Antioxidants in Athlete's Basic Nutrition: Considerations towards a Guideline for the Intake of Vitamin C and Vitamin E

Antioxidants in acute physical exercise and exercise training remain a hot topic in sport nutrition, exercise physiology and biology, in general (Jackson, 2008; Margaritis and Rousseau, 2008; Gomez-Cabrera et al., 2012; Nikolaidis et al., 2012). During the past few decades, antioxidants have received attention predominantly as a nutritional strategy for preventing or minimising detrimental effects of reactive oxygen and nitrogen species (RONS), which are generated during and after strenuous exercise (Jackson, 2008, 2009; Powers and Jackson, 2008). Antioxidant supplementation has become a common practice among athletes as a means to (theoretically) reduce oxidative stress, promote recovery and enhance performance (Peternelj and Coombes, 2011). However, until now, requirements of antioxidant micronutrients and antioxidant compounds for athletes training for and competing in different sport events, including marathon running, triathlon races or team sport events involving repeated sprinting, have not been determined sufficiently (Williams et al., 2006; Margaritis and Rousseau, 2008). Crucially, evidence has been emerging that higher dosages of antioxidants may not necessarily be beneficial in this context, but can also elicit detrimental effects by interfering with performance-enhancing (Gomez-Cabrera et al., 2008) and health-promoting training adaptations (Ristow et al., 2009). As originally postulated in a pioneering study on exercise-induced production of RONS by Davies et al. (1982) in the early 1980s, evidence has been increasing in recent years that RONS are not only damaging agents, but also act as signalling molecules for regulating muscle function (Reid, 2001; Jackson, 2008) and for initiating adaptive responses to exercise (Jackson, 2009; Powers et al., 2010). The recognition that antioxidants could, vice versa, interact with the signalling pathways underlying the responses to acute (and repeated) bouts of exercise has contributed important novel aspects to the continued discussion on antioxidant requirements for athletes. In view of the recent advances in this field, it is the aim of this report to examine the current knowledge of antioxidants, in particular of vitamins C and E, in the basic nutrition of athletes. While overviews on related topics including basic mechanisms of exercise-induced oxidative stress, redox biology, antioxidant defence systems and a summary of studies on antioxidant supplementation during exercise training are provided, this does not mean that this report is comprehensive. Several issues of the expanding and multidisciplinary field of antioxidants and exercise are covered elsewhere in this book and/or in the literature. Exemplarily, the reader is referred to reviews on oxidative stress (Konig et al., 2001; Vollaard et al., 2005; Knez et al., 2006; Powers and Jackson, 2008; Nikolaidis et al., 2012), redox-sensitive signalling and muscle function (Reid, 2001; Vollaard et al., 2005; Jackson, 2008; Ji, 2008; Powers and Jackson, 2008; Powers et al., 2010; Radak et al., 2013) and antioxidant supplementation (Williams et al., 2006; Peake et al., 2007; Peternelj and Coombes, 2011) in the context with exercise. Within the scope of the report, we rather aim to address the question regarding requirements of antioxidants, specifically vitamins C and E, during exercise training, draw conclusions and provide practical implications from the recent research.

The political decisions and policy leading to the Royal Australian Air Force having no fighters or interceptors for the coming war against Japan

The thesis provides an understanding of the ignored need for a modern air defence system for the Australian air force to meet the growing threat from Japan in the 1930s and early 1940s. The quality of advice provided to, and accepted by, Australian politicians was misleading and eliminated the need for fighters and interceptors despite glaring evidence to the contrary. Based on primary source material, including official documents, Allied and Axis pilot memoirs, popular aviation literature and newspaper and magazine articles and interviews, the thesis highlights the inability of Australian politicians to face the reality of the international situation.

