Nutritional antioxidants as therapeutic and preventive modalities in exercise-induced muscle damage.

Several mechanisms have been forwarded to explain the etiology of exercise-induced muscle damage. Free-radical mediated processes appear to be an important component of the inflammatory mediated response. Free radicals have also been demonstrated to be a contributing factor in the loss of calcium homeostasis within the cell. Therefore, one of the proposed treatments for preventing or reducing the extent of this damage is the intervention of free-radical mediated processes. Antioxidants are agents that typically work to prevent free-radical mediated alterations within cells by quenching free radicals. The traditional dietary antioxidants most commonly investigated to inhibit free-radical damage are vitamin E, vitamin C, and beta carotene. Other nutritional agents have also been noted to contain antioxidant properties. Isofavonoids and some phytochemicals have been proposed to contain antioxidant properties. This paper briefly reviews some aspects of these agents and the! ! ir role, either proven or proposed, in the prevention of oxidative stress and muscle damage.     

Metabolic gene variants associated with chromosomal aberrations in healthy humans

Nonspecific chromosomal aberrations (CAs) are found in about 1% of lymphocytes drawn from healthy individuals. They include chromosome‐type aberrations (CSAs), which are increased in exposure to ionizing radiation, and chromatid‐type aberrations (CTAs) which in experimental systems are formed by DNA binding carcinogens and mutagens. The frequency of CAs is associated with the risk of cancer, but the causes of CAs in general population are unknown. Here, we want to test whether variants in metabolic genes associate with CAs in healthy volunteers. Cases were considered those whose total CA (CAtot) frequency was >2% and for CSA and CTA the limit was >1%. Controls had lower frequencies of CAs. Functional polymorphisms in seven genes were selected for analysis: cytochrome P450 1B1 (CYP1B1), epoxide hydrolase 1 (EPHX1), NAD(P)H:quinone oxidoreductase 1 (NQO1), each coding for phase 1 enzymes, and glutathione S‐transferase P1 (GSTP1), glutathione S‐transferases M1 (GSTM1) and T1 (GSTT1), coding for enzymes which conjugate reactive metabolites, that is, phase 2 enzymes. The number of volunteers genotyped for each gene varied from 550 to 1,500. Only EPHX1 was individually associated with CAtot; high activity genotypes decreased CAtot. A total of six significant (P < 0.01) pair‐wise interactions were observed, most including a GST variant as one of the pair. In all genotype combinations with significant odds ratios for CAs a GST variant was involved. The present data provide evidence that variants in genes coding for metabolic enzymes, which individually have small effects, interact and are associated with CA frequencies in peripheral lymphocytes of healthy volunteers. © 2015 Wiley Periodicals, Inc.     

Vitamin E supplementation decreases muscular and oxidative damage but not inflammatory response induced by eccentric contraction

The purpose of this study was to investigate the effects of vitamin E supplementation on muscular and oxidative damage, as well as the inflammatory response induced by eccentric exercise (EE) in humans. Twenty-one participants with a mean age of 22.5 ± 4 years, weight of 68.2 ± 4.9 kg, and height of 173 ± 4.3 cm were selected and divided randomly into two groups: supplemented (S) (n = 11) and placebo (P) (n = 10). Fourteen days after starting supplementation, subjects performed EE (three sets until exhaustion with elbow flexion and extension on the Scott bench, 80% 1 RM). Blood samples were collected on days 0, 2, 4, and 7 after EE. Muscle soreness (MS), lactate dehydrogenase (LDH) activity, lipid peroxidation, protein carbonylation, tumor necrosis factor-α (TNF-α), and interleukin 10 (IL-10) levels were determined. We measured a significant increase in MS, LDH, lipid peroxidation, and carbonylation in both groups on days 2, 4, and 7 after eccentric contractions (EC). Values of the supplement group were lower than those of the placebo group at 4 and 7 days after EC in all parameters. Both groups showed significantly increased TNF-α on the second day and IL-10 concentration on the fourth and seventh days after EE. The results suggest that vitamin E supplementation represents an important factor in the defense against oxidative stress and muscle damage but not against the inflammatory response in humans.     

Bleomycin-induced chromosomal damage in tuberous sclerosis.

