CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2007
Yu Yamaguchi
SUMMARY 1Oxidative stress has been recognized as an important factor in the biology of lifestyle-related diseases. Systemic oxidative stress may increase in metabolic syndrome characterized by a cluster of metabolic risk factors. To confirm this hypothesis, we investigated systemic oxidative/nitrative stress in a new congenic model of metabolic syndrome, namely SHRSP/ZF rats, which are derived from stroke-prone spontaneously hypertensive (SHRSP) and Zucker fatty (Zucker) rats. 2The SHRSP/ZF rats display obesity, hypertension, hyperlipidaemia, hyperglycaemia and glucose intolerance. At 6 weeks of age, SHRSP/ZF rats already showed increases in serum levels of thiobarbituric acid-reactive substances (TBARS) and oxidatively modified low-density lipoprotein (Ox-LDL) compared with lean SHRSP littermates and Zucker rats, whereas serum levels of 8-hydroxy-2,-deoxyguanine (8-OHdG), 3-nitrotyrosine, 3-chlorotyrosine and high-sensitivity C-reactive protein (hsCRP), an inflammatory marker, did not differ significantly among the three rat strains. However, levels of these oxidative/nirative stress markers in SHRSP/ZF rats, as well as in SHRSP, increased gradually with age. After 36 weeks of age, the levels of TBARS, 8-OHdG, 3-nitrotyrosine and hsCRP in SHRSP/ZF rats increased rapidly and three of six rats died thereafter. Increased oxidative/nitrative stress may be associated with death in these rats. 3Our findings indicate that systemic oxidative/nitrative stress is evidently increased in metabolic syndrome. [source]

Oxidative and excitotoxic insults exert differential effects on spinal motoneurons and astrocytic glutamate transporters: Implications for the role of astrogliosis in amyotrophic lateral sclerosis

GLIA, Issue 2 2009
Chrissandra J. Zagami
Abstract In amyotrophic lateral sclerosis (ALS) non-neuronal cells play key roles in disease etiology and loss of motoneurons via noncell-autonomous mechanisms. Reactive astrogliosis and dysfunctional transporters for L -glutamate [excitatory amino acid transporters, (EAATs)] are hallmarks of ALS pathology. Here, we describe mechanistic insights into ALS pathology involving EAAT-associated homeostasis in response to a destructive milieu, in which oxidative stress and excitotoxicity induce respectively astrogliosis and motoneuron injury. Using an in vitro neuronal-glial culture of embryonic mouse spinal cord, we demonstrate that EAAT activity was maintained initially, despite a loss of cellular viability induced by exposure to oxidative [3-morpholinosydnonimine chloride (SIN-1)] and excitotoxic [(S)-5-fluorowillardiine (FW)] conditions. This homeostatic response of EAAT function involved no change in the cell surface expression of EAAT1/2 at 0.5,4 h, but rather alterations in kinetic properties. Over this time-frame, EAAT1/2 both became more widespread across astrocytic arbors in concert with increased expression of glial fibrillary acidic protein (GFAP), although at 8,24 h there was gliotoxicity, especially with SIN-1 rather than FW. An opposite picture was found for motoneurons where FW, not SIN-1, produced early and extensive neuritic shrinkage and blebbing (,0.5 h) with somata loss from 2 h. We postulate that EAATs play an early homeostatic and protective role in the pathologic milieu. Moreover, the differential profiles of injury produced by oxidative and excitotoxic insults identify two distinct phases of injury which parallel important aspects of the pathology of ALS. © 2008 Wiley-Liss, Inc. [source]