Neuro- and immunotoxic effects of fumonisin B1 in cells

Fumonisin B1 (FB1) is a mycotoxin produced by the fungus Fusarium verticillioides, which commonly infects corn and other agricultural products. Fusarium species can also be found in moisture-damaged buildings, and therefore there may also be human exposure to Fusarium mycotoxins, including FB1. FB1 affects the metabolism of sphingolipids by inhibiting the enzyme ceramide synthase. It is neuro-, hepato- and nephrotoxic, and it is classified as possibly carcinogenic to humans. This study aimed to clarify the mechanisms behind FB1-induced neuro- and immunotoxicity. Four neural and glial cell lines of human, rat and mouse origin were exposed to graded doses of FB1 and the effects on the production of reactive oxygen species, lipid peroxidation, intracellular glutathione levels, cell viability and apoptosis were investigated. Furthermore, the effects of FB1, alone or together with lipopolysaccharide (LPS), on the mRNA and protein expression levels of different cytokines and chemokines were studied in human dendritic cells (DC). FB1 induced oxidative stress and cell death in all cell lines studied. Generally, the effects were only seen after prolonged exposure at 10 and 100 µM of FB1. Signs of apoptosis were also seen in all four cell lines. The sensitivities of the cell lines used in this study towards FB1 may be classified as human U-118MG glioblastoma > mouse GT1-7 hypothalamic > rat C6 glioblastoma > human SH-SY5Y neuroblastoma cells. When comparing cell lines of human origin, it can be concluded that glial cells seem to be more sensitive towards FB1 toxicity than those of neural origin. After exposure to FB1, significantly increased levels of the cytokine interferon-γ (IFNγ) were detected in human DC. This observation was further confirmed by FB1-induced levels of the chemokine CXCL9, which is known to be regulated by IFNγ. During co-exposure of DC to both LPS and FB1, significant inhibitions of the LPS-induced levels of the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-1β, and their regulatory chemokines CCL3 and CCL5 were observed. FB1 can thus affect immune responses in DC, and therefore, it is rather likely that it also affects other types of cells participating in the immune defence system. When evaluating the toxicity potential of FB1, it is important to consider the effects on different cell types and cell-cell interactions. The results of this study represent new information, especially about the mechanisms behind FB1-induced oxidative stress, apoptosis and immunotoxicity, as well as the varying sensitivities of different cell types towards FB1.

An unusual combination in papaya ( Carica papaya): the good (glucosinolates) and the bad (cyanogenic glycosides)

Glucosinolates are a group of sulphur-containing glycosides found in the plant order Brassicales which includes the Brassica vegetables such as broccoli, cabbage and cauliflower. When brought into contact with the plant enzymes, myrosinases, the glucosinolates break down releasing glucose and other products which serve principally in plant defence against herbivores. The most important of the products from a human nutritional viewpoint, are the isothiocyanates. These potent inducers of detoxifying enzymes bestow the distinct anti-cancer properties on these plants. Unique among tropical fruits, papaya is known to contain an abundance of one particular glucosinolate, glucotropaeolin. Other compounds that play a pivotal role in the chemical defence system of many plants are the cyanogenic glycosides. Cyanogenic glycosides are activated by plant enzymes in the event of pest attack, releasing the deterrent: toxic hydrogen cyanide. Papaya, in addition to glucosinolates, also contains low levels of cyanogenic glycosides, an unusual occurrence because it was assumed that the two classes of metabolites were mutually exclusive. Studies measuring the levels of both in the edible parts of the papaya fruit and other utilised tissues are discussed and considered in the context of potential human health ramifications. All rights reserved, Elsevier.

Ativação do estresse oxidativo e da resposta antioxidante por ExoU de Pseudomonas aeruginosa

