Audrey Jaussent

Homocysteine and inflammation as main determinants of oxidative stress in the elderly

Oxidative stress is commonly observed in the elderly and could be involved in age-related diseases. However, the determinants of superoxide anion overproduction are not clearly understood. Superoxide anion production was evaluated using a lucigenin-based chemiluminescence method in 478 elderly subjects (304 women, 174 men; 79.5+/-7.1 years). Homocysteine (HCy) metabolism (homocysteinemia, vitamin B12, plasma, and erythrocyte folates), inflammation (CRP, fibrinogen, alpha-1 acid glycoprotein), lipid parameters (total cholesterol, triglycerides, HDL and LDL cholesterol), and nutritional parameters (albumin, transthyretin) were determined. The results show that HCy levels (p<0.001) and superoxide anion production (p=0.04) increase with aging, but CRP does not. Highest HCy (>20 microM) (OR 1.83 (1.09-3.07), p=0.02) and CRP over 5 mg/L (adjusted OR 2.01 (1.15-3.51), p=0.01) are the main determinants in superoxide anion production in the elderly. These clinical data are confirmed in an in vitro study using THP-1 monocyte-like cells. Incubation with HCy thiolactone (HTL) (0-200 microM) and LPS (0-20 ng/ml) dramatically enhances NADPH oxidase expression and activation. Moreover, a synergic action was evidenced for low concentrations of HTL (20 microM) and LPS (5 ng). Taken together, the clinical data and in vitro experiments support the hypothesis that moderate homocysteinemia and low-grade inflammation synergically enhance NADPH oxidase activity in the elderly.

Appendicular skeletal muscle mass is the strongest independent factor associated with femoral neck bone mineral density in adult and older men.

The relationship between bone mass and muscle mass may be due to the site-specific effects of loading on bone in adults and to lifestyle, nutritional, and hormonal factors. Another hypothesis is that the maintenance with aging of both appendicular muscle and bone mass may be determined by factors independent of all these previous factors, including genetic factors. In 160 healthy men aged 20 to 72years, we recorded femoral neck bone mineral density (FN BMD), relative appendicular skeletal muscle mass [RASM; appendicular skeletal muscle mass (kg)/height (cm)], age, body mass, maximum grip and knee extension strength, lifetime physical activities, calcium intake, tobacco smoking, and serum parathyroid hormone (PTH), estradiol (E2), free testosterone, dehydroepiandrosterone sulphate (DHEAS), insulin-like growth factor (IGF-I), sex hormone-binding globulin (SHBG), calcium, 25(OH) vitamin D, albumin, and creatinine clearance. The correlation between FN BMD and RASM (that includes upper and lower limb muscle mass) was of slightly greater magnitude than that between FN BMD and the relative upper limb muscle mass and between FN BMD and the relative leg muscle mass (r=0.39; p< or =0.001 versus r=0.36; p< or =0.001 and r=0.34; p< or =0.001, respectively). The stepwise multiple linear regression model showed that FN BMD was significantly associated with RASM (15% of FN BMD variance, p<0.0001), age (10% of FN BMD variance, p<0.0001), physical activities from age 11-20years (5% of FN BMD variance, p<0.01), and blood PTH, IGF-I, and creatinine clearance, (2%, 2%, and 1% of FN BMD variance, respectively, p<0.05). These results show that RASM, with ASM measured by DXA, is the strongest factor associated with FN BMD in men. It remains to be determined whether assessing RASM by anthropometric methods would help screening adult men at risk of low FN BMD. Furthermore, since RASM is associated with FN BMD independently of appendicular skeletal loads and other lifestyle, nutritional, and hormonal factors, this suggests that common factors, possibly genetic factors, might also influence the coupled maintenance of appendicular muscle mass and FN BMD in adult men.

Low-grade chronic inflammation and superoxide anion production by NADPH oxidase are the main determinants of physical frailty in older adults

Abstract Background. Physical performance measured by gait speed is being recognized as a major instrument for clinical evaluation in older adults, because it predicts physical frailty, loss of autonomy, hospitalization and decreased survival. Low-grade chronic inflammation and oxidative stress, mediated partly by the superoxide anion produced by NADPH oxidase, are closely linked and could be involved in age-related physical decline. Objective. To determine whether slow gait speed is associated with superoxide anion overproduction by NADPH oxidase and low-grade chronic inflammation. Design and setting. Observational study among the 280 elderly of an ambulatory geriatric care unit (191 women, 89 men, 79.9 ± 6.1 years old). Methods. Gait speed was evaluated by walking at self-chosen usual pace. Usual gait speed < 0.8 m/s was defined as slow gait speed. Superoxide anion production was evaluated using a lucigenin-based chemiluminescence method. Inflammation was evaluated by CRP, fibrinogen and leukocyte count. Results. Among the 280 participants, 179 (63.9%) walked with a gait speed < 0.8 m/s (slow walkers) and 101 (36.1%) with a gait speed ≥ 0.8 m/s. Superoxide production and inflammation markers, such as fibrinogen, were more important in slow walkers (p = 0.004 and p = 0.006, respectively). In multivariate analysis, superoxide anion overproduction and fibrinogen were independently associated with physical frailty assessed by slow gait speed (p = 0.028 and p = 0.007, respectively). Conclusion. Physical frailty in older people is associated with superoxide anion overproduction by NADPH oxidase and low-grade chronic inflammation.

