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Sample records for metabolite differences including

  1. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation

    Carroll, Jeffrey B.; Deik, Amy; Fossale, Elisa; Weston, Rory M.; Guide, Jolene R.; Arjomand, Jamshid; Kwak, Seung; Clish, Clary B.; MacDonald, Marcy E.

    2015-01-01

    The HTT CAG expansion mutation causes Huntington’s Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue), using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219) in the striatum to 12% (25/212) in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219) of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224) in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and most evident

  2. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation.

    Jeffrey B Carroll

    Full Text Available The HTT CAG expansion mutation causes Huntington's Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue, using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219 in the striatum to 12% (25/212 in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219 of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224 in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and

  3. Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

    Prueksaritanont, Thomayant; Lin, Jiunn H.; Baillie, Thomas A.

    2006-01-01

    This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models

  4. Subcellular localization of secondary lipid metabolites including fragrance volatiles in carnation petals

    Hudak, K.A.; Thompson, J.E.

    1997-01-01

    Pulse-chase labeling of carnation (Dianthus caryophyllus L. cv Improved White Sim) petals with [14C]acetate has provided evidence for a hydrophobic subcompartment of lipid-protein particles within the cytosol that resemble oil bodies, are formed by blebbing from membranes, and are enriched in lipid metabolites (including fragrance volatiles) derived from membrane fatty acids. Fractionation of the petals during pulse-chase labeling revealed that radiolabeled fatty acids appear first in microsomal membranes and subsequently in cytosolic lipid-protein particles, indicating that the particles originate from membranes. This interpretation is supported by the finding that the cytosolic lipid-protein particles contain phospholipid as well as the same fatty acids found in microsomal membranes. Radiolabeled polar lipid metabolites (methanol/ water-soluble) were detectable in both in situ lipid-protein particles isolated from the cytosol and those generated in vitro from isolated radiolabeled microsomal membranes. The lipid-protein particles were also enriched in hexanal, trans-2-hexenal, 1-hexanol, 3-hexen-1-ol, and 2-hexanol, volatiles of carnation flower fragrance that are derived from membrane fatty acids through the lipoxygenase pathway. Therefore, secondary lipid metabolites, including components of fragrance, appear to be formed within membranes of petal tissue and are subsequently released from the membrane bilayers into the cytosol by blebbing of lipid-protein particles

  5. Metabolite analysis of endophytic fungi from cultivars of Zingiber officinale Rosc. identifies myriad of bioactive compounds including tyrosol.

    Anisha, C; Radhakrishnan, E K

    2017-06-01

    Endophytic fungi associated with rhizomes of four cultivars of Zingiber officinale were identified by molecular and morphological methods and evaluated for their activity against soft rot pathogen Pythium myriotylum and clinical pathogens. The volatile bioactive metabolites produced by these isolates were identified by GC-MS analysis of the fungal crude extracts. Understanding of the metabolites produced by endophytes is also important in the context of raw consumption of ginger as medicine and spice. A total of fifteen isolates were identified from the four varieties studied. The various genera identified were Acremonium sp., Gliocladiopsis sp., Fusarium sp., Colletotrichum sp., Aspergillus sp., Phlebia sp., Earliella sp., and Pseudolagarobasidium sp. The endophytic community was unique to each variety, which could be due to the varying host genotype. Fungi from phylum Basidiomycota were identified for the first time from ginger. Seven isolates showed activity against Pythium, while only two showed antibacterial activity. The bioactive metabolites identified in the fungal crude extracts include tyrosol, benzene acetic acid, ergone, dehydromevalonic lactone, N-aminopyrrolidine, and many bioactive fatty acids and their derivatives which included linoleic acid, oleic acid, myristic acid, n-hexadecanoic acid, palmitic acid methyl ester, and methyl linoleate. The presence of these varying bioactive endophytic fungi may be one of the reasons for the differences in the performance of the different ginger varieties.

  6. BIOLOGIC AND ECONOMIC EFFECTS OF INCLUDING DIFFERENT ...

    The biologic and economic effects of including three agro-industrial by-products as ingredients in turkey poult diets were investigated using 48 turkey poults in a completely randomised design experiment. Diets were formulated to contain the three by-products – wheat offal, rice husk and palm kernel meal, each at 20% level ...

  7. Metabolite Profiling of Italian Tomato Landraces with Different Fruit Types

    Svetlana eBaldina

    2016-05-01

    Full Text Available Increased interest towards traditional tomato varieties is fueled by the need to rescue desirable organoleptic traits and to improve the quality of fresh and processed tomatoes in the market. In addition, the phenotypic and genetic variation preserved in tomato landraces represents a means to understand the genetic basis of traits related to health and organoleptic aspects and improve them in modern varieties. To establish a framework for this approach, we studied the content of several metabolites in a panel of Italian tomato landraces categorized into three broad fruit type classes (flattened/ribbed, pear/oxheart, round/elongate. Three modern hybrids, corresponding to the three fruit shape typologies, were included as reference. Red ripe fruits were morphologically characterized and biochemically analyzed for their content in glycoalkaloids, phenols, amino acids and Amadori products. The round/elongate types showed a higher content in glycoalkaloids, whereas flattened types had higher levels of phenolic compounds. Flattened tomatoes were also rich in total amino acids and in particular in glutamic acid. Multivariate analysis of amino acid content clearly separated the three classes of fruit types. Making allowance of the very low number of genotypes, phenotype-marker relationships were analyzed after retrieving single nucleotide polymorphisms (SNPs among the landraces available in the literature. Sixty-six markers were significantly associated with the studied traits. The positions of several of these SNPs showed correspondence with already described genomic regions and QTLs supporting the reliability of the association. Overall the data indicated that significant changes in quality-related metabolites occur depending on the genetic background in traditional tomato germplasm, frequently according to specific fruit shape categories. Such a variability is suitable to harness association mapping for metabolic quality traits using this germplasm

  8. Posterior paralimbic and frontal metabolite impairments in asymptomatic hypertension with different treatment outcomes

    Garcia Santos, J.M.; Fuentes, L.J.; Vidal, J.B.

    2010-01-01

    Hypertension is associated with cognitive decline in elderly persons. We studied asymptomatic hypertensive subjects using brain magnetic resonance (MR) spectroscopy to evaluate metabolite impairments before the appearance of symptoms in patients with different treatment outcomes. In all, 14 healthy controls and 37 asymptomatic hypertensive patients (17 controlled and 20 resistant) underwent brain structural MR and MR spectroscopy of the posterior paralimbic (PPL) area and left frontal white matter. Ischemic burden (IB), global cortical atrophy and microbleeds were analyzed with visual scales. Metabolite ratios involving N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho) and myoinositol (ml) were computed. Ultrasound measurements, including intima-media thickness, plaques and hemodynamic ratios, were obtained. Intergroup differences in IB, atrophy and metabolite ratios, and the atrophy and IB relationship were assessed with parametric and nonparametric statistical tests. In addition, the impacts of demographic, analytic and clinical factors, ischemia and atrophy, and ultrasound measurements on metabolite ratios were assessed. The significance level was set at P≤0.05. Higher atrophy scores presented with higher total or frontal IB (P<0.05). However, there was no intergroup difference in atrophy and IB. PPL ml/Cr was increased in resistant hypertension (P<0.021), whereas frontal NAA/Cr (P<0.007) showed opposite trends between controlled (increased ratios) and resistant (decreased ratios) hypertension. Unlike PPL ml/Cr, frontal NAA/Cr showed significant correlations with the lipid profile and ultrasound measurements. PPL ml/Cr increases in resistant hypertension, and frontal NAA/Cr diverges between controlled and resistant hypertension before physical and neuropsychological symptoms appear. (author)

  9. Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders.

    Kang, Dae-Wook; Ilhan, Zehra Esra; Isern, Nancy G; Hoyt, David W; Howsmon, Daniel P; Shaffer, Michael; Lozupone, Catherine A; Hahn, Juergen; Adams, James B; Krajmalnik-Brown, Rosa

    2018-02-01

    Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using 1 H-NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies; children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites-caprate, nicotinate, glutamine, thymine, and aspartate-may potentially function as a modest biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of phylotypes most closely related to Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. Despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further

  10. Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders

    Kang, Dae-Wook; Ilhan, Zehra Esra; Isern, Nancy G.; Hoyt, David W.; Howsmon, Daniel P.; Shaffer, Michael; Lozupone, Catherine A.; Hahn, Juergen; Adams, James B.; Krajmalnik-Brown, Rosa

    2018-02-01

    Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies; children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites- caprate, nicotinate, glutamine, thymine, and aspartate- may potentially function as a biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. Despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further investigation of metabolites in larger cohorts.

  11. Seed metabolomic study reveals significant metabolite variations and correlations among different soybean cultivars.

    Lin, Hong; Rao, Jun; Shi, Jianxin; Hu, Chaoyang; Cheng, Fang; Wilson, Zoe A; Zhang, Dabing; Quan, Sheng

    2014-09-01

    Soybean [Glycine max (L.) Merr.] is one of the world's major crops, and soybean seeds are a rich and important resource for proteins and oils. While "omics" studies, such as genomics, transcriptomics, and proteomics, have been widely applied in soybean molecular research, fewer metabolomic studies have been conducted for large-scale detection of low molecular weight metabolites, especially in soybean seeds. In this study, we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed. Among the 169 detected metabolites, 104 were found to be significantly variable in their levels across tested cultivars. Metabolite markers that could be used to distinguish genetically related soybean cultivars were also identified, and metabolite-metabolite correlation analysis revealed some significant associations within the same or among different metabolite groups. Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield. © 2014 Institute of Botany, Chinese Academy of Sciences.

