Reference values of fat-free and fat masses by bioelectrical impedance analysis in 3393 healthy subjects.

Determination of fat-free mass (FFM) and fat mass (FM) is of considerable interest in the evaluation of nutritional status. In recent years, bioelectrical impedance analysis (BIA) has emerged as a simple, reproducible method used for the evaluation of FFM and FM, but the lack of reference values reduces its utility to evaluate nutritional status. The aim of this study was to determine reference values for FFM, FM, and %FM by BIA in a white population of healthy subjects, to observe the changes in these values with age, and to develop percentile distributions for these parameters. Whole-body resistance of 1838 healthy white men and 1555 women, aged 15-64 y, was determined by using four skin electrodes on the right hand and foot. FFM and FM were calculated according to formulas validated for the subject groups and analyzed for age decades. This is the first study to present BIA-determined age- and sex-specific percentiles for FFM, FM, and %FM for healthy subjects, aged 15-64 y. Mean FM and %FM increased progressively in men and after age 45 y in women. The results suggest that any weight gain noted with age is due to a gain in FM. In conclusion, the data presented as percentiles can serve as reference to evaluate the normality of body composition of healthy and ill subject groups at a given age.

Metabolic and physiologic effects of an endotoxin challenge in healthy obese subjects.

Aim: The obesity epidemic has increased the number of obese patients admitted to the ICU. In vitro studies suggest that adipose tissue response to inflammation is enhanced: in vivo data are not conclusive yet. The aim of this study was to test the physiologic response of healthy obese subjects to a standardized intravenous LPS challenge.Methods: Prospective single-blind, randomized, cross-over study in eight subjects (four men, four women), aged 34 +/- 7 years, BMI 34.7 +/- 4.2, without glucose intolerance and lipid abnormalities, testing the impact of intravenous LPS (2 ng kg(-1) of actual body weight) versus placebo.Results: Temperature, hemodynamic variables, indirect calorimetry and blood samples (TNF-alpha, IL-6, stress hormones, hs-CRP) were collected. After LPS temperature, heart rate. TNF-alpha and IL-6 concentrations and stress hormones (cortisol and glucagon) increased significantly, with maximal responses between 120 and 240 min after the injection. The pattern, the timing and the magnitude of change were similar to those observed in lean subjects.Conclusion: This study shows that healthy obese subjects have a similar response pattern to intravenous LPS as described in lean subjects.

Measurement of plasma endothelin-1 in experimental hypertension and in healthy subjects.

BACKGROUND: Endothelin-1 is an endothelium-derived potent vasoconstrictor peptide of 21 amino acids. To establish reference values in different models of hypertension and in human subjects an assay for plasma immunoreactive endothelin-1 (ET-1) was optimized. METHODS: ET-1 is extracted by acetone from 1 mL of plasma and subjected to a sensitive enzyme-linked immunosorbent assay. RESULTS: The detection limit for plasma ET-1 is 0.05 fmol/mL. Mean recoveries of the 1, 2, 5, and 10 fmol of ET-1 added to 1 mL of plasma were 66%, 75%, 85%, and 92%, respectively. Within- and between-assay coefficients of variation were < or =12% and < or =10%, respectively. Assay accuracy was demonstrated by consistent recoveries of added ET-1 over the entire physiologic range of plasma concentrations and by the linearity of ET-1 concentrations measured in serially diluted plasma extracts (r = 0.99). No ET-1 was detected when albumin buffer was extracted instead of plasma. Using this method, we found increased ET-1 levels in plasma of three experimental rat models of hypertension: stroke prone spontaneously hypertensive rats (SP-SHR), deoxycorticosterone acetate-salt hypertensive rats, and one kidney-one clip hypertensive rats. In contrast, plasma ET-1 levels of SHR were half those of normotensive Wistar rats. In two kidney-one clip hypertensive rats, plasma ET-1 concentrations were not different from those found in sham-operated control rats. Plasma ET-1 concentrations of 37 healthy men were 0.85 +/- 0.26 fmol/ml (mean +/- SD). CONCLUSIONS: The present assay reliably measures ET-1 levels in rat and human plasma. It allows to discriminate between different forms of hypertension with high or low circulating levels of ET-1.