To investigate the possible involvement of mutagen-induced chromosomal instability in tuberous sclerosis the blood lymphocytes obtained from eleven patients with this disease and eleven healthy controls of comparable age and sex were exposed to bleomycin in vitro during the late S and G2 phases of the cell cycle. Neither the spontaneous aberration yields nor the bleomycin-induced chromosomal sensitivity differed between the two groups. The chromosomal distribution of 578 and 478 induced breaks in patients and controls, respectively, was similar. Thus, bleomycin-induced G2 chromosomal hypersensitivity in lymphocytes of patients with tuberous sclerosis is not an intrinsic feature of this hereditary disease.     

Cerebral oxygenation decreases during exercise in humans with beta‐adrenergic blockade

Aim: Beta‐blockers reduce exercise capacity by attenuated increase in cardiac output, but it remains unknown whether performance also relates to attenuated cerebral oxygenation. Methods: Acting as their own controls, eight healthy subjects performed a continuous incremental cycle test to exhaustion with or without administration of the non‐selective beta‐blocker propranolol. Changes in cerebral blood flow velocity were measured with transcranial Doppler ultrasound and those in cerebral oxygenation were evaluated using near‐infrared spectroscopy and the calculated cerebral mitochondrial oxygen tension derived from arterial to internal jugular venous concentration differences. Results: Arterial lactate and cardiac output increased to 15.3 ± 4.2 mm and 20.8 ± 1.5 L min^?1 respectively (mean ± SD). Frontal lobe oxygenation remained unaffected but the calculated cerebral mitochondrial oxygen tension decreased by 29 ± 7 mmHg (P < 0.05). Propranolol reduced resting heart rate (58 ± 6 vs. 69 ± 8 beats min^?1) and at exercise exhaustion, cardiac output (16.6 ± 3.6 L min^?1) and arterial lactate (9.4 ± 3.7 mm ) were attenuated with a reduction in exercise capacity from 239 ± 42 to 209 ± 31 W (all P < 0.05). Propranolol also attenuated the increase in cerebral blood flow velocity and frontal lobe oxygenation (P < 0.05) whereas the cerebral mitochondrial oxygen tension decreased to a similar degree as during control exercise (delta 28 ± 10 mmHg; P < 0.05). Conclusion: Propranolol attenuated the increase in cardiac output of consequence for cerebral perfusion and oxygenation. We suggest that a decrease in cerebral oxygenation limits exercise capacity.     

Arterial stiffness acutely decreases after whole-body vibration in humans

Background: Increased arterial stiffness is a well‐established cardiovascular risk factor. Mechanical stimuli to artery, such as compression, elicit vasodilation and acutely decrease arterial stiffness. As whole‐body vibration (WBV)‐induced oscillation is propagated at least to lumbar spine, WBV mechanically stimulates abdominal and leg arteries and may decrease arterial stiffness. WBV is feasible in vulnerable and immobilized humans. Therefore, it is worthwhile to explore the possibility of WBV as a valuable adjunct to exercise training. Aim: The aim of this study was to investigate the acute effects of WBV on arterial stiffness. Methods: Ten healthy men performed WBV and control (CON) trials on separate days. The WBV session consisted of 10 sets of vibration (frequency, 26 Hz) for 60 s with an inter‐set rest period of 60 s. Subjects maintained a static squat position with knees bent on a platform. In the CON trial, WBV stimulation was not imposed. Blood pressure, heart rate and brachial‐ankle pulse wave velocity (baPWV), an index of arterial stiffness, were measured before and 20, 40 and 60 min after both trials. Results and conclusion: Heart rate and blood pressure did not change from baseline after both trials. Although baPWV did not change in the CON trial (baseline vs. after 20, 40 and 60 min; 1144 ± 35 vs. 1164 ± 41, 1142 ± 39, and 1148 ± 34 cm s^?1), baPWV decreased 20 and 40 min after the WBV trial and recovered to baseline 60 min after the trial (1137 ± 28 vs. 1107 ± 30, 1108 ± 28, and 1128 ± 25 cm s^?1). These results suggest that WBV acutely decreases arterial stiffness.     