Role of topical and nutritional supplement to modify the oxidative stress,

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 6 2002
P. Morganti
Synopsis Background: Evidence suggests that signs of skin ageing such as wrinkling, ragging and actinic lentigines, may be connected to cumulative oxidative damage incurred throughout our lifetimes. To counteract this oxidative injury, skin is equipped with a network on enzymatic and non-enzymatic antioxidant systems, such as tocopherols, ascorbate polyphenols. All these compounds administered topically by cosmetics or by oral route by diet supplements, have been shown to exert an antioxidant/protective effect in skin or skin cells. Objective: The object of this study was to evaluate both in vitro and in vivo the activity performed by different topical antioxidants and nutritional supplements. Methods: A randomized double-blind placebo-controlled study was carried out for 8 weeks on 30 dry-skinned elderly volunteers, women aged between 48 and 59 years, with moderate xerosis and photoageing. Surface skin lipids, skin hydration and MDA determination were topically detected by 3C System. ROS was evaluated on the blood serum and on IL-3 stimulated human leukocytes by ROS Meter System at 505 nm. All the subjects applied twice a day for 2 months a nanocolloidal gel and/or take a diet supplement by oral route at the quantity of two capsules per day. All the formulations used were antioxidant-enriched (ascorbic acid, tocopherol, alpha-lipoic acid, melatonin, emblica). Results: Oxidative stress and consequently lipids peroxidation decreased from 30 to 40% (P < 0.005) in blood serum of all the subjects treated with antioxidant compounds topically and by oral route. Both free radicals recovered in blood serum and on skin (in vivo) and ROS induced by irradiation of leucocytes with UVB light (in vitro), appear sensibly lower in subjects antioxidant-treated. Conclusions: From the obtained data, it seems possible to conclude that all the compounds used play interesting role as topical and systemic photoprotectants, thanks to their interesting antioxidant property. Moreover, the antioxidant treatment seems to be a promising therapeutic approach also in reducing the oxidative stress of people affected by photoaging. Résumé Les faits semblent montrer que les signes du vieillissement cutané tels que les rides, la perte d'élasticité ou les taches de vieillesse, peuvent être liés aux effets oxydants cumulés subis tout au long de la vie. Pour contrer ces effets oxydants, la peau est équipée d'un réseau de systèmes antioxydants enzymatiques et non enzymatiques tels que les tocophérols, l'ascorbate et les polyphénols. Tous ces composés, administrés par voie topique par des cosmétiques ou par voie orale avec des suppléments alimentaires, se sont révélés exercer un effet antioxydant/protecteur sur la peau ou les cellules de la peau. L'objet de cette étude était d'évaluer aussi bien in-vitro qu'in-vivo l'activité de différents antioxydants topiques et suppléments alimentaires. Une étude randomisée contre placebo en double aveugle a été conduite sur 8 semaines avec 30 volontaires,gés à peau sèche, des femmes de 48 à 59 ans, présentant une xérose et un viellissement modéré. Les lipides à la surface de la peau, l'hydratation de la peau et la MDA ont été suivis de façon topique par le SYSTEM 3 C. Les ROS (Reactive Oxygen Species) ont été déterminés dans le sérum sanguin et sur les leucocytes humains 12-3 stimulés par un SYSTEM ROS-METER à 505 nm. Tous les sujets ont appliqué deux fois par jour pendant deux mois un gel nanocolloïdal et/ou pris des suppléments alimentaires par voie orale à raison de deux gélules par jour. Toutes les formulations utilisées étaient enrichies en antioxydant (acide ascorbique, tocophérol, acide alpha-lipoïque, mélatonine, emblica). Le stress oxydant et par conséquent la péroxydation des lipides diminue de 30 à 40% (p < 0.005) dans le sérum sanguin de tous les sujets traités avec des composés antioxydants par voie topique ou orale. Les radicaux libres retrouvés aussi bien dans le sérum sanguin que dans la peau (in-vivo) et la ROS induite par l'irradiation des leucocytes avec la lumière ultraviolette (in-vitro) apparaissent significativement moins élevés chez les sujets traités aux antioxydants par voie topique ou orale. D'après les données obtenues il semble possible de conclure que tous les composés utilisés jouent un rôle intéressant comme photoprotecteurs topiques et systémiques grâce à leurs intéressantes propriétés antioxydantes. De plus, le traitement antioxydant semble être une approche thérapeutique prometteuse en ce qu'elle réduit aussi le stress oxydant des personnes touchées par le vieillissement. [source]

Assessment of the Oxidative and Hydrolytic Degradation of Oils Used as Liquid Medium of In-oil Preserved Vegetables

JOURNAL OF FOOD SCIENCE, Issue 1 2003
F. Caponio
ABSTRACT: An experimental investigation was carried out on several in-oil preserved vegetables to evaluate the quality and genuineness of different oils used as liquid medium. The results obtained showed that the lipids released by vegetables to the oils are negligible, and that the routine analyses are not fully effective to assess the quality of the oils. More reliable results may be achieved from the percent determination of trans isomers, and from the classes of oxidation, polymerization, and hydrolysis substances contained in the polar compounds. In sunflower seed oils, much higher contents of trans isomers (p < 0.001), triglyceride oligopolymers, and oxidized triglycerides (p < 0.01) have been observed as compared to olive and extra virgin olive oils. [source]

Inhibition of Oxidative and Antioxidative Enzymes by Trans-Resveratrol

JOURNAL OF FOOD SCIENCE, Issue 2 2001
X. Fan
ABSTRACT: Trans-resveratrol, a phytoalexin produced by a variety of plants, has been shown to inhibit oxidative enzymes in an animal cell system. Its effect on several oxidative and antioxidative enzymes from plants was investigated using in vitro assays. Trans-resveratrol inhibited superoxide dismutase, lipoxygenase, catalase, peroxidase, polyphenol oxidase, and 1-aminocyclopropane-1-carboxylic acid oxidase with apparent KI's of 10, 90, 100, 255, 305, and 350 ,M, respectively. Trans-resveratrol inhibited lipoxygenase activity more effectively than other lipoxygenase inhibitors, including propyl gallate, ibuprofen, ursolic acid, acetylsalicylic acid, and salicylhydroxamic acid. [source]

Can coenzyme Q10 improve vascular function and blood pressure?

BIOFACTORS, Issue 1-4 2003
Potential for effective therapeutic reduction in vascular oxidative stress
Abstract Coenzyme Q10 (CoQ) is an endogenously synthesised compound that acts as an electron carrier in the mitochondrial electron transport chain. The presence of adequate tissue concentrations of CoQ may be important in limiting oxidative and nitrosative damage in vivo. Oxidative and nitrosative stress are likely to be elevated in conditions such as diabetes and hypertension. In these conditions elevated oxidative and nitrosative stress within the arterial wall may contribute to increased blood pressure and vascular dysfunction. The major focus of this review is the potential of CoQ to improve vascular function and lower blood pressure. Although there is substantial indirect support for the putative mechanism of effect of CoQ on the vascular system, to date there is little direct support for an effect of CoQ on in vivo markers of oxidative or nitrosative stress. The limited data available from studies in animal models and from human intervention studies are generally consistent with a benefit of CoQ on vascular function and blood pressure. The observed effects of CoQ on these endpoints are potentially important therapeutically. However, before any firm clinical recommendations can be made about CoQ supplementation, further intervention studies in humans are needed to investigate the effects of CoQ on vascular function, blood pressure and cardiovascular outcomes. The particularly relevant groups of patients for these studies are those with insulin resistance, type 2 diabetes, hypertension and the metabolic syndrome. [source]

ChemInform Abstract: Palladium-Catalyzed Oxidative sp2 C,H Bond Acylation with Aldehydes.

