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Aims Endothelial function is essential for cardiovascular health, and flow-mediated dilation (FMD) is an established technique to measure it. This paper aims to assess FMD values in apparently healthy individuals and provides reference values to facilitate wider clinical use. Methods and results In 1,579 apparently healthy individuals (aged 18–76), fasted FMD values (data from 44 studies, 6 institutions, 22 operators) were normally distributed and inversely univariately correlated with age, body mass index, glucose, cholesterol, blood pressure, and brachial artery (BA) diameter. Significant multivariate predictors of FMD were age (−0.4%/decade), BMI (0.04%/kg/m2), smoking (−0.7%), and BA diameter (−0.44%/mm) that together explained 19% of the variability independent of operator, institution or ultrasound machine. Individuals in the high FMD tertile (>6.8%) were younger, had smaller BA diameter, lower blood pressure and cholesterol. In individuals with low- and intermediate fatal cardiovascular risk (SCORE), 26% and 53% of individuals, respectively, had FMD values in the low tertile (<5.4%). After adding data from 385 patients with stable coronary artery disease (CAD), ROC analysis (c = 0.841 , P < 0.001) showed that FMD of >6.5% excluded CAD (95% sensitivity; 60% specificity) and FMD <3.1% excluded 95% healthy individuals (95% specificity, 31% sensitivity). A meta-analysis and meta-regression of 82 clinical trials (11 countries, n = 3,509) using similar FMD methodology showed that despite considerable heterogeneity (I 2 = 0.97) FMD in healthy individuals was on average 6.4% (95%CI: 6.2%, 6.7%) with no significant differences between countries but a significant age-dependent decline (−0.3%/decade, R 2 = 0.13). Conclusions We provide an age-adapted frame of FMD reference intervals in apparently healthy individuals for use as a biomarker of cardiovascular health. As the degree of vascular endothelial function integrates environmental and genetic factors with classical CV risk factors, FMD may more comprehensively classify individuals with and without standard modifiable cardiovascular risk factors and serve as a target for cardiovascular prevention. [ABSTRACT FROM AUTHOR]

Redox reactions are linked to fundamental life processes. Recent research revealed a central role of hydrogen peroxide (H2O2) in redox regulation and oxidative stress responses. A physiological low level of H2O2 is essential in redox signaling, "oxidative eustress", whereas supraphysiological H2O2 is detrimental, causing molecular damage, "oxidative distress". Fine-tuning H2O2 steady-states in specific cell-types and subcellular organelles represents a challenge for a future redox medicine. [ABSTRACT FROM AUTHOR]

The subsequent years coincided with an explosion of interest in free radicals in biology generally, and Robin's contributions expanded rapidly to include major contributions to diverse areas of free radical chemistry and biology. The Newcastle group focused on reactions of radicals produced on radiolysis of aqueous solutions of nucleic acids, and Robin's first papers were in this area; he was awarded his PhD in 1966. It is with great sadness that we announce the passing of one of the "founding fathers" of the free radical and redox fields, Professor Robin Linhope Willson. In thinking about what highlights to include of the many discoveries associated with Robin Willson, and particularly those of the widest and most-enduring interest to the field of free radical chemistry and biology, the direct observation of the "repair" of radicals formed from the antioxidants, vitamin E and thiols, by ascorbate (vitamin C) immediately springs to mind [[1]]. [Extracted from the article]

Research on oxidants and electrophiles has shifted from focusing on damage to biomolecules to the more fine‐grained physiological arena. Redox transitions as excursions from a steady‐state redox set point are continually ongoing in maintenance of redox balance. Current excitement on these topics results from the fact that recent research provided mechanistic insight, which gives rise to more concrete and differentiated questions. This Commentary focuses on redox eustress and the feedback restoration of steady state as concepts in active maintenance of physiological health, with brief discussion of redox stress response to viral infection, exemplified by COVID‐19. [ABSTRACT FROM AUTHOR]

Oxidative stress is two sided: Whereas excessive oxidant challenge causes damage to biomolecules, maintenance of a physiological level of oxidant challenge, termed oxidative eustress, is essential for governing life processes through redox signaling. Recent interest has focused on the intricate ways by which redox signaling integrates these converse properties. Redox balance is maintained by prevention, interception, and repair, and concomitantly the regulatory potential of molecular thiol-driven master switches such as Nrf2/Keap1 or NF-κB/IκB is used for system-wide oxidative stress response. Nonradical species such as hydrogen peroxide (H2O2) or singlet molecular oxygen, rather than free-radical species, perform major second messenger functions. Chemokine-controlled NADPH oxidases and metabolically controlled mitochondrial sources of H2O2 as well as glutathione- and thioredoxin-related pathways, with powerful enzymatic back-up systems, are responsible for fine-tuning physiological redox signaling. This makes for a rich research field spanning from biochemistry and cell biology into nutritional sciences, environmental medicine, and molecular knowledge-based redox medicine. [ABSTRACT FROM AUTHOR]