Life-long vitamin C supplementation in combination with cold exposure does not affect oxidative damage or lifespan in mice, but decreases expression of antioxidant protection genes

Oxidative stress is suggested to be central to the ageing process, with endogenous antioxidant defence and repair mechanisms in place to minimize damage. Theoretically, supplementation with exogenous antioxidants might support the endogenous antioxidant system, thereby reducing oxidative damage, ageing-related functional decline and prolonging life- and health-span. Yet supplementation trials with antioxidants in animal models have had minimal success. Human epidemiological data are similarly unimpressive, leading some to question whether vitamin C, for example, might have pro-oxidant properties in vivo. We supplemented cold exposed (7 ± 2 °C) female C57BL/6 mice over their lifespan with vitamin C (ascorbyl-2-polyphosphate), widely advocated and self administered to reduce oxidative stress, retard ageing and increase healthy lifespan. No effect on mean or maximum lifespan following vitamin C treatment or any significant impact on body mass, or on parameters of energy metabolism was observed. Moreover, no differences in hepatocyte and lymphocyte DNA oxidative damage or hepatic lipid peroxidation was seen between supplemented and control mice. Using a DNA macroarray specific for oxidative stress-related genes, we found that after 18 months of supplementation, mice exhibited a significantly reduced expression of several genes in the liver linked to free-radical scavenging, including Mn-superoxide dismutase. We confirmed these effects by Northern blotting and found additional down-regulation of glutathione peroxidase (not present on macroarray) in the vitamin C treated group. We suggest that high dietary doses of vitamin C are ineffective at prolonging lifespan in mice because any positive benefits derived as an antioxidant are offset by compensatory reductions in endogenous protection mechanisms, leading to no net reduction in accumulated oxidative damage.     

“Nutritional insurance” supplementation and corticosteroid toxicity

Specialized “nutritional insurance” supplementation may reduce the risk of many important complications of long-term corticosteroid treatment. Supplementation with calcium, fluoride, activated vitamin D metabolites, and GTF, should help prevent osteoporosis. GTF, vitamin C, zinc and fluoride might help offset the inhibitory effect of corticosteroids on fibroblast and osteoblast function. Diabetic, hyperlipidemic and protein-losing effects might be compensated with supplementary GTF. Antioxidant nutrients could support humoral immunity and neutrophil function, while complementing the anti-inflammatory actions of corticosteroids. Supplementary magnesium could reduce the risk of nephrocalcinosis and nephrolithiasis.     

Aging decreases auditory event-related potentials to unexpected stimuli in humans

A P300 event-related potential (P3a) was recorded to unexpected, deviant auditory stimuli requiring no behavioral response. This brain potential underwent systematic latency prolongation and amplitude decrease with advancing age. The age-related changes paralleled those of the P300 (P3b) recorded in target detection tasks. These results provide physiological evidence of a decremented CNS response to unexpected stimuli with aging.     

High intensity exercise decreases global brain glucose uptake in humans

Physiological activation increases glucose uptake locally in the brain. However, it is not known how high intensity exercise affects regional and global brain glucose uptake. The effect of exercise intensity and exercise capacity on brain glucose uptake was directly measured using positron emission tomography (PET) and [¹⁸F]fluoro-deoxy-glucose ([¹⁸F]FDG). Fourteen healthy, right-handed men were studied after 35 min of bicycle exercise at exercise intensities corresponding to 30, 55 and 75% of     on three separate days. [¹⁸F]FDG was injected 10 min after the start of the exercise. Thereafter exercise was continued for another 25 min. PET scanning of the brain was conducted after completion of the exercise. Regional glucose metabolic rate (rGMR) decreased in all measured cortical regions as exercise intensity increased. The mean decrease between the highest and lowest exercise intensity was 32% globally in the brain (38.6 ± 4.6 versus 26.1 ± 5.0 μmol (100 g)⁻¹ min⁻¹, P < 0.001). Lactate availability during exercise tended to correlate negatively with the observed brain glucose uptake. In addition, the decrease in glucose uptake in the dorsal part of the anterior cingulate cortex (37% versus 20%, P < 0.05 between 30% and 75% of     ) was significantly more pronounced in subjects with higher exercise capacity. These results demonstrate that brain glucose uptake decreases with increase in exercise intensity. Therefore substrates other than glucose, most likely lactate, are utilized by the brain in order to compensate the increased energy needed to maintain neuronal activity during high intensity exercise. Moreover, it seems that exercise training could be related to adaptive metabolic changes locally in the frontal cortical regions.     