CHEMINFORM, Issue 38 2010
Olivier Basle
Abstract An efficient method to prepare aromatic, aliphatic, and optically active ketones is reported. [source]

ChemInform Abstract: Tandem Oxidative ,-Tosyloxylation of Alcohols/Nucleophilic Addition of Azide/Copper-Catalyzed 1,3-Dipolar Cycloaddition.

CHEMINFORM, Issue 18 2010
P. Surendra Reddy
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]

Oxidative and Reductive Carbodiazenylation Nonactivated Olefins.

CHEMINFORM, Issue 21 2007
Markus R. Heinrich
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source]

Potassium-transporting proteins in skeletal muscle: cellular location and fibre-type differences

ACTA PHYSIOLOGICA, Issue 2 2010
M. Kristensen
Abstract Potassium (K+) displacement in skeletal muscle may be an important factor in the development of muscle fatigue during intense exercise. It has been shown in vitro that an increase in the extracellular K+ concentration ([K+]e) to values higher than approx. 10 mm significantly reduce force development in unfatigued skeletal muscle. Several in vivo studies have shown that [K+]e increases progressively with increasing work intensity, reaching values higher than 10 mm. This increase in [K+]e is expected to be even higher in the transverse (T)-tubules than the concentration reached in the interstitium. Besides the voltage-sensitive K+ (Kv) channels that generate the action potential (AP) it is suggested that the big-conductance Ca2+ -dependent K+ (KCa1.1) channel contributes significantly to the K+ release into the T-tubules. Also the ATP-dependent K+ (KATP) channel participates, but is suggested primarily to participate in K+ release to the interstitium. Because there is restricted diffusion of K+ to the interstitium, K+ released to the T-tubules during AP propagation will be removed primarily by reuptake mediated by transport proteins located in the T-tubule membrane. The most important protein that mediates K+ reuptake in the T-tubules is the Na+,K+ -ATPase ,2 dimers, but a significant contribution of the strong inward rectifier K+ (Kir2.1) channel is also suggested. The Na+, K+, 2Cl, 1 (NKCC1) cotransporter also participates in K+ reuptake but probably mainly from the interstitium. The relative content of the different K+ -transporting proteins differs in oxidative and glycolytic muscles, and might explain the different [K+]e tolerance observed. [source]

Low-volume muscle endurance training prevents decrease in muscle oxidative and endurance function during 21-day forearm immobilization

ACTA PHYSIOLOGICA, Issue 4 2009
T. Homma
Abstract Aim:, To examine the effects of low-volume muscle endurance training on muscle oxidative capacity, endurance and strength of the forearm muscle during 21-day forearm immobilization (IMM-21d). Methods:, The non-dominant arm (n = 15) was immobilized for 21 days with a cast and assigned to an immobilization-only group (Imm-group; n = 7) or an immobilization with training group (Imm+Tr-group; n = 8). Training comprised dynamic handgrip exercise at 30% of pre-intervention maximal voluntary contraction (MVC) at 1 Hz until exhaustion, twice a week during the immobilization period. The duration of each exercise session was 51.7 ± 3.4 s (mean ± SE). Muscle oxidative capacity was evaluated by the time constant for phosphocreatine recovery (,offPCr) after a submaximal handgrip exercise using 31phosphorus-magnetic resonance spectroscopy. An endurance test was performed at 30% of pre-intervention MVC, at 1 Hz, until exhaustion. Results:,,offPCr was significantly prolonged in the Imm-group after 21 days (42.0 ± 2.8 and 64.2 ± 5.1 s, pre- and post-intervention respectively; P < 0.01) but did not change for the Imm+Tr-group (50.3 ± 3.0 and 48.8 ± 5.0 s, ns). Endurance decreased significantly for the Imm-group (55.1 ± 5.1 and 44.7 ± 4.6 s, P < 0.05) but did not change for the Imm+Tr-group (47.9 ± 3.0 and 51.7 ± 4.0 s, ns). MVC decreased similarly in both groups (P < 0.01). Conclusions:, Twice-weekly muscle endurance training sessions, each lasting approx. 50 s, effectively prevented a decrease in muscle oxidative capacity and endurance; however, there was no effect on MVC decline with IMM-21d. [source]

Depression gets old fast: do stress and depression accelerate cell aging?,

DEPRESSION AND ANXIETY, Issue 4 2010
Owen M. Wolkowitz M.D.
Abstract Depression has been likened to a state of "accelerated aging," and depressed individuals have a higher incidence of various diseases of aging, such as cardiovascular and cerebrovascular diseases, metabolic syndrome, and dementia. Chronic exposure to certain interlinked biochemical pathways that mediate stress-related depression may contribute to "accelerated aging," cell damage, and certain comorbid medical illnesses. Biochemical mediators explored in this theoretical review include the hypothalamic,pituitary,adrenal axis (e.g., hyper- or hypoactivation of glucocorticoid receptors), neurosteroids, such as dehydroepiandrosterone and allopregnanolone, brain-derived neurotrophic factor, excitotoxicity, oxidative and inflammatory stress, and disturbances of the telomere/telomerase maintenance system. A better appreciation of the role of these mediators in depressive illness could lead to refined models of depression, to a re-conceptualization of depression as a whole body disease rather than just a "mental illness," and to the rational development of new classes of medications to treat depression and its related medical comorbidities. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc. [source]

Acetyl-CoA carboxylases 1 and 2 show distinct expression patterns in rats and humans and alterations in obesity and diabetes