IFN-gamma-producing CD45RA+CD8+ and IL-10-producing CD45RA-CD4+ T cells generated in response to LACK in naive subjects never exposed to Leishmania.

Leishmania guyanensis (L.g.)-specific CD8+ T cells can be isolated from PBMC of subjects who have never been previously exposed to Leishmania. Cells that produce IFN-gamma in response to live L.g. are generated from naive CD45RA+CD8+ T cells. The generation of L.g.-specific CD8+ T cells requires the presence of whole L.g. or UV-irradiated parasite but not the soluble antigens from L.g. promastigotes. The IFN-gamma-producing T cells recognize a specific antigen, the Leishmania homologue of receptors of activated C kinases (LACK) and this antigen but not live L.g. can produce a strong IL-10 response in CD45RA-CD4+ memory T cells from naive subjects. A single epitope (amino acid 156-173) is found to induce the IL-10 synthesis. While the IFN-gamma-producing cells are present among CD45RA+CD8+ T cells that are CD62L-CDR7- and CLA-, the LACK-reactive IL-10-producing cells are CD4+ T cells that are CD62L+CCR7- and CLA-.

Soft tissue artifact assessment during treadmill walking in subjects with total knee arthroplasty.

Accurate measurement of knee kinematics during functional activities suffers mainly from soft tissue artifact (STA): the combination of local surface deformations and rigid movement of markers relative to the underlying bone (also called rigid STA movement: RSTAM). This study proposes to assess RSTAM on the thigh, shank, and knee joint and to observe possible features between subjects. Nineteen subjects with knee arthroplasty were asked to walk on a treadmill while a biplane fluoroscopic system (X-rays) and a stereophotogrammetric system (skin markers) recorded their knee movement. The RSTAM was defined as the rigid movement of the cluster of skin markers relative to the prosthesis. The results showed that RSTAM amplitude represents approximately 80-100% of the STA. The vertical axis of the anatomical frame of the femur was influenced the most by RSTAM. Combined with tibial error, internal/external rotation angle and distraction-compression were the knee kinematics parameters most affected by RSTAM during the gait cycle, with average rms values of 3.8° and 11.1 mm. This study highlighted higher RSTAM during the swing phase particularly in the thigh segment and suggests new features for RSTAM such as the particular shape of some RSTAM waveforms and the absence of RSTAM in certain kinematics during the gait phases. The comparison of coefficient of multiple correlations showed some similarities of RSTAM between subjects, while some correlations were found with gait speed and BMI. These new insights could potentially allow the development of new methods of compensation to avoid STA.

Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes.

BACKGROUND: Both nutritional and genetic factors are involved in the pathogenesis of nonalcoholic fatty liver disease and insulin resistance. OBJECTIVE: The aim was to assess the effects of fructose, a potent stimulator of hepatic de novo lipogenesis, on intrahepatocellular lipids (IHCLs) and insulin sensitivity in healthy offspring of patients with type 2 diabetes (OffT2D)--a subgroup of individuals prone to metabolic disorders. DESIGN: Sixteen male OffT2D and 8 control subjects were studied in a crossover design after either a 7-d isocaloric diet or a hypercaloric high-fructose diet (3.5 g x kg FFM(-1) x d(-1), +35% energy intake). Hepatic and whole-body insulin sensitivity were assessed with a 2-step hyperinsulinemic euglycemic clamp (0.3 and 1.0 mU x kg(-1) x min(-1)), together with 6,6-[2H2]glucose. IHCLs and intramyocellular lipids (IMCLs) were measured by 1H-magnetic resonance spectroscopy. RESULTS: The OffT2D group had significantly (P < 0.05) higher IHCLs (+94%), total triacylglycerols (+35%), and lower whole-body insulin sensitivity (-27%) than did the control group. The high-fructose diet significantly increased IHCLs (control: +76%; OffT2D: +79%), IMCLs (control: +47%; OffT2D: +24%), VLDL-triacylglycerols (control: +51%; OffT2D: +110%), and fasting hepatic glucose output (control: +4%; OffT2D: +5%). Furthermore, the effects of fructose on VLDL-triacylglycerols were higher in the OffT2D group (group x diet interaction: P < 0.05). CONCLUSIONS: A 7-d high-fructose diet increased ectopic lipid deposition in liver and muscle and fasting VLDL-triacylglycerols and decreased hepatic insulin sensitivity. Fructose-induced alterations in VLDL-triacylglycerols appeared to be of greater magnitude in the OffT2D group, which suggests that these individuals may be more prone to developing dyslipidemia when challenged by high fructose intakes. This trial was registered at clinicaltrials.gov as NCT00523562.