ExoU, uma citotoxina produzida pelo patógeno oportunista Pseudomonas aeruginosa e translocada para o citosol de células hospedeiras via sistema de secreção do tipo III, é associada à gravidade de infecções agudas. No presente trabalho, o efeito de ExoU na ativação do estresse oxidativo e da resposta antioxidante foi avaliado em culturas de células epiteliais respiratórias humanas infectadas com a cepa PA103 de P. aeruginosa (produtora de ExoU), com a mutante deletada no gene exoU, PA103∆exoU, ou com a mutante complementada com exoU sem atividade tipo fosfolipase A2, PA103∆UT/S142A. Análises das dosagens de hidroperóxidos lipídicos e isoprostanos, considerados marcadores de estresse oxidativo, revelaram que ExoU promoveu um aumento em suas concentrações. Foi observado, também, que ExoU estimulou a produção de espécies reativas de oxigênio, óxido nítrico e peroxinitrito nas células infectadas, assim como a expressão de iNOS e eNOS, mas não de nNOS. Além disso, ExoU foi responsável pelo aumento da atividade de SOD1 e pela redução dos níveis de GSH, mas não afetou a atividade da catalase ou de NQO1. No modelo in vivo, a dosagem de malondialdeído, um subproduto da lipoperoxidação de membranas, evidenciou uma maior produção deste composto no pulmão de camundongos infectados pela cepa produtora de ExoU, em comparação ao pulmão de camundongos infectados pela cepa mutante. Em conjunto, estes resultados mostram que ExoU ativa a produção de espécies reativas de oxigênio e nitrogênio, levando à peroxidação lipídica e modulando o sistema de defesa antioxidante

外来入侵种紫茎泽兰生理生态学研究

紫茎泽兰(Eupatorium adenophorum Spreng.)种子萌发的温度范围是10-30 ℃，最适宜的萌发温度是25℃，高温显著抑制其萌发，35 ℃恒温即没有种子萌发。紫茎泽兰种子萌发对于光的需求为中等，在黑暗中发芽率为17%。紫茎泽兰种子萌发的pH 范围是5.0-7.0，最高发芽率是以蒸馏水为介质，其pH为5.7。紫茎泽兰种子的萌发率随着水势的加大而逐渐降低，在水势大于-0.7 MPa 条件下，即没有种子萌发。在盐分含量小于100 mM NaCl 条件下，其发芽率均大于65%;在盐分含量小于250 mM条件下，其发芽率仍大于10%，当盐分含量达到300 mM NaCl时，即没有种子萌发。紫茎泽兰种子在土壤表层其发芽率最高，当埋藏深度为1.5 cm时即没有种子萌发。根据我们所得的实验结果，对比其原产地的气候条件并结合我国的气候条件和土壤条件进行分析，我们预测紫茎泽兰未来在中国的分布范围将局限在云贵高原，尽管在某些气候和土壤环境适宜的条件下仍有可能会形成零星分布区。 研究了紫茎泽兰和飞机草(Eupatorium odoratum L.)在三种环境胁迫条件下（高温、低温、干旱）七种抗氧化酶活性的变化。结果表明：这三种环境胁迫都对两种植物的生物膜系统造成了损伤，造成了植物体内丙二醛含量的升高。紫茎泽兰在这三种环境胁迫条件下，DHAR活性都升高;SOD活性也都升高，但是在低温处理时与对照的差别并不明显;POD和GR活性在低温和干旱处理时升高，在高温处理时降低;CAT活性在高温和干旱处理时降低，在低温处理时升高;MDAR活性在在高温和干旱处理时降低，在低温处理时略微上升，但是与对照的差别并不明显;APX活性则在三种环境胁迫下表现各不相同。通过这些结果可以说明：DHAR对紫茎泽兰抵抗不良环境的损伤具有重要作用。 而飞机草的抗氧化酶系统的变化为：SOD、APX和DHAR在三种环境胁迫下酶活性都升高;CAT在高温胁迫下升高，而在低温和干旱胁迫下酶活性降低;POD和MDAR在高温和干旱胁迫下酶活性升高，而在低温胁迫下酶活性降低;GR在高温和干旱胁迫下酶活性升高，而在低温胁迫下保持不变。以上的研究结果说明，SOD、APX和DHAR是飞机草抵御环境胁迫的关键酶。 通过比较两种植物在温度胁迫下抗氧化酶系统的不同响应，我们研究发现：两种植物之所以对温度的忍耐性不同，在一定程度上是由于它们在温度胁迫时抗氧化酶系统所作出的不同响应，抗氧化酶系统很可能在两种植物抵抗温度胁迫过程中扮演重要角色，即通过有效调节抗氧化酶活性来减少植物体内有害物质-活性氧自由基的积累，从而减少对植物细胞膜的损伤。两者的差别主要是：紫茎泽兰在低温胁迫时，清除活性氧的抗氧化酶都增加，这就减轻了活性氧自由基在植物细胞中的积累，从而可以在一定程度上保护植物。但是，在高温胁迫时CAT, POD, APX, GR和MDAR酶活性并没有随着SOD活性的升高而升高，所以很有可能造成对细胞有毒害作用的H2O2累积，其结果就造成了紫茎泽兰在高温胁迫下叶片细胞膜的过氧化程度较强。而飞机草的情况正相反，在低温胁迫下飞机草叶片细胞膜的过氧化程度较强，抗氧化酶的协调上升出现在飞机草遭受高温胁迫时，而当其处于低温胁迫时抗氧化酶间的变化趋势则出现了很大分歧，这说明飞机草在高温胁迫时较低温胁迫时能够较好地保护自身遭受活性氧自由基的伤害。