Eimeriosis, a widespread infectious disease of livestock, is caused by coccidian protozoans of the genus Eimeria. These obligate intracellular parasites strike the digestive tract of their hosts and give rise to enormous economic losses, particularly in poultry, ruminants including cattle, and rabbit farming. Vaccination, though a rational prophylactic measure, has not yet been as successful as initially thought. Numerous broad-spectrum anti-coccidial drugs are currently in use for treatment and prophylactic control of eimeriosis. However, increasing concerns about parasite resistance, consumer health, and environmental safety of the commercial drugs warrant efforts to search for novel agents with anti- Eimeria activity. This review summarizes current approaches to prevent and treat eimeriosis such as vaccination and commercial drugs, as well as recent attempts to use dietary antioxidants as novel anti- Eimeria agents. In particular, the trace elements selenium and zinc, the vitamins A and E, and natural products extracted from garlic, barberry, pomegranate, sweet wormwood, and other plants are discussed. Several of these novel anti- Eimeria agents exhibit a protective role against oxidative stress that occurs not only in the intestine of Eimeria-infected animals, but also in their non-parasitized tissues, in particular, in the first-pass organ liver. Currently, it appears to be promising to identify safe combinations of low-cost natural products with high anti- Eimeria efficacy for a potential use as feed supplementation in animal farming. [ABSTRACT FROM AUTHOR]

In mammalian tissues, ultraweak chemiluminescence arising from biomolecule oxidation has been attributed to the radiative deactivation of singlet molecular oxygen [O2 (1Δg)] and electronically excited triplet carbonyl products involving dioxetane intermediates. Herein, we describe evidence of the generation of O2 (1Δg) in aqueous solution via energy transfer from excited triplet acetone. This involves thermolysis of 3,3,4,4-tetramethyl-1,2-dioxetane, a chemical source, and horseradish peroxidase-catalyzed oxidation of 2-methylpropanal, as an enzymatic source. Both sources of excited carbonyls showed characteristic light emission at 1,270 nm, directly indicative of the monomolecular decay of O2 (1Δg). Indirect analysis of O2 (1Δg) by electron paramagnetic resonance using the chemical trap 2,2,6,6-tetramethylpiperidine showed the formation of 2,2,6,6-tetramethylpiperidine-1-oxyl. Using [18O]-labeled triplet, ground state molecular oxygen [18O2 (3∑g -)], chemical trapping of 18O2 (1Δg) with disodium salt of anthracene-9,10-diyldiethane-2,1-diyl disulfate yielding the corresponding double-[18O]-labeled 9,10-endoperoxide, was detected through mass spectrometry. This corroborates formation of O2 (1Δg). Altogether, photoemission and chemical trapping studies clearly demonstrate that chemically and enzymatically nascent excited carbonyl generates 18O2 (1Δg) by triplet-2 (3∑g -), and supports the long formulated hypothesis of O2 (1Δg) involvement in physiological and pathophysiological events that might take place in tissues in the absence of light. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide acts as a signaling molecule in early adipogenesis. In differentiating adipocytes, elevated hydrogen peroxide generation is balanced through induction of antioxidant enzymes such as catalase and peroxiredoxins. Thioredoxin reductases (TrxR) and glutathione peroxidases (GPx) are selenoenzymes that constitute part of the major thiol-dependent antioxidant systems in cells. Here we show that the protein levels of cytoplasmic/nuclear TrxR1 and mitochondrial TrxR2 increase in the course of adipocyte differentiation of 3T3- L1 cells together with the TrxR2 substrate thioredoxin 2 (Trx2), resulting in elevated TrxR activity in mature adipocytes. Gene and protein expression of the GPx isoenzyme GPx4 was also stimulated during adipogenesis. Chronic exposure of 3T3-L1 cells to the anti-adipogenic factors tumor necrosis factor a (TNF-a) or rapamycin during differentiation suppressed TrxR1 and Trx2 upregulation, concomitantly with inhibition of adipogenesis and lipogenesis. In contrast, TNF-α or rapamycin did not affect expression of TrxRs and their Trx substrates in mature adipocytes. These results indicate that upregulation of the thioredoxin-dependent redox system is linked to the development of an adipocyte phenotype. [ABSTRACT FROM AUTHOR]

Here, we investigated the effect of the trace element selenium (Se) on course and outcome of Eimeria-paplllata-induced coccidiosis in mice. Male mice were fed on Se-adequate (0.15 ppm), Se-deficient, and Se-high diets (1.0 ppm) for 6 weeks. Mice were orally infected with 1,000 oocysts. The prepatent period lasts for 3 days, but the course of infections varied. At Se-adequate diet, the maximum fecal output of oocysts amounted to 68,300 ooccysts/g feces on day 5 p.i.. However, fecal shedding of oocysts was accelerated in mice on Se-deficient diet and occurred already on day 4 p.i.. By contrast, maximal shedding is impaired in mice on high-Se diet, which takes place on day 5 p.i., but with a decreased output of only 7,300 oocysts/g feces. Light microscopy reveals that all developmental stages are affected: meronts, micro- and macrogamonts, and developing oocysts are increased in comparison with mice fed on selenium-adequate diet. At high Se, the number of parasitic stages in the jejunum is substantially higher than at Se-deficient diet. Se does not affect the number of jejunal Alcian blue-stained goblet cells. Se deficiency increased the number of apoptotic cells in the jejunum. Substantially increased histological injury scores reveal more injuries in jejunum tissue infected by E. papillata. Our data indicate that high dietary Se exerts potential anticoccidial activity. This may be taken advantage of in control measures towards Eimeriosis as a feed additive, potentially alleviating the need for concomitantly utilized anti-coccidial drugs in the feed. [ABSTRACT FROM AUTHOR]

