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  • OXYGEN  (4)
  • 1
    Keywords: brain ; RECEPTOR ; CELL ; Germany ; KINASE ; EXPOSURE ; NEW-YORK ; PATIENT ; INDEX ; treatment ; cell culture ; culture ; TRIAL ; PLASMA ; DECREASE ; ATP ; SKELETAL-MUSCLE ; GLUCOSE ; DOUBLE-BLIND ; OXIDATIVE STRESS ; SMOKERS ; OXYGEN ; insulin ; INSULIN-RECEPTOR ; 3T3-L1 ADIPOCYTES ; CREATINE SUPPLEMENTATION ; HYDROGEN-PEROXIDE PRODUCTION ; LOW-CARBOHYDRATE ; obesity,hyperlipidemia,body fat,insulin reactivity,thiol antioxidant treatment ; REDOX STATE ; REVERSES ENDOTHELIAL DYSFUNCTION ; STRESS IMPAIRS INSULIN ; SUPPLEMENTATION ; TYROSINE KINASE DOMAIN
    Abstract: Insulin signaling is enhanced by moderate concentrations of reactive oxygen species (ROS) and suppressed by persistent exposure to ROS. Diabetic patients show abnormally high ROS levels and a decrease in insulin reactivity which is ameliorated by antioxidants, such as N-acetylcysteine (NAC). A similar effect of NAC has not been reported for non-diabetic subjects. We now show that the insulin receptor (IR) kinase is inhibited in cell culture by physiologic concentrations of cysteine. In two double-blind trials involving a total of 140 non-diabetic subjects we found furthermore that NAC increased the HOMA-R index (derived from the fasting insulin and glucose concentrations) in smokers and obese patients, but not in nonobese non-smokers. In obese patients NAC also caused a decrease in glucose tolerance and body fat mass. Simultaneous treatment with creatine, a metabolite utilized by skeletal muscle and brain for the interconversion of ADP and ATP, reversed the NAC-mediated increase in HOMA-R index and the decrease in glucose tolerance without preventing the decrease in body fat. As the obese and hyperlipidemic patients had lower plasma thiol concentrations than the normolipidemic subjects, our results suggest that low thiol levels facilitate the development of obesity. Supplementation of thiols plus creatine may reduce body fat without compromising glucose tolerance
    Type of Publication: Journal article published
    PubMed ID: 15007512
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  • 2
    Keywords: CELLS ; CELL ; Germany ; THERAPY ; PROTEIN ; MOLECULES ; TISSUE ; MICE ; MECHANISM ; TISSUES ; mechanisms ; HEALTH ; Drosophila ; GLUTATHIONE ; PLASMA ; STRESS ; AGE ; NECROSIS-FACTOR-ALPHA ; DAMAGE ; LIFE-SPAN ; CAENORHABDITIS-ELEGANS ; MUSCLE ; PARAMETERS ; SKELETAL-MUSCLE ; DIET ; LIPID-PEROXIDATION ; OXIDATIVE STRESS ; OXYGEN ; antioxidants ; reactive oxygen species ; signaling ; OXIDATIVE-STRESS ; INCREASE ; INSULIN-RECEPTOR ; WEIGHT ; clinical trials ; LIFE ; REACTIVE OXYGEN ; LEVEL ; PROTEIN-TYROSINE PHOSPHATASES ; AGE-RELATED-CHANGES ; function ; LOSSES ; ROS ; PRECURSOR ; age-related decrease in ; ageing related functions ; CALORIE RESTRICTION ; cysteine deficit and ageing ; cysteine supplementation ; GLUTATHIONE REDOX STATE ; improvement of ; insulin receptor signaling and ageing ; limiting availability in old age ; oxidative shift in redox status ; redox signaling 'and ageing ; thiols
    Abstract: The popular use of antioxidative vitamins illustrates the growing awareness of oxidative stress as an important hazard to our health and as an important factor in the ageing process. Superoxide radicals and superoxide-derived reactive oxygen species (ROS) are constantly formed in most cells and tissues. To ensure that ROS can function as biological signaling molecules without excessive tissue damage, ROS are typically scavenged by antioxidants such as glutathione and the vitamins A, C, and E. "Oxidative stress" occurs if the production of ROS is abnormally increased or antioxidant concentrations are decreased. Genetic studies in mice, Drosophila, and Celegans suggested that ageing may be mechanistically linked to oxidative stress. Several manifestations of oxidative stress were shown to increase with age, whereas tissue levels of vitamin E, plasma concentrations of vitamin C, and intracellular glutathione concentrations decrease with age. In at least two independent studies, cysteine supplementation on top of the normal protein diet has shown significant beneficial effects on each of several different parameters relevant to ageing, including skeletal muscle functions. As the quality of life in old age is severely compromised by the loss of skeletal muscle function, and as muscle function can be measured with satisfactory precision, loss of muscle function is one of the most attractive surrogate parameters of ageing. The mechanisms by which a deficit in glutathione and its precursor cysteine contributes to various ageing-related degenerative processes appears to be related largely but not exclusively to the dysregulation of redox-regulated biological signaling cascades
    Type of Publication: Journal article published
    PubMed ID: 17100590
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  • 3