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2009
Sebastian Kreuz
Abstract Background Acetyl-CoA carboxylases (ACC) 1 and 2 are central enzymes in lipid metabolism. To further investigate their relevance for the development of obesity and type 2 diabetes, expression of both ACC isoforms was analyzed in obese fa/fa Zucker fatty and Zucker diabetic fatty rats at different ages in comparison to Zucker lean controls. Methods ACC1 and ACC2 transcript levels were measured by quantitative real-time polymerase chain reaction in metabolically relevant tissues of Zucker fatty, Zucker diabetic fatty and Zucker lean control animals. Quantitative real-time polymerase chain reaction was also applied to measure ACC tissue distribution in human tissues. For confirmation on a protein level, quantitative mass spectrometry was used. Results Disease-related transcriptional changes of both ACC isoforms were observed in various tissues of Zucker fatty and Zucker diabetic fatty rats including liver, pancreas and muscle. Changes were most prominent in oxidative tissues of diabetic rats, where ACC2 was significantly increased and ACC1 was reduced compared with Zucker lean control animals. A comparison of the overall tissue distribution of both ACC isoforms in humans and rats surprisingly revealed strong differences. While in rats ACC1 was mainly expressed in lipogenic and ACC2 in oxidative tissues, ACC2 was predominant in oxidative and lipogenic tissues in humans. Conclusion Our data support a potential role for both ACC isoforms in the development of obesity and diabetes in rats. However, the finding of fundamental species differences in ACC1 and ACC2 tissue expression might be indicative for different functions of both isoforms in humans and rats and raises the question to which degree these models are predictive for the physiology and pathophysiology of lipid metabolism in humans. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Detection of chlorinated quinones using interdigitated electrodes coupled with capillary electrophoresis

ELECTROPHORESIS, Issue 6 2003
Keith B. Male
Abstract An array of eight interdigitated microband gold electrodes (IDEs) has been developed together with electrophoretic separation for analysis of chlorinated hydroquinones (ClHQs) and benzoquinones (ClBQs). The IDE chip positioned very close to the separation capillary outlet served as an amplification/detection system without the requirement for frequent "capillary-electrode" alignment. ClHQs, electrophoretically migrating to the IDE surface, were oxidized at +1.1 V by seven electrodes of the array and then detected by the remaining electrode, poised at ,0.1 V. Conversely, ClBQs were detected at +1.1 V by the detecting electrode after having been reduced at the 7 adjacent electrodes poised at ,0.1 V. There was an amplification effect on both the detecting electrode as well as the adjacent electrodes because of the recycle between ClHQs and ClBQs. The detecting "amplification" current response was dependent on the potentials applied, the position of the detecting electrode on the array, the number of adjacent electrodes being used for recycling and the distance between the oxidative and reductive electrodes. Micellar electrokinetic chromatography (MEKC) separation of the analytes was achieved using 30 mM sodium dodecyl sulfate (SDS) with a detection limit in the range of 2,20 ,M. In addition to a facile "capillary-electrode" alignment, the important aspect described here was the capability of detecting through recycling a reduced compound (in the case of ClHQs) at a negative potential to circumvent fouling and electroactive interferences. An appealing feature was also the concurrent oxidation/reduction detection for each compound to ascertain peak assignment, as interfering compounds are less likely to exhibit the same oxidative/reductive characteristics and electrophoretic mobilities as the target analytes. [source]

Influence of the SCGE protocol on the amount of basal DNA damage detected in the Mediterranean mussel, Mytilus galloprovincialis

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2006
Nicola Machella
Abstract Genotoxicity studies using the single cell gel electrophoresis (SCGE) assay indicate that basal levels of DNA strand breaks (SBs) in marine invertebrates are higher and more variable than those in marine vertebrates. This elevated level of DNA damage was attributed to a large number of alkali-labile sites, which are characteristic of the tightly-packaged DNA in invertebrate cells. To investigate if altering the SCGE protocol can artificially modulate high levels of SBs, SCGE experiments were performed on haemocytes from the Mediterranean mussel (Mytilus galloprovincialis) using proteinase K (PK) digestion in combination with assay buffers containing various concentrations of EDTA. In addition, the effects of Trolox® (soluble antioxidant) and aurintricarboxylic acid (ATA; inhibitor of Ca2+/Mg2+ -dependent nucleases) also were tested. The levels of SBs in M. galloprovicialis cells were compared with SBs in cells from a terrestrial mollusk (the snail Helix aspersa), and a teleost fish (the seabass Dicentrarchus labrax). The integrity of M. galloprovincialis DNA isolated with phenol extractions using EDTA, Trolox, and ATA was further assayed by gel electrophoresis. High SBs in mussel cells were reduced by combining EDTA with PK digestion, or using Trolox® or ATA during cell processing for the SCGE assay. Snails and seabass had lower levels of SBs in the SCGE assay, and the levels were not affected by the protocol modifications. Adding EDTA, Trolox®, or ATA to phenol extractions of M. galloprovincialis genomic DNA also reduced the extent of DNA fragmentation. These results suggest that the internal fluids of M. galloprovincialis may increase the basal levels of DNA SBs through oxidative and/or enzyme-mediated pathways. M. galloprovincialis is used extensively as a sentinel species for assessing the genotoxic hazard of marine pollutants. Our data suggest that the SCGE protocol should be carefully considered when assessing DNA damage in these species. Environ. Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc. [source]

Elemental sulfur: Toxicity in vivo and in vitro to bacterial luciferase, in vitro yeast alcohol dehydrogenase, and bovine liver catalase