  12. Seed metabolomic study reveals significant metabolite variations and correlations among different soybean cultivars

    Hong Lin; Jun Rao; Jianxin Shi; Chaoyang Hu; Fang Cheng; Zoe AWilson; Dabing Zhang; Sheng Quan

    2014-01-01

    Soybean [Glycine max (L.) Merr.] is one of the world’s major crops, and soybean seeds are a rich and important resource for proteins and oils. While “omics”studies, such as genomics, transcriptomics, and proteomics, have been widely applied in soybean molecular research, fewer metabolomic studies have been conducted for large-scale detection of low molecular weight metabolites, especial y in soybean seeds. In this study, we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed. Among the 169 detected metabolites, 104 were found to be significantly variable in their levels across tested cultivars. Metabolite markers that could be used to distinguish genetical y related soybean cultivars were also identified, and metabolite-metabolite correlation analysis revealed some significant associations within the same or among different metabolite groups. Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield.

  13. Differences in metabolite profiles caused by pre-analytical blood processing procedures.

    Nishiumi, Shin; Suzuki, Makoto; Kobayashi, Takashi; Yoshida, Masaru

    2018-05-01

    Recently, the use of metabolomic analysis of human serum and plasma for biomarker discovery and disease diagnosis in clinical studies has been increasing. The feasibility of using a metabolite biomarker for disease diagnosis is strongly dependent on the metabolite's stability during pre-analytical blood processing procedures, such as serum or plasma sampling and sample storage prior to centrifugation. However, the influence of blood processing procedures on the stability of metabolites has not been fully characterized. In the present study, we compared the levels of metabolites in matched human serum and plasma samples using gas chromatography coupled with mass spectrometry and liquid chromatography coupled with mass spectrometry. In addition, we evaluated the changes in plasma metabolite levels induced by storage at room temperature or at a cold temperature prior to centrifugation. As a result, it was found that 76 metabolites exhibited significant differences between their serum and plasma levels. Furthermore, the pre-centrifugation storage conditions significantly affected the plasma levels of 45 metabolites. These results highlight the importance of blood processing procedures during metabolome analysis, which should be considered during biomarker discovery and the subsequent use of biomarkers for disease diagnosis. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  14. Characteristic differences in metabolite profile in male and female ...

    2012-10-30

    Oct 30, 2012 ... CSIR-Central Drug Research Institute, Lucknow 226 001, India. 3Indian Institute of ... representing two metabolic types. [Bajpai V ... Material and methods. Fully grown ... gender-associated qualitative or quantitative difference.

  15. Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions

    Eugene B. Chang

    2013-01-01

    Full Text Available Compound K (20-O-beta-D-glucopyranosyl-20(S-protopanaxadiol, CK, an intestinal bacterial metabolite of ginseng protopanaxadiol saponins, has been shown to inhibit cell growth in a variety of cancers. However, the mechanisms are not completely understood, especially in colorectal cancer (CRC. A xenograft tumor model was used first to examine the anti-CRC effect of CK in vivo. Then, multiple in vitro assays were applied to investigate the anticancer effects of CK including antiproliferation, apoptosis and cell cycle distribution. In addition, a qPCR array and western blot analysis were executed to screen and validate the molecules and pathways involved. We observed that CK significantly inhibited the growth of HCT-116 tumors in an athymic nude mouse xenograft model. CK significantly inhibited the proliferation of human CRC cell lines HCT-116, SW-480, and HT-29 in a dose- and time-dependent manner. We also observed that CK induced cell apoptosis and arrested the cell cycle in the G1 phase in HCT-116 cells. The processes were related to the upregulation of p53/p21, FoxO3a-p27/p15 and Smad3, and downregulation of cdc25A, CDK4/6 and cyclin D1/3. The major regulated targets of CK were cyclin dependent inhibitors, including p21, p27, and p15. These results indicate that CK inhibits transcriptional activation of multiple tumor-promoting pathways in CRC, suggesting that CK could be an active compound in the prevention or treatment of CRC.

  16. Suddenly included: cultural differences in experiencing re-inclusion.

    Pfundmair, Michaela; Graupmann, Verena; Du, Hongfei; Frey, Dieter; Aydin, Nilüfer

    2015-03-01

    In the current research, we examined whether re-inclusion (i.e. the change from a previous state of exclusion to a new state of inclusion) was perceived differently by people with individualistic and collectivistic cultural backgrounds. Individualists (German and Austrian participants) but not collectivists (Chinese participants) experienced re-inclusion differently than continued inclusion: While collectivistic participants did not differentiate between both kinds of inclusion, individualistic participants showed reduced fulfilment of their psychological needs under re-inclusion compared to continued inclusion. The results moreover revealed that only participants from individualistic cultures expressed more feelings of exclusion when re-included than when continually included. These exclusionary feelings partially mediated the relationship between the different states of inclusion and basic need fulfilment. © 2014 International Union of Psychological Science.

  17. Quantitative comparison and metabolite profiling of saponins in different parts of the root of Panax notoginseng.

    Wang, Jing-Rong; Yau, Lee-Fong; Gao, Wei-Na; Liu, Yong; Yick, Pui-Wing; Liu, Liang; Jiang, Zhi-Hong

    2014-09-10

    Although both rhizome and root of Panax notoginseng are officially utilized as notoginseng in "Chinese Pharmacopoeia", individual parts of the root were differently used in practice. To provide chemical evidence for the differentiated usage, quantitative comparison and metabolite profiling of different portions derived from the whole root, as well as commercial samples, were carried out, showing an overall higher content of saponins in rhizome, followed by main root, branch root, and fibrous root. Ginsenoside Rb2 was proposed as a potential marker with a content of 0.5 mg/g as a threshold value for differentiating rhizome from other parts. Multivariate analysis of the metabolite profile further suggested 32 saponins as potential markers for the discrimination of different parts of notoginseng. Collectively, the study provided comprehensive chemical evidence for the distinct usage of different parts of notoginseng and, hence, is of great importance for the rational application and exploitation of individual parts of notoginseng.

  18. Quantitative Comparison and Metabolite Profiling of Saponins in Different Parts of the Root of Panax notoginseng

    Wang, Jing-Rong; Yau, Lee-Fong; Gao, Wei-Na; Liu, Yong; Yick, Pui-Wing; Liu, Liang; Jiang, Zhi-Hong

    2014-01-01

    Although both rhizome and root of Panax notoginseng are officially utilized as notoginseng in ?Chinese Pharmacopoeia?, individual parts of the root were differently used in practice. To provide chemical evidence for the differentiated usage, quantitative comparison and metabolite profiling of different portions derived from the whole root, as well as commercial samples, were carried out, showing an overall higher content of saponins in rhizome, followed by main root, branch root, and fibrous ...

  19. Cytoplasmic Acidification and Secondary Metabolite Production in Different Plant Cell Suspensions (A Comparative Study).

    Hagendoorn, MJM.; Wagner, A. M.; Segers, G.; Van Der Plas, LHW.; Oostdam, A.; Van Walraven, H. S.

    1994-10-01

    In this study, a correlation is described between low cytoplasmic pH, measured with the fluorescent probes 2[prime],7[prime]-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (acetoxymethyl ester) and bis- [3-propyl-5-oxoisoxazol-4-yl]pentamethine oxonol, and the production of secondary metabolites for several plant cell-suspension systems. Anthraquinone production in Morinda citrifolia suspensions is negligible in the presence of 2,4-dichlorophenoxyacetic acid (2,4-D), whereas with naphthalene acetic acid (NAA) a significant accumulation is realized. NAA-grown cells showed a lower cytoplasmic pH than did 2,4-D-grown cells. Addition of 2,4-D or parachlorophenoxy acetic acid to NAA-grown cells resulted in an inhibition of anthraquinone production and an increase of the cytoplasmic pH, whereas addition of parachlorophenyl acetic acid had no effect on either parameter. Lignin production in Petunia hybrida cells could be induced by subculturing them in a medium without iron. These cells showed a lower cytoplasmic pH than control cells. Addition of Fe3+ led to a decreased lignin content and an increased cytoplasmic pH. Two cell lines of Linum flavum showed a different level of coniferin and lignin concentration in their cells. Cells that accumulated coniferin and lignin had a lower cytoplasmic pH than cells that did not accumulate these secondary metabolites. Apparently, in different species and after different kinds of treatment there is a correlation between acidification of the cytoplasm and the production of different secondary metabolites. The possible role of this acidification in secondary metabolite production is discussed.

  20. Race and sex differences in small-molecule metabolites and metabolic hormones in overweight and obese adults.

    Patel, Mahesh J; Batch, Bryan C; Svetkey, Laura P; Bain, James R; Turer, Christy Boling; Haynes, Carol; Muehlbauer, Michael J; Stevens, Robert D; Newgard, Christopher B; Shah, Svati H

    2013-12-01

    In overweight/obese individuals, cardiometabolic risk factors differ by race and sex categories. Small-molecule metabolites and metabolic hormone levels might also differ across these categories and contribute to risk factor heterogeneity. To explore this possibility, we performed a cross-sectional analysis of fasting plasma levels of 69 small-molecule metabolites and 13 metabolic hormones in 500 overweight/obese adults who participated in the Weight Loss Maintenance trial. Principal-components analysis (PCA) was used for reduction of metabolite data. Race and sex-stratified comparisons of metabolite factors and metabolic hormones were performed. African Americans represented 37.4% of the study participants, and females 63.0%. Of thirteen metabolite factors identified, three differed by race and sex: levels of factor 3 (branched-chain amino acids and related metabolites, phormones regulating body weight homeostasis. Among overweight/obese adults, there are significant race and sex differences in small-molecule metabolites and metabolic hormones; these differences may contribute to risk factor heterogeneity across race and sex subgroups and should be considered in future investigations with circulating metabolites and metabolic hormones.