Effects of vitamin C, vitamin E, zinc gluconate, and selenomethionine supplementation on muscle function and oxidative stress biomarkers in patients with facioscapulohumeral dystrophy: a double-blind randomized controlled clinical trial.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by progressive weakness and atrophy of specific skeletal muscles. As growing evidence suggests that oxidative stress may contribute to FSHD pathology, antioxidants that might modulate or delay oxidative insults could help in maintaining FSHD muscle function. Our primary objective was to test whether oral administration of vitamin C, vitamin E, zinc gluconate, and selenomethionine could improve the physical performance of patients with FSHD. Adult patients with FSHD (n=53) were enrolled at Montpellier University Hospital (France) in a randomized, double-blind, placebo-controlled pilot clinical trial. Patients were randomly assigned to receive 500 mg vitamin C, 400mg vitamin E, 25mg zinc gluconate and 200 μg selenomethionine (n=26), or matching placebo (n=27) once a day for 17 weeks. Primary outcomes were changes in the two-minute walking test (2-MWT), maximal voluntary contraction, and endurance limit time of the dominant and nondominant quadriceps (MVCQD, MVCQND, TlimQD, and TlimQND, respectively) after 17 weeks of treatment. Secondary outcomes were changes in the antioxidant status and oxidative stress markers. Although 2-MWT, MVCQ, and TlimQ were all significantly improved in the supplemented group at the end of the treatment compared to baseline, only MVCQ and TlimQ variations were significantly different between groups (MVCQD: P=0.011; MVCQND: P=0.004; TlimQD: P=0.028; TlimQND: P=0.011). Similarly, the vitamin C (P<0.001), vitamin E as α-tocopherol (P<0.001), vitamin C/vitamin E ratio (P=0.017), vitamin E γ/α ratio (P=0.022) and lipid peroxides (P<0.001) variations were significantly different between groups. In conclusion, vitamin E, vitamin C, zinc, and selenium supplementation has no significant effect on the 2-MWT, but improves MVCQ and TlimQ of both quadriceps by enhancing the antioxidant defenses and reducing oxidative stress. This trial was registered at clinicaltrials.gov (number: NCT01596803).

Bone mass acquisition in female rhythmic gymnasts during puberty: no direct role for leptin

Objectives  Although hypoleptinaemia has been reported in female peripubertal athletes, data are lacking on leptin and bone mass variations in puberty and the effects of leptin on bone mineralization during this period. This study therefore investigated the variations in leptin level and bone mineral density (BMD) in young elite female rhythmic gymnasts (FRG) according to pubertal stage. The effects of leptin, IGF‐1 and sex hormones on bone mineral acquisition were also evaluated.

Cost‐effectiveness analysis of epilepsy surgery in a controlled cohort of adult patients with intractable partial epilepsy: A 5‐year follow‐up study

Despite its well‐known effectiveness, the cost‐effectiveness of epilepsy surgery has never been demonstrated in France. We compared cost‐effectiveness between resective surgery and medical therapy in a controlled cohort of adult patients with partial intractable epilepsy.

Low serum IL-6 is associated with high 6-minute walking performance in asymptomatic women aged 20 to 70 years

Cross-sectional associations between low physical performance and inflammatory biomarkers have been reported in healthy subjects and in persons with specific disease conditions. In asymptomatic subjects, whether the inverse association between physical fitness and inflammatory biomarkers is dependent or is independent of fat mass, a significant source of inflammatory cytokines, and is independent of age, muscle mass and strength, endocrine, metabolic, and lifestyle factors is not known. Two hundred and twenty asymptomatic women aged 20 to 72years with a C-reactive protein <5mg/L were assessed for their mean speed over the 6-minute walking test (6MWS) and their serum IL-6, as well as body height, body weight, body lean and fat mass (measured by DXA), waist-to-hip ratio, grip and knee extension strength, physical activities (quantified by the QUANTAP questionnaire), tobacco consumption, serum 25(OH) vitamin D, parathyroid hormone (PTH), estradiol (E2), free testosterone, dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor (IGF-I), sex hormone-binding globulin (SHBG), calcium, albumin, and creatinine. In the stepwise multiple linear regression model, a 6MWS in the highest quartile (over 1.4m/s) was associated with lower values of serum IL-6 (p=0.02) and with higher values of grip strength (p=0.04) and creatinine (p=0.04). In conclusion, present results demonstrate that the relationship between lower levels of serum IL-6 and higher values of physical fitness in asymptomatic women is independent of age, body composition, and lifestyle, endocrine and metabolic confounders. It remains to be determined whether the inverse relationship between IL-6 and fitness reflects the presence of preclinical inflammatory diseases that could potentially influence fitness in asymptomatic women.