ENVIRONMENTAL TOXICOLOGY, Issue 4 2004
Anolda, etkauskait
Abstract The aim of this research was to analyze the effects and the modes of action of elemental sulfur (S0) in bioluminescence and respiration of Vibrio fischeri cells and the enzymes crude luciferase, pure catalase, and alcohol dehydrogenase (ADH). Metallic copper removed sulfur and reduced the toxicity of acetone extracts of sediment samples analyzed in the bioluminescence test. The sulfur inhibition of cell bioluminescence was noncompetitive with decanal, the luciferase substrate; reversible, with maximum toxicity after 15 min (EC50 = 11.8 ,g/L); and almost totally recovered after 2 h. In vitro preincubation of crude luciferase extract with sulfur (0.28 ppm) weakly inhibited bioluminescence at 5 min, but at 30 min the inhibition reached 60%. Increasing the concentration of sulfur in the parts per million concentration range in vitro decreased bioluminescence, which was not constant, but depended on exposure time, and no dead-end/total inhibition was observed. The redox state of enzymes in the in vitro system significantly affected inhibition. Hydrogen peroxide restored fully and the reducing agent dithiothreitol, itself toxic, restored only partially luciferase activity in the presence of sulfur. Sulfur (5.5 ppm) slightly inhibited ADH and catalase, and dithiothreitol enhanced sulfur inhibition. High sulfur concentrations (2.2 ppm) inhibited the bioluminescence and enhanced the respiration rate of V. fischeri cells. Elemental sulfur data were interpreted to show that sulfur acted on at least a few V. fischeri cell sites: reversibly modifying luciferase at sites sensitive to/protected by oxidative and reducing agents and by affecting electron transport processes, resulting in enhanced oxygen consumption. Sulfur together with an enzyme reducing agent inhibited the oxidoreductive enzymes ADH and catalase, which have SH groups, metal ion cofactors, or heme, respectively, in their active centers. © 2004 Wiley Periodicals, Inc. Environ Toxicol 19: 372,386, 2004. [source]

Acute toxicity of (chloro-)catechols and (chloro-)catechol-copper combinations in Escherichia coli corresponds to their membrane toxicity in vitro

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2001
Nina Schweigert
Abstract (Chloro-)catechols are toxic for bacteria and higher organisms, but the mode of action is not yet clearly understood. We have compared the acute toxicity of different chlorinated catechols to Escherichia coli with membrane toxic effects, namely narcosis and uncoupling that we have determined in an in vitro assay. In vitro membrane toxicity was quantified by measuring the accelerated decay of the membrane potential of chromatophores isolated from Rhodobacter sphaeroides. Both acute and membrane toxicity increased with increasing degree of chlorination. Analysis of dose-response curves, pH dependence, and estimated membrane concentrations gave a consistent picture of the mechanisms of membrane toxicity: At pH 7, the higher-chlorinated catechols acted as uncouplers of oxidative and photophosphorylation, and the lower-chlorinated catechols and catechol acted as narcotics. In the case of 3,5-dichlorocatechol and 4-monochlorocatechol at pH 8.8, both mechanisms appeared to contribute to the overall toxicity. Copper exhibited a diverging effect on the toxicity of catechols and of (chloro-)catechols to E. coli. Whereas the presence of copper increased the toxicity of catechol and 4-monochlorocatechol, the toxicity of 3,5-dichlorocatechol, 3,4,5-trichlorocatechol, and tetrachlorocatechol decreased. Again, the results obtained with in vitro assays agreed with the acute toxicity observed in E. coli: The presence of copper accelerated decay of the membrane potential of catechol and 4-monochlorocatechol; however, the effect was reversed by copper in experiments with 3,5-dichlorocatechol, 3,4,5-trichlorocatechol, and tetrachlorocatechol. We have proposed a mechanistic model to explain the diverging effects of copper on the uncoupling activities of the different catechols. [source]

Structure-Dependent Electrochemical Behavior of Thienylplatinum(II) Complexes of N,N-Heterocycles

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 1 2004
Feng Zhao
Abstract trans -[Pt(MeCN)(PPh3)2(2-thienyl)]BF4 (1) serves as a convenient precursor to bifunctional mononuclear trans -[Pt(PPh3)2(,1 - N - N)(2-thienyl)]BF4 [N - N = pyrazine (2); 2-chloropyrazine, (3)] and dinuclear trans,trans -[Pt2(PPh3)4(,- N - N)(2-thienyl)2](BF4)2 [(N - N = 4,4, -bipyridine (4); 4,4, -vinylenedipyridine (5)] complexes. The nuclear selectivity is conveniently controlled by the choice of the heterocyclic ligands or spacers. Both structural types 3 and 5 were confirmed by single-crystal X-ray crystallographic analyses. Their solution identities were established by positive-ion Electrospray Mass Spectrometry (ESMS). The electroactivities of these complexes were studied by cyclic voltammetry (CV). Continuous CV scans of 4 and 5 revealed variations in the redox waves with the number of scans. While the initial oxidative scan exhibited only a broad, irreversible wave, further cycling showed the growth of two additional redox couples up to about the tenth cycle. The peak currents of these redox couples began to decay with prolonged potential cycling beyond the tenth cycle. These findings are consistent with the formation of electroactive oligomers/polymers, and this conclusion is supported by visible thin film formation on the electrodes. In contrast, the mononuclear complexes (2 and 3) do not show such behavior. The films formed were further studied by repetitive potential cycling and XPS. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source]

Lipid damage during frozen storage of Gadiform species captured in different seasons

EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 6 2007
Santiago P. Aubourg
Abstract Quality loss of two gadiform fish species (blue whiting, Micromesistius poutassou; hake, Merluccius merluccius) during frozen storage (,30 and ,10,°C; up to 12,months) was studied. For this, hydrolytic (formation of free fatty acids, FFA) and oxidative (conjugated dienes, peroxide and interaction compound formation) lipid damage were analysed. For both species, individual fishes captured in two different trials (May and November) were considered. Increasing (p,<0.05) lipid hydrolysis and oxidation (peroxide and interaction compound formation) were observed for all kinds of samples throughout the frozen storage. Interaction compound detection by fluorescence analysis showed the best correlation values with storage time. Some higher (p,<0.05) hydrolysis development could be observed in hake captured in May than in its counterpart from the November trial, while frozen blue whiting did not provide definite differences for FFA formation between both trials. Concerning peroxide formation, higher (p,<0.05) values were obtained for individual blue whiting and hake captured in November when compared to their corresponding May fish for both frozen storage conditions. Interaction compound formation was also found to be higher (p,<0.05) for November hake fish than for its counterpart captured in May, while blue whiting did not provide definite differences between trials. [source]

Correlation between physicochemical analysis and radical-scavenging activity of vegetable oil blends as affected by frying of French fries

EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 8 2006
Mohamed Fawzy Ramadan
Abstract The main goal of the present work was to compare and correlate the results of physicochemical parameters and antiradical performance of some oil blends during deep-frying, which will be an initial indicator for applying antiradical tests for monitoring deep-frying oils. Two oil blends were prepared. The first blend was a mixture (1,:,1, wt/wt) of sunflower seed oil and palm olein (SO/PO) and the second was a mixture (1,:,1, wt/wt) of cottonseed oil and palm olein (CO/PO). The oil blends were evaluated during intermittent frying of French fries on two consecutive days for 16,h, with oil replenishing after 8,h. Changes in the fatty acid profile and some physicochemical parameters (peroxide value, color index, viscosity, total polar compounds and UV absorbance at 232 and 270,nm) were used to evaluate the alterations during frying. A quick spectrophotometric method was developed to assess deep-frying oil quality. With the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, the neutralization of the stable radical DPPH by antioxidants present in the oil during frying was measured. Radical-scavenging activity (RSA) of both oil blends was recorded during frying, wherein the results showed that the SO/PO blend had the highest RSA. It was evident from the results that a proportional correlation and positive relationship existed between the levels of fatty acids and the physicochemical characteristics of the vegetable oil blends and their RSA. The initial results obtained allow us to suggest that antiradical measurements could be used to quantify the oxidative and hydrolytic deterioration of vegetable oils upon frying. [source]

Hydrogen Atom Transfer Experiments Provide Chemical Evidence for the Conformational Differences between C - and O -Disaccharides

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 27 2010
Elisa I. León
Abstract The glycopyran-6- O -yl radical promoted hydrogen atom transfer reaction (HAT) between the two pyranose units of ,- D -Manp -(1,4)-,- D -Glcp and ,- D -Manp -(1,4a)-4a-carba-,- D -Glcp disaccharides provides supporting chemical evidence for the conformational differences between O - and C -glycosyl compounds. In the O -disaccharide the 6-alkoxyl radical, generated under oxidative or reductive conditions, abstracts exclusively the hydrogen at C-5, via a completely regioselective 1,8-HAT reaction. This may be attributable to the conformational restriction of the glycosidic and aglyconic bonds due principally to steric and stereoelectronic effects. On the contrary, very little regioselectivity is observed in the homologous C -disaccharide and a mixture of compounds generated by 1,5-, 1,6-, and 1,8-HAT processes where the abstraction occurs at hydrogen atoms positioned at C-4a, C-1,, and C-5,, respectively, has been obtained. This study has been extended to simpler O - and C -glycosides, where the aglycon was a straight n -alkyl alcohol tether of five atoms; in general, all of the results obtained are shown to be consistent with a major conformational flexibility of the C -glycosidic bond. [source]

Functional properties of the protein disulfide oxidoreductase from the archaeon Pyrococcus furiosus

FEBS JOURNAL, Issue 16 2004
A member of a novel protein family related to protein disulfide-isomerase
Protein disulfide oxidoreductases are ubiquitous redox enzymes that catalyse dithiol,disulfide exchange reactions with a CXXC sequence motif at their active site. A disulfide oxidoreductase, a highly thermostable protein, was isolated from Pyrococcus furiosus (PfPDO), which is characterized by two redox sites (CXXC) and an unusual molecular mass. Its 3D structure at high resolution suggests that it may be related to the multidomain protein disulfide-isomerase (PDI), which is currently known only in eukaryotes. This work focuses on the functional characterization of PfPDO as well as its relation to the eukaryotic PDIs. Assays of oxidative, reductive, and isomerase activities of PfPDO were performed, which revealed that the archaeal protein not only has oxidative and reductive activity, but also isomerase activity. On the basis of structural data, two single mutants (C35S and C146S) and a double mutant (C35S/C146S) of PfPDO were constructed and analyzed to elucidate the specific roles of the two redox sites. The results indicate that the CPYC site in the C-terminal half of the protein is fundamental to reductive/oxidative activity, whereas isomerase activity requires both active sites. In comparison with PDI, the ATPase activity was tested for PfPDO, which was found to be cation-dependent with a basic pH optimum and an optimum temperature of 90 °C. These results and an investigation on genomic sequence databases indicate that PfPDO may be an ancestor of the eukaryotic PDI and belongs to a novel protein disulfide oxidoreductase family. [source]