Up-regulated 14-3-3β and 14-3-3ζ proteins in prefrontal cortex of subjects with schizophrenia: effect of psychotropic treatment.

14-3-3 is a family of conserved regulatory proteins that bind to a multitude of functionally diverse signalling proteins. Various genetic studies and gene expression and proteomic analyses have involved 14-3-3 proteins in schizophrenia (SZ). On the other hand, studies about the status of these proteins in major depressive disorder (MD) are still missing. Immunoreactivity values of cytosolic 14-3-3β and 14-3-3ζ proteins were evaluated by Western blot in prefrontal cortex (PFC) of subjects with schizophrenia (SZ; n=22), subjects with major depressive disorder (MD; n=21) and age-, gender- and postmortem delay-matched control subjects (n=52). The modulation of 14-3-3β and 14-3-3ζ proteins by psychotropic medication was also assessed. The analysis of both proteins in SZ subjects with respect to matched control subjects showed increased 14-3-3β (Δ=33±10%, p<0.05) and 14-3-3ζ (Δ=29±6%, p<0.05) immunoreactivity in antipsychotic-free but not in antipsychotic-treated SZ subjects. Immunoreactivity values of 14-3-3β and 14-3-3ζ were not altered in MD subjects. These results show the specific up-regulation of 14-3-3β and 14-3-3ζ proteins in PFC of SZ subjects and suggest a possible down-regulation of both proteins by antipsychotic treatment.

Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk

Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 55-80 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function.We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.151-1.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.010-0.316) and 0.294 (0.055-0.534), respectively];walnuts with working memory [1.191 (0.061-2.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.006-0.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.236-2.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline.

The effects of milk as a food matrix for polyphenols on the excretion profile of cocoa (-)-Epicatechin metabolites in healthy humans subjects

The effect of different food matrices on the metabolism and excretion of polyphenols is uncertain. The objective of the study was to evaluate the possible effect of milk on the excretion of (2)-epicatechin metabolites from cocoa powder after its ingestion with and without milk. Twenty-one volunteers received the following three test meals each in a randomised cross-over design with a 1-week interval between meals: (1) 250 ml whole milk as a control; (2) 40 g cocoa powder dissolved in 250 ml whole milk (CC-M); (3) 40 g cocoa powder dissolved in 250 ml water (CC-W). Urine was collected before consumption and during the 0-6, 6-12 and 12-24 h periods after consumption. (2)-Epicatechin metabolite excretion was measured using liquid chromatography-MS. One (2)-epicatechin glucuronide and three (2)-epicatechin sulfates were detected in urine excreted after the intake of the two cocoa beverages (CC-M and CC-W). The results show that milk does not significantly affect the total amount of metabolites excreted in urine. However, differences in metabolite excretion profiles were observed; there were changes in the glucuronide and sulfate excretion rates, and the sulfation position between the period of excretion and the matrix. The matrix in which polyphenols are consumed can affect their metabolism and excretion, and this may affect their biological activity. Thus, more studies are needed to evaluate the effect of these different metabolite profiles on the body.