSEP population, the estimated 30-year PMS ranged from 7.5 [6.4-8.7] to 24.0% [19.1-28.9] in R-MS patients and from 25.4 [21.1-29.7] to 36.8% [28.3-45.3] in primary progressive patients, depending on sex and age.Discussion: EMF has the strong advantage of not requiring death certificates, which quality is sub-optimal. Conceptually, it also appears more relevant as it avoids having to state, for each individual, if death was directly or indirectly caused by MS or if it would have occurred anyway, which is especially difficult in such chronic diseases

Multivariate analyses of (A) main determinants of maximal voluntary force and of (B) variables associated with muscle torque.

<p>(after adjustment for age, gender, dialysis center and dialysis vintage).</p

Flow chart diagram depicting number of patients evaluated for eligibility and number of patients included in analysis.

<p>Flow chart diagram depicting number of patients evaluated for eligibility and number of patients included in analysis.</p

Discordance between maximal voluntary force and skeletal muscle mass.

<p>(CKD chronic kidney disease; hs-CRP: serum high-sensitive C-reactive protein; MVF: maximal voluntary force; nPCR: normalised protein catabolism rate).</p