Protection against skin damage from sunlight by nutritional means has been examined. Likewise, there has been work on the topical application of phytochemicals to the skin. This review focuses on the nutritional aspect of phytochemicals in humans--ie, the provision of carotenoid micronutrients by dietary means to the skin and their role in protection. Human intervention studies have documented protective effects for β-carotene or for lycopene provided either by a carotenoid-rich diet or by supplementation. In exposed tissues, light induces primary and secondary photooxidative processes. Scavenging of reactive oxygen species is considered to be a mechanism of action underlying the protective activity of carotenoids. However, food comprises a complex mixture of numerous constituents, so that other components may also contribute to the observed activity. Molecules with suitable structures absorb UV light and prevent direct damage of cellular targets. Phytoene and phytofluene are precursor molecules of higher unsaturated carotenoids and occur in various fruit and vegetables. Their absorption spectra cover the UVB and UVA range, respectively, thus potentially contributing to photoprotective effects of carotenoid-rich food. Because of the physiologic turnover time of skin, several weeks are required for protective effects to appear. Photoprotection through individual dietary components such as β-carotene or lycopene in terms of sun protection factor is considerably lower than that achieved by using topical sunscreens. However, an optimal supply of antioxidant micronutrients in the skin increases basal dermal defense against UV irradiation, supports longer-term protection, and contributes to maintenance of skin health and appearance. [ABSTRACT FROM AUTHOR]

Aim A double-blind randomized controlled trial to determine whether dietary supplementation with fruit/vegetable/berry juice powder concentrates, simultaneously with non-surgical periodontal therapy, improved 2-month treatment outcomes. Methods Volunteers with chronic periodontitis were randomly assigned to one of three groups: fruit/vegetable (FV), fruit/vegetable/berry (FVB) or placebo. Supplements were taken daily during non-surgical debridement and maintenance and outcomes assessed at 2, 5 and 8 months after completion. Primary outcomes were mean probing pocket depth (PPD), clinical attachment gain, % sites bleeding on probing (% BOP) at 2 months. Adherence and plasma β-carotene were determined. Results Sixty-one nutritionally replete (by serum biochemistry) volunteers enrolled and 60 ( n = 20 per arm) completed the 2-month review. Clinical outcomes improved in all groups at 2 months, with additional improvement in PPD versus placebo for FV ( p < 0.03). Gingival crevicular fluid volumes diminished more in supplement groups than placebo (FVB; p < 0.05) at 2 months, but not at later times. The % BOP (5 months) and cumulative plaque scores (8 months) were lowered more in the FV group ( p < 0.05). Conclusions Adjunctive juice powder concentrates appear to improve initial pocket depth reductions in nutritionally replete patients, where plasma micronutrient bioavailability is attainable. Definitive multicentre studies in untreated and treated patients are required to ascertain the clinical significance of such changes. [ABSTRACT FROM AUTHOR]

Background: The dietary flavanol (−)-epicatechin has been suggested to mediate its vasodilatory effect by increasing nitric oxide levels in endothelial cells. Aim of the study: To directly prove the formation of nitric oxide (NO) in human endothelial cells (HUVEC) in vitro by trapping NO to yield a fluorescent nitrosamine. Methods: HUVEC were treated with (−)-epicatechin; nitrite and NO formation were determined by reductive chemiluminescence detection and the NO-sensitive fluorophore 5-methoxy-2-(1 H-naphthol[2,3-d]imidazol-2-yl)-phenol copper complex (MNIP-Cu), respectively. MNIP was synthesized in a rapid and convenient one-step microwave reaction. Endothelial nitric oxide synthase (eNOS) mRNA levels and mRNA stability were measured. Results: Incubation with (−)-epicatechin (0.3-10 μM) led to elevated NO levels in HUVEC measured via reductive chemiluminescence detection and visualized as the fluorescent NO derivative of MNIP. Expression of eNOS mRNA and mRNA stability were not affected by (−)-epicatechin treatment within the time frame studied. Conclusion: (−)-Epicatechin augments the level of NO in endothelial cells, a process suggested to be responsible for the vasodilatory properties of the compound. [ABSTRACT FROM AUTHOR]

Background: The dietary flavanol (−)-epicatechin has been suggested to mediate its vasodilatory effect by increasing nitric oxide levels in endothelial cells. Aim of the study: To directly prove the formation of nitric oxide (NO) in human endothelial cells (HUVEC) in vitro by trapping NO to yield a fluorescent nitrosamine. Methods: HUVEC were treated with (−)-epicatechin; nitrite and NO formation were determined by reductive chemiluminescence detection and the NO-sensitive fluorophore 5-methoxy-2-(1 H-naphthol[2,3-d]imidazol-2-yl)-phenol copper complex (MNIP-Cu), respectively. MNIP was synthesized in a rapid and convenient one-step microwave reaction. Endothelial nitric oxide synthase (eNOS) mRNA levels and mRNA stability were measured. Results: Incubation with (−)-epicatechin (0.3-10 μM) led to elevated NO levels in HUVEC measured via reductive chemiluminescence detection and visualized as the fluorescent NO derivative of MNIP. Expression of eNOS mRNA and mRNA stability were not affected by (−)-epicatechin treatment within the time frame studied. Conclusion: (−)-Epicatechin augments the level of NO in endothelial cells, a process suggested to be responsible for the vasodilatory properties of the compound. [ABSTRACT FROM AUTHOR]