Biochemical and ultrastructural changes of the liver and kidney of the phytoplanktivorous silver carp feeding naturally on toxic Microcystis blooms in Taihu Lake, China

Many experimental studies have documented the impact of microcystins (MC) on fish based on either intraperitoneal injection, or oral gavaging via the diet, but few experiments were conducted by MC exposure through natural food uptake in lakes. In this study, the phytoplanktivorous silver carp were stocked in a large pen set in Meiliang Bay of Taihu Lake where toxic Microcystis blooms occurred in the warm seasons. Fish samples were collected monthly and MC concentrations in liver and kidney of the fish were determined by LC-MS. The maximum MC concentrations in liver and kidney were present in July when damages in ultrastructures of the liver and kidney were revealed by electron microscope. In comparison with previous studies on common carp, silver carp showed less damage and presence of lysosome proliferation in liver and kidney. Silver carp might eliminate or lessen cell damage caused by MC through lysosome activation. Recovery in the ultrastructures of liver and kidney after Microcystis blooms was companied with a significant decrease or even disappearance of MC. Catalase and glutathione S-transferase in liver and kidney of silver carp during Microcystis blooms were significantly higher than before and after Microcystis blooms. The high glutathione pool in liver and kidney of silver carp suggests their high resistance to MC exposure. The efficient antioxidant defence may be an important mechanism of phytoplanktivorous fish like silver carp to counteract toxic Microcystis blooms. (C) 2007 Published by Elsevier Ltd.