Biomimetic Approach to Confer Redox Activity to Thin Chitosan Films

ADVANCED FUNCTIONAL MATERIALS, Issue 16 2010
Eunkyoung Kim
Abstract Electron transfer in biology occurs with individual or pairs of electrons, and is often mediated by catechol/o -quinone redox couples. Here, a biomimetic polysaccharide-catecholic film is fabricated in two steps. First, the stimuli-responsive polysaccharide chitosan is electrodeposited as a permeable film. Next, the chitosan-coated electrode is immersed in a solution containing catechol and the electrode is biased to anodically-oxidize the catechol. The oxidation products covalently graft to the chitosan films as evidenced by electrochemical quartz crystal microbalance (EQCM) studies. Cyclic voltammetry (CV) measurements demonstrate that the catechol-modified chitosan films are redox-active although they are non-conducting and cannot directly transfer electrons to the underlying electrode. The catechol-modified chitosan films serve as a localized source or sink of electrons that can be transferred to soluble mediators (e.g., ferrocene dimethanol and Ru(NH3) 6Cl3). This electron source/sink is finite, can be depleted, but can be repeatedly regenerated by brief (30 s) electrochemical treatments. Further, the catechol-modified chitosan films can i) amplify currents associated with the soluble mediators, ii) partially-rectify these currents in either oxidative or reductive directions (depending on the mediator), and iii) switch between regenerated-ON and depleted-OFF states. Physical models are proposed to explain these novel redox properties and possible precedents from nature are discussed. [source]

Mutation of residues in the coenzyme binding pocket of Dopa decarboxylase

FEBS JOURNAL, Issue 10 2001
Effects on catalytic properties
Residues D271, H192, H302 and N300 of l -3,4-dihydroxyphenylalanine decarboxylase (DDC), a homodimeric pyridoxal 5,-phosphate (PLP) enzyme, were mutated in order to acquire information on the catalytic mechanism. These residues are potential participants in catalysis because they belong to the common PLP-binding structural motif of group I, II and III decarboxylases and other PLP enzymes, and because they are among the putative active-site residues of structural modelled rat liver DDC. The spectroscopic features of the D271E, H192Q, H302Q and N300A mutants as well as their dissociation constants for PLP suggest that substitution of each of these residues causes alteration of the state of the bound coenzyme molecule and of the conformation of aromatic amino acids, possibly in the vicinity of the active site. This supports, but does not prove, the possibility that these residues are located in the coenzyme-binding cleft. Interestingly, mutation of each residue generates an oxidative decarboxylase activity towards l -3,4-dihydroxyphenylalanine (l -Dopa), not inherent in the wild-type in aerobiosis, and reduces the nonoxidative decarboxylase activity of l -Dopa from 3- to 390-fold. The partition ratio between oxidative and nonoxidative decarboxylation ranges from 5.7 × 10,4 for N300A mutant to 946 × 10,4 for H302Q mutant. Unlike wild-type enzyme, the mutants catalyse these two reactions to the same extent either in the presence or absence of O2. In addition, all four mutants exhibit an extremely low level of the oxidative deaminase activity towards serotonin with respect to wild-type. All these findings demonstrate that although D271, H192, H302 and N300 are not essential for catalysis, mutation of these residues alters the nature of catalysis. A possible relationship among the integrity of the PLP cleft, the productive binding of O2 and the transition to a closed conformational state of DDC is discussed. [source]

RpoS involvement and requirement for exogenous nutrient for osmotically induced cross protection in Vibrio vulnificus

FEMS MICROBIOLOGY ECOLOGY, Issue 3 2005
Thomas M. Rosche
Abstract Vibrio vulnificus is an opportunistic human pathogen which is the causative agent of food-borne disease and wound infections. V. vulnificus is able to adapt to a variety of potentially stressful environmental changes, such as osmotic, nutrient, and temperature variations in estuarine environments, as well as oxidative, osmotic, and acidity differences following infection of a human host. After exposure to sub-lethal levels of a particular environmental stress, many bacteria become resistant to unrelated stresses, a phenomenon termed cross protection. In this study, we examined the ability of osmotic shock to cross protect V. vulnificus to high temperature as well as oxidative stress. Log phase cells of V. vulnificus strain C7184o were cross protected by prior osmotic shock to both heat and oxidative challenge, but only when exogenous nutrient was present during the osmotic upshift. Further, and unlike other bacteria, nutrient starvation alone did not result in cross protection against either stress. When small amounts of nutrient were present during osmotic shock, cross protection to an otherwise lethal heat challenge developed extremely rapidly, with significant protection seen within 10 min. Cross protection to oxidative stress was slower to develop, requiring several hours. Although stationary phase alone conferred some cross protection to heat and oxidative stress, the alternate sigma factor RpoS was required for complete cross protection of log phase cells to oxidative stress but not for resistance to heat challenge. Together these findings suggest that the cross protective response in V. vulnificus is complex and appears to involve multiple mechanisms. [source]

Drug metabolism and disposition in children

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2003
M. Strolin Benedetti
Abstract Key factors undergoing maturational changes accounting for differences in drug metabolism and disposition in the pediatric population compared with adults are reviewed. Gastric and duodenal pH, gastric emptying time, intestinal transit time, bacterial colonization and probably P-glycoprotein are important factors for drug absorption, whereas key factors explaining differences in drug distribution between the pediatric population and adults are membrane permeability, plasma protein concentration and plasma protein characteristics, endogenous substances in plasma, total body and extracellular water, fat content, regional blood flow and probably P-glycoprotein, mainly that present in the gut, liver and brain. As far as drug metabolism is concerned, important differences have been found in the pediatric population compared with adults both for phase I enzymes [oxidative (e.g. cytochrome CYP3A7 vs. CYP3A4 and CYP1A2), reductive and hydrolytic enzymes] and phase II enzymes (e.g. N -methyltransferases and glucuronosyltransferases). Finally, key factors undergoing maturational changes accounting for differences in renal excretion in the pediatric population compared with adults are glomerular filtration and tubular secretion. It would be important to generate information on the developmental aspects of renal P-glycoprotein and of other renal transporters as done and still being done with the different isozymes involved in drug metabolism. [source]