Human studies provide evidence for beneficial effects of polyphenol-rich foods on cardiovascular health. The antioxidant activity of polyphenols potentially explains these effects, but is the antioxidant activity a reliable predictor for these effects? An International Life Sciences Institute Europe working group addressed this question and explored the potential of antioxidant clairris for polyphenols in relation to cardiovascular health by using the so-called Process for the Assessment of Scientific Supp4 for Claims on Foods project criteria. In this process, analytical aspects of polyphenols, their occurrence in foods, dietary intale, and bioavailability were reviewed. Human studies on polyphenols and cardiovascular health were reviewed together with methods for biomarkers of oxidative damage and total antioxidant capacity ITAC). In retrospective studies, F2-isoprostanes and oxidized LDL, the most reliable biomarkers of lipid peroxidation, and measures for TAC showed the expected differences between cardiovascular disease patients and healthy controls, but prospective studies are lacking, and a causal relationship between these biomarkers and cardiovascular health could not be established. Therefore, the physiological relevance of a potential change in these biomarkers is unclear. We found limited evidence that some types of polyphenol-rich products modify these biomarkers in humans. A direct antioxidant effect of polyphenols in vivo is questionable, however, because concentrations in blood are low compared with other antioxidants and extensive metabolism following ingestion lowers their antioxidant activity. Therefore, the biological relevance of direct antioxidant effects of polyphenbls for cardiovascular health could not be established. Overall, although some polyphenol-rich foods exert beneficial effects on some biomarkers of cardiovascular health, there is no evidence that this is caused by improvements in antioxidant functior biomarkers loxidative damage or antioxidant capacity). [ABSTRACT FROM AUTHOR]

The heat shock response is a highly conserved process essential for surviving environmental stress, including extremes of temperature. To investigate whether heat shock has an impact on intracellular Zn2+ homeostasis, cells were subjected to heat shock, and subsequently the intracellular free zinc concentration was investigated. Sublethal heat shock induced a temperature-dependent and transient intracellular Zn2+ release that was repeatable after 24 h. The free zinc was localized in round-shaped nuclear bodies identified as nucleoli. Metallothionein, the main cellular zinc storing protein, was found to be not functionally essential for this heat-shock-induced effect. No significant oxidative stress within the cells was detected after heat shock. Cold shock and subsequent rewarming did not result in disturbed intracellular zinc homeostasis. These results show that heat shock and cold shock differ with respect to intracellular Zn2+ release. A role for zinc as signaling ion during fever is conceivable. J. Cell. Physiol. 223: 103–109, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The extended abstracts in this report are based on presentations from the 12th Special Conference on Functional Foods for Health Promotion, cosponsored by the North American branch of the International Life Sciences Institute (ILSI North America) Project Committee on Flavonoids and the American Society for Nutrition at the Experimental Biology meeting in April 2009. The theme of this year's special conference was “State-of-the-Science on Dietary Flavonoids.” The conference began with a general introduction and overview of flavonoids and their presence in the diet as well as the estimated intake levels in the US population. Subsequent presentations addressed issues pertaining to study design and interpretation, mechanisms of action, and the potential health impacts related to inflammation, the vasculature, and the brain. The present summary of the current science indicates that dietary flavonoids, particularly flavanols, show promising potential for reducing cardiovascular disease risk via reduction of inflammation and improvement in vascular function. However, the existing data must be interpreted cautiously, with consideration given to the compound tested (i.e., parent or metabolite), the use of controls, and the practicality of the concentrations used. While more data are needed on the long-term health impacts of dietary flavonoids in humans, including the efficacious dose, current data indicate it may soon be possible to develop public health messages about flavonoid-rich foods. [ABSTRACT FROM AUTHOR]

A higher daily intake of fruits and vegetables in healthy elderly is associated with an improved antioxidant status in comparison to subjects consuming diets poor in fruits and vegetables, but the impact on cognitive performance is unclear. Healthy community dwellers (45 to 102 years old, n=193) underwent cognitive testing and blood withdrawal for the measurement of antioxidant micronutrients and biomarkers of oxidative stress as well as administration of a food frequency questionnaire to assess the daily intake of fruits and vegetables (high intake HI, low intake LI). Ninety-four subjects of the HI group had significantly higher cognitive test scores, higher levels of carotenoids, α- and γ-tocopherol as well as lower levels of F_{2α} isoprostanes than the 99 subjects of the LI group. Cognitive scores were directly correlated with blood levels of α-tocopherol and lycopene and negatively correlated with F_{2α} isoprostanes and protein carbonyls. The results were independent of age, gender, body mass index, education, total cholesterol, LDL- and HDL-cholesterol, triglycerides, and albumin. Healthy subjects of any age with a high daily intake of fruits and vegetables have higher antioxidant levels, lower levels of biomarkers of oxidative stress, and better cognitive performance than healthy subjects of any age consuming low amounts of fruits and vegetables. Modification of nutritional habits aimed at increasing intake of fruits and vegetables should be encouraged to lower prevalence of cognitive impairment in later life. [ABSTRACT FROM AUTHOR]