    Keywords: EXPRESSION ; SURVIVAL ; CELL ; Germany ; KINASE ; imaging ; NEW-YORK ; PATIENT ; ACTIVATION ; MARKER ; prognosis ; QUALITY ; TYPE-1 ; MAGNETIC-RESONANCE ; magnetic resonance imaging ; FIBER COMPOSITION ; BREAST-CANCER ; NO ; PERFORMANCE ; PLASMA ; AGE ; genetics ; FIBER ; MUSCLE ; PARAMETERS ; MORPHOLOGY ; SKELETAL-MUSCLE ; PREDICTION ; BODY ; POOR-PROGNOSIS ; heredity ; OXYGEN ; BIOPSY ; exercise ; MASSES ; BODIES ; REGRESSION ; INCREASE ; WEIGHT ; LIFE ; PHYSICAL-ACTIVITY ; HEIGHT ; QUALITY-OF-LIFE ; LEVEL ; MYOPATHY ; PLASMA-LEVELS ; technique ; USA ; LOSSES ; uptake ; correlation ; cachexia ; myopathies ; PREDICT ; BIOPSIES ; INCREASES ; - ; RESONANCE ; CANCER DIAGNOSIS ; TRACK ; FOXO TRANSCRIPTION FACTORS ; cancer cachexia ; muscle biopsy ; muscle morphology ; muscle wasting
    Abstract: Progressive muscle wasting is a central feature of cancer-related cachexia and has been recognized as a determinant of poor prognosis and quality of life. However, until now, no easily assessable clinical marker exists that allows to predict or to track muscle wasting. The present study evaluated the potential of myoglobin (MG) plasma levels to indicate wasting of large locomotor muscles and, moreover, to reflect the loss of MG-rich fiber types, which are most relevant for daily performance. In 17 cancer-cachectic patients (weight loss 22%) and 27 age- and gender-matched healthy controls, we determined plasma levels of MG and creatine kinase (CK), maximal quadriceps muscle cross-sectional area (CSA) by magnetic resonance imaging, muscle morphology and fiber composition in biopsies from the vastus lateralis muscle, body cell mass (BCM) by impedance technique as well as maximal oxygen uptake (VO(2)max). In cachectic patients, plasma MG, muscle CSA, BCM, and VO(2)max were 30-35% below control levels. MG showed a significant positive correlation to total muscle CSA (r=0.65, p 〈 0.001) and to the CSA fraction formed by type 1 and 2a fibers (r=0.80, p 〈 0.001). However, when adjusted for body height and age by multiple regression, MG yielded a largely improved prediction of total CSA (multiple r=0.83, p 〈 0.001) and of fiber type 1 and 2a CSA (multiple r=0.89, p 〈 0.001). The correlations between CK and these muscle parameters were weaker, and elevated CK values were observed in 20% of control subjects despite a prior abstinence from exercise for 5 days. In conclusion, plasma MG, when adjusted for anthropometric parameters unaffected by weight, may be considered as a novel marker of muscle mass (CSA) indicating best the mass of MG-rich type 1 and 2a fibers as well as VO(2)max as an important functional readout. CK plasma levels appear to be less reliable because prolonged increases are observed in even subclinical myopathies or after exercise. Notably, cancer-related muscle wasting was not associated with increases in plasma MG or CK in this study
    Type of Publication: Journal article published
    PubMed ID: 17605115
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  • 4
    Keywords: AGENTS ; BLOOD ; Germany ; PERFUSION ; QUANTIFICATION ; VOLUME ; BLOOD-FLOW ; FLOW ; SIGNAL ; PARAMETERS ; RECRUITMENT ; KINETICS ; BODY ; SONOGRAPHY ; OXYGEN ; POWER DOPPLER SONOGRAPHY ; VASCULARIZATION ; ULTRASOUND-INDUCED DESTRUCTION ; exercise ; RE ; WEIGHT ; HEALTHY-VOLUNTEERS ; replenishment kinetics ; TUMOR PERFUSION ; muscle perfusion ; replenishment kinetics of microbubbles ; CAPILLARIES ; microvascular density ; contrast-enhanced sonography
    Abstract: Objective. The purpose of this study was to compare skeletal muscle perfusion measured by contrast-enhanced ultrasonography (CEUS) with microvascular density in muscle biopsies. Methods. Power Doppler sonography after intravenous bolus injection of Levovist (SH U 508A; Schering AG, Berlin, Germany) was used to examine perfusion of vastus lateralis muscle in 23 healthy volunteers. Local blood volume (B), blood flow velocity (v), and blood flow (f) were calculated by analyzing replenishment kinetics. CEUS perfusion was compared with vascularization of biopsy samples from vastus lateralis muscle. Subjects were selected such that their aerobic capacity (maximal oxygen uptake [VO(2)max]) per body weight ranged between 23 and 66 mL - min(-1) - kg(-1) to render a large variability of skeletal muscle capillarization. Moreover, subjects' venous blood hematocrit (Hkt) was determined to estimate the plasmatic intravascular volume fraction (1 - Hkt = PVF) in which the microbubbles can distribute. Results. Median capillary density was 331/mm(2) (range, 207-469/mm(2)), and median capillary fiber contacts (CFC) were 3.6 (range, 2.3-6.5). CFC was correlated with VO2max (r= 0.59; P 〈.01). Among CEUS parameters, B showed the closest correlation to CFC (r = 0.53; P 〈.01). When CFC was normalized for PVF, correlation of B to CFC was r = 0.64 (P 〈.01). CEUS could depict the physiologic large variability of vastus lateralis muscle perfusion at rest (median [range]: B, 2.5 [0.1-12.3] similar to mL; v, 0.3 [0.1-3.7] mm/s; f, 0.7 [0.1-5.3] similar to mL - min(-1) - 100 g tissue(-1)). Conclusions. B is significantly related to fiber-adjacent capillarization and may represent physiologic capillary recruitment (eg, through metabolic fiber-related signals). CEUS is feasible for skeletal muscle perfusion quantification
    Type of Publication: Journal article published
    PubMed ID: 16632781
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