bluuebunny/crossref_metadata_2025 huggingface dataset:
Monounsaturated diet lowers LDL oxidisability in type IIb and type IV dyslipidemia without affecting coenzyme Q10 and vitamin E contents
Authors: Baroni Silvia Svegliati , Amelio Mauro , Fiorito Alessia , Gaddi Antonio , Littarru Gianpaolo , Battino Maurizio
Published: December 2008

The purpose of the present study was to evaluate the effects of MUFA vs PUFA enriched diets on the plasma and LDL lipid profile and antioxidant contents in mild hypercholesterolemic and triglyceridemic subjects. The study was divided in two consecutive diet periods. Two groups of 11 dyslipidemic patients each (type IIb and type IV) were recruited and during the first period (lasting four weeks) received a linoleic rich diet while during the following four weeks took an oleate rich diet.

Both groups showed no significant changes in cholesterol and TG concentration either in plasma or in LDL. Coenzyme Q10 and vitamin E were also unaffected by the dietary treatments. LDL proneness to be oxidatively modified increased after dietary PUFA administration and markedly decreased following the virgin olive oil enriched diet. In fact, LDL from hypertrigliceridemic subjects on a oleate‐enriched diet displayed a 26% (p<0.05) longer lag‐phase in conjugated dienes generation than during linoleate‐enriched diet and at recruitment. In hypecholesterolemic subjects similar results were obtained: the lag‐phase was 28% longer after MUFA diet that after PUFA diet. No differences were found in the maximum propagation rate and maximum concentration of conjugated dienes among dietary periods and at recruitment. Since we found that the vit. E and CoQ10 levels in plasma and in LDL particles remained unchanged during the course of the study, we may conclude that LDL proneness to undergo oxidative modifications is mainly the result of compositional change due to the enrichment from the different diets of the relative fats.
Virgin olive oil and coenzyme Q10 protect heart mitochondria from peroxidative damage during aging
Authors: Huertas J. R. , Martinez‐Velasco E. , Ibáñez S. , López‐Frias M. , Ochoa J. J. , Quiles J. , Castelli G. Parenti , Mataix J. , Lenaz G.
Published: December 2008

The mitochondrial theory of aging suggests that this phenomenon is the consequence of random somatic mutations in mitochondrial DNA, induced by long‐term exposure to free radical attack. There are two potential dietary means of delaying the effects of free radicals on cellular aging, i.e., enrichment of mitochondrial membranes with monounsaturated fatty acids and supplementation with antioxidants. We have performed a preliminary study on male rats, 6 or 12 month old, fed with diets differing in the nature of the fat (virgin olive oil or sunflower oil) and/or with antioxidant supplementation (coenzyme Q10), analysing hydroperoxide and coenzyme Q9 and Q10 in heart mitochondria. Preliminary results allow us to conclude that the CoQ10 dietetic supplementation as well as the enrichment of the cellular membranes with monounsaturated fatty acids, successfully protect mitochondrial membranes from aged rats against the free radical insult.
Coenzyme Q10, a cutaneous antioxidant and energizer
Authors: Hoppe U. , Bergemann J. , Diembeck W. , Ennen J. , Gohla S. , Harris I. , Jacob J. , Kielholz J. , Mei W. , Pollet D. , Schachtschabel D. , Sauermann G. , Schreiner V. , Stäb F. , Steckel F.
Published: December 2008

The processes of aging and photoaging are associated with an increase in cellular oxidation. This may be in part due to a decline in the levels of the endogenous cellular antioxidant coenzyme Q10 (ubiquinone, CoQ10). Therefore, we have investigated whether topical application of CoQ10 has the beneficial effect of preventing photoaging.

We were able to demonstrate that CoQ10 penetrated into the viable layers of the epidermis and reduce the level of oxidation measured by weak photon emission. Furthermore, a reduction in wrinkle depth following CoQ10 application was also shown. CoQ10 was determined to be effective against UVA mediated oxidative stress in human keratinocytes in terms of thiol depletion, activation of specific phosphotyrosine kinases and prevention of oxidative DNA damage. CoQ10 was also able to significantly suppress the expression of collagenase in human dermal fibroblasts following UVA irradiation. These results indicate that CoQ10 has the efficacy to prevent many of the detrimental effects of photoaging.
Fructose‐2,6‐bisphosphate and control of carbohydrate metabolism in eukaryotes
Authors: Okar David A. , Lange Alex J.
Published: December 2008

Fructose‐2,6‐bisphosphate is an important intracellular biofactor in the control of carbohydrate metabolic fluxes in eukaryotes. It is generated from ATP and fructose‐6‐phosphate by 6‐phosphofructo‐2‐kinase and degraded to fructose‐6‐phosphate and phosphate ion by fructose‐2,6‐bisphosphatase. In most organisms these enzymatic activities are contained in a single polypeptide. The reciprocal modulation of the kinase and bisphosphatase activities by post‐translational modifications places the level of the biofactor under the control of extra‐cellular signals. In general, these signals are generated in response to changing nutritional states, therefore, fructose‐2,6‐bisphosphate plays a role in the adaptation of organisms, and the tissues within them, to changes in environmental and metabolic states. Although the specific mechanism of fructose‐2,6‐bisphosphate action varies between species and between tissues, most involve the allosteric activation of 6‐phosphofructo‐1‐kinase and inhibition of fructose‐1,6‐bisphosphatase. These highly conserved enzymes regulate the fructose‐6‐phosphate/fructose‐1,6‐bisphosphate cycle, and thereby, determine the carbon flux. It is by reciprocal modulation of these activities that fructose‐2,6‐bisphosphate plays a fundamental role in eukaryotic carbohydrate metabolism.
Evidence for A1and A2Badenosine receptors in baby hamster kidney (BHK) cells
Authors: Mittal Rashmi A. , Tan Chee‐Hong , Khoo Hoon‐Eng
Published: December 2008