Carotenoids are used for systemic photoprotection in humans. Regarding mechanisms underlying photoprotective effects of carotenoids, here we compared the modulation of UVA-related injury by carotenoids. Human dermal fibroblasts (HDF) were exposed to moderate doses of UVA, which stimulated apoptosis, increased levels of reactive oxygen species and thiobarbituric acid reactive substances, decreased antioxidant enzymes activities, promoted membrane perturbation, and induced the expression of heme oxygenase-1 (HO-1). The carotenoids astaxanthin (AX), canthaxanthin (CX) and β-carotene (βC) were delivered to HDF 24 h before exposure to UVA. Astaxanthin exhibited a pronounced photoprotective effect and counteracted all of the above-mentioned UVA-induced alterations to a significant extent. β-Carotene only partially prevented the UVA-induced decline of catalase and superoxide dismutase activities, but it increased membrane damage and stimulated HO-1 expression. Moreover, βC dose-dependently induced caspase-3 activity following UVA exposure. In contrast, CX had no effect on oxidative damage, except for HO-1 expression, which was augmented. Uptake of AX by fibroblasts was higher than that of the other two carotenoids. The photostability of the three compounds in fibroblasts was AX > CX >> βC. The data indicate that the oxo-carotenoid AX has a superior preventive effect towards photo-oxidative changes in cell culture. [ABSTRACT FROM AUTHOR]

Ingestion of selected nutrients modulates dermal properties. In the present study, two groups of women ingested flaxseed or borage oil for 12 weeks. The control group received a placebo containing medium-chain fatty acids. Dose was 2·2 g total fatty acids/d with α-linolenic acid and linoleic acid as major constituents in the flaxseed oil group; in the borage oil group linoleic and γ-linolenic acid were predominant. In the flaxseed oil group, the contribution of α-linolenic acid to total fatty acids in plasma was significantly increased on weeks 6 and 12, whereas there was an increase in γ-linolenic acid in the borage oil group (P < 0·05). Skin irritation was performed by nicotinate treatment, and changes in skin reddening and blood flow were monitored. Compared to week 0, skin reddening was diminished in both groups; blood flow was also lowered. Skin hydration was significantly increased after 12 weeks of treatment compared to week 0, with flaxseed or borage oil (P < 0·05). Transepidermal water loss was decreased in both oil groups by about 10 % after 6 weeks of supplementation. A further decrease was determined after 12 weeks in the flaxseed oil group. Surface evaluation of living skin revealed that roughness and scaling of the skin were significantly decreased with flaxseed and borage oil comparing week 0 and week 12 (P < 0·05). Except for hydration, none of the parameters was affected in the placebo group. The present data provide evidence that skin properties can be modulated by an intervention with dietary lipids. [ABSTRACT FROM PUBLISHER]

To explore the effects of increasing fruit and vegetable intake and the resulting effects on levels of circulating micronutrients in a community-dwelling population with an already high consumption of fruits and vegetables, 112 volunteers (86% women) underwent targeted dietary counseling for three months. At the beginning of the study and after 4, 8 and 12 weeks a food frequency questionnaire was filled in, and plasma levels of dietary antioxidants as well as biomarkers of oxidative lipid and protein damage were determined. Compared to baseline, especially the intake of fruits was significantly improved after 3 months of intervention, and mean plasma levels of lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene, retinol, alpha-tocopherol, vitamin C and vitamin B6 were increased. Biomarkers of oxidative stress remained unchanged. Thus, a nutritional counseling program is capable of improving plasma levels of antioxidants even in a health-conscious population. A decrease in biomarkers of oxidative stress, however, does not occur. [ABSTRACT FROM AUTHOR]

Aberrant gap junctional intercellular communication (GJIC) has been implicated in tumor development and progression. UltravioletA (UVA)-induced oxidative stress has been associated with skin carcinogenesis. We report a potential link between GJIC and the cellular stress response induced by UVA in normal human keratinocytes (NHK). In this study, UVA irradiation (10 J/cm2) compromised GJIC integrity in absence of cytotoxic effects as demonstrated by the absence of cell death and by the reversibility of GJIC down-regulation. Inhibition of communication by UVA was associated with hyperphosphorylation and decreased expression of connexin43 (Cx43), the most abundant gap junction protein expressed by keratinocytes. Cx43 hyperphosphorylation induced by UVA is, at least in part, mediated through mitogen-activated protein kinase (MAPK) activation as Ser279 and Ser282 sites, two downstream direct targets of p38 MAPK were found to be phosphorylated after UVA treatment. However, inhibition of p38 MAPK activity did not significantly protect from cell–cell communication inhibition because of a strong cellular cytotoxicity observed with SB202190 and SB203580, two selective inhibitors of p38 MAPK, in combination with UVA that compromises the outcome of dye transfer assay. By contrast, in Hacat cell line, inhibition of p38 activity reduced both phosphorylation and degradation of Cx43, demonstrating that these events are correlated. [ABSTRACT FROM AUTHOR]