模拟增温与UV-B 辐射增强对云杉种子萌发和幼苗生长的影响

臭氧层损耗导致的地球表面UV-B辐射增强以及温室气体增多引起的气候变暖是当今两大全球环境问题。UV-B辐射增强和气候变暖对陆地植物和生态系统产生深远影响，并已成为全球变化研究的重要议题。作为世界第三极的青藏高原，UV-B 辐射增强以及气候变暖现象尤为突出。本试验所在林区是青藏高原东缘的主要林区，具有大面积的亚高山人工针叶成熟林，在全球变化背景下该森林的天然更新潜力如何是急待回答的重要问题。基于此，本研究围绕森林树种的种子和幼苗这一更新的重要阶段，开展了气候变暖、UV-B辐射增强和联合胁迫对云杉种子萌发及幼苗定居影响的研究，旨在全球变化背景下，探讨全球变暖、UV-B 辐射增强和联合胁迫是否对西南地区大面积人工亚高山针叶林更新的种子萌发和幼苗定居阶段产生影响。 本文以青藏高原东缘亚高山针叶林主要树种云杉为研究对象，研究云杉种子萌发及幼苗的生长和生理对UV-B辐射增强与气候变暖的响应。采用UV-B荧光灯（UV-lamp）来模拟增强的UV-B 辐射，此外，采用开顶式有机玻璃罩（OTCs）来模拟气候变暖。本试验包括四个处理：（1）大气UV-B 辐射+大气温度（C）；（2）大气UV-B 辐射+模拟气候变暖（W）；（3）增强的UV-B辐射+大气温度（U）；（4）增强的UV-B辐射+模拟气候变暖（U+W）。 根据本试验结果，UV-B辐射增强对云杉种子萌发没有显著影响，它对萌发云杉幼苗的影响主要体现在幼叶展开以后。根据两年的试验结果，增强的UV-B辐射降低了云杉幼苗抗氧化酶活性，降低了抗氧化物质的含量，此外，造成了膜质的过氧化，表现为MDA在针叶中的积累。增强的UV-B照射处理萌发云杉幼苗两年后，幼苗的生长受到显著抑制。我们的结果显示，OTCs分别提高了空气（10 cm）和土壤（5 cm）温度1.74℃和0.94 ℃。增温显著地促进了云杉种子提前萌发，提高了萌发速率和萌发比率，而且，明显地促进了幼苗的生长，表现为株高和生物量累积的显著增长。此外增温还有利于云杉幼苗根的伸长生长以及生物量的累积，这可以使云杉幼苗更好地利用土壤中的水分和营养元素。 根据本试验结果，温度升高显著地促进了增强UV-B辐射下云杉萌发幼苗的生长，这说明，温度升高缓解了UV-B辐射增强对云杉萌发幼苗的负面影响。这种缓解作用可能是温度升高对UV-B辐射增强处理下幼苗的抗氧化系统活性改善的结果。温度升高还缓解了高UV-B辐射对云杉幼苗根生长的抑制作用，这也可能是增温缓解伤害的原因之一。此外，根据我们的试验结果，增温与UV-B辐射增强联合作用（U+W）下云杉萌发幼苗的生长状况好于大气温度与大气UV-B辐射联合（C）处理，表现为株高、地径、根长和生物量积累均高于C处理，因此可以推断，UV-B辐射增强与气候变暖同时存在对萌发幼苗在两年之内的生长没有产生抑制作用，也就是说，气候变暖的缓解作用完全弥补了UV-B辐射增强的有害作用。 同样，增强的UV-B辐射显著影响了云杉幼苗的光合作用，表现为净光合速率（Pn）和表观量子效率（Φ）的提高，此外，根据我们的试验结果，它还造成了PSII的光抑制。增强的UV-B辐射显著抑制了云杉幼苗对营养元素的吸收，表现为大量营养元素、碳、钙、镁和锌含量的降低，但是，它却显著促进了铁在植株体内的积累。增温显著地提高了净光合速率，但是，它对光系统II（PSII）的光化学效率影响不大。温度升高缓解了UV-B增强对云杉幼苗光合作用的伤害，表现为净光合速率、表观量子效率以及PSII光化学效率的提高。此外，温度升高还缓解了UV-B辐射增强对离子吸收的抑制作用。 Enhanced UV-B radiation due to the reduction of O3 layer and global warming induced by increased greenhouse gases in the air have become the two pressing aspects of global climate changes. Moreover, enhanced UV-B radiation and warming have profound and long-term impacts on terrestrial plants and ecosystems, and the studies focusing on the two factors have attracted many attentions. Qinghai-Tibetan Plateau is the third in elevation in the world, and enhanced UV-B radiation and climate warming are especially prominent in this region. Our research located in the main forest belt in the eastern Qinghai-Tibetan Plateau where large areas of subalpine coniferous forests distributed. Based on that, we carried out a research to study the effects of enhanced UV-B radiation and climate warming on seed germination and seedlings growth of seedlings which are the important basic stage in forest regeneration. This research was arranged by a complete factorial design and included two factors (UV-B radiation and temperature) with two levels. The UV-lamps were used to manipulate the supplemental UV-B radiation and open-top chambers (OTCs) were adopted to increase temperature. The four treatments were: (1) C, ambient UV-B without warming; (2) U, enhanced UV-B without warming; (3) W, ambient UV-B with OTCs warming; (4) U+W, enhanced UV-B with OTCs warming. The main results were exhibited as follows: 1. Based on our results in this research, OTCs increased temperature on average 1.74℃ in air (10 cm above ground) and 0.92 ℃ in soil (5 cm beneath ground). Furthermore, OTCs also slightly reduced soil moisture and relative air humidity, however, the differences was not statistically significant. 2. Our results showed that enhanced UV-B had no significant effects on the seeds germination of P. asperata. Enhanced UV-B affected sprouts of P. asperata until the needles unfolded. During two years, enhanced UV-B inhibited the efficiency of the antioxidant defense systems, and as a result, it induced oxidant stress and the accumulation of MDA in needles. After two years of exposure to enhanced UV-B, the growth of P. asperata sprouts was markedly restrained compared with those under ambient UV-B radiation and temperature (C). Warming significantly stimulated the germination speed and increased the germination rate of P. asperata seeds. In the next place, it prominently facilitated the growth of P. asperata sprouts, represented as improvements in stem elongation and biomass accumulation. Furthermore, warming also increased root growth of P. asperata sprouts, which could made sprouts more efficient to use water and nutrient elements in soil. In this research, warming alleviated the deleterious effects of enhanced UV-B on P. asperata sprouts. It markedly stimulated the growth of P. asperata sprouts exposed to enhanced UV-B. The ease effects of warming on the abilities of the antioxidant defense systems might account for its amending effects on growth. After two years of exposure to enhanced UV-B radiation and warming, the growth of P. asperata sprouts was better than those under ambient UV-B radiation without warming (C), which could be seen from the higher plant height, basal diameter, root length and total biomass accumulation compared with C. 3. Enhanced UV-B radiation significantly influenced the photosynthesis processes of two-year old P. asperata seedlings. Our results showed that enhanced UV-B reduced the net photosynthetic rate (Pn) and the apparent quantum efficiency (Φ), and induced photoinhibition of photosynthetic system II (PSII). Enhanced UV-B significantly decreased the concentration of nitrogen (N), phosphorous (P), potassium (K), calcium (Ca), magnesium (Mg) and zinc (Zn), however, it increased the accumulation of iron (Fe) in the whole plant of P. asperata seedlings. Warming significantly stimulated Pn of P. asperata seedlings but it had no prominent impacts on the photochemical efficiency of PSII. In our research, warming also alleviated the harmful effects of enhanced UV-B on photosynthesis and absorption of ions of P. asperata seedlings. It increased Pn, Φ and the photochemical efficiency of PSII in seedlings exposed to enhanced UV-B. Moreover, warming also increased the absorption of ions of the seedlings exposed to enhanced UV-B radiation.