Adenosine is known to produce biphasic effects in the renal tissues via adenosine receptors. However, the presence of more than one subtype of adenosine receptor on a type of kidney cell or tissue has not been conclusively demonstrated. To address this issue, we investigated the presence of A1and A2adenosine receptors in baby hamster kidney (BHK) cells by use of radioligand binding and the reverse transcription‐polymerase chain reaction. Ligand binding studies with (3H)‐DPCPX revealed a single class of binding site with a KDof 9.2 ± 2.0 nM, a Bmaxof 1.7 ± 0.2 pmol/mg protein and a pharmacological profile characteristic of A1adenosine receptor on the BHK cell membrane. As the presence of A2adenosine receptors could not be conclusively determined by ligand binding studies, the more sensitive method of RT‐PCR was employed. The presence of A1and A2Badenosine receptors was detected by RT‐PCR with specific primers and the subsequent sequencing of the resultant amplification product. The sequences obtained were 75—90% homologous to the respective adenosine receptor mRNA of rat, mouse and human.
Captopril increased mitochondrial coenzyme Q10 level, improved respiratory chain function and energy production in the left ventricle in rabbits with smoke mitochondrial cardiomyopathy
Authors: Gvozdjáková Anna , Šimko Fedor , Kucharská Jarmila , Braunová Zuzana , Pšenek Peter , Kyselovič JÁN
Published: December 2008

The aim of the study was to show whether the ACE inhibitor captopril is able to protect the heart against the deleterious effect of passive cigarette smoking on left ventricular mitochondria. Four groups of rabbits were investigated: control (C), passive smoking of three cigarettes twice daily/30 minutes (S), control + captopril (7.5 mg/kg body weight twice daily) (Cap), and smoking + captopril (SCap) as in group 2 and 3. Three weeks lasting passive smoking impaired oxidative phosphorylation, diminished cytochrome oxidase activity and increased the mitochondrial F1‐ATPase protein concentration. Moreover, the level of coenzyme Q10 (CoQ10) and coenzyme Q9 were decreased. Simultaneous treatment with captopril prevented partly the decrease of CoQ10 level, deterioration of oxidative phosphorylation, diminution of cytochrome oxidase activity and enhancement of F1‐ATPase level. We conclude that captopril protected the myocardium against the harmful effect of passive smoking in rabbits.
Biological functions of carotenoids ‐ diversity and evolution
Authors: Vershinin Alexander
Published: December 2008

Carotenoids first emerged in archaebacteria as lipids reinforcing cell membranes. To serve this function their long molecules have extremely rigid backbone due to the linear chain of usually 10 to 11 conjugated C=C bonds in trans‐configuration — the length corresponding the thickness of hydrophobic zone of membrane which they penetrate as “molecular rivets”. Carotenoids retain their membrane‐reinforcing function in some fungi and animals.

The general structure of carotenoid molecule, originally having evolved for mechanical functions in membranes, possess a number of other properties that were later used for independent functions. The most striking fact is that these properties proved to fit some new functions to perfection.

— The polyene chain of 9—11 double bonds absorbs light precisely in the gap of chlorophyll absorption — function as accessory light‐harvesting pigments in all plants;

— Unique arrangement of electronic levels owing to the by polyene chain structure makes carotenoids the only natural compounds capable of excitation energy transfer both (i) from carotenoid excited state to chlorophyll in the light‐harvesting complex and (ii) from triplet chlorophyll or singlet oxygen to carotenoid in photosynthetic reaction centers — protection of RC from photodamage.

The linear system of conjugated C=C bonds provides high reducing potential of carotenoid molecules making them potent antioxidants in lipid formations. Still, there is a lack of evidence of the chemical antioxidant function of carotenoids, especially in higher organisms; most data demonstrate an antioxidant ability rather than a function.

Carotenoids have many other independent biological functions, including: specific coloration patterns in plants and animals, screening from excessive light and spectral filtering, defense of egg proteins from proteases in some invertebrates; the direct carotenoid derivative — retinal — acts as visual pigment in all animals and as chromophore in bacteriorhodopsin photosynthesis, retinoic acid in animals and abscisic acid in plants serve as hormones. All these functions utilize various properties (mechanical, electronic, stereospecific) of a single structure evolved in bacteria for a single membrane‐reinforcing function, thus demonstrating an example of pure evolutionary preadaptation.

One of the practical conclusions that can be reached by reviewing uniquely diverse properties and functions of carotenoids is that, when considering possible mechanisms of their effects in organisms (e.g., anticarcinogenic action), all their functional traits should be taken into account.
Oxidative stress in hemodialysis patients treated with a dialysis membrane which has alpha‐tocopherol bonded to its surface
Authors: Sommerburg O. , Sostmann K. , Grune T. , Ehrich J. H. H.
Published: December 2008

Background: MDA, a major product of LPO, was shown to be increased in plasma of patients with end‐stage renal failure (ESRF) undergoing hemodialysis (HD). Elevated oxidative stress in ESRF patients is a result of multiple pathogenetic factors. HD treatment has been shown to be one important cause of accelerated radical generation. The aim of our study was to examine whether treatment with a dialysis membrane which has alpha‐tocopherol hydrophobically bonded to its surface (Excebrane by Terumo, Japan) can decrease oxidative stress due to HD.