Selenoprotein P (SeP) is a highly glycosylated plasma protein containing up to 10 selenocysteine residues. It is secreted by hepatocytes and also by the human hepatoma cell line HepG2. Pharmacological inhibitors interfering with N-glycosylation, intracellular trafficking and calcium homeostasis were applied to examine post-translational processing and secretion of SeP by HepG2 cells. In parallel, the prototypic secretory glycoprotein α1-antitrypsin was used as technical control. Secretion of SeP was stimulated by increasing the extracellular calcium concentration and by inhibiting the release of sequestered calcium through dantrolene or U-73122. In contrast, brefeldin A and thapsigargin suppressed SeP secretion. Tunicamycin and monensin induced the synthesis of truncated non-glycosylated and partially glycosylated forms of SeP, which were secreted in spite of their impaired glycosylation. Both non-glycosylated and partially glycosylated SeP is utilised as selenium donor by target cells: impaired glycosylation affected neither the ability of SeP to induce the synthesis of the selenoenzyme cytosolic glutathione peroxidase nor its capacity to protect endothelial cells from oxidative stress. [ABSTRACT FROM AUTHOR]

The concept of photoprotection by dietary means is gaining momentum. Plant constituents such as carotenoids and flavonoids are involved in protection against excess light in plants and contribute to the prevention of UV damage in humans. As micronutrients, they are ingested with the diet and are distributed into light-exposed tissues, such as skin or the eye where they provide systemic photoprotection. β-Carotene and lycopene prevent UV-induced erythema formation. Likewise, dietary flavanols exhibit photoprotection. After about 10–12 weeks of dietary intervention, a decrease in the sensitivity toward UV-induced erythema was observed in volunteers. Dietary micronutrients may contribute to life-long protection against harmful UV radiation. [ABSTRACT FROM AUTHOR]

The impact of nutrients on gene expression can be mediated by the availability of amino acids. The aim of this study is to examine the effect of limited availability of l-arginine on the DNA-binding activity of NF-κB, a dominant transcription factor in inflammation, and the consequence for the expression pattern of inducible nitric oxide synthase (iNOS) in murine keratinocytes. Low availability of l-arginine leads to activation and increased DNA-binding activity of NF-κB and induction of iNOS messenger RNA (mRNA) in the absence of cytokines, but not to translation into iNOS protein. Cytokine challenge at low l-arginine also enhances iNOS mRNA expression, but translation into iNOS protein is diminished, leading to lowered nitric oxide production. The decrease in iNOS protein expression is mediated by the phosphorylation of the translation initiation factor eIF2α subunit, a key regulator of cellular translation. In contrast, the mRNA expression of the NF-κB-dependent genes IL-1α and cationic amino acid transporter-2 (CAT-2) are not affected by the availability of l-arginine. These results demonstrate that the availability of l-arginine can play a role in the control of gene expression by augmenting the DNA-binding activity of NF-κB, which can affect the initiation and progression of dermal inflammation. [ABSTRACT FROM AUTHOR]

The article relates the author's experience in becoming a chemist. His first exposure to the delights of nature in his hometown in Seesen, Northern Germany made lasting impressions. His sense of appreciation of the treasures provided by nature was fostered by his parents and to a large extent by his first teacher in elementary school.

Lipid peroxidation plays an important role in the development of atherosclerosis, a chronic, age-related disease process of the arterial wall with onset decades prior to its clinical manifestations. The aim of the study was to assess the association between the intima media thickness (IMT) of the major arteries as a clinical marker of atherosclerosis and markers of lipid peroxidation along with the antioxidant status in humans.Case-control study.A university-affiliated outpatient clinic.Thirty patients (22 males, 8 females; 70.4 ± 7.3 years) with atherosclerosis of the carotid or iliofemoral arteries and 62 healthy controls (30 males, 32 females; 68.3 ± 4.3 years).Plasma levels of 8,12-isoprostane F2α-VI (8,12-IPF2α-VI) were measured by gas chromatography/mass spectrometry, whereas levels of malondialdehyde (MDA), vitamins A (retinol) and E (α- and γ-tocopherol), and carotenoids were determined by high-performance liquid chromatography. The IMT was measured by B-mode ultrasonography.Patients showed, independent of fruit and vegetable intake, significantly lower plasma levels of retinol, α-tocopherol, and all carotenoids excluding β-cryptoxanthin compared with controls. On the contrary, plasma 8,12-IPF2α-VI levels were almost doubled (p < .001) and MDA levels increased by one-third (p < .01) in atherosclerotic patients compared with controls.The analyses of isoprostanes and antioxidant nutrients in plasma as markers of oxidative stress and the parallel evaluation of IMT as a structural marker of atherosclerosis are suitable tools for investigating the role of antioxidants and oxidative stress in atherosclerosis. [ABSTRACT FROM AUTHOR]