The responsive expression of heat shock protein 22 gene in zhikong scallop Chlamys farreri against a bacterial challenge

HSP22 is a member of a small HSP subfamily contributing to the growth, transformation and apoptosis of the cell as well as acting as a molecular chaperone. In the present study, CfHSP22 cDNA was cloned from Chlamys farreri by the rapid amplification of cDNA ends technique. The full-length cDNA of CfHSP22 was of 1279 bp, consisting of a 5'-terminal untranslated region (5'UTR) of 122 bp, a 3'UTR of 581 bp with a canonical polyadenylation signal sequence AATAAA and a poly( A) tail, and an open reading frame of 576 bp encoding a polypeptide with a molecular mass of 22.21 kDa and a predicted isoelectric point of 9.69. There was an alpha-crystallin domain, a hallmark of the sHSP subfamily, in the C-terminus, and the deduced amino acid sequence of CfHSP22 showed high similarity to previously identified HSP22s. CfHSP22 was constitutively expressed in the haemocyte, muscle, kidney, gonad, gill, heart and hepatopancreas, and the expression level in the hepatopancreas was higher than that in the other tissues. CfHSP22 transcription was up-regulated and reached a maximal level at 12 h after the bacterial challenge, and then declined progressively to the original level at 48 h. These results suggested that CfHSP22 perhaps play a critical role in response to the bacterial challenge in haemocytes of scallop C. farreri.