Oxidative and excitotoxic insults exert differential effects on spinal motoneurons and astrocytic glutamate transporters: Implications for the role of astrogliosis in amyotrophic lateral sclerosis

A Donor,Acceptor Polymer with a Peculiar Negative-Charge-"Trapping" Characteristic,

ADVANCED FUNCTIONAL MATERIALS, Issue 4 2003
G. Casalbore-Miceli
Abstract Voltammetric and spectrophotometric measurements of poly(3,3,-dipentoxy-3,-dicyanoethenyl-2,2,:5,,2,-terthiophene) (polyCN) films, in connection with other experimental evidence, reveal a normal oxidative, but a peculiar reductive behavior consisting of trapping of the negative charge during the cathodic scan. Another interesting property of polyCN films is the tendency to form strong intramolecular and intermolecular associations, probably charge-transfer (CT) complexes. These properties could account for the fact that the photovoltaic performance does not improve when polyCN is blended with a polythiophene donor. [source]

Use of activated protein C has no avail in the early phase of acute pancreatitis

HPB, Issue 6 2008
Sinan Akay
Abstract Objectives. Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. Subjects and method. Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancratitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activites were collected, and blood for serum amylase, urea, creatinine, and inleukin-6 measurements was withdrawn. Results. Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435±432 U/L vs. 27,426±118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970±323 pg/mL vs. 330±368 pg/mL, respectively). Conclusion. In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions. [source]

Fluorescence and coloration of grey hair

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2009
S. Daly
Synopsis Grey hair samples were collected from 11 individuals and separated into un-pigmented and pigmented fibres (International Hair Importers). Fluorescence measurements were obtained by using a double-grating fluorescence spectrophotometer and a bifurcated fibre optics accessory to measure the spectra directly from the surface of hair at various distances from the fibre root. Colour measurements were carried out by using a Hunter colorimeter. The fluorescence spectra of un-pigmented hair obtained by the excitation at 290 nm show a peak at 356 nm [tryptophan (Trp)], and multi-peak emissions in the range from 395 to 500 nm. A significant variation in the Trp emission intensity at 356 nm vs. the intensity of emission in the 395,500 nm range was observed for hair collected from various individuals with yellow coloured hair producing stronger relative emission in 395,500 nm range. Quantitative measurements of coloration and the calculation of the Yellowness Index (YI) showed linear correlation between YI and the ratio of fluorescence intensities I440/I356 The spectra obtained by excitation at 320 nm showed the emission peaks at 395 nm (unidentified), 420 nm (N -formylkynurenine), 460 nm (kynurenine), and 495 nm (3-hydroxykynurenine), which are the products of oxidative or metabolic conversion of tryptophan. Un-pigmented, yellow hair showed a build-up of the fluorescence band corresponding to 3-hydroxykynurenine at 495 nm. The data also showed the fluorescence quenching effect of melanin resulting in the lowering of the fluorescence intensity of pigmented hair. The spectra obtained at various positions along the fibres demonstrated gradual photo-decomposition of hair chromophores during their lifetimes. This was indicated by a decrease of Trp fluorescence intensity, which was relatively fast (8·10,4,1.5·10,3 [day,1] as calculated for hair obtained from various individuals) for un-pigmented hair and slower for pigmented hair. A decrease in Trp emission was accompanied by an increase in the yellow coloration toward the ends of un-pigmented fibres. Resume Des échantillons de cheveux gris ont été collectés chez onze personnes et triés entre fibres non pigmentés et fibres pigmentés (International Hair Importers). Les mesures de fluorescence ont été réalisées à l'aide d'un spectrophotomètre de fluorescence double grille et d'un accessoire constitué d'une fibre optique bifurquée. Ce dispositif permet la mesure du spectre directement depuis la surface d'un cheveu à diverses distances de sa racine. Les mesures de couleur ont été réalisées à l'aide d'un colorimètre HUNTER. Le spectre de fluorescence d'un cheveu non pigmenté obtenu par excitation à 290 nm montre un pic à 356 nm (tryptophane : Trp) et des émissions multi pics dans l'intervalle 395 à 500 nm. On observe une variation significative de l'intensité du Trp à 356 nm par rapport à l'intensité d'émission dans l'intervalle 395,500 nm sur les cheveux prélevés sur diverses personnes, les cheveux colorés en jaune produisant une émission relative plus forte dans l'intervalle 395,500 nm. Les mesures quantitatives de la couleur et le calcul de l'indice de jaunissement (YI) montrent une corrélation linéaire entre YI et le rapport des intensités de fluorescence I 440/I356. Le spectre obtenu par excitation à 320 nm montre des pics d'émission à 395 nm (non identifiés), 420 nm (N-formylkynurenine), 460 nm (kynurenine), 495 nm (3-hydroxy kinurenine) propres aux produits d'oxydation ou de conversion métabolique du Tryptophane. Les cheveux jaunes non pigmentés présentent une saturation de la bande de fluorescence correspondant à la 3-hydroxykynurenine à 495 nm. Ces données montrent également l'effet de quenching de la mélanine entraînant un affaiblissement de l'intensité de la fluorescence des cheveux pigmentés. Le spectre obtenu en divers endroits le long des fibres indique une photodécomposition graduelle des chromophores des cheveux durant leur temps de vie. Ceci se traduit par une diminution de l'intensité de fluorescence du Trp qui est relativement rapide pour les cheveux non pigmentés (8,10,4,1,5,10,3 [jour , 1], conformément aux calculs effectués sur des cheveux prélevés sur différents individus) et par une diminution plus lente pour les cheveux pigmentés. Une diminution de l'émission du Trp s'accompagne d'une augmentation de la coloration jaune de l'extrémité des cheveux, détectable sur des cheveux non pigmentés. [source]