Long term cocoa ingestion leads to an increased resistance against UV-induced erythema and a lowered transepidermal water loss. To investigate the acute effects of a single dose of cocoa rich in flavanols on dermal microcirculation. In a crossover design study, 10 healthy women ingested a cocoa drink (100 ml) with high (329 mg) or low (27 mg) content of flavanols. The major flavanol monomer in both drinks was epicatechin, 61 mg in the high flavanol, and 6.6 mg in the low flavanol product per 100 ml. Dermal blood flow and oxygen saturation of hemoglobin were examined by laser Doppler flowmetry and spectroscopically at 1 mm skin depth at t = 0, 1, 2, 4, and 6 h. At the same time points, plasma levels of total epicatechin (free compound plus conjugates) were measured by means of HPLC. Subsequent to the intake of high flavanol cocoa, dermal blood flow was significantly increased by 1.7-fold at t = 2 h and oxygen saturation was elevated 1.8-fold. No statistically significant changes were found upon intake of low flavanol cocoa. Maximum plasma levels of total epicatechin were observed 1 h after ingestion of the high flavanol cocoa drink, 11.6 ± 7.4 nmol/l at baseline, and 62.9 ± 35.8 nmol/l at 1 h. No change of total epicatechin was found in the low flavanol group. Flavanol-rich cocoa consumption acutely increases dermal blood flow and oxygen saturation. [ABSTRACT FROM AUTHOR]

The Rho-like GTPase Rac regulates distinct actin cytoskeleton changes required for adhesion, migration and invasion of cells. Tiam1 specifically activates Rac, and Rac has been shown to affect several signaling pathways in a partly cell-type-specific manner. Recently, we demonstrated that Rac activation inhibits Matrigel invasion of human carcinoma cells by transcriptional upregulation of tissue inhibitor of metalloproteinase-1. The purpose of the present study was to identify key mediators of Tiam1/Rac-induced tissue inhibitor of metalloproteinase-1 expression. Mutational analysis of the human tissue inhibitor of metalloproteinase-1 promoter revealed a major role for a distinct activating protein-1 site at −92/−86 and a minor role for an adjacent polyoma enhancer A3 site. Moreover, Rac activation induced the generation of reactive oxygen species and subsequent reactive oxygen species-dependent activation of extracellular signal-regulated kinase 1,2. In contrast, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activities were not affected. In line with this, Tiam1/Rac-induced tissue inhibitor of metalloproteinase-1 expression as well as Tiam1/Rac-induced binding of nuclear extracts to the activating protein-1 site at −92/−86 were inhibited by catalase and by specific inhibitors of the extracellular signal-related kinase-1,2 activators, mitogen-activated protein kinase kinase-1 and mitogen-activated protein kinase kinase-2 (PD098059, U0126). In conclusion, Rac-induced transcriptional upregulation of tissue inhibitor of metalloproteinase-1 is mediated by reactive oxygen species-dependent activation of extracellular signal-related kinase-1,2 and by transcription factors of the activating protein-1 family. [ABSTRACT FROM AUTHOR]

Recent data suggest an inverse epidemiological association between intake of flavanol-rich cocoa products and cardiac mortality. Potential beneficial effect of cocoa may be attributed to flavanol-mediated improvement of endothelial function, as well as to enhancement of bioavailability and bioactivity of nitric oxide in vivo. ( - )-Epicatechin is one bioactive flavanol found in cocoa. This review deals with protective actions of ( - )-epicatechin on two key processes in atherogenesis, oxidation of LDL and damage to endothelial cell by oxidized LDL (oxLDL), with emphasis on data from this laboratory. ( - )-Epicatechin not only abrogates or attenuates LDL oxidation but also counteracts deleterious actions of oxLDL on vascular endothelial cells. These protective actions are only partially shared by other vasoprotective agents such as vitamins C and E or aspirin. Thus, ( - )-epicatechin appears to be a pleiotropic protectant for both LDL and endothelial cells. [ABSTRACT FROM AUTHOR]

Singlet oxygen (1O2), an electronically excited form of molecular oxygen, is a mediator of biological effects of ultraviolet A radiation, stimulating signaling cascades in human cells. We demonstrate here that 1O2 generated by photosensitization or by thermodecomposition of 3,3′-(1,4-naphthylidene)dipropionate-1,4-endoperoxide inactivates isolated protein tyrosine phosphatases (PTPases). PTPase activities of PTP1B or CD45 were abolished by low concentrations of 1O2, but were largely restored by post-treatment with dithiothreitol. Electrospray ionization mass spectrometry analysis of tryptic digests of PTP1B exposed to 1O2 revealed oxidation of active-site Cys215 as the only cysteine residue oxidized. In summary, 1O2 may activate signaling cascades by interfering with phosphotyrosine dephosphorylation. [ABSTRACT FROM AUTHOR]

A major fraction of the essential trace element selenium circulating in human blood plasma is present as selenoprotein P (SeP). As SeP associates with endothelial membranes, the participation of SeP in selenium-mediated protection against oxidative damage was investigated, using the human endothelial cell line Ea.hy926 as a model system. Hepatocyte-derived SeP prevented tert-butylhydroperoxide (t-BHP)-induced oxidative cell death of Ea.hy926 cells in a similar manner as did sodium selenite, counteracting a t-BHP-induced loss of cellular membrane integrity. Protection was detected after at least 10 h of SeP supplementation and it peaked at 24 h. SeP time-dependently stimulated the expression of cytosolic glutathione peroxidase (cGPx) and increased the enzymatic activities of glutathione peroxidase (GPx) and thioredoxin reductase (TR). The cGPx inhibitor mercaptosuccinate as well as the γ-glutamylcysteine synthetase inhibitor buthionine sulfoximine counteracted the SeP-mediated protection, while the TR inhibitors cisplatin and auranofin had no effect. The presented data suggest that selenium supplementation by SeP prevents oxidative damage of human endothelial cells by restoring expression and enzymatic activity of GPx. [ABSTRACT FROM AUTHOR]