Rola wojsk specjalnych w systemie obronnym RP

Na przestrzeni ostatnich dwóch dekad wojska specjalne stały się ważnym elementem systemów obronnych wielu państw, wnosząc istotny wkład w prowadzone operacje wojskowe, oraz ogólny potencjał realizacji stawianych przed nimi zadań. Wynika to z unikalnych zdolności tego rodzaju wojsk, czyniących je szczególnie użytecznymi we współczesnym środowisku bezpieczeństwa międzynarodowego. Czynniki te zadecydowały również o daleko idącej ewolucji i dynamicznym rozwoju polskich Wojsk Specjalnych. Celem artykułu jest analiza użyteczności jednostek specjalnych dla realizacji zasadniczych misji Sil Zbrojnych RP (zapisanych w Strategii Obronności RP) oraz prezentacja perspektyw ich dalszego rozwoju (przez pryzmat szans, wyzwań, ryzyk i zagrożeń).

Role of creatine supplementation on exercise-induced cardiovascular function and oxidative stress

Many degenerative diseases are associated with increased oxidative stress. Creatine has the potential to act as an indirect and direct antioxidant; however, limited data exist to evaluate the antioxidant capabdities of creatine supplementation within in vivo human systems. This study aimed to investigate the effects of oral creatine supplementation on markers of oxidative stress and antioxidant defenses following exhaustive cycling exercise. Following preliminary testing and two additional familiarization sessions, 18 active males repeated two exhaustive incremental cycling trials (T1 and T2) separated by exactly 7 days. The subjects were assigned, in a double-blind manner, to receive either 20 g of creatine (Cr) or a placebo (P) for the 5 days preceding T2. Breath-by-breath respiratory data and heart rate were continually recorded throughout the exercise protocol and blood samples were obtained at rest (preexercise), at the end of exercise (postexercise), and the day following exercise (post24 h). Serum hypdroperoxide concentrations were elevated at postexercise by 17 +/- 5% above preexercise values (p = 0.030). However, supplementation did not influence lipid peroxidation (serum hypdroperoxide concentrations), resistance of low density lipoprotein to oxidative stress (t(1/2max) LDL oxidation) and plasma concentrations of non-enzymatic antioxidants (retinol, alpha-carotene, beta-carotene, alpha-tocopherol, gamma-tocopherol, lycopene and vitamin Q. Heart rate and oxygen uptake responses to exercise were not affected by supplementation. These findings suggest that short-term creatine supplementation does not enhance non-enzymatic antioxidant defence or protect against lipid peroxidation induced by exhaustive cycling in healthy males.

Antioxidants in health and disease

Free radical production occurs continuously in all cells as part of normal cellular function. However, excess free radical production originating from endogenous or exogenous sources might play a role in many diseases. Antioxidants prevent free radical induced tissue damage by preventing the formation of radicals, scavenging them, or by promoting their decomposition. This article reviews the basic chemistry of free radical formation in the body, the consequences of free radical induced tissue damage, and the function of antioxidant defence systems, with particular reference to the development of atherosclerosis.

FAD binding overcomes defects in activity and stability displayed by cancer-associated variants of human NQO1

NAD(P)H quinone oxidoreductase 1 is involved in antioxidant defence and protection from cancer, stabilizing the apoptosis regulator p53 towards degradation. Here, we studied the enzymological, biochemical and biophysical properties of two cancer-associated variants (p.R139W and p.P187S). Both variants (especially p.187S) have lower thermal stability and greater susceptibility to proteolysis compared to the wild-type. p.P187S also has reduced activity due to a lower binding affinity for the FAD cofactor as assessed by activity measurements and direct titrations. Native gel electrophoresis and dynamic light scattering also suggest that p.P187S has a higher tendency to populate unfolded states under native conditions. Detailed thermal stability studies showed that all variants irreversibly denature causing dimer dissociation, while addition of FAD restores the stability of the polymorphic forms to wild-type levels. The kinetic destabilization induced by polymorphisms as well as the kinetic protection exerted by FAD was confirmed by measuring denaturation kinetics at temperatures close to physiological. Our data suggest that the main molecular mechanisms associated with these cancer-related variants are their low binding affinity for FAD and/or kinetic instability. Thus, pharmacological chaperones may be useful in the treatment of patients bearing these polymorphisms.

