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PubMed2000

Thickening infant formula with digestible and indigestible carbohydrate: availability of calcium, iron, and zinc in vitro.

BACKGROUND: Regurgitation is common in infants and is usually due to gastroesophageal reflux. Often parental reassurance and dietary management by feeding thickened formulas are the only therapeutic steps necessary. Adding fibers may interfere with the absorption of micronutrients. METHODS: A continuous-flow dialysis in vitro method with a preliminary intraluminal digestive phase, modified to simulate the conditions of infants less than 6 months of age and children from 6 months of age on, was used to study the availability of calcium, iron, and zinc from thickened and nonthickened first-and second-age infant formulas. Pooled mature human milk was used as the reference standard. The elemental content of the samples and dialysate fractions of calcium, iron, and zinc after digestion was determined by atomic absorption spectrometry. RESULTS: In human milk, calcium, iron, and zinc were highly available for absorptive processes. Availability of calcium, iron, and zinc from nonthickened first- and second-age infant formulas tends to be significantly better than in the corresponding products thickened with locust bean gum. Thickening infant formulas with pregelatinized rice starch, however, does not affect the availability of calcium, iron, and zinc. CONCLUSIONS: It appears that human milk provides optimal conditions for the availability of calcium, iron, and zinc. Availability of calcium, iron, and zinc seems to lower when infant formulas are thickened with indigestible carbohydrates, whereas it does not by adding digestible carbohydrates.

Biological Availability↗
PubMed2005

Profiling of structurally labile oxylipins in plants by in situ derivatization with pentafluorobenzyl hydroxylamine.

A GC-MS-based method for the simultaneous quantification of common oxylipins along with labile and highly reactive compounds based on in situ derivatization with pentafluorobenzyl hydroxylamine to the corresponding O-2,3,4,5,6-pentafluorobenzyl oximes (PFB oximes) is presented. The approach covers oxo derivatives such as jasmonic acid (JA), 12-oxophytodienoic acid (OPDA), certain phytoprostanes, unsaturated oxo-acids, oxo-hydroxy acids, and aldehyde fragments from the polar head of fatty acids. In the positive electron impact-MS mode, the PFB oximes display characteristic fragment ions that greatly facilitate the identification of oxylipins in complex matrices. In addition, the fluorinated derivatives allow a highly selective and low-background analysis by negative chemical ionization. Besides showing the general value of the method for the identification of a broad range of oxylipins (18 examples), we also demonstrate sensitivity, linearity, and reproducibility for the quantification of JA, OPDA, 11-oxo-9-undecenoic acid, and 13-oxo-9,11-tridecadienoic acid. The efficiency of the method is demonstrated by differential profiling of these four oxylipins in lima bean leaves after mechanical wounding and feeding by the herbivore Spodoptera littoralis. Caterpillar feeding induced several oxylipins, whereas after wounding only the level of JA increased. The rapid in situ derivatization prevents the isomerization of cis-JA to trans-JA. The resting level of JA in lima beans showed an isomer ratio of 80:20 for trans/cis-JA. After wounding, de novo synthesis of JA alters the ratio to 20:80 in favor of the cis isomer.

Animals↗
PubMed2003

Blue-light- and phosphorylation-dependent binding of a 14-3-3 protein to phototropins in stomatal guard cells of broad bean.

Phototropins are blue-light (BL) receptor serine (Ser)/threonine kinases, and contain two light, oxygen, and voltage (LOV) domains, and are members of the PAS domain superfamily. They mediate phototropism, chloroplast movement, leaf expansion, and stomatal opening of higher plants in response to BL. In stomatal guard cells, genetic analysis has revealed that phototropins mediate activation of the plasma membrane H+-ATPase by phosphorylation and drive stomatal opening. However, biochemical evidence for the involvement of phototropins in the BL response of stomata is lacking. Using guard cell protoplasts, we showed that broad bean (Vicia faba) phototropins (Vfphots) were phosphorylated by BL, and that this phosphorylation of Vfphots reached to the maximum level earlier than that of the H+-ATPase. Phosphorylation of both Vfphots and H+-ATPase showed similar sensitivity to BL and were similarly suppressed by protein kinase and flavoprotein inhibitors. We found that a 14-3-3 protein was bound to Vfphots upon phosphorylation, and this binding occurred earlier than the H+-ATPase phosphorylation. Vfphots (Vfphot1a and Vfphot1b) were expressed in Escherichia coli, and phosphorylation sites were determined to be Ser-358 for Vfphot1a and Ser-344 for Vfphot1b, which are localized between LOV1 and LOV2. We conclude that Vfphots act as BL receptors in guard cells and that phosphorylation of a Ser residue between LOV1 and LOV2 and subsequent 14-3-3 protein binding are likely to be key steps of BL response in stomata. The binding of a 14-3-3 protein to Vfphot was found in etiolated seedlings and leaves in response to BL, suggesting that this event was common to phototropin-mediated responses.

14-3-3 Proteins↗
PubMed1995

The bioavailability of iron in different weaning foods and the enhancing effect of a fruit drink containing ascorbic acid.

There is limited information on the bioavailability of Fe in infant weaning foods, mainly because of the difficulties of measuring Fe utilization directly in infants. The aim of this study was to develop a safe and relatively noninvasive method for studying Fe bioavailability (measured as percent Fe incorporation into red blood cells) in infants using 54Fe, 57Fe, and 58Fe stable isotopes. Four commonly used weaning foods were selected for study, labeled extrinsically with 57Fe- or 58Fe-enriched ferrous sulfate, and fed to five female and five male 9-mo-old fasting infants, using a multiple-dosing technique. Each food was given three times, labeled with one isotope, with a fruit juice drink containing 50 mg of ascorbic acid, and three times, labeled with a different isotope, with an ascorbic acid-free drink. Fourteen days after the last test meal, a blood sample was obtained from a heel-prick, spiked with a known amount of 54Fe, digested, and purified by ion exchange; isotopic enrichment and total Fe content were measured by quadrupole thermal ionization mass spectrometry. The proportion of administered dose of isotope circulating in the blood was calculated from an estimate of blood volume. The geometric mean bioavailability (range) was 3.0% (1.2-9.5%) in a proprietary dehydrated vegetable product, 3.0% (1.1-21.2%) in Weetabix whole-wheat breakfast cereal, 3.1% (1.2-15.4%) in wholemeal bread, and 4.3% (1.7-10.3%) in baked beans. When taken with the drink containing ascorbic acid, there was a 2-fold increase in bioavailability in all foods except the vegetable meal, presumably because this was already fortified with ascorbic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1996

Structure of a Kunitz-type chymotrypsin from winged bean seeds at 2.95 A resolution.

Thc crystal structure of an alpha-chymotrypsin inhibitor (P6(1)22; a = 61.4, c = 210.9 A) isolated from winged bean (Psophocarpus. tetragonolobus) seeds has been determined at 2.95 A resolution by the molecular-replacement method using the 2.6 A coordinates of Erythrina trypsin inhibitor (ETI) as the starting model (57% sequence homology). This protease inhibitor, WCI, belongs to the Kunitz (STI) family and is a single polypeptide chain with 183 amino-acid residues having a molecular weight of 20 244 Da. Structure refinement with RESTRAIN and X-PLOR has led to a crystallographic R factor of 19.1% for 3469 observed reflections (I > 2sigma) in the resolution range 8-2.95 A. A total of 56 water molecules have been incorporated in the refined model containing 181 amino-acid residues. In the refined structure the deviations of bond lengths and bond angles from ideal values are 0.015 A and 2.2 degrees, respectively. The inhibitor molecule is spherical and consists of 12 antiparallel beta-strands with connecting loops arranged in a characteristic folding (a six-stranded beta-barrel and a six-stranded lid on one hollow end of the barrel) common to other homologous serine protease inhibitors in the Kunitz (STI) family as well as to some non-homologous proteins like interleukin-lalpha and interleukin-lbeta. In the structure the conformation of the protruding reactive-site loop is stabilized through hydrogen bonds mainly formed by the side chain of Asnl4, which intrudes inside the cavity of the reactive-site loop, with the side-chain and main-chain atoms of some residues in the loop region. A pseudo threefold axis exists parallel to the barrel axis of the structure. Each of the three subdomains comprises of four beta-strands with connecting loops.

Journal Article↗
PubMed1983

Influenza B: hospital activity during a community epidemic.

During a community epidemic of influenza B, surveillance throat cultures for influenza were collected from febrile adult patients and hospital employees on three medical wards to determine the frequency and source of influenza among hospitalized patients. Twenty-five cases of influenza B (18.5% of febrile patients) were identified; no clusters of influenza-like illness occurred. The attack rate on two wards was 4.6%. Peak hospital influenza incidence followed that in the community by 1-2 weeks. Twelve of the cases were community-acquired and 13 were nosocomial. 75% of community-acquired cases had three or more common influenza B symptoms, compared with only 39% of nosocomial cases. A viral etiology of fever was suspected clinically in one-half of the cases, but influenza was specifically suspected in only one case. Two ill culture-positive nurses were identified on the job but no asymptomatic carriers were found among ward personnel. We conclude that influenza B cases were present among hospitalized patients in the absence of recognizable clusters of disease and that patients with community-acquired illness as well as nursing personnel may have introduced influenza into the hospital. Influenza B may be difficult to diagnose clinically in hospitalized patients, but viral throat cultures performed in all suspected cases should identify many infected patients.

Adult↗
PubMed2004

What are the health effects of fat?

In order to answer the question which health benefits are to be expected from dietary fat, we have to differentiate between different kinds of fat with varying fatty acid composition. Saturated fatty acids are commonly judged to have a negative health impact as they lead to increased serum cholesterol levels and a higher risk of coronary heart disease. Therefore, all recommendations stress the importance to limit the intake of saturated fatty acids. Monounsaturated fatty acids, on the other hand, have a positive impact on the serum lipid profile, lead to decreased LDL-oxidation and favorably influence the metabolism of diabetics. However, it is essential that monounsaturated fatty acids be mainly supplied by plant oils like rape seed or olive oil and not by foods that are simultaneously rich in saturated fatty acids. Concerning polyunsaturated fatty acids, it is important to increase the supply of n-3 fatty acids (ratio of n-6:n-3: about 5:1) as there is substantial evidence for their protective effects. If the fatty acid composition of the diet is optimized, even a total dietary fat content of 35% of total energy intake can be adequate as long as there is enough physical activity and the diet is rich in plant-derived foods like vegetables, fruits, cereals, potatoes, beans and legumes.

Cholesterol↗
PubMedDate not supplied

Using laboratory-based surveillance data for prevention: an algorithm for detecting Salmonella outbreaks.

By applying cumulative sums (CUSUM), a quality control method commonly used in manufacturing, we constructed a process for detecting unusual clusters among reported laboratory isolates of disease-causing organisms. We developed a computer algorithm based on minimal adjustments to the CUSUM method, which cumulates sums of the differences between frequencies of isolates and their expected means; we used the algorithm to identify outbreaks of Salmonella Enteritidis isolates reported in 1993. By comparing these detected outbreaks with known reported outbreaks, we estimated the sensitivity, specificity, and false-positive rate of the method. Sensitivity by state in which the outbreak was reported was 0%(0/1) to 100%. Specificity was 64% to 100%, and the false-positive rate was 0 to 1.

Algorithms↗
PubMed1984

Fasting breath hydrogen concentration: normal values and clinical application.

Excretion of hydrogen in breath commonly persists despite an overnight fast. Although elevation of hydrogen concentration above the fasting value after administration of a test sugar is evidence of malabsorption, the significance of the fasting value itself is unknown. We determined the normal limits of fasting breath hydrogen in healthy children and adults, and in patients with chronic diarrhea or recurrent abdominal pain. Fasting breath hydrogen in 221 healthy children and 9 healthy adults averaged 7.1 +/- 5.0 parts per million (mean +/- SD), exceeding 30 parts per million in less than 1%. No value exceed 42 parts per million. In 73 patients with recurrent abdominal pain and 76 patients with chronic diarrhea, fasting breath hydrogen was less than 42 parts per million in 97% and 83%, respectively. History and laboratory data were reviewed in the 15 patients where fasting breath hydrogen exceeded 42 parts per million. Seven had documented small bowel bacterial overgrowth and an additional 3 patients had radiographic evidence of intestinal stasis. Using test dinner meals, we prospectively evaluated the effect of previously ingested foods containing complex carbohydrates on fasting breath hydrogen. Dinner meals consisting of rice, wheat, or beans influenced fasting breath hydrogen values, but did not result in elevated fasting breath hydrogen in healthy individuals. Rice bread resulted in uniformly low fasting breath hydrogen values in healthy subjects (2.0 +/- 2.5 parts per million), but fasting breath hydrogen remained elevated in patients with bacterial overgrowth. Our studies indicate that conditions for measurement of the fasting breath hydrogen value may be standardized to improve discrimination between normal and abnormal values.

Abdomen↗
PubMed2006

Lineage-specific expansions provide genomic complexity among sea urchin GTPases.

In every organism, GTP-binding proteins control many aspects of cell signaling. Here, we examine in silico several GTPase families from the Strongylocentrotus purpuratus genome: the monomeric Ras superfamily, the heterotrimeric G proteins, the dynamin superfamily, the SRP/SR family, and the "protein biosynthesis" translational GTPases. Identified were 174 GTPases, of which over 90% are expressed in the embryo as shown by tiling array and expressed sequence tag data. Phylogenomic comparisons restricted to Drosophila, Ciona, and humans (protostomes, urochordates, and vertebrates, respectively) revealed both common and unique elements in the expected composition of these families. Galpha and dynamin families contain vertebrate expansions, consistent with whole genome duplications, whereas SRP/SR and translational GTPases are highly conserved. Unexpectedly, Ras superfamily analyses revealed several large (5+) lineage-specific expansions in the sea urchin. For Rho, Rab, Arf, and Ras subfamilies, comparing total human gene numbers to the number of sea urchin genes with vertebrate orthologs suggests reduced genomic complexity in the sea urchin. However, gene duplications in the sea urchin increase overall numbers such that total sea urchin gene numbers approximate vertebrate gene numbers for each monomeric GTPase family. These findings suggest that lineage-specific expansions may be an important component of genomic evolution in signal transduction.

Animals↗
PubMed1991

Evolution of influenza A virus nucleoprotein genes: implications for the origins of H1N1 human and classical swine viruses.

A phylogenetic analysis of 52 published and 37 new nucleoprotein (NP) gene sequences addressed the evolution and origin of human and swine influenza A viruses. H1N1 human and classical swine viruses (i.e., those related to Swine/Iowa/15/30) share a single common ancestor, which was estimated to have occurred in 1912 to 1913. From this common ancestor, human and classical swine virus NP genes have evolved at similar rates that are higher than in avian virus NP genes (3.31 to 3.41 versus 1.90 nucleotide changes per year). At the protein level, human virus NPs have evolved twice as fast as classical swine virus NPs (0.66 versus 0.34 amino acid change per year). Despite evidence of frequent interspecies transmission of human and classical swine viruses, our analysis indicates that these viruses have evolved independently since well before the first isolates in the early 1930s. Although our analysis cannot reveal the original host, the ancestor virus was avianlike, showing only five amino acid differences from the root of the avian virus NP lineage. The common pattern of relationship and origin for the NP and other genes of H1N1 human and classical swine viruses suggests that the common ancestor was an avian virus and not a reassortant derived from previous human or swine influenza A viruses. The new avianlike H1N1 swine viruses in Europe may provide a model for the evolution of newly introduced avian viruses into the swine host reservoir. The NPs of these viruses are evolving more rapidly than those of human or classical swine viruses (4.50 nucleotide changes and 0.74 amino acid change per year), and when these rates are applied to pre-1930s human and classical swine virus NPs, the predicted date of a common ancestor is 1918 rather than 1912 to 1913. Thus, our NP phylogeny is consistent with historical records and the proposal that a short time before 1918, a new H1N1 avianlike virus entered human or swine hosts (O. T. Gorman, R. O. Donis, Y. Kawaoka, and R. G. Webster, J. Virol. 64:4893-4902, 1990). This virus provided the ancestors of all known human influenza A virus genes, except for HA, NA, and PB1, which have since been reassorted from avian viruses. We propose that during 1918 a virulent strain of this new avianlike virus caused a severe human influenza pandemic and that the pandemic virus was introduced into North American swine populations, constituting the origin of classical swine virus.

Amino Acid Sequence↗
PubMed1994

In vitro effect of vegetable and fruit juices on the mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline.

The antimutagenic potencies of the juices of 28 fruits and 34 vegetables commonly consumed in Germany were investigated with respect to the mutagenic activities induced by 2-amino-3-methyl[4,5-f]-quinoline (IQ), and in part by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in Salmonella typhimurium TA98 and TA100. With IQ, weak to strong antimutagenic activities were found in 68% of the fruits and 73% of the vegetables that were tested. In fruits, strong antimutagenic activities were detected in bananas, blackberries, blueberries, sweet and sour cherries, blackcurrants and redcurrants, pineapple and watermelon. Moderate antimutagenic activities were detected in greengage, kiwi, mangos, honeydew melons and plums. Weak antimutagenic activities were detected in apple, apricot, mirabelle, pears, peaches and strawberries, whereas white and red grapes and raspberries were inactive, and gooseberries and citrus fruits in general possessed marginal or no antimutagenic activities. In vegetables, strong to moderate antimutagenic activities were found for all cruciferous vegetables, except Chinese cabbage, which had only weak antimutagenic activity. Other vegetables with strong antimutagenic activities were beets, chives, horseradish, onions, rhubarb and spinach. Moderate antimutagenic activities were found with green beans and tomatoes, weak activities in eggplant, garden cress, many lettuces, leeks, mangold, cucumber, pumpkin, radish and summer squash. Asparagus, carrots, fennel leaves, parsley, green peppers and radishes were inactive. When fruit and vegetable juices were heated, a considerable reduction of antimutagenic potencies was seen with apple, apricot, kiwi, pineapple, beets, cabbage (Chinese, Savoy, red and white), cauliflower, leafy lettuce, cucumber, onions, radish and rhubarb. Antimutagenic factors in blackberries, blueberries, sweet and sour cherries, honeydew melons, mirabelle, plums, strawberries, Brussels sprouts, chicory greens, eggplant, garden cress, mangold, pumpkin, lamb's lettuce and spinach were, however, remarkably heat stable. Antimutagenic potencies in bananas, blackcurrants and redcurrants, greengages, gooseberries, mangos, watermelon, green beans, kohlrabi, horseradish, tomatoes and chives were partially reduced. Antimutagenic activities in the juices of eight apple cultivars were moderate in two, weak in four, and marginal or absent in two. No major differences, however, were detected in five batches of oranges and three batches each of grapefruits, asparagus, green beans, broccoli, cauliflower, spinach and tomatoes. No (or only minor) differences were seen between IQ, MeIQ and MeIQx and tester strains TA98 and TA100. Pineapple and celeriac juices inhibited the enzymatic system responsible for the activation of IQ, but had no desmutagenic activity. Peroxidase activity found to be present in broccoli, cauliflower, green beans and tomatoes may contribute to antimutagenic activities in these vegetables.

Animals↗
PubMed2002

Nucleotide sequence shows that Bean leafroll virus has a Luteovirus-like genome organization.

The complete nucleotide sequence of the Bean leafroll virus (BLRV) genomic RNA and the termini of its smallest subgenomic RNAs were determined to better understand its mechanisms of gene expression and replication and its phylogenetic position within the Luteoviridae: The number and placement of open reading frames (ORFs) within the BLRV genome was Luteovirus-like. The nucleotide and predicted amino acid sequences of BLRV were most similar to those of Soybean dwarf virus (SbDV). Phylogenetic analyses employing the neighbour-joining method and sister-scanning analysis indicated that the BLRV nonstructural proteins were closely related to those of Barley yellow dwarf virus-PAV (BYDV-PAV), a luteovirus: The region surrounding the frameshift at the junction between ORFs 1 and 2 also contained sequences very similar to those of BYDV-PAV and a Dianthovirus, Red clover necrotic mosaic virus. Similar analyses showed that the structural proteins were most similar to those of the Polerovirus genus. The 3'-noncoding regions downstream of ORF5 contained sequences similar to translational control elements identified in the BYDV-PAV genome. These data suggest that BLRV, like SbDV, is derived either through selection from a common ancestor with BYDV-PAV or that BLRV is the product of two recombination events between luteovirus-like and polerovirus-like ancestors where the 5' 2900 nt and 3' 700 nt of the BLRV genome are from a Luteovirus and the intervening sequences are derived from a Polerovirus:

3' Untranslated Regions↗
PubMed1976

Fibrinolysis in normal plasma and blood: evidence for significant mechanisms independent of the plasminogen-plasmin system.

Fibrinolytic activity of normal plasma and blood has been measured by 125l-fibrin solid phase assay. Activity of plasma is not affected by removal of plasminogenplasmin by affinity chromatography. Activities of euglobulin and pseudoglobulin fractions are approximately equal. epsilon-aminocaproic acid (EACA) (10 mM), tranexamic acid (10 mM), diisopropylfluorophosphate (DFP, 50 mM), and soybean and lima bean trypsin inhibitors (100 mug/ml) do not inhibit plasma activity at concentrations that inhibit pure plasmin and urokinase-activated plasma. Activity is not affected by glass contact and is not inhibited by inhibitors of contact or enzymatic activation of Hageman factor (hexadimethrine bromide, 100 mug/ml; cytochrome C, 250 mug/ml; spermidine, 2 mM; phenylmethylsulfonylfluoride, 1 mM). It is inhibited partially (30%-40%) by heating (56 degrees C, 30 min) and by zymosan (2.5 mg/ml; 40%-90% inhibition), and is increased by hydrazine (20 mM), salicylaldoxime (20 mM), DFP (50 mM), and tosyl-L-arginine methyl ester (TAMe, 10 mM)-the latter two at concentrations known to inhibit Cls of the classic, and factor D of the alternate complement pathways. Increase fibrinolytic activity with TAMe is associated with reciprocal decrease in classic and alternate complement pathway activity. It is concluded that normal plasma fibrinolytic activity is relatively independent of plasmin as the ultimate fibrinolytic enzyme, that Hageman factor-dependent pathways are of minor importance, and that significant heat-stable and heat-labile nonplasmin fibrinolytic activities are operative. These may include proteinases involved in complement activation, and in common control of classic and alternate complement pathways, as well as other nonplasmin proteinases.

Aminocaproates↗
PubMed2005

Digital biology: an emerging and promising discipline.

This article examines the role of computation and quantitative methods in modern biomedical research to identify emerging scientific, technical, policy and organizational trends. It identifies common concerns and practices in the emerging community of computationally-oriented bio-scientists by reviewing a national symposium, Digital Biology: the Emerging Paradigm, held at the National Institutes of Health in Bethesda, Maryland, November 6th and 7th 2003. This meeting showed how biomedical computing promises scientific breakthroughs that will yield significant health benefits. Three key areas that define the emerging discipline of digital biology are: scientific data integration, multi-scale modeling and networked science. Each area faces unique technical challenges and information policy issues that must be addressed as the field matures. Here we summarize the emergent challenges and offer suggestions to academia, industry and government on how best to expand the role of computation in their scientific activities.

Computational Biology↗
PubMed1984

Effects of rotenoids on isolated plant mitochondria.

The effects of several rotenoids have been studied on potato (Solanum tuberosum L.) tuber and etiolated mung bean (Phaseolus aureus Roxb.) hypocotyls mitochondria. The selective inhibition of mitochondrial complex I is characterized by several tests: (a) no effect can be observed on exogenous NADH or succinate oxidation; (b) malate oxidation is inhibited at pH 7.5; (c) one-third decrease of ADP/O ratio appears during malate oxidation at pH 6.5 or during alpha-ketoglutarate, citrate, or pyruvate oxidation at a pH about 7; (d) during malate oxidation at pH 6.5, a transient inhibition appears which can be maintained by addition of exogenous oxaloacetate; (e) in potato mitochondria, the inhibition of malate oxidation disappears at pH 6.5 when NAD(+) is added. Then, a one-third decrease of the ADP/O ratio can be measured.Such a selective inhibition of complex I is obtained with deguelin, tephrosin, elliptone, OH-12 rotenone, and almost all the rotenoids extracted from Derris roots. The presence of the rings A, B, C, D, E seems to be necessary for the selective inhibition. Opening of the E ring and hydroxylation of the 9 position (rot-2'-enoic acid) give a rotenoid derivative with multisite inhibitory activities on flavoproteins, which are quite comparable to those of common flavonoids such as kaempferol (Ravanel et al. 1982 Plant Physiol 69: 375-378).

Journal Article↗
PubMed2000

Cell signaling and regulators of cell cycle as molecular targets for prostate cancer prevention by dietary agents.

Prostate cancer (PCA) is the most common invasive malignancy and leading cause (after lung) of cancer deaths in males. Since PCA is initially androgen-dependent, strategies are targeted toward androgen depletion for its control. However, tumor re-growth mostly occurs following this modality, and is androgen-independent. A loss of functional androgen receptor and an enhanced expression of growth factor receptors (e.g. erbB family members) and associated ligands have been shown to be the causal genetic events in PCA progression. These genetic alterations lead to an epigenetic mechanism where a feed-back autocrine loop between membrane receptor (e.g. epidermal growth factor receptor [erbB1] and associated ligand (e.g. transforming growth factor-alpha) results in an enhanced activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) as an essential component of the uncontrolled growth of PCA at an advanced and androgen-independent stage. Together, we rationalized that inhibiting these epigenetic events would be useful in controlling advanced PCA growth. Dietary polyphenolic flavonoids and isoflavones are being studied extensively as cancer-preventive and interventive agents. Therefore, we focused our attention on silymarin, genistein, and epigallocatechin 3-gallate (EGCG), present in milk thistle, soy beans, and green tea, respectively. The effect of these agents was assessed on the erbB1-Shc-ERK1/2 signal transduction pathway, cell cycle regulatory molecules, and cell growth and death. In androgen-independent human prostate carcinoma DU145 cells, silymarin, genistein, and EGCG resulted in a significant to complete inhibition of transforming growth factor-alpha-caused activation of membrane receptor erbB1 followed by inhibition of downstream cytoplasmic signaling target Shc activation and a decrease in its binding with erbB1, without an alteration in their protein expression. Silymarin and genistein also inhibited ERK1/2 activation, suggesting that these agents impair the activation of erbB1-Shc-ERK1/2 signaling in DU145 cells. In the case of EGCG, a further increase in ERK1/2 activation was observed that was related to its pro-oxidant and apoptotic activities. Silymarin, genistein, and EGCG also resulted in a significant induction of Cip1/p21 and Kip1/p27 and a decrease in cyclin-dependent kinase (CDK) 4, but a moderate inhibition of CDK2, cyclin D1, and cyclin E was observed. An enhanced level of Cip1/p21 and Kip1/27 also led to an increase in their binding to CDK4 and CDK2. Treatment of cells with silymarin, genistein, and EGCG also resulted in strong cell growth inhibition at lower doses, and complete inhibition at higher doses. In contrast to silymarin, higher doses of genistein also showed cell death. A more profound cytotoxic effect was observed in the case of EGCG, with strong cell death at lower doses and complete loss of viability at higher doses. Together, these results suggest that cell signaling and regulators of cell cycle are potential epigenetic molecular targets for prostate cancer prevention by dietary agents. More studies, therefore, are needed with these agents to explore their anticarcinogenic potential against human prostate cancer.

Anticarcinogenic Agents↗
PubMed2006

A newly constructed and validated isoflavone database for the assessment of total genistein and daidzein intake.

The principal phyto-oestrogens (PO) in food are isoflavones, lignans, coumestans and prenylated flavonoids, with isoflavones and lignans being the most commonly found in UK diets. Until recently obtaining accurate data on the PO content of foods was hampered by lack of suitable analytical methods and validation techniques. Furthermore, although PO data exist for some foods, these foods may not be available in the UK. The aim of the present study was to construct a new, comprehensive isoflavone (total genistein + daidzein) database. Using data, mainly from recent GC-MS analysis, for approximately 300 foods available in the UK, and extensive recipe calculations, a new database was constructed containing approximately 6000 foods allocated an isoflavone value. By analysing 7 d weighed food diaries, the database was subsequently used to estimate isoflavone intake in two groups of healthy volunteers, omnivores (n 9) and vegetarians (n 10). Mean isoflavone intake in the vegetarian and omnivorous group was 7.4 (sem 3.05) and 1.2 (sem 0.43) mg/d, respectively. Mean intake for the total group was 4.5 (sem 1.89) mg/d. Main food sources of isoflavones for the vegetarian group were soya milk (plain), meat-substitute foods containing textured vegetable protein and soya protein isolate, soya mince, wholemeal bread and rolls, white bread and rolls, croissants and pitta breads, beans, raisins and soya sauce. Main food sources of isoflavones for the omnivorous group were soya yogurts, wholemeal bread and rolls, white bread and rolls, garlic bread, nan bread and brown bread, sultanas and scones.

Adult↗