Dietary antioxidants contribute to endogenous photoprotection and are important for the maintenance of skin health. In the present study, 2 groups of women consumed either a high flavanol (326 mg/d) or low flavanol (27 mg/d) cocoa powder dissolved in 100 mL water for 12 wk. Epicatechin (61 mg/d) and catechin (20 mg/d) were the major flavanol monomers in the high flavanol drink, whereas the low flavanol drink contained 6.6 mg epicatechin and 1.6 mg catechin as the daily dose. Photoprotection and indicators of skin condition were assayed before and during the intervention. Following exposure of selected skin areas to 1.25 x minimal erythemal dose (MED) of radiation from a solar simulator, UV-induced erythema was significantly decreased in the high flavanol group, by 15 and 25%, after 6 and 12 wk of treatment, respectively, whereas no change occurred in the low flavanol group. The ingestion of high flavanol cocoa led to increases in blood flow of cutaneous and subcutaneous tissues, and to increases in skin density and skin hydration. Skin thickness was elevated from 1.11 +/- 0.11 mm at wk 0 to 1.24 +/- 0.13 mm at wk 12; transepidermal water loss was diminished from 8.7 +/- 3.7 to 6.3 +/- 2.2 g/(h x m2) within the same time frame. Neither of these variables was affected in the low flavanol cocoa group. Evaluation of the skin surface showed a significant decrease of skin roughness and scaling in the high flavanol cocoa group compared with those at wk 12. Dietary flavanols from cocoa contribute to endogenous photoprotection, improve dermal blood circulation, and affect cosmetically relevant skin surface and hydration variables. [ABSTRACT FROM AUTHOR]

There are enzymatic and non-enzymatic mechanisms that generate NO• from nitrite in blood, stomach, saliva, urine and skin. In blood vessels, nitrite-derived NO• can provide protection via compensatory vasodilation during hypoxia, and in various body fluids it may have antibacterial activity. In the skin, nitrite-derived NO• may contribute to skin tanning, as well as to protection against UV-induced cell damage. Current knowledge on nitrite acting like an NO• ‘prodrug’ is presented, emphasizing the role of nitrite in skin. [ABSTRACT FROM AUTHOR]

Abstract: Activation of ErbB receptor tyrosine kinases triggers multiple signaling pathways that regulate cellular proliferation and survival. We here demonstrate that ErbB2 is activated via the epidermal growth factor receptor (EGFR) upon exposure of cultured human keratinocytes to 2-methyl-1,4-naphthoquinone (menadione). Both ErbB2 and EGFR are shown to be regulated by protein tyrosine phosphatases that are inhibited by menadione, giving rise to the hypothesis that phosphatase inhibition by menadione may result in a net activation of EGFR and an enhanced ErbB2 phosphorylation. Isolated PTP-1B, a protein tyrosine phosphatase known to be associated with ErbB receptors, is demonstrated to be inhibited by menadione. [Copyright &y& Elsevier]

Epidemiological and medical anthropological investigations suggest that flavanol-rich foods exert cardiovascular health benefits. Endothelial dysfunction, a prognostically relevant key event in atherosclerosis, is characterized by a decreased bioactivity of nitric oxide (NO) and impaired flow-mediated vasodilation (FMD). We show in healthy male adults that the ingestion of flavanol-rich cocoa was associated with acute elevations in levels of circulating NO species, an enhanced FMD response of conduit arteries, and an augmented microcirculation. In addition, the concentrations and the chemical profiles of circulating flavanol metabolites were determined, and multivariate regression analyses identified (-)-epicatechin and its metabolite, epicatechin-7-O-glucuronide, as independent predictors of the vascular effects after flavanol-rich cocoa ingestion. A mixture of flavanols/metabolites, resembling the profile and concentration of circulating flavanol compounds in plasma after cocoa ingestion, induced a relaxation in preconstricted rabbit aortic rings ex vivo, thus mimicking acetylcholine-induced relaxations. Ex vivo flavanol- induced relaxation, as well as the in vivo increases in FMD, were abolished by inhibition of NO synthase. Oral administration of chemically pure (-)-epicatechin to humans closely emulated acute vascular effects of flavanol-rich cocoa. Finally, the concept that a chronic intake of high-flavanol diets is associated with prolonged, augmented NO synthesis is supported by data that indicate a correlation between the chronic consumption of a cocoa flavanol-rich diet and the augmented urinary excretion of NO metabolites. Collectively, our data demonstrate that the human ingestion of the flavanol (-)-epicatechin is. at least in part, causally linked to the reported vascular effects observed after the consumption of flavanol-rich cocoa. [ABSTRACT FROM AUTHOR]