L’impact d’une diète néonatale déficiente en nutriments essentiels à la défense antioxydante sur le métabolisme énergétique à long terme

Les prématurés subissent un stress oxydant qui résulte d’une défense antioxydante faible et/ou d’une charge oxydante. Des données suggèrent qu’un stress oxydant peut affecter le métabolisme énergétique et mener au syndrome métabolique. Hypothèse: Une faible défense antioxydante tôt dans la vie est suffisante pour affecter le métabolisme énergétique à long terme. Méthodes: Quatre groupes de cobayes (n=21) ont reçu entre leurs 3e et 7e jours de vie une diète standard (C-1sem, C-14sem) ou une diète déficiente (DC-1sem, DC-14sem). À 7 jours, les groupes C-1sem et DC-1sem ont été sacrifiés, le plasma et le foie collectés. Les groupes C-14sem et DC-14sem ont reçu la diète standard jusqu’à 14sem de vie. La glycémie et les triglycérides plasmatiques ont été mesurés à 1, 3, 11, et 13-14sem. La tolérance au glucose a été évaluée à 13sem. Les antioxydants hépatiques et les protéines régulant le métabolisme énergétique ont été analysés à 1 et 14sem. Résultats: Un statut redox oxydé du glutathion était associé avec la diète déficiente et était maintenu oxydé au moins jusqu’à 14sem (p<0.01). Les faibles niveaux de triglycérides plasmatiques et de glycémies, ainsi qu’une meilleure tolérance au glucose à 14sem (p<0.05) étaient associés avec un statut redox plus oxydé. Conclusion: Le faible taux de glutathion observé chez les prématurés a été reproduit dans notre modèle. Puisque nos données suggèrent un rôle protecteur d’un redox plus oxydé et que l’environnement redox est un important régulateur métabolique influençant le développement, il faudrait faire attention avant d’initier des traitements antioxydants agressifs chez les prématurés.

Virus-Host Interaction during Therapy against Hepatitis C Virus

Le virus de l’hépatite C (VHC) est un problème mondial. La majorité des personnes infectées (70-85%) développent une infection chronique qui cause des complications hépatiques. Le seul régime thérapeutique approuvé pour le VHC est l'interféron alpha (IFN-α). Ce traitement a un taux de réussite de 50-80% selon le génotype de virus et le moment de l'initiation de la thérapie. Les facteurs régissant la réponse au traitement ne sont pas bien définis. Des études antérieures ont suggéré un rôle potentiel de la réponse immunitaire de l'hôte au succès de la thérapie, toutefois, ces résultats sont controversés. Nous avons émis l'hypothèse que la réponse immunitaire de l’hôte sera plus efficace chez les patients qui commencent la thérapie tôt pendant la phase aiguë de l'infection. En revanche, la réponse immunitaire sera épuisée lorsque le traitement est initié pendant la phase chronique. L'objectif principal de ce mémoire est d’étudier les facteurs immunologiques qui régissent la réponse à la thérapie, et de déterminer si la contribution de la réponse immunitaire de l'hôte peut être influencée par la période de l'infection. Nos résultats démontrent l'efficacité de la restauration de la réponse immunitaire spécifique au VHC lorsque la thérapie par l'interféron est initiée tôt. Ceci est démontré par le sauvetage des cellules T efficaces spécifiques au VHC efficace similaires à celles observées chez les individus qui ont résolu spontanément, suggérant ainsi qu'elles jouent un rôle actif dans la réponse au traitement. Toutefois, cette réponse n'a pas été restaurée chez les patients traités au cours de la phase chronique. Ces résultats ont des implications importantes dans la compréhension des mécanismes sous-jacents à la réponse aux traitements actuels et au développement des nouvelles thérapies.