Impact of genioplasty on mandibular growth during puberty.

AIM Genioplasty has been validated for the correction of mandibular vertical excess and is generally performed at the end of the growth period, either alone or in association with other forms of osteotomy. Our aim was to assess whether genioplasty performed at an earlier age can impact mandibular growth. METHODS This comparative prospective study included 25 high-angle, mouth-breathing adolescents following orthodontic and ENT treatment. Subjects were divided into two groups according to their stage of puberty, either early (group 1: Tanners stage 3, n=12) or late stage (group 2: Tanner stage 4-5, n=13). Genioplasty was performed in both groups. Cephalometric comparison was made on the overall population and for each group, before and after genioplasty (at 1, 6, 12 and 18months). RESULTS In the immediate postoperative period, significant variation of all the cephalometric measures was observed within each group showing reduction of the vertical dimension and sagittal augmentation. Eighteen months post-surgery, only group 1 exhibited a significant increase in SNPog. Augmentation of the SNB and anterior mandibular rotation were also significantly greater in group 1. The difference in the direction of growth of the mandible before genioplasty (18months of orthodontics) and postgenioplasty (18months of postoperative monitoring) was also significant. CONCLUSION Early genioplasty permits redirection of mandibular growth conducive to orthopedic correction of high angle Class II.

Physical function decline and degradation of postural sway dynamics in asymptomatic sedentary postmenopausal women

BackgroundPostural control is an important aspect of physical functioning.ObjectiveTo determine whether postural sway complexity could discriminate asymptomatic sedentary postmenopausal women with normal or subnormal physical function from those with lower physical function.DesignCross-sectional study.SettingDepartment of Geriatrics, University Hospital of Montpellier.Participants126 community-dwelling women aged 55 to 76 recruited though public meetings aimed at promoting physical activity in postmenopausal women.MeasurementsWomen were asked to stand still on a force platform, either with eyes open (EO) or eyes closed (EC). Physical function was estimated using the Six-Minute Walking Distance (6MWD) test, expressed as a percentage of the predicted 6MWD (%-pred 6MWD) based on age, gender, body height, and weight. In addition to traditional stabilometric measures, dynamical measures (percentage of determinism of recurrence quantification analysis [DETRQA], sample entropy [SampEn] and complexity index of multiscale entropy [CIMSE]) were used to quantify the complexity of center of pressure (COP) time series (DETRQA: predictability, SampEn: regularity, CIMSE: multiscale regularity).ResultsNone of the traditional stabilometric measures differentiated women with lower (%-pred 6MWD ≤ 85.5%) from those with subnormal or normal (%-pred 6MWD > 85.5%) physical function. Conversely, women with lower physical function showed lower SampEn values in the AP direction in both EO and EC conditions, as well as lower SampEn and higher DETRQA values in the ML direction in EC condition. No significant difference in the CIMSE values was found between the two groups.ConclusionLower physical function was found to be associated with lower postural sway complexity (higher regularity and predictability) in asymptomatic sedentary postmenopausal women, especially in the absence of vision. Future work is needed to determine whether a decrease in postural sway complexity could predict future decline in physical function in these women.

Hyperventilation during Exercise in Very Low Birth Weight School-Age Children may Implicate Inspiratory Muscle Weakness

OBJECTIVES To study the ventilatory response during exercise in 8- to 10-year-old children born in 1998 to 2000 with a birthweight <1500 g (very low birthweight [VLBW]). STUDY DESIGN We studied 19 VLBW children and 20 full-term children paired for age and sex. A physical activity questionnaire was administered. Lean body mass, spirometry, and maximal inspiratory pressure were assessed at rest. Gas exchange, breathing pattern, and the tension-time index of the inspiratory muscles, a noninvasive indicator of inspiratory muscle effort, were evaluated during a continuous incremental cycling protocol. RESULTS VLBW children had lower weight, height, lean body mass, and maximal inspiratory pressure than control subjects. Their physical activity level was not different. During exercise, they had a higher respiratory rate and minute ventilation for the same metabolic level (VCO(2)/kg) and a higher tension-time index of the inspiratory muscles for the same exercise level (percentage of maximal oxygen consumption). CONCLUSIONS The lower inspiratory muscle strength observed in school-age VLBW children resulted in a higher inspiratory effort during incremental exercise. The rapid but not shallow breathing pattern adopted by this population during exercise may have been in response to their lower inspiratory muscle resistance to fatigue. VLBW children complaining of dyspnea should be investigated with exercise testing.