Developing SyrinOX total antioxidant capacity assay for measuring antioxidants in humans

Accurate monitoring of the antioxidant status or of oxidative stress in patients is still a big challenge in clinical laboratories. This study investigates the possibility of applying a newly developed total antioxidant capacity assay method based on laccase or peroxidase oxidized syringaldazine [Tetramethoxy azobismethylene quinone (TMAMQ)] which is referred to here as SyrinOX, as a diagnostic tool for monitoring both oxidative stress and antioxidant status in patients. Attempts to adapt the Randox total antioxidant procedure [simultaneous incubation of the radical generating system (metmyoglobin and H₂O₂) and antioxidant sample] for SyrinOX were abandoned after it was discovered that the H₂O₂ reacted with enzymatically generated TMAMQ and ABTS radicals at a rate of 6.4 × 10⁻²/μM/s and 5.7 × 10⁻³/μM/s respectively. Thus this study for the first time demonstrates the negative effects of H₂O₂ in the Randox system. This leads to erroneous results because the total antioxidant values obtained are the sum of radicals reduced by antioxidants plus those reacting with the radical generating system. Therefore they should be avoided not only for this particular method but also when using other similar methods. Consequently, SyrinOX is best applied using a three-step approach involving, production of TMAMQ, recovery and purification (free from enzyme and other impurities) and then using TMAMQ for measuring the total antioxidant capacity of samples. Using this approach, the reaction conditions for application of SyrinOX when measuring the total antioxidant capacity of plasma sample were determined to be 50% (v/v) ethanol/50 mM sodium succinate buffer pH 5.5, between 20 and 25 °C for at least 1 h.     

Clinical effects of insular damage in humans

Multiple disturbances following lesions of the insula are reviewed in the present article, including those related to autonomic function; gustatory, olfactory, auditory, somatosensory, and multimodal perception, as well as body awareness; the emotion of disgust; mood and willed action, addiction behavior, and language. Given the multiple and varied nature of the impairments revealed by lesion studies, we suggest that the insula, as a multimodal area, has a major role as a convergence zone implicated in the coordination between internal and external information through emotional subjective awareness. Methodological issues are discussed with attention paid to lesion etiology, and lesions involving adjacent areas to the insular cortex.     

Selective chromosomal damage caused by human cytomegalovirus

The effect of human cytomegalovirus (CMV) on human foetal cell chromosomes was investigated. Cultures of foetal skin fibroblasts were infected with human CMV (AD-169 strain) and their chromosomes analysed at intervals. The distribution of chromosomal abnormalities was independent of chromosome length.     

Effects of prohormone supplementation in humans: a review.

Despite a relative dearth of information on their effects, supplementation with prohormones has become a popular practice. Unlike synthetic anabolic-androgenic steroids, many of these over-the-counter androgens are produced endogenously by adrenal, gonadal and peripheral steroidogenic pathways as part of the normal sexual and reproductive hormonal milieu. It has been contended that peripheral enzymatic conversion of these prohormones to testosterone or nortestosterone (via ingestion of androstenedione/androstenediol or 19-nor-androstenedione/androstenediol, respectively) might lead to anabolic and/or ergogenic effects. Existing data suggest that acute oral ingestion of >or=200 mg androstenedione or androstenediol modestly and transiently increases serum testosterone concentrations in men; however, this is accompanied by greater increases in circulating estrogen(s). At doses < 300 mg/d, oral supplementation for as long as 12-weeks with androstenedione or androstenediol has no effect on body composition or physical performance and decreases high-density lipoprotein cholesterol. Similarly, oral supplementation with norandrostenedione and norandrostenediol for up to eight weeks has no effect on body composition or physical performance. In light of these data, new products have been developed that use alternative modes of prohormone administration (sublingual/transbuccal and cyclodextrin-complexation). Future studies should critically examine the effects of these approaches. However, within the framework of the research reviewed, over-the-counter oral prohormone supplementation is ineffective at increasing muscle mass or athletic performance. As a result of the potential health concerns that have been raised, the risk to benefit ratio of using these substances orally seems unfavorable.     

Multi-site neural tube closure in humans and maternal folate supplementation

A group of 13 individuals with neural tube defects (NTD) despite maternal periconceptional folate supplementation was examined to determine precisely which closure sites along the neural tube had failed during embryogenesis. All the common forms of NTD, and thus all the usual closure sites, were represented. This suggests that folate deficiency does not act specifically on one region of the neural tube; rather, it may be more generally involved in the cause of human NTD. © 1995 Wiley-Liss, Inc.