  1. [Effect of different fertilization treatments on yield and secondary metabolites of Codonopsis pilosula].

    Hu, Jia-Dong; Mao, Ge; Zhang, Zhi-Wei; Ma, Cun-de; Liang, Zong-Suo; Xia, Guang-Dong; Dong, Juan-E

    2017-08-01

    The research studies the effect of different fertilization treatments on yield and accumulation of secondary metabolites of Codonopsis pilosula by using single factor randomized block design, in order to ensure reasonable harvesting time and fertilization ratio, and provide the basis for standardized cultivation of C. pilosula. According to the clustering results, the nitrogen fertilizer benefitted for the improvement of root diameter and biomass of C. pilosula. The phosphate fertilizer could promote the content of C. pilosula polysaccharide. The organic fertilizers could increase the content of lobetyolin. With the time going on, C. pilosula's yield, polysaccharide and ehanol-soluble extracts increased while the content of lobetyolin decreased. According to various factors, October is a more reasonable harvest period. Organic fertilizers are more helpful to the yield and accumulation of secondary metabolites of C. pilosula. Copyright© by the Chinese Pharmaceutical Association.

  2. Synchronized Regulation of Different Zwitterionic Metabolites in the Osmoadaption of Phytoplankton

    Georg Pohnert

    2013-06-01

    Full Text Available The ability to adapt to different seawater salinities is essential for cosmopolitan marine phytoplankton living in very diverse habitats. In this study, we examined the role of small zwitterionic metabolites in the osmoadaption of two common microalgae species Emiliania huxleyi and Prorocentrum minimum. By cultivation of the algae under salinities between 16‰ and 38‰ and subsequent analysis of dimethylsulfoniopropionate (DMSP, glycine betaine (GBT, gonyol, homarine, trigonelline, dimethylsulfonioacetate, trimethylammonium propionate, and trimethylammonium butyrate using HPLC-MS, we could reveal two fundamentally different osmoadaption mechanisms. While E. huxleyi responded with cell size reduction and a nearly constant ratio between the major metabolites DMSP, GBT and homarine to increasing salinity, osmolyte composition of P. minimum changed dramatically. In this alga DMSP concentration remained nearly constant at 18.6 mM between 20‰ and 32‰ but the amount of GBT and dimethylsulfonioacetate increased from 4% to 30% of total investigated osmolytes. Direct quantification of zwitterionic metabolites via LC-MS is a powerful tool to unravel the complex osmoadaption and regulation mechanisms of marine phytoplankton.

  3. Differences in Urinary Arsenic Metabolites between Diabetic and Non-Diabetic Subjects in Bangladesh

    Tamie Nakajima

    2013-03-01

    Full Text Available Ingestion of inorganic arsenic (iAs is considered to be related to the development of diabetes mellitus. In order to clarify the possible differences in the metabolism in diabetics, we measured urinary iAs metabolites in diabetic cases and non-diabetic control subjects in Faridpur, an arsenic-contaminated area in Bangladesh. Physician-diagnosed type 2 diabetic cases (140 persons and non-diabetic controls (180 persons were recruited. Drinking water and spot urine samples were collected. Mean concentrations of total arsenic in drinking water did not differ between cases (85.1 μg/L and controls (85.8 μg/L. The percentage of urinary iAs (iAs% was significantly lower in cases (8.6% than in controls (10.4%, while that of dimethylarsinic acid (DMA% was higher in cases (82.6% than in controls (79.9%. This may have been due to the higher secondary methylation index (SMI in the former (11.6 rather than the latter (10.0. Adjusting for matching factors (sex and unions, and the additional other covariates (age and water arsenic significantly attenuated the differences in iAs%, SMI, and DMA%, respectively, though the difference in monomethylarsonic acid% was newly significant in the latter adjustment. Our study did not suggest any significant differences in urinary arsenic metabolites between diabetic and non-diabetic subjects.

  4. Characteristic differences in metabolite profile in male and female plants of dioecious Piper betle L.

    Bajpai, Vikas; Pandey, Renu; Negi, Mahendra Pal Singh; Bindu, K Hima; Kumar, Nikhil; Kumar, Brijesh

    2012-12-01

    Piper betle is a dioecious pan-Asiatic plant having cultural and medicinal uses. It belongs to the family Piperaceae and is a native of the tropics although it is also cultivated in subtropical areas. Flowering in P. betle occurs only in tropical regions. Due to lack of inductive floral cycles the plant remains in its vegetative state in the subtropics. Therefore, due to lack of flowering, gender distinction cannot be made the in the subtropics. Gender distinction in P. betle in vegetative state can be made using Direct Analysis in Real Time Mass Spectroscopy (DARTMS), a robust highthroughput method. DARTMS analysis of leaf samples of two male and six female plants showed characteristic differences in the spectra between male and female plants. Semi-quantitative differences in some of the identified peaks in male and female landraces showed gender-based differences in metabolites. Cluster analysis using the peaks at m/z 151, 193, 235 and 252 showed two distinct clusters of male and female landraces. It appears that male and female plants besides having flowers of different sexes also have characteristic differences in the metabolites representing two metabolic types.

  5. Cerebral metabolite differences in adolescents with low birth weight: assessment with in vivo proton MR spectroscopy

    Bathen, Tone F.; Gribbestad, Ingrid S.; Sjoebakk, Torill E.; Skranes, Jon; Brubakk, Ann-Mari; Martinussen, Marit; Vik, Torstein; Myhr, Gunnar E.; Axelson, David

    2006-01-01

    Children with very low birth weight (VLBW) have a significantly increased risk of later neurodevelopmental problems, while infants born small for gestational age (SGA) at term are also at some risk of developing neurological impairment. To investigate possible brain metabolite differences in adolescents with VLBW, SGA at term and controls by proton in vivo magnetic resonance spectroscopy (MRS) at 1.5 T. MR spectra were acquired from volumes localized in the left frontal lobe, containing mainly white matter (54 subjects). Peak areas of N-acetyl aspartate (NAA), choline (Cho) and creatine (Cr) were determined, and the peak area ratio of NAA to Cr, total Cho to Cr, or NAA to Cho calculated. Probabilistic neural network (PNN) analysis was performed utilizing the chemical shift region containing resonances from NAA, Cho and Cr as inputs. No significant difference in the peak area ratios could be found using the Kruskal-Wallis test. By application of PNN, a correct classification of 52 of the 54 adolescents with a sensitivity and specificity exceeding 93% for all groups was achieved. Small, yet systematic, differences in brain metabolite distribution among the groups were confirmed by PNN analysis. (orig.)

  6. Cerebral metabolite differences in adolescents with low birth weight: assessment with in vivo proton MR spectroscopy

    Bathen, Tone F.; Gribbestad, Ingrid S. [Norwegian University of Science and Technology, Department of Circulation and Medical Imaging, Trondheim (Norway); Sjoebakk, Torill E. [Department of Neuroscience, Norwegian University of Science and Technology, Trondheim (Norway); Skranes, Jon; Brubakk, Ann-Mari; Martinussen, Marit [St. Olavs Hospital HF, Department of Laboratory Medicine, Children' s and Women' s Health, Norwegian University of Science and Technology, Trondheim (Norway); Vik, Torstein [Norwegian University of Science and Technology, Department of Public Health and General Practise, Trondheim (Norway); Myhr, Gunnar E. [St. Olavs University Hospital, Department of Radiology, Trondheim (Norway); Axelson, David [MRi Consulting, Ontario (Canada)

    2006-08-15

    Children with very low birth weight (VLBW) have a significantly increased risk of later neurodevelopmental problems, while infants born small for gestational age (SGA) at term are also at some risk of developing neurological impairment. To investigate possible brain metabolite differences in adolescents with VLBW, SGA at term and controls by proton in vivo magnetic resonance spectroscopy (MRS) at 1.5 T. MR spectra were acquired from volumes localized in the left frontal lobe, containing mainly white matter (54 subjects). Peak areas of N-acetyl aspartate (NAA), choline (Cho) and creatine (Cr) were determined, and the peak area ratio of NAA to Cr, total Cho to Cr, or NAA to Cho calculated. Probabilistic neural network (PNN) analysis was performed utilizing the chemical shift region containing resonances from NAA, Cho and Cr as inputs. No significant difference in the peak area ratios could be found using the Kruskal-Wallis test. By application of PNN, a correct classification of 52 of the 54 adolescents with a sensitivity and specificity exceeding 93% for all groups was achieved. Small, yet systematic, differences in brain metabolite distribution among the groups were confirmed by PNN analysis. (orig.)

  7. Coke formation on hydrodesulphurization catalysts. [Including effects of different promoters

    Ternan, M.; Furimsky, E.; Parsons, B.I.

    1979-02-01

    The extent of coke formation was measured on a number of different hydrodesulfurization catalysts, primarily as a function of the catalyst chemical composition. Variations in the concentration of MoO/sub 3/ on the alumina, the type of catalyst promoter, the promoter/MoO/sub 3/ ratio, the presulfiding material and the reaction temperature were made. Increases in the reaction rate caused by either changes in the catalyst composition or by moderate changes in the reaction temperature were compared to the catalyst coke content. It was suggested that two types of coke were present on the catalyst, a reactive coke which is subsequently converted to reaction products and an unreactive coke which blocks catalytic sites.

  8. Cooperative effects for CYP2E1 differ between styrene and its metabolites

    Hartman, Jessica H.; Boysen, Gunnar; Miller, Grover P.