Methods: 10 ESRF patients undergoing HD three times weekly were examined. First, analysis was done when patients were still dialysed with the membranes used before the study. Thereafter, samples were taken when patients were dialysed first time with the Excebrane membrane, and six weeks after Excebrane treatment. Samples were collected always before and after HD session. A method with HPLC‐separation and flourimetric detection was used to measure plasma concentration of MDA.

Results: After HD with the regularly used membranes MDA was found significantly increased (before HD 1.92 [1.81—2.02]μM (median and interquartile ranges) vs. after HD 2.26 [2.02—2.60]μM, p<0.05) suggesting that MDA was produced during HD. The first time Excebrane was used MDA was decreased significantly (before HD 2.04 [1.95—2.88]μM vs. after HD 1.35 [1.19—1.92]μM, p<0.05). After six weeks of Excebrane treatment, plasma MDA did not change significantly during HD (before HD 2.01 [1.69—2.62]μM vs. after HD 1.95 [1.42—2.20]μM).

Conclusion: Oxidative stress due to HD might be significantly decreased by the Excebrane membrane. However, after six weeks of treatment with Excebrane no effect was seen on the initial plasma concentration of MDA compared to the time before.
Redox regulation of TNF signaling
Authors: Goossens Vera , Vos Kurt De , Vercammen Dominique , Steemans Margino , Vancompernolle Katia , Fiers Walter , Vandenabeele Peter , Grooten Johan
Published: December 2008

TNF is produced during inflammation and induces, among other activities, cell death in sensitive tumour cells. We previously reported an increased generation of ROS in TNF‐treated L929 fibrosarcoma cells prior to cell death. These ROS are of mitochondrial origin and participate in the cell death process. Presently, we focus on the identification of parameters that control ROS production and subsequent cytotoxicity. From the cytotoxic properties and susceptibility to scavenging of TNF‐induced ROS as compared to pro‐oxidant‐induced ROS we conclude that TNF‐mediated ROS generation and their lethal action are confined to the inner mitochondrial membrane. Oxidative substrates, electron‐transport inhibitors, glutathione and thiol‐reactive agents but also caspase inhibitors modulate TNF‐induced ROS production and imply the existence of a negative regulator of ROS production. Inactivation of this regulator by a TNF‐induced reduction of NAD(P)H levels and/or formation of intraprotein disulfides would be responsible for ROS generation.
Changes in several functions of murine peritoneal macrophages by N‐acetylcysteine and thioproline ingestion. Comparative effect between two strains of mice
Authors: Blanco B. , Ferrández M. D. , Correa R. , Del Rio M. , Guaza C. , Hernanz A. , De La Fuente M.
Published: December 2008

The administration of the thiol compounds, N‐acetylcysteine (NAC) and in particular thioproline (thiazolidine‐4‐carboxylic acid) at 0.1% w/w concentration in the diet, improves lymphocyte functions in old female Swiss mice, as has been shown in our previous studies. In the present work, adult mice from two different strains, namely BALB/c (an inbred strain) and OF1‐Swiss (noninbred strain), were fed a diet supplemented with the above dose of each thiol compound jointly for five weeks. At 28 weeks of age, peritoneal cell suspensions were obtained and different steps of the phagocytic process, the most representative activity of macrophages, as well as interleukin‐1β (IL‐1β) production, were studied. Thus, adherence to substrate, mobility directed to a chemoattractant gradient (chemotaxis), ingestion of inert particles and superoxide anion production were analysed. The results show that diet supplementation with NAC plus thioproline increased all macrophage functions studied with the exception of superoxide anion production, which was decreased. These effects were more evident in macrophages from Swiss mice, whereas in BALB/c mice the stimulation of phagocytosis and IL‐1β production was lower and no differences were seen after treatment in adherence and superoxide anion production. These data suggest that immune function can be improved in adult mice by administration of the above thiol compounds, especially in the noninbred strain of OF1‐Swiss mice.
N‐Acetyl‐cysteine inhibition of encephalomyelitis Theiler's virus‐induced nitric oxide and tumour necrosis factor‐α production by murine astrocyte cultures
Authors: Molina‐Holgado F. , Hernanz A. , De La Fuente M. , Guaza C.
Published: December 2008

The pathological mechanisms that cause central nervous system (CNS) dysfunction in most neurological diseases are not well established. Theiler's murine encephalomyelitis virus (TMEV) is known to interact with cells of the CNS and its intracerebral inoculation to susceptible mice strains causes neurological disorders resembling multiple sclerosis (MS). In this study, we reported that primary astrocyte cultures from SJL/J susceptible mice when infected with TMEV released important amounts of nitrites (NO2−) to the culture medium, as measured in the supernatants 24 hours after infection. In addition, we observed an increment in the production of tumour necrosis factor alpha (TNF‐α) by susceptible SJL/J strain derived astrocytes infected with TMEV. The treatment with the thiolic antioxidant N‐acetyl‐cysteine partially suppressed the virus‐stimulated production of nitric oxide and TNF‐α, in a dose response fashion. These results indicate that during viral infection astrocytes are an important cellular source of nitric oxide and TNF‐α, substances which play important roles during CNS inflammatory events. The effects of the antioxidant N‐acetyl‐cysteine, modulating the production of the above compounds by TMEV‐infected astrocytes may be a significant factor in preventing CNS demyelination.
Gastrointestinal glutathione peroxidase
Authors: Wingler Kirstin , Brigelius‐Flohé Regina
Published: December 2008

The gastrointestinal glutathione peroxidase (GI‐GPx) is the fourth member of the GPx family. In rodents, it is exclusively expressed in the gastrointestinal tract, in humans also in liver. It has, therefore, been discussed to function as a primary barrier against the absorption of ingested hydroperoxides. A vital function of GI‐GPx can be deduced from the unusual stability of its mRNA under selenium‐limiting conditions, the presence of low amounts of GI‐GPx protein in selenium deficiency where cGPx is absent, and the fast reappearance of the GI‐GPx protein upon refeeding of cultured cells with selenium compared to the slower reappearance of cGPx protein. Furthermore, the Secis efficiency of GI‐GPx is low when compared to cGPx and PHGPx. It is, however, almost independent of the selenium status of the cells tested. All these characteristics rank GI‐GPx high in the hierarchy of selenoproteins and point to a role of GI‐GPx which might be more crucial than that of cGPx, at least in the gastrointestinal system.
Various functions of selenols and thiols in anaerobic Gram‐positive, amino acids‐utilizing bacteria
Authors: Andreesen Jan R. , Wagner Matthias , Sonntag Denise , Kohlstock Martin , Harms Claudia , Gursinsky Torsten , Jäge Jana , Parther Tina , Kabisch Ute , Gräntzdöffer Andrea , Pich Andreas , Söhling Brigitte
Published: December 2008

Electron transfer reactions for the reduction of glycine in Eubacterium acidaminophilum involve many selenocysteine (U)‐ and thiol‐containing proteins, as shown by biochemical and molecular analysis. These include an unusual thioredoxin system (‐CXXC‐), protein A (‐CXXU‐) and the substrate‐specific protein B of glycine reductase (‐UXXCXXC‐). Most probably a selenoether is formed at protein B by splitting the C‐N‐bond after binding of the substrate. The carboxymethyl group is then transferred to the selenocysteine of protein A containing a conserved motif. The latter protein acts as a carbon and electron donor by giving rise to a protein C‐bound acetyl‐thioester and a mixed selenide‐sulfide bond at protein A that will be reduced by the thioredoxin system. The dithiothreitol‐dependent D‐proline reductase of Clostridium sticklandii exhibits many similarities to protein B of glycine reductase including the motif containing selenocysteine. In both cases proprotein processing at a cysteine residue gives rise to a blocked N‐terminus, most probably a pyruvoyl group. Formate dehydrogenase and some other proteins from E. acidaminophilum contain selenocysteine, e.g., a 22 kDa protein showing an extensive homology to peroxiredoxins involved in the detoxification of peroxides.
Molecular and cellular mechanisms of transepithelial iodide transport in the thyroid
Authors: Nilsson Mikael
Published: December 2008

Thyroid hormone is an essential regulator of developmental growth and metabolism in vertebrates. Iodine is a necessary constituent of thyroid hormone. Due to the scarcity and uneven distribution of iodine on the Earth's crust, the structure of the thyroid gland is adjusted to collect and store this element in order to secure a continuous supply of thyroid hormone throughout life. Still, disease resulting from hypothyroidism due to iodine deficiency is a global health problem, illustrating the great biological significance that iodine saving mechanisms have evolved. Iodide is accumulated together with prohormone (thyroglobulin) in the lumen of the thyroid follicles. The rate‐limiting step of this transport is the sodium/iodide symporter located in the basolateral plasma membrane of the thyroid follicular cells. Iodide is also transferred across the apical plasma membrane into the lumen where hormonogenesis takes place. In this review, recent progress in the understanding of transepithelial iodide transport in the thyroid is summarized.
Folate status and neural tube defects
Authors: Molloy Anne M. , Mills James L. , Kirke Peadar N. , Weir Donald G. , Scott John M.
Published: December 2008

Periconceptional folic acid supplementation prevents approximately 70% of neural tube defects (NTDs). While most women carrying affected fetuses do not have deficient blood folate levels, the risk of having an NTD affected child is inversely correlated with pregnancy red cell folate levels. Current research is focused on the discovery of genetic abnormalities in folate related enzymes which might explain the role of folate in NTD prevention. The first candidate gene to emerge was the C677T variant of 5,10‐methylenetetrahydrofolate reductase. Normal subjects who are homozygous for the mutation (TT) have red cell folate status some 20% lower than expected. It is now established that the prevalence of the TT genotype is significantly higher among spina bifida cases and their parents. Nevertheless, our studies show that the variant does not account for the reduced blood folate levels in many NTD affected mothers. We conclude that low maternal folate status may in itself be the most important risk factor for NTDs and that food fortification may be the only population strategy of benefit in the effort to eliminate NTDs.
Proposed standard for human blood vitamin B1 value using HPLC
Authors: Itokawa Y. , Hashizume N. , Asano M. , Igarashi O. , Mino M. , Ihara H. , Ishiwata Y. , Kadowaki H. , Kubota N. , Okazaki M. , Sueki K. , Ishida Y. , Gorin M. , Sato T. , Sayama Y. , Shimomura K. , Takano H. , Nakamura T. , Hanawa M. , Niimura H. , Morio T. , Chibata I. , Okuda K.
Published: December 2008

Standard reference ranges for all laboratory test values are mandatory. This study was designed to establish a reference range for blood vitamin B1 levels, since the normal range has not been determined in the Japanese population. We founded the Japan Committee for Vitamin Laboratory Standards, which was incorporated with the Vitamin Society of Japan and the Japanese Society of Nutrition and Food Science. We standardized whole blood vitamin B1 levels using three HPLC techniques (post‐column reverse‐phase HPLC, pre‐column reverse‐phase HPLC, and precolumn GP‐HPLC). The reference range was obtained in 54 volunteers administered a 1,800 kcal diet with 2 mg of vitamin B1 (1.74 mg measured) daily to avoid marginal vitamin B1 deficiency in the population. The range for each assay was 26—47, 28—51, and 28—56 ng/ml, respectively. Our data suggest that 26—28 ng/ml is the lower limit of normal for whole blood vitamin B1, but further studies in a larger population are needed in order to obtain more definitive results.
Pyruvate dehydrogenase kinase 4 mRNA is increased in the hypertrophied ventricles of carnitine‐deficient juvenile visceral steatosis (JVS) mice
Authors: Horiuchi Masahisa , Kobayashi Keiko , Masuda Mina , Terazono Hiroki , Saheki Takeyori
Published: December 2008

We isolated a mouse homologue cDNA of pyruvate dehydrogenase (PDH) kinase 4 (PDK4) with differential mRNA display as an up‐regulated gene in the hypertrophied ventricles of juvenile visceral steatosis (JVS) mice with systemic carnitine deficiency. The PDK4 mRNA level was 5 times higher in JVS mice than in control mice under fed conditions. After 24 h starvation, this level increased to 20 times in JVS and 7 times in control, compared with the control fed level. On the other hand, carnitine administration reduced the high level of PDK4 mRNA in JVS mice to the control fed level. In control mice, the change in PDK4 mRNA was inversely correlated with the change in PDH activity. In JVS mice, however, the PDK4 mRNA level was not always correlated with the active‐form PDH level.
Morphological and biochemical responses of Bacillus subtilis to selenite stress
Authors: Garbisu Carlos , Carlson Donald , Adamkiewicz Mike , Yee Boihon C. , Wong Joshua H. , Resto Edgar , Leighton Terrance , Buchanan Bob B.
Published: December 2008

When introduced into a chemically defined minimal medium supplemented with 1 mM sodium selenite (79 ppm Se°), Bacillus subtilis was found to undergo a series of morphological and biochemical adaptations. The morphological changes included the formation of “round bodies” associated with the detoxification of selenite to elemental selenium. Round bodies observed transiently were not apparent during balanced growth of cells adapted previously to selenite‐containing medium. Under balanced growth conditions, cell structures similar to “round bodies”, could be produced by treating cells with lysozyme. The selenite‐induced structural alterations in cells were accompanied by an increase in the content of thioredoxin and the associated enzyme, NADP‐thioredoxin reductase. The results suggest that the biovalence transformation of high levels of selenite may involve a dithiol system.
Modulation of murine macrophage function by N‐acetylcysteine in a model of endotoxic shock
Authors: Víctor V. M. , Guayerbas N. , Garrote D. , Del Río M. , De La Fuente M.
Published: December 2008

In previous studies we have observed changes in several functions of peritoneal macrophages from BALB/c mice with irreversible endotoxic shock caused by intraperitoneal injection of E. coli lipopolysaccharide (LPS) (100 mg/kg), which were associated with a high production of superoxide anion. Since antioxidants, such as N‐acetylcysteine (NAC), are free radical scavengers that improve the immune response, in the present work we have studied different functions of peritoneal macrophages from BALB/c mice suffering the endotoxic shock above indicated and administered N‐acetylcysteine (150 mg/kg i.p.) at 30 minutes after LPS injection. In the peritoneal macrophages obtained at 2, 4, 12 and 24 h after LPS injection, the following functions were studied: adherence to substrate, mobility, ingestion of particles, and production of superoxide anion and tumour necrosis factor (TNFα). The increase in adherence, ingestion and superoxide anion and TNFα production shown by macrophages from animals with endotoxic shock was counteracted by NAC injection. Moreover, the survival time of mice with endotoxic shock was increased in the presence of NAC. These data suggest that NAC, administered intraperitoneally, may be useful for the treatment of irreversible endotoxic shock by modulation of the function of macrophages with decreased superoxide anion and TNFα production and concomitant increase of survival time.
An investigation into a possible relationship between vitamin D, parathyroid hormone, calcium and magnesium in a normally pigmented and an albino rural black population in the Northern Province of South Africa
Authors: Cornish Daryl A. , Maluleke Vusi , Mhlanga Thulani
Published: December 2008

Vitamin D levels are important in the management of patients with various disorders of calcium metabolism associated with rickets, osteomalacia, osteodystrophy osteoporosis and hypoparathyroidism. 82 albinos and 58 normally pigmented children resident at the Siloe School for the Visually Impaired were sampled. Blood samples of fasting subjects were collected over a two‐day period and analyzed for vitamin D, parathyroid hormone, plasma calcium and both plasma and red blood cell magnesium measurements. The height and weight of each subject was also recorded. The results are discussed in relation to the different skin pigmented groups, for specific age groups, sex and visual status. Statistical outliers were excluded from the results. It appears that the Albino group has significantly (p=0.06) higher vitamin D levels against the background of a similar dietary intake and similar exposure to sunlight/day length. Thus black children/subjects require a significantly higher intake of vitamin D to attain the same level as their Albino counterparts. In spite of significantly higher vit D levels, the other homeostatic control mechanisms were not altered (i.e., PTH levels are similar in both groups). This study supports the postulate that a dark complexion predisposes to sub‐optimal vit D status.
Inhibition of cathepsin activities by vitamin B6 derivatives
Authors: Matsui A. , Tsuzuki H. , Murata E. , Tada Y. , Asao T. , Katunuma N.
Published: December 2008

We found that pridoxal phosphate (PLP), a coenzyme form of vitamin B6, inhibited the activity of cathepsins B, K, S and L in vitro. Cathepsins activities in cultured splenocytes were suppressed by the addition of pridoxal (PL) or pridoxine (PI) in to the culture medium. A newly synthesized artificial vitamin B6 derivative, a pridoxal propionate derivative, CLIK‐164, showed selective inhibition of cathepsin O/K.
Is chromium a trace essential metal?
Authors: Stearns Diane M.
Published: December 2008

If chromium is an essential metal it must have a specific role in an enzyme or cofactor, and a deficiency should produce a disease or impairment of function. To date, no chromium‐containing glucose tolerance factor has been characterized, the purpose of the low‐molecular‐weight chromium‐binding protein is questionable, and no direct interaction between chromium and insulin has been found. Furthermore, chromium3+is treated like the toxic metals arsenic, cadmium, lead and mercury in animals. Chromium3+may be involved in chromium6+‐induced cancers because chromium6+is converted to chromium3+in vivo, and chromium3+is genotoxic and mutagenic. Although there is no direct evidence of chromium deficiencies in humans, dietary supplements exist to provide supraphysiological doses of absorbable chromium3+. Chromium3+may act clinically by interfering with iron absorption, decreasing the high iron stores that are linked to diabetes and heart disease. If so, this would make chromium3+a pharmacological agent, not an essential metal.
Properties of fucoidan from Cladosiphon okamuranus tokida in gastric mucosal protection
Authors: Shibata Hideyuki , Kimura‐Takagi Itsuko , Nagaoka Masato , Hashimoto Shusuke , Aiyama Ritsuo , Iha Masahiko , Ueyama Sadao , Yokokura Teruo
Published: December 2008

To elucidate the anti‐ulcer potential of Cladosiphon fucoidan, anti‐peptic activity, bFGF stabilizing activity and inflammatory properties of this and related substances were investigated. Anti‐peptic activity was observed with this and other sulfated polysaccharides such as dextran sulfate, carrageenan, and Fucus fucoidan. However, non‐sulfated polysaccharides such as mannan and dextran did not exert the anti‐peptic activity. The loss of bFGF bioactivity was prevented by all sulfated polysaccharides tested except chondroitin sulfate, at pH 7.4 and at pH 4.0. At pH 2.0, only heparin protected the bFGF activity. The generation of superoxide by macrophages and PMNs was stimulated by dextran sulfate, carrageenan, and Fucus fucoidan, whereas Cladosiphon fucoidan, heparin and chondroitin did not. Dextran sulfate, carrageenan, and Fucus fucoidan also stimulated the secretion of TNFα from macrophages, while Cladosiphon fucoidan did not. Thus, Cladosiphon fucoidan is a sulfated polysaccharide without inflammatory action. These results suggest that Cladosiphon fucoidan is a safe substance with potential for gastric protection.
Inhibition of angiotensin‐converting enzyme protects endothelial cell against hypoxia/reoxygenation injury
Authors: Fujita Noriko , Manabe Hiroki , Yoshida Norimasa , Matsumoto Naohito , Ochiai Jun , Masui Yasuharu , Uemura Manabu , Naito Yuji , Yoshikawa Toshikazu
Published: December 2008

Cardiovascular tissue injury in ischemia/reperfusion has been shown to be prevented by angiotensin‐converting enzyme (ACE) inhibitors. However, the mechanism on endothelial cells has not been assessed in detail. Cultured human aortic endothelial cells (HAEC) were exposed to hypoxia with or without reoxygenation. Hypoxia enhanced apoptosis along with the activation of caspase‐3. Reoxygenation increased lactate dehydrogenase release time‐dependently, along with an increase of intracellular oxygen radicals. ACE inhibitor quinaprilat and bradykinin significantly lessened apoptosis and lactate dehydrogenase release with these effects being diminished by a kinin B2 receptor antagonist and a nitric oxide synthase inhibitor. In conclusion, hypoxia activated the suicide pathway leading to apoptosis of HAEC by enhancing caspase‐3 activity, while subsequent reoxygenation induced necrosis by enhancing oxygen radical production. Quinaprilat could ameliorate both apoptosis and necrosis through the upregulation of constitutive endothelial nitric oxide synthase via an increase of bradykinin, with the resulting increase of nitric oxide.
The concept of intracellular‐, extracellular‐ and bone‐minerals
Authors: Nishimuta Mamoru
Published: December 2008

A new concept of grouping of minerals, which will be helpful for understanding the actual status of human health, on the basic of elementological biology.
Prevention of cancer and other chronic diseases worldwide based on sound mechanisms
Authors: Weisburger John H.
Published: December 2008

The transformation of normal cells by DNA reactive, genotoxic carcinogens and the growth promotion and development of mutated cells by enhancing factors is involved in the overall basic mechanism of cancer induction. Thus, discrimination between genotoxic carcinogens and nongenotoxic chemicals is essential. The dose‐response curves, reversibility, and organ‐and species specificity are distinct. Genotoxic carcinogens are mutagenic, form DNA adducts, induce DNA repair, and form hydroxy radicals and inappropriate peroxidation reactions that antioxidants such as those in vegetables, fruits, and tea can decrease. In contrast, promoters do not form DNA adducts, but raise cell duplication rates, among other attributes. In the USA, about 35% about 55% decreased by avoiding the formation of carcinogens, reducing their metabolic activation, or increasing their detoxification. Excessive dietary salt, and heterocyclic arylamines formed in cooking of meats or fish, and high intake of 40% vegetables, fruits, tea, soy products, and fibers are protective. We review nutritional factors involved in cancer and chronic disease causation and prevention.
Bioactive peptides derived from food proteins preventing lifestyle‐related diseases
Authors: Yoshikawa Masaaki , Fujita Hiroyuki , Matoba Nobuyuki , Takenaka Yasuyuki , Yamamoto Taichi , Yamauchi Rena , Tsuruki Hirotaka , Takahata Kyoya
Published: December 2008

Many kinds of bioactive peptides which might prevent lifestyle‐related diseases are released from food proteins after enzymatic digestion. Inhibitory peptides for angiotensin I‐converting enzyme (ACE) having anti‐hypertensive effect have been isolated from enzymatic digests of various food proteins. LKPNM, which was isolated from the thermolysin digest of dried bonito was activated 8‐fold by ACE itself and showed a prolonged effect after oral administration. Two vasorelaxing peptides, ovokinin and ovokinin(2–7), showing antihypertensive effect after oral administration were obtained from ovalbumin digests. We found that low molecular weight peptides derived from food proteins lowered serum cholesterol without increasing excretion of cholesterol and bile acids. An immunostimulating peptide isolated from an enzymatic digest of soybean protein prevented alopecia induced by cancer chemotherapy.
Anticancer activity of hydrophobic peptides from soy proteins
Authors: Kim Song E , Kim Hyuck Hwa , Kim Ji Yeon , Kang Young Im , Woo Hee Jong , Lee Hyong Joo
Published: December 2008

An anticancer peptide from soy protein was purified and isolated. Defatted soy protein was hydrolyzed with thermoase and hydrophobic peptides were extracted with ethanol. The peptide extract was fractionated by XAD‐2 hydrophobic, gel filtration chromatography, and different C18 HPLCs. Anticancer activity of each fraction was assayed by measuring in vitro cytotoxicity on P388D1, a mouse monocyte macrophage cell line. IC50 value of a peptide fraction from Sephadex G‐25 chromatography was 0.16 mg/ml. This peptide fraction at 1 mg/ml significantly affected cell cycle progression by arresting P388D1 at G2/M phases. Finally purified peptide from analytical C18 HPLC was nonapeptide of which molecular weight was 1157 Da and the sequence was X‐Met‐Leu‐Pro‐Ser‐Tye‐Ser‐Pro‐Tyr.
Respective bioavailability of quercetin aglycone and its glycosides in a rat model
Authors: Morand Christine , Manach Claudine , Crespy Vanessa , Remesy Christian
Published: December 2008

A large number of flavonoids, mostly O‐glycosides, are found in foods of plant origin. The bound sugar moiety is known to influence their bioavailability. We examined here the effect of the nature of the sugar on the absorption of the glycosides. Four groups of rats (n=6) received a meal containing 20 mg of quercetin equivalents supplied as aglycone, quercetin 3‐glucoside, quercetin 3‐rhamnoside or rutin. Plasma were hydrolysed by a βglucuronidase/sulfatase and analyzed by HPLC coupled to UV detection at 370 nm. Four hours after the beginning of the meal, the quercetin metabolites present in plasma were identical in all groups but their total concentrations were quite different. With pure quercetin the circulating levels were 11.7± 1.8 μM, but this level was three fold higher when quercetin was supplied as quercetin 3‐glucoside (33.2± 3.5 μM). By contrast, the plasma concentrations of quercetin metabolites was quite low with the rutin meal (about 3 μM) and undetectable after the quercetin 3‐rhamnoside meal. These data suggest that the 3‐O‐glucosylation improves the absorption of quercetin in the small intestine, whereas the binding of a rhamnose or of a glucose‐rhamnose moiety to the aglycone markedly depressed its absorption. Additionnal experiments have shown that the higher plasma levels measured after the meal containing quercetin 3‐glucoside compared to quercetin were maintained throughout a 24 hour period following the meal.

In conclusion, the nature of the glycosylation markedly influences the efficiency of quercetin absorption in rats. Quercetin 3‐glucose can be absorbed in the small intestine and is better absorbed than quercetin itself. By contrast, glycosides containing a rhamnose moiety could not be absorbed in the small intestine.
Suppressive effects of citrus fruits on free radical generation and nobiletin, an anti‐inflammatory polymethoxyflavonoid
Authors: Murakami Akira , Nakamura Yoshimasa , Ohto Yoshimi , Yano Masamichi , Koshiba Teruaki , Koshimizu Koichi , Tokuda Harukuni , Nishino Hoyoku , Ohigashi Hajime
Published: December 2008

Citrus fruit intake is known to be associated with a reduction of cancer incidence. Free radicals, including superoxide (O−2) and nitric oxide (NO), are involved in some epithelial carcinogenesis processes. In the present study, we screened thirty‐one citrus fruits for their suppressive activities toward three lines of free radical generating systems: 1) O−2 generation by the xanthine (XA)‐xanthine oxidase (XOD) system; 2) O−2 generation induced by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in differentiated human promyelocytic HL‐60 cells; and 3) NO generation in murine macrophage RAW264.7 cells stimulated with lipopolysaccharide (LPS) and interferon (IFN)‐γ. As a result, the inhibitory activities of peel parts were largely found to be higher than those of the corresponding juice sac parts. In particular, the peel portion of Dancy tangerine (Citrus tangerina) showed marked anti‐oxidative activities in these systems. In addition, nobiletin, a polymethoxyflavonoid isolated from C. nobilis, showed a higher anti‐inflammatory activity than indomethacin in a TPA‐induced edema formation test in mouse ears. These results indicate that citrus fruits could be notable sources of anti‐oxidative, anti‐inflammatory, and cancer preventive compounds.
Mechanisms involved in the chemoprevention of flavonoids
Authors: Siess Marie‐HÉLÉNe , Bon Anne‐Marie Le , Canivenc‐Lavier Marie‐Chantal , Suschetet Marc
Published: December 2008

Flavonoids, widespread in edible plants, have been studied extensively for their anticarcinogenic properties. However, only few studies have been done with these constituents being administered by the dietary route. In our research, the effects of feeding rats with flavone, flavanone, tangeretin, and quercetin were investigated on two steps of aflatoxin B1 (AFB1)‐induced hepatocarcinogenesis (initiation and promotion). Nonpolar flavonoids such as flavone, flavanone and tangeretin administered through the initiation period, decreased the number of γ‐glutamyl transpeptidase‐preneoplastic foci. In the same conditions of administration, quercetin, a polyhydroxylated flavonoid, showed no protective effect. Moreover, feeding rats with flavanone during the phenobarbital‐induced promotion step significantly reduced the areas of placental glutathione S‐transferase preneoplastic foci. Quercetin, flavone, and tangeretin, administered in the same conditions, caused no significant effect. Therefore flavanone act as an anti‐initiator as well as an anti‐promotor. Several mechanisms were involved in the anti‐initiating effects of flavone, flavanone, and tangeretin: enhancement of enzymes involved in the detoxication of AFB1 (glutathione S‐transferase, UDP‐glucuronyl transferase), increase of the formation of AFB1‐glutathione conjugates and inhibition of the binding of AFB1 to DNA. Although the relevance of these data to the human situation remains to be demonstrated, they confirm that several flavonoids administered by the dietary route possess promising chemoprotective effects.
Isoflavonoids and chronic disease: Mechanisms of action
Authors: Barnes S. , Boersma B. , Patel R. , Kirk M. , Darley‐Usmar V. M. , Kim H. , Xu J.
Published: December 2008

Soy and its isoflavones are associated with a reduced risk of chronic disease. The mechanisms of action of isoflavones include their roles as weak estrogens, inhibitors of tyrosine kinase‐dependent signal transduction processes and as cellular antioxidants. Although estrogen receptor beta binds genistein with an affinity close to that of 17β‐estradiol, it remains to be determined whether it is a mediator of genistein's activity in vivo. Genistein's inhibition of protein tyrosine kinases is not limited to direct effect on these kinases, but may result from alteration in kinase expression. Genistein is not a particularly good scavanger of cellular oxidants; however, it reacts vigorously with the prooxidant hypochlorous acid, produced by neutrophils as part of the inflammatory response. The chlorinated isoflavones may have altered biochemical and biological effects compared to their parent compounds and may provide increased protection against inflammatory disease.
Comparison of plasma and urinary phytoestrogens in Japanese and Finnish women by time‐resolved fluoroimmunoassay
Authors: Uehara Mariko , Arai Yusuke , Watanabe Shaw , Adlercreutz Herman
Published: December 2008

Time‐resolved fluoroimmunoassays (TR‐FIA), with europium labeled phytoestrogens as tracers, were developed for the quantitative measurement of genistein, daidzein and enterolactone in plasma and urine for the purpose of screening large populations and studies on possible correlation between the values in biological fluids and the risk of western diseases.

The mean values of the three phytoestrogens in plasma as determined by TR‐FIA were similar to those obtained by gas chromatography‐mass spectrometry (GC‐MS). The urinary excretion levels of total individual phytoestrogens were higher than those obtained by GC‐MS, with the exception of the daidzein values. However, comparing the assay results obtained by the present method and those obtained by GC‐MS, a strong correlation was evident (r=0.87‐0.99, p<0.001).

We measured plasma levels of genistein, daidzein and enterolactone in 111 healthy Japanese women. The mean and median levels of genistein were 406.8 and 306.3 nmol/l, respectively, and those of daidzein were 118.4 and 76.8 nmol/l, respectively. These levels are higher than those reported for Americans and Western Europeans. Isoflavone intake as calculated from dietary records (genistein: mean, 86.5 μmol/day and daidzein: mean, 57.4 μmol/day) was correlated with the plasma concentrations observed (genistein: r=0.287, p<0.01 and daidzein: r=0.313, p<0.01). Plasma enterolactone levels were low in Japanese women (mean, about 10 nmol/l). The levels of urinary excretions of genistein, daidzein were also measured and it was found that, in the majority, the levels ranged between 5–25 and 5–50 μmol/24 h, respectively. In contrast, healthy Finnish women showed very low values of isoflavones (below 10nmol/l in plasma (n=87) and below 0.6 μmol/24h in urine (n=126) for both compounds) and high levels of enterolactone in both plasma and urine (plasma: mean, 25nmol/l and urine: majority range, 1–7 μmol/24 h).
Attenuation of neurodegeneration‐relevant modifications of brain proteins by dietary soy
Authors: Kim Helen , Xia Hongli , Li Lin , Gewin John
Published: December 2008

Epidemiological studies show that postmenopausal women who undertake estrogen‐replacement therapy have significantly lower risk for the onset of Alzheimer's disease (AD) than women who do not. Animal behavior studies have shown that ovariectomy results in the development of cognitive dysfunction that is prevented by estrogen‐replacement, suggesting that normal mammalian cognitive function is impaired by estrogen reduction. Soy isoflavones in particular genistein have been demonstrated to have weak and selective estrogenic actions in various models of human chronic diseases. A hallmark of several human dementias including AD and fronto temporal dementia with Parkinsonism on chromosome 17 (FTDP‐17) is the hyperphosphorylation of the microtubule‐associated protein tau. Preliminary experiments are discussed here which show that isoflavones delivered in a soy protein matrix attenuated selected AD‐relevant tau phosphorylations in a primate model of menopause. The rationale is discussed for the use of soy‐based foods for protection against postmenopausal neurodegeneration.