    2014-01-01

    Cooperative interactions are frequently observed in the metabolism of drugs and pollutants by cytochrome P450s; nevertheless, the molecular determinants for cooperativity remain elusive. Previously, we demonstrated that steady-state styrene metabolism by CYP2E1 exhibits positive cooperativity.We hypothesized that styrene metabolites have lower affinity than styrene toward CYP2E1 and limited ability to induce cooperative effects during metabolism. To test the hypothesis, we determined the potency and mechanism of inhibition for styrene and its metabolites toward oxidation of 4-nitrophenol using CYP2E1 Supersomes® and human liver microsomes.Styrene inhibited the reaction through a mixed cooperative mechanism with high affinity for the catalytic site (67 μM) and lower affinity for the cooperative site (1100 μM), while increasing substrate turnover at high concentrations. Styrene oxide and 4-vinylphenol possessed similar affinity for CYP2E1. Styrene oxide behaved cooperatively like styrene, but 4-vinylphenol decreased turnover at high concentrations. Styrene glycol was a very poor competitive inhibitor. Among all compounds, there was a positive correlation with binding and hydrophobicity.Taken together, these findings for CYP2E1 further validate contributions of cooperative mechanisms to metabolic processes, demonstrate the role of molecular structure on those mechanisms and underscore the potential for heterotropic cooperative effects between different compounds. PMID:23327532

  9. Circulating zearalenone and its metabolites differ in women due to body mass index and food intake.

    Mauro, T; Hao, L; Pop, L C; Buckley, B; Schneider, S H; Bandera, E V; Shapses, S A

    2018-04-17

    The environmental estrogen, zearalenone (ZEA), is found in the food supply from Fusarium fungal contamination in grains and sometimes used as a growth promoter for beef cattle. Long-term exposure to ZEA and its metabolites may present health risk due to higher estrogenic activity. Serum ZEA metabolites were measured to determine the exposure and the association with food intake in 48 overweight/obese women (52 ± 9 years). The free and conjugated ZEA indicated the highest detection rate of all the metabolites. Conjugated ZEA and total ZEA metabolites were lower (p = 0.02) in overweight/obese than normal weight women, and free metabolites were either the same or showed a trend to be higher. In addition, those with highest (280-480 g/d) compared those with lowest (metabolite concentrations (p metabolites. These findings indicate that ZEA and its metabolites are detectable in nearly all women and concentrations are associated with greater meat intake, and influenced by body mass index. Determining how the food supply influences human concentrations of ZEA metabolites is warranted, as well as determining vulnerable populations. Copyright © 2018. Published by Elsevier Ltd.

  10. Secondary metabolite profiling of Curcuma species grown at different locations using GC/TOF and UPLC/Q-TOF MS.

    Lee, Jueun; Jung, Youngae; Shin, Jeoung-Hwa; Kim, Ho Kyoung; Moon, Byeong Cheol; Ryu, Do Hyun; Hwang, Geum-Sook

    2014-07-04

    Curcuma, a genus of rhizomatous herbaceous species, has been used as a spice, traditional medicine, and natural dye. In this study, the metabolite profile of Curcuma extracts was determined using gas chromatography-time of flight mass spectrometry (GC/TOF MS) and ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) to characterize differences between Curcuma aromatica and Curcuma longa grown on the Jeju-do or Jin-do islands, South Korea. Previous studies have performed primary metabolite profiling of Curcuma species grown in different regions using NMR-based metabolomics. This study focused on profiling of secondary metabolites from the hexane extract of Curcuma species. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) plots showed significant differences between the C. aromatica and C. longa metabolite profiles, whereas geographical location had little effect. A t-test was performed to identify statistically significant metabolites, such as terpenoids. Additionally, targeted profiling using UPLC/Q-TOF MS showed that the concentration of curcuminoids differed depending on the plant origin. Based on these results, a combination of GC- and LC-MS allowed us to analyze curcuminoids and terpenoids, the typical bioactive compounds of Curcuma, which can be used to discriminate Curcuma samples according to species or geographical origin.

  11. Secondary Metabolite Profiling of Curcuma Species Grown at Different Locations Using GC/TOF and UPLC/Q-TOF MS

    Jueun Lee

    2014-07-01

    Full Text Available Curcuma, a genus of rhizomatous herbaceous species, has been used as a spice, traditional medicine, and natural dye. In this study, the metabolite profile of Curcuma extracts was determined using gas chromatography-time of flight mass spectrometry (GC/TOF MS and ultrahigh-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS to characterize differences between Curcuma aromatica and Curcuma longa grown on the Jeju-do or Jin-do islands, South Korea. Previous studies have performed primary metabolite profiling of Curcuma species grown in different regions using NMR-based metabolomics. This study focused on profiling of secondary metabolites from the hexane extract of Curcuma species. Principal component analysis (PCA and partial least-squares discriminant analysis (PLS-DA plots showed significant differences between the C. aromatica and C. longa metabolite profiles, whereas geographical location had little effect. A t-test was performed to identify statistically significant metabolites, such as terpenoids. Additionally, targeted profiling using UPLC/Q-TOF MS showed that the concentration of curcuminoids differed depending on the plant origin. Based on these results, a combination of GC- and LC-MS allowed us to analyze curcuminoids and terpenoids, the typical bioactive compounds of Curcuma, which can be used to discriminate Curcuma samples according to species or geographical origin.

  12. Comparative “Omics” of the Fusarium fujikuroi Species Complex Highlights Differences in Genetic Potential and Metabolite Synthesis

    Niehaus, Eva-Maria; Münsterkötter, Martin; Proctor, Robert H.; Brown, Daren W.; Sharon, Amir; Idan, Yifat; Oren-Young, Liat; Sieber, Christian M.; Novák, Ondřej; Pěnčík, Aleš; Tarkowská, Danuše; Hromadová, Kristýna; Freeman, Stanley; Maymon, Marcel; Elazar, Meirav; Youssef, Sahar A.; El-Shabrawy, El Said M.; Shalaby, Abdel Baset A.; Houterman, Petra; Brock, Nelson L.; Burkhardt, Immo; Tsavkelova, Elena A.; Dickschat, Jeroen S.; Galuszka, Petr; Güldener, Ulrich; Tudzynski, Bettina

    2016-01-01

    Species of the Fusarium fujikuroi species complex (FFC) cause a wide spectrum of often devastating diseases on diverse agricultural crops, including coffee, fig, mango, maize, rice, and sugarcane. Although species within the FFC are difficult to distinguish by morphology, and their genes often share 90% sequence similarity, they can differ in host plant specificity and life style. FFC species can also produce structurally diverse secondary metabolites (SMs), including the mycotoxins fumonisins, fusarins, fusaric acid, and beauvericin, and the phytohormones gibberellins, auxins, and cytokinins. The spectrum of SMs produced can differ among closely related species, suggesting that SMs might be determinants of host specificity. To date, genomes of only a limited number of FFC species have been sequenced. Here, we provide draft genome sequences of three more members of the FFC: a single isolate of F. mangiferae, the cause of mango malformation, and two isolates of F. proliferatum, one a pathogen of maize and the other an orchid endophyte. We compared these genomes to publicly available genome sequences of three other FFC species. The comparisons revealed species-specific and isolate-specific differences in the composition and expression (in vitro and in planta) of genes involved in SM production including those for phytohormome biosynthesis. Such differences have the potential to impact host specificity and, as in the case of F. proliferatum, the pathogenic versus endophytic life style. PMID:28040774

  13. Differences between flocculating yeast and regular industrial yeast in transcription and metabolite profiling during ethanol fermentation

    Lili Li

    2017-03-01

    Full Text Available Objectives: To improve ethanolic fermentation performance of self-flocculating yeast, difference between a flocculating yeast strain and a regular industrial yeast strain was analyzed by transcriptional and metabolic approaches. Results: The number of down-regulated (industrial yeast YIC10 vs. flocculating yeast GIM2.71 and up-regulated genes were 4503 and 228, respectively. It is the economic regulation for YIC10 that non-essential genes were down-regulated, and cells put more “energy” into growth and ethanol production. Hexose transport and phosphorylation were not the limiting-steps in ethanol fermentation for GIM2.71 compared to YIC10, whereas the reaction of 1,3-disphosphoglycerate to 3-phosphoglycerate, the decarboxylation of pyruvate to acetaldehyde and its subsequent reduction to ethanol were the most limiting steps. GIM2.71 had stronger stress response than non-flocculating yeast and much more carbohydrate was distributed to other bypass, such as glycerol, acetate and trehalose synthesis. Conclusions: Differences between flocculating yeast and regular industrial yeast in transcription and metabolite profiling will provide clues for improving the fermentation performance of GIM2.71.

  14. Metabolite profiling of Clinacanthus nutans leaves extracts obtained from different drying methods by 1H NMR-based metabolomics

    Hashim, Noor Haslinda Noor; Latip, Jalifah; Khatib, Alfi

    2016-11-01

    The metabolites of Clinacanthus nutans leaves extracts and their dependence on drying process were systematically characterized using 1H nuclear magnetic resonance spectroscopy (NMR) multivariate data analysis. Principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) were able to distinguish the leaves extracts obtained from different drying methods. The identified metabolites were carbohydrates, amino acid, flavonoids and sulfur glucoside compounds. The major metabolites responsible for the separation in PLS-DA loading plots were lupeol, cycloclinacosides, betulin, cerebrosides and choline. The results showed that the combination of 1H NMR spectroscopy and multivariate data analyses could act as an efficient technique to understand the C. nutans composition and its variation.

  15. Metabolism of albendazole, ricobendazole and flubendazole in Haemonchus contortus adults: Sex differences, resistance-related differences and the identification of new metabolites

    Lucie Raisová Stuchlíková

    2018-04-01

    Full Text Available Haemonchus contortus (family Trichostrongylidae, Nematoda, a hematophagous gastrointestinal parasite found in small ruminants, has a great ability to develop resistance to anthelmintic drugs. We studied the biotransformation of the three benzimidazole anthelmintics: albendazole (ABZ, ricobendazole (albendazole S-oxide; RCB and flubendazole (FLU in females and males of H. contortus in both a susceptible ISE strain and resistant IRE strain. The ex vivo cultivation of living nematodes in culture medium with or without the anthelmintics was used. Ultrasensitive UHPLC/MS/MS analysis revealed 9, 7 and 12 metabolites of ABZ, RCB and FLU, respectively, with most of these metabolites now described in the present study for the first time in H. contortus. The structure of certain metabolites shows the presence of biotransformation reactions not previously reported in nematodes. There were significant qualitative and semi-quantitative differences in the metabolites formed by male and female worms. In most cases, females metabolized drugs more extensively than males. Adults of the IRE strain were able to form many more metabolites of all the drugs than adults of the ISE strain. Some metabolites were even found only in adults of the IRE strain. These findings suggest that increased drug metabolism may play a role in resistance to benzimidazole drugs in H. contortus. Keywords: Drug resistance, Drug metabolism, Anthelmintics, Benzimidazole, Nematode

  16. Beef, Chicken, and Soy Proteins in Diets Induce Different Gut Microbiota and Metabolites in Rats

    Yingying Zhu

    2017-07-01

    Full Text Available Previous studies have paid much attention to the associations between high intake of meat and host health. Our previous study showed that the intake of meat proteins can maintain a more balanced composition of gut bacteria as compared to soy protein diet. However, the associations between dietary protein source, gut bacteria, and host health were still unclear. In this study, we collected colonic contents from the growing rats fed with casein, beef, chicken or soy proteins for 90 days, and analyzed the compositions of gut microbiota and metabolites. Compared to the casein group (control, the chicken protein group showed the highest relative abundance of Lactobacillus and the highest levels of organic acids, including lactate, which can in turn promote the growth of Lactobacillus. The soy protein group had the highest relative abundance of Ruminococcus but the lowest relative abundance of Lactobacillus. Long-term intake of soy protein led to the up-regulation of transcription factor CD14 receptor and lipopolysaccharide-binding protein (LBP in liver, an indicator for elevated bacterial endotoxins. In addition, the intake of soy protein also increased the levels of glutathione S-transferases in liver, which implicates elevated defense and stress responses. These results confirmed that meat protein intake may maintain a more balanced composition of gut bacteria and reduce the antigen load and inflammatory response from gut bacteria to the host.

  17. Changes of Enzymes Activity and Production of Secondary Metabolites of Artemisia aucheri in Different Altitudes and Its Relation to Adaptation

    Hassan Zare-maivan

    2014-08-01

    Full Text Available Artemisia plants are the most abundant plants species in Iran which contain strong antioxidant properties and as such, have medicinal and economic value. Despite wide distribution of Artemisisa species, ecophysiology of its adaptation to changes in altitude and soil property had not been investigated. In this study, the relationships between ecophysiological and adaptation capabilities of A. aucheri to altitude changes through measuring changes in the activity of its antioxidant enzymes and secondary metabolites in situ was investigated based on a completely randomized experiment. The enzyme activities of superoxide dismutase, catalase, peroxidase, and the amount of total phenolics, flavonoids, anthocyanins, malondialdehyde and chlorophylls A and B were measured in A. aucheri plants growing in three different altitudes at and above the 36° latitude on the southern slopes of Eastern Alborz Mountain ranges in triplicate 10*10 m quadrates. Statistical analysis of data showed that soil type was loamy significantly becoming more sandy- loam with lowering in altitude and the soil contained greater amounts of oxides of silicone, aluminum, magnesium, sodium, potassium and phosphorus in upper altitude except calcium which was present in greater quantity in lower altitude. With increasing altitude, activity of superoxide dismutase and quantities of chlorophylls and total phenols in leaves increased. Some biochemical factors in A. aucheri showed significant positive correlation(P ≤ 0.05 between them. Adaptation of A. aucheri to changes in altitude occurred through changing its antioxidant enzymes activity and production of secondary metabolites in response to factors related to the altitude including soil type and texture, moisture level, temperature and most importantly radiation

  18. Association of plasma IL-6 and Hsp70 with HRV at different levels of PAHs metabolites.

    Jian Ye

    Full Text Available Exposure to polycyclic aromatic hydrocarbons (PAHs is associated with reduced heart rate variability (HRV, a strong predictor of cardiovascular diseases, but the mechanism is not well understood.We hypothesized that PAHs might induce systemic inflammation and stress response, contributing to altered cardiac autonomic function.HRV indices were measured using a 3-channel digital Holter monitor in 800 coke oven workers. Plasma levels of interleukin-6 (IL-6 and heat shock protein 70 (Hsp70 were determined using ELISA. Twelve urinary PAHs metabolites (OH-PAHs were measured by gas chromatography-mass spectrometry.We found that significant dose-dependent relationships between four urinary OH-PAHs and IL-6 (all Ptrend<0.05; and an increase in quartiles of IL-6 was significantly associated with a decrease in total power (TP and low frequency (LF (Ptrend = 0.014 and 0.006, respectively. In particular, elevated IL-6 was associated in a dose-dependent manner with decreased TP and LF in the high-PAHs metabolites groups (all Ptrend<0.05, but not in the low-PAHs metabolites groups. No significant association between Hsp70 and HRV in total population was found after multivariate adjustment. However, increased Hsp70 was significantly associated with elevated standard deviation of NN intervals (SDNN, TP and LF in the low-PAHs metabolites groups (all Ptrend<0.05. We also observed that both IL-6 and Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV.In coke oven workers, increased IL-6 was associated with a dose-response decreased HRV in the high-PAHs metabolites groups, whereas increase of Hsp70 can result in significant dose-related increase in HRV in the low-PAHs metabolites groups.

  19. Different Polar Metabolites and Protein Profiles between High- and Low-Quality Japanese Ginjo Sake.

    Kei Takahashi

    Full Text Available Japanese ginjo sake is a premium refined sake characterized by a pleasant fruity apple-like flavor and a sophisticated taste. Because of technical difficulties inherent in brewing ginjo sake, off-flavors sometimes occur. However, the metabolites responsible for off-flavors as well as those present or absent in higher quality ginjo sake remain uncertain. Here, the relationship between 202 polar chemical compounds in sake identified using capillary electrophoresis coupled with time-of-flight mass spectrometry and its organoleptic properties, such as quality and off-flavor, was examined. First, we found that some off-flavored sakes contained higher total amounts of metabolites than other sake samples. The results also identified that levels of 2-oxoglutaric acid and fumaric acid, metabolites in the tricarboxylic acid cycle, were highly but oppositely correlated with ginjo sake quality. Similarly, pyridoxine and pyridoxamine, co-enzymes for amino transferase, were also highly but oppositely correlated with ginjo sake quality. Additionally, pyruvic acid levels were associated with good quality as well. Compounds involved in the methionine salvage cycle, oxidative glutathione derivatives, and amino acid catabolites were correlated with low quality. Among off-flavors, an inharmonious bitter taste appeared attributable to polyamines. Furthermore, protein analysis displayed that a diversity of protein components and yeast protein (triosephosphate isomerase, TPI leakage was linked to the overall metabolite intensity in ginjo sake. This research provides insight into the relationship between sake components and organoleptic properties.

  20. Analysis of human plasma metabolites across different liquid chromatography/mass spectrometry platforms: Cross-platform transferable chemical signatures.

    Telu, Kelly H; Yan, Xinjian; Wallace, William E; Stein, Stephen E; Simón-Manso, Yamil

    2016-03-15

    The metabolite profiling of a NIST plasma Standard Reference Material (SRM 1950) on different liquid chromatography/mass spectrometry (LC/MS) platforms showed significant differences. Although these findings suggest caution when interpreting metabolomics results, the degree of overlap of both profiles allowed us to use tandem mass spectral libraries of recurrent spectra to evaluate to what extent these results are transferable across platforms and to develop cross-platform chemical signatures. Non-targeted global metabolite profiles of SRM 1950 were obtained on different LC/MS platforms using reversed-phase chromatography and different chromatographic scales (conventional HPLC, UHPLC and nanoLC). The data processing and the metabolite differential analysis were carried out using publically available (XCMS), proprietary (Mass Profiler Professional) and in-house software (NIST pipeline). Repeatability and intermediate precision showed that the non-targeted SRM 1950 profiling was highly reproducible when working on the same platform (relative standard deviation (RSD) HPLC, UHPLC and nanoLC) on the same platform. A substantial degree of overlap (common molecular features) was also found. A procedure to generate consistent chemical signatures using tandem mass spectral libraries of recurrent spectra is proposed. Different platforms rendered significantly different metabolite profiles, but the results were highly reproducible when working within one platform. Tandem mass spectral libraries of recurrent spectra are proposed to evaluate the degree of transferability of chemical signatures generated on different platforms. Chemical signatures based on our procedure are most likely cross-platform transferable. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA.

  1. Feeding different dietary protein to energy ratios to Holstein heifers: effects on growth performance, blood metabolites and rumen fermentation parameters.

    Dong, L F; Zhang, W B; Zhang, N F; Tu, Y; Diao, Q Y

    2017-02-01

    Eighteen Chinese Holstein heifers average age 230 ± 14 days were allocated to 1 of 3 dietary crude protein (CP) to metabolizable energy (ME) ratios to examine the effects on growth performance, blood metabolites and rumen fermentation parameters with 90-days experiment. Three different dietary CP:ME ratios were targeted based on the formulation of dietary CP contents of 10.85%, 12.78% and 14.63% on dry matter (DM) basis with similar ME contents (10.42 MJ/kg DM), which were categorized as low, medium and high dietary CP:ME ratios. The actual CP:ME ratios obtained in this study significantly increased from low to high CP:ME ratio groups with a value of 10.59, 11.83 and 13.38 g/MJ respectively. Elevated CP:ME ratios significantly increased CP intake (kg/day) and feed efficiency (FE) which was defined as dry matter intake as a proportion of average daily gain (ADG), whereas little difference was observed in body weight (kg), ADG (kg/day), DM intake (kg/day) and ME intake (MJ/day) among the three different CP:ME ratio groups. Increasing dietary CP to ME ratios significantly increased CP digestibility, whereas digestibility of DM and gross energy remained constant in the current experiment. Blood urea nitrogen and insulin-like growth factor-1 linearly increased with increasing dietary CP:ME ratios. There was significantly dietary treatment effect on rumen fermentation parameters including acetate, propionate, butyrate and total volatile fatty acids. Therefore, this study indicated that increasing dietary CP levels with similar energy content contributed to increased protein intake and its digestibility, as well as FE. Holstein heifers between 200 and 341 kg subjected to 13.38 dietary CP:ME ratio showed improved feed efficiency, nutrient digestibility, some blood metabolites and rumen fermentation characteristics for 0.90 kg/day rate of gain. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  2. Metabolite changes in nine different soybean varieties grown under field and greenhouse conditions.

    Maria John, K M; Natarajan, Savithiry; Luthria, Devanand L

    2016-11-15

    Global food security remains a worldwide concern due to changing climate, increasing population, and reduced agriculture acreages. Greenhouse cultivation increases productivity by extending growing seasons, reducing pest infestations and providing protection against short term drastic weather fluctuations like frost, heat, rain, and wind. In the present study, we examined and compared the metabolic responses of nine soybean varieties grown under field and greenhouse conditions. Extracts were assayed by GC-FID, GC-MS, and LC-MS for the identification of 10 primary (amino acids, organic acids, and sugars) and 10 secondary (isoflavones, fatty acid methyl esters) metabolites. Sugar molecules (glucose, sucrose, and pinitol) and isoflavone aglycons were increased but the isoflavones glucoside content decreased in the greenhouse cultivated soybeans. The amino acids and organic acids varied between the varieties. The results show that clustering (PCA and PLS-DA) patterns of soybean metabolites were significantly influenced by the genetic variation and growing conditions. Published by Elsevier Ltd.

  3. Different levels of UV-B resistance in Vaccinium corymbosum cultivars reveal distinct backgrounds of phenylpropanoid metabolites.

    Luengo Escobar, Ana; Magnum de Oliveira Silva, Franklin; Acevedo, Patricio; Nunes-Nesi, Adriano; Alberdi, Miren; Reyes-Díaz, Marjorie

    2017-09-01

    UV-B radiation induces several physiological and biochemical effects that can influence regulatory plant processes. Vaccinium corymbosum responds differently to UV-B radiation depending on the UV-B resistance of cultivars, according to their physiological and biochemical features. In this work, the effect of two levels of UV-B radiation during long-term exposure on the phenylpropanoid biosynthesis, and the expression of genes associated with flavonoid biosynthesis as well as the absolute quantification of secondary metabolites were studied in two contrasting UV-B-resistant cultivars (Legacy, resistant and Bluegold, sensitive). Multivariate analyses were performed to understand the role of phenylpropanoids in UV-B defense mechanisms. The amount of phenylpropanoid compounds was generally higher in Legacy than in Bluegold. Different expression levels of flavonoid biosynthetic genes for both cultivars were transiently induced, showing that even in longer period of UV-B exposure; plants are still adjusting their phenylpropanoids at the transcription levels. Multivariate analysis in Legacy indicated no significant correlation between gene expression and the levels of the flavonoids and phenolic acids. By contrast, in the Bluegold cultivar higher number of correlations between secondary metabolite and transcript levels was found. Taken together, the results indicated different adjustments between the cultivars for a successful UV-B acclimation. While the sensitive cultivar depends on metabolite adjustments to respond to UV-B exposure, the resistant cultivar also possesses an intrinsically higher antioxidant and UV-B screening capacity. Thus, we conclude that UV-B resistance involves not only metabolite level adjustments during the acclimation period, but also depends on the intrinsic metabolic status of the plant and metabolic features of the phenylpropanoid compounds. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Combined Mass Spectrometry-Based Metabolite Profiling of Different Pigmented Rice (Oryza sativa L. Seeds and Correlation with Antioxidant Activities

    Ga Ryun Kim

    2014-09-01

    Full Text Available Nine varieties of pigmented rice (Oryza sativa L. seeds that were black, red, or white were used to perform metabolite profiling by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS and gas chromatography (GC TOF-MS, to measure antioxidant activities. Clear grouping patterns determined by the color of the rice seeds were identified in principle component analysis (PCA derived from UPLC-Q-TOF-MS. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimer, proanthocyanidin trimer, apigenin-6-C-glugosyl-8-C-arabiboside, tricin-O-rhamnoside-O-hexoside, and lipids were identified as significantly different secondary metabolites. In PCA score plots derived from GC-TOF-MS, Jakwangdo (JKD and Ilpoom (IP species were discriminated from the other rice seeds by PC1 and PC2. Valine, phenylalanine, adenosine, pyruvate, nicotinic acid, succinic acid, maleic acid, malonic acid, gluconic acid, xylose, fructose, glucose, maltose, and myo-inositol were significantly different primary metabolites in JKD species, while GABA, asparagine, xylitol, and sucrose were significantly distributed in IP species. Analysis of antioxidant activities revealed that black and red rice seeds had higher activity than white rice seeds. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimers, proanthocyanidin trimers, and catechin were highly correlated with antioxidant activities, and were more plentiful in black and red rice seeds. These results are expected to provide valuable information that could help improve and develop rice-breeding techniques.

  5. Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging.

    Bültmann, Eva; Nägele, Thomas; Lanfermann, Heinrich; Klose, Uwe

    2017-01-01

    We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging. From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months-20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum. The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu. CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic.

  6. Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging

    Bueltmann, Eva; Lanfermann, Heinrich; Naegele, Thomas; Klose, Uwe

    2017-01-01

    We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging. From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months-20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum. The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu. CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic. (orig.)

  7. Variability of Secondary Metabolites of the Species Cichorium intybus L. from Different Habitats

    Nenad M. Zlatić

    2017-09-01

    Full Text Available The principal aim of this paper is to show the influence of soil characteristics on the quantitative variability of secondary metabolites. Analysis of phenolic content, flavonoid concentrations, and the antioxidant activity was performed using the ethanol and ethyl acetate plant extracts of the species Cichorium intybus L. (Asteraceae. The samples were collected from one saline habitat and two non-saline habitats. The values of phenolic content from the samples taken from the saline habitat ranged from 119.83 to 120.83 mg GA/g and from non-saline habitats from 92.44 to 115.10 mg GA/g. The amount of flavonoids in the samples from the saline locality varied between 144.36 and 317.62 mg Ru/g and from non-saline localities between 86.03 and 273.07 mg Ru/g. The IC50 values of antioxidant activity in the samples from the saline habitat ranged from 87.64 to 117.73 μg/mL and from 101.44 to 125.76 μg/mL in the samples from non-saline habitats. The results confirmed that soil types represent a significant influence on the quantitative content of secondary metabolites. The greatest concentrations of phenols and flavonoids and the highest level of antioxidant activity were found in the samples from saline soil. This further corroborates the importance of saline soil as an ecological factor, as it is proven to give rise to increased biosynthesis of secondary metabolites and related antioxidant activity.

  8. Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging

    Bueltmann, Eva; Lanfermann, Heinrich [Hannover Medical School, Institute of Diagnostic and Interventional Neuroradiology, Hannover (Germany); Naegele, Thomas [University of Tuebingen, Department of Diagnostic and Interventional Neuroradiology, Radiological University Hospital, Tuebingen (Germany); Klose, Uwe [University of Tuebingen, Section of Experimental MR of the CNS, Department of Neuroradiology, Radiological University Hospital, Tuebingen (Germany)

    2017-01-15

    We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging. From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months-20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum. The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu. CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic. (orig.)

  9. Dynamic microbial succession of Shanxi aged vinegar and its correlation with flavor metabolites during different stages of acetic acid fermentation.

    Zhu, Yunping; Zhang, Feifei; Zhang, Chengnan; Yang, Li; Fan, Guangsen; Xu, Youqiang; Sun, Baoguo; Li, Xiuting

    2018-06-05

    Shanxi aged vinegar (SAV), one of the famous Chinese vinegars, is produced by multispecies solid-state fermentation in which the acetic acid fermentation stage (AAF) is especially important. However, how bacterial succession and their metabolites change along with the different stages of AAF is still poorly understood. In this study, we investigated the dynamic bacterial succession and flavor formation in three batches of SAV using high-throughput sequencing and metabolomics approaches. It is interesting to find that AAF can be divided into three stages based on its bacterial community succession (early stage, days 0-4; medium stage, days 5-21; and later stage, days 22-26). Pantoea, Pediococcus, Lactococcus and Rhizobium played an important role in the early stage; Lactobacillus was dominant in the medium stage (67.72%); and Acetobacter, Komagataeibacter and Kroppenstedtia were the key bacteria in the later stage. A total of seven organic acids and 42 volatile constituents (esters, alcohol, ketones and aldehydes) were detected during the AAF. Spearman correlation analysis showed a significant correlation between the bacterial community and these flavor metabolites during the AAF of the SAV. This is the first report to explore the relationships between volatile flavor metabolites and bacterial community succession by a three-staged method and provide theoretical support for a flavor formation mechanism in traditional SAV.

  10. Influence of Different Drying Treatments and Extraction Solvents on the Metabolite Profile and Nitric Oxide Inhibitory Activity of Ajwa Dates.

    Abdul-Hamid, Nur Ashikin; Abas, Faridah; Ismail, Intan Safinar; Shaari, Khozirah; Lajis, Nordin H

    2015-11-01

    This study aimed to examine the variation in the metabolite profiles and nitric oxide (NO) inhibitory activity of Ajwa dates that were subjected to 2 drying treatments and different extraction solvents. (1)H NMR coupled with multivariate data analysis was employed. A Griess assay was used to determine the inhibition of the production of NO in RAW 264.7 cells treated with LPS and interferon-γ. The oven dried (OD) samples demonstrated the absence of asparagine and ascorbic acid as compared to the freeze dried (FD) dates. The principal component analysis showed distinct clusters between the OD and FD dates by the second principal component. In respect of extraction solvents, chloroform extracts can be distinguished by the absence of arginine, glycine and asparagine compared to the methanol and 50% methanol extracts. The chloroform extracts can be clearly distinguished from the methanol and 50% methanol extracts by first principal component. Meanwhile, the loading score plot of partial least squares analysis suggested that beta glucose, alpha glucose, choline, ascorbic acid and glycine were among the metabolites that were contributing to higher biological activity displayed by FD and methanol extracts of Ajwa. The results highlight an alternative method of metabolomics approach for determination of the metabolites that contribute to NO inhibitory activity. The association between metabolite profiles and nitric oxide (NO) inhibitory activity of the various extracts of Ajwa dates was evaluated by utilizing partial least squares (PLS) model. The validated PLS model can be employed to predict the NO inhibitory activity of new samples of date fruits based on their NMR spectra which was important for assessing fruit quality. The information gained might be used as guidance for quality control, nutritional values and as a basis for the preparation of any food supplements for human health that employs date palm fruit as the raw material. © 2015 Institute of Food

  11. Comparative transcriptome and metabolite analysis of oil palm and date palm mesocarp that differ dramatically in carbon partitioning

    Bourgis, Fabienne; Kilaru, Aruna; Cao, Xia; Ngando-Ebongue, Georges-Frank; Drira, Noureddine; Ohlrogge, John B.; Arondel, Vincent

    2011-01-01

    Oil palm can accumulate up to 90% oil in its mesocarp, the highest level observed in the plant kingdom. In contrast, the closely related date palm accumulates almost exclusively sugars. To gain insight into the mechanisms that lead to such an extreme difference in carbon partitioning, the transcriptome and metabolite content of oil palm and date palm were compared during mesocarp development. Compared with date palm, the high oil content in oil palm was associated with much higher transcript levels for all fatty acid synthesis enzymes, specific plastid transporters, and key enzymes of plastidial carbon metabolism, including phosphofructokinase, pyruvate kinase, and pyruvate dehydrogenase. Transcripts representing an ortholog of the WRI1 transcription factor were 57-fold higher in oil palm relative to date palm and displayed a temporal pattern similar to its target genes. Unexpectedly, despite more than a 100-fold difference in flux to lipids, most enzymes of triacylglycerol assembly were expressed at similar levels in oil palm and date palm. Similarly, transcript levels for all but one cytosolic enzyme of glycolysis were comparable in both species. Together, these data point to synthesis of fatty acids and supply of pyruvate in the plastid, rather than acyl assembly into triacylglycerol, as a major control over the storage of oil in the mesocarp of oil palm. In addition to greatly increasing molecular resources devoted to oil palm and date palm, the combination of temporal and comparative studies illustrates how deep sequencing can provide insights into gene expression patterns of two species that lack genome sequence information. PMID:21709233

  12. The metabolites in peripheral blood mononuclear cells showed greater differences between patients with impaired fasting glucose or type 2 diabetes and healthy controls than those in plasma.

    Kim, Minjoo; Kim, Minkyung; Han, Ji Yun; Lee, Sang-Hyun; Jee, Sun Ha; Lee, Jong Ho

    2017-03-01

    To determine differences between peripheral blood mononuclear cells and the plasma metabolites in patients with impaired fasting glucose or type 2 diabetes and healthy controls. In all, 65 nononobese patients (aged 30-70 years) with impaired fasting glucose or type 2 diabetes and 65 nonobese sex-matched healthy controls were included, and fasting peripheral blood mononuclear cell and plasma metabolomes were profiled. The diabetic or impaired fasting glucose patients showed higher circulating and peripheral blood mononuclear cell lipoprotein phospholipase A 2 activities, high-sensitivity C-reactive protein and tumour necrosis factor-α than controls. Compared with controls, impaired fasting glucose or diabetic subjects showed increases in 11 peripheral blood mononuclear cell metabolites: six amino acids (valine, leucine, methionine, phenylalanine, tyrosine and tryptophan), l-pyroglutamic acid, two fatty acid amides containing palmitic amide and oleamide and two lysophosphatidylcholines. In impaired fasting glucose or diabetic patients, peripheral blood mononuclear cell lipoprotein phospholipase A 2 positively associated with peripheral blood mononuclear cell lysophosphatidylcholines and circulating inflammatory markers, including tumour necrosis factor-α, high-sensitivity C-reactive protein and lipoprotein phospholipase A 2 activities. In plasma metabolites between patients and healthy controls, we observed significant increases in only three amino acids (proline, valine and leucine) and decreases in only five lysophosphatidylcholines. This study demonstrates significant differences in the peripheral blood mononuclear cell metabolome in patients with impaired fasting glucose or diabetes compared with healthy controls. These differences were greater than those observed in the plasma metabolome. These data suggest peripheral blood mononuclear cells as a useful tool to better understand the inflammatory pathophysiology of diabetes.

  13. Metabolite Profiling of Barley Grains Subjected to Water Stress: To Explain the Genotypic Difference in Drought-Induced Impacts on Malting Quality

    Xiaojian Wu

    2017-09-01

    Full Text Available Grain weight and protein content will be reduced and increased, respectively, when barley is subjected to water stress after anthesis, consequently deteriorating the malt quality. However, such adverse impact of water stress differs greatly among barley genotypes. In this study, two Tibetan wild barley accessions and two cultivated varieties differing in water stress tolerance were used to investigate the genotypic difference in metabolic profiles during grain-filling stage under drought condition. Totally, 71 differently accumulated metabolites were identified, including organic acids, amino acids/amines, and sugars/sugar alcohols. Their relative contents were significantly affected by water stress for all genotypes and differed distinctly between the wild and cultivated barleys. The principal component analysis of metabolites indicated that the Tibetan wild barley XZ147 possessed a unique response to water stress. When subjected to water stress, the wild barley XZ147 showed the most increase of β-amylase activity among the four genotypes, as a result of its higher lysine content, less indole-3-acetic acid (IAA biosynthesis, more stable H2O2 homeostasis, and more up-regulation of BMY1 gene. On the other hand, XZ147 had the most reduction of β-glucan content under water stress than the other genotypes, which could be explained by the faster grain filling process and the less expression of β-glucan synthase gene GSL7. All these results indicated a great potential for XZ147 in barley breeding for improving water stress tolerance.

  14. Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii.

    Maifiah, Mohd Hafidz Mahamad; Cheah, Soon-Ee; Johnson, Matthew D; Han, Mei-Ling; Boyce, John D; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S; Hertzog, Paul; Purcell, Anthony W; Song, Jiangning; Velkov, Tony; Creek, Darren J; Li, Jian

    2016-02-29

    Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03-149.1 (polymyxin-susceptible) and 03-149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii.

  15. Phyto-oestrogens and their metabolites in milk produced on two pastures with different botanical compositions

    Adler, S. A.; Purup, S.; Hansen-Møller, J.

    2014-01-01

    . The objective of this study was to assess the effects of grazing a recently established pasture containing red clover (Trifolium pratense L.) and an older pasture containing a variety of sown and unsown plant species on milk concentrations of phyto-oestrogens. Sixteen Norwegian Red dairy cows [mean (standard......Phyto-oestrogens are a group of secondary plant metabolites that may bind to oestrogen receptors and exert oestrogenic or anti-oestrogenic effects in humans and can protect against cancer diseases. When ingested by dairy cows, phyto-oestrogens can be metabolised and transferred to the milk...... deviation); body weight 599 (45.1). kg, stage of lactation 73 (15.0) d in milk, milk yield 29.9 (2.90) kg/d at the start of the experiment] were divided into two groups and grazed either a short-term pasture (SP) or a long-term pasture (LP). The SP was representative of organically managed leys in Norway...

  16. Infrared-metabolomics approach in detecting changes in Andrographis paniculata metabolites due to different harvesting ages and times.

    Yusof, Nur A'thifah; Isha, Azizul; Ismail, Intan Safinar; Khatib, Alfi; Shaari, Khozirah; Abas, Faridah; Rukayadi, Yaya

    2015-09-01

    The metabolite changes in three germplasm accessions of Malaysia Andrographis paniculata (Burm. F.) Nees, viz. 11265 (H), 11341 (P) and 11248 (T), due to their different harvesting ages and times were successfully evaluated by attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy and translated through multivariate data analysis of principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). This present study revealed the feasibility of ATR-FTIR in detecting the trend changes of the major metabolites - andrographolide and neoandrographolide - functional groups in A. paniculata leaves of different accessions. The harvesting parameter was set at three different ages of 120, 150 and 180 days after transplanting (DAT) and at two different time sessions of morning (7:30-10:30 am) and evening (2:30-5.30 pm). OPLS-DA successfully discriminated the A. paniculata crude extracts into groups of which the main constituents - andrographolide and neoandrographolide - could be mainly observed in the morning session of 120 DAT for P and T, while H gave the highest intensities of these constituents at 150 DAT. The information extracted from ATR-FTIR data through OPLS-DA could be useful in tailoring this plant harvest stage in relation to the content of its two major diterpene lactones: andrographolide and neoandrographolide. © 2014 Society of Chemical Industry.

  17. Effect of different in vitro culture extracts of black pepper (Piper nigrum L.) on toxic metabolites-producing strains.

    Ahmad, Nisar; Abbasi, Bilal Haider; Fazal, Hina

    2016-03-01

    In the present study, the effect of different in vitro cultures (callus, in vitro shoots) and commercially available peppercorn extract was investigated for its activity against toxic metabolite-producing strains (Escherichia coli, Pseudomonas aeroginosa, Salmonella typhi, Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, and Candida albicans). These in vitro cultures were extracted with ethanol, hexane, and chloroform, and the antipathogenic activity was determined by well-diffusion method. Hexane extract of callus showed 22 mm zone of inhibition against B. cereus, 23 mm against S. aureus, while regenerated shoots and seeds have shown 24.3 and 26 mm zones of inhibition. The ethanolic extracts of regenerated Piper shoots have shown 25 mm activity against S. aureus, 21 mm against B. cereus, and 16 mm in the case of C. albicans in comparison with standard antibiotics. Peppercorn extracts in chloroform and ethanol had shown activities against B. cereus (23.6 mm) and B. subtilis (23.5 mm). During in vitro organogenesis and morphogenesis, cells and tissues produced a comparable phytochemicals profile like mother plant. Morphogenesis is critically controlled by the application of exogenous plant-growth regulators. Such addition alters the hormonal transduction pathways, and cells under in vitro conditions regenerate tissues, which are dependant on the physiological state of cells, and finally enhance the production of secondary metabolites. To the best of our knowledge, this is the first report to compare the antimicrobial potential of in vitro regenerated tissues and peppercorn with standard antibiotics. In conclusion, most of the extracts showed pronounced activities against all the pathogenic microbes. This is a preliminary work, and the minimum inhibitory concentration values needs to be further explored. Regenerated tissues of P. nigrum are a good source of biologically active metabolites for antimicrobial activities, and callus culture presented itself as

  18. Different effects of clopidogrel and clarithromycin on the enantioselective pharmacokinetics of sibutramine and its active metabolites in healthy subjects.

    Shinde, Dhananjay D; Kim, Ho-Sook; Choi, Jae-Seok; Pan, Wei; Bae, Soo Kyung; Yeo, Chang-Woo; Shon, Ji-Hong; Kim, Dong-Hyun; Shin, Jae Gook

    2013-05-01

    In this study, we assessed the effects of clopidogrel and clarithromycin, known CYP2B6 and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans. Sibutramine showed enantioselective plasma profiles with consistently higher concentrations of R-enantiomers. Clopidogrel and clarithromycin significantly increased the sibutramine plasma concentration, but their effects differed between enantiomers; a 2.2-fold versus 4.1-fold increase in the AUC in S-enantiomer and 1.8-fold versus 2.0-fold for the R-enantiomer, respectively. The AUCs of S- and R-desmethyl metabolites changed significantly during the clopidogrel phase (P sibutramine was higher in subjects with the CYP2B6*6/*6 genotype, but no statistical difference was observed among the CYP2B6 genotypes. These results suggest that the enantioselective disposition of sibutramine and its active metabolites are influenced by the altered genetic and environmental factors of CYP2B6 and CYP3A activity in vivo. © The Author(s) 2013.

  19. Arsenic Metabolites, Including N-Acetyl-4-hydroxy-m-arsanilic Acid, in Chicken Litter from a Roxarsone-Feeding Study Involving 1600 Chickens.

    Yang, Zonglin; Peng, Hanyong; Lu, Xiufen; Liu, Qingqing; Huang, Rongfu; Hu, Bin; Kachanoski, Gary; Zuidhof, Martin J; Le, X Chris

    2016-07-05

    The poultry industry has used organoarsenicals, such as 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, ROX), to prevent disease and to promote growth. Although previous studies have analyzed arsenic species in chicken litter after composting or after application to agricultural lands, it is not clear what arsenic species were excreted by chickens before biotransformation of arsenic species during composting. We describe here the identification and quantitation of arsenic species in chicken litter repeatedly collected on days 14, 24, 28, 30, and 35 of a Roxarsone-feeding study involving 1600 chickens of two strains. High performance liquid chromatography separation with simultaneous detection by both inductively coupled plasma mass spectrometry and electrospray ionization tandem mass spectrometry provided complementary information necessary for the identification and quantitation of arsenic species. A new metabolite, N-acetyl-4-hydroxy-m-arsanilic acid (N-AHAA), was identified, and it accounted for 3-12% of total arsenic. Speciation analyses of litter samples collected from ROX-fed chickens on days 14, 24, 28, 30, and 35 showed the presence of N-AHAA, 3-amino-4-hydroxyphenylarsonic acid (3-AHPAA), inorganic arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMA(V)), dimethylarsinic acid (DMA(V)), and ROX. 3-AHPAA accounted for 3-19% of the total arsenic. Inorganic arsenicals (the sum of As(III) and As(V)) comprised 2-6% (mean 3.5%) of total arsenic. Our results on the detection of inorganic arsenicals, methylarsenicals, 3-AHPAA, and N-AHAA in the chicken litter support recent findings that ROX is actually metabolized by the chicken or its gut microbiome. The presence of the toxic metabolites in chicken litter is environmentally relevant as chicken litter is commonly used as fertilizer.

  20. Brain metabolite differences in one-year-old infants born small at term and association with neurodevelopmental outcome.

    Simões, Rui V; Cruz-Lemini, Mónica; Bargalló, Núria; Gratacós, Eduard; Sanz-Cortés, Magdalena

    2015-08-01

    We assessed brain metabolite levels by magnetic resonance spectroscopy (MRS) in 1-year-old infants born small at term, as compared with infants born appropriate for gestational age (AGA), and their association with neurodevelopment at 2 years of age. A total of 40 infants born small (birthweight growth restriction or as small for gestational age, based on the presence or absence of prenatal Doppler and birthweight predictors of an adverse perinatal outcome, respectively. Single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) data were acquired from the frontal lobe at short echo time. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales of Infant and Toddler Development, Third Edition, assessing cognitive, language, motor, social-emotional, and adaptive behavior scales. As compared with AGA controls, infants born small showed significantly higher levels of glutamate and total N-acetylaspartate (NAAt) to creatine (Cr) ratio at age 1 year, and lower Bayley Scales of Infant and Toddler Development, Third Edition scores at 2 years. The subgroup with late intrauterine growth restriction further showed lower estimated glutathione levels at age 1 year. Significant correlations were observed for estimated glutathione levels with adaptive scores, and for myo-inositol with language scores. Significant associations were also noticed for NAA/Cr with cognitive scores, and for glutamate/Cr with motor scores. Infants born small show brain metabolite differences at 1 year of age, which are correlated with later neurodevelopment. These results support further research on MRS to develop imaging biomarkers of abnormal neurodevelopment. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Comparative "Omics" of the Fusarium fujikuroi Species Complex Highlights Differences in Genetic Potential and Metabolite Synthesis

    Niehaus, E.-M.; Münsterkötter, M.; Proctor, R.H.; Brown, D.W.; Sharon, A.; Idan, Y.; Oren-Young, L.; Sieber, C.M.; Novák, O.; Pěnčík, A.; Tarkowská, D.; Hromadová, K.; Freeman, S.; Maymon, M.; Elazar, M.; Youssef, S.A.; El-Shabrawy, E.S.M.; Shalaby, A.B.A.; Houterman, P.; Brock, N.L.; Burkhardt, I.; Tsavkelova, E.A.; Dickschat, J.S.; Galuszka, P.; Güldener, U.; Tudzynski, B.

    2016-01-01

    Species of the Fusarium fujikuroi species complex (FFC) cause a wide spectrum of often devastating diseases on diverse agricultural crops, including coffee, fig, mango, maize, rice, and sugarcane. Although species within the FFC are difficult to distinguish by morphology, and their genes often share

  2. In vitro characterization of the impact of different substrates on metabolite production, energy extraction and composition of gut microbiota from lean and obese subjects.

    Aguirre, Marisol; Jonkers, Daisy M A E; Troost, Freddy J; Roeselers, Guus; Venema, Koen

    2014-01-01

    The aim of this study was to investigate the effect of galacto-oligosaccharides, lactulose, apple fiber and sugar beet pectin on the composition and activity of human colonic microbiota of lean and obese healthy subjects using an in vitro model of the proximal colon: TIM-2. Substrate fermentation was assessed by measuring the production of short-chain and branched-chain fatty acids, lactate and ammonia and by studying the composition of the bacterial communities over time. The results suggest that energy harvest (in terms of metabolites) of lean and obese microbiotas is different and may depend on the fermentable substrate. For galacto-oligosaccharides and lactulose, the cumulative amount of short-chain fatty acids plus lactate produced in TIM-2 was lower in the fermentation experiments with the lean microbiota (123 and 155 mmol, respectively) compared to the obese (162 and 173 mmol, respectively). This was reversed for the pectin and the fiber. The absolute amount produced of short-chain fatty acids including lactate was higher after 72 h in the fermentation experiments with apple fiber-L (108 mmol) than with apple fiber-O (92 mmol). Sugar beet-L was also higher (130 mmol) compared to sugar beet-O (103 mmol). Galacto-oligosaccharides and lactulose boosted the balance of health-promoting over toxic metabolites produced by the microbiota from obese subjects. Firmicutes were more predominant in the inoculum prepared from feces of obese subjects compared to lean subjects. The average abundance at time zero was 92% and 74%, respectively. On the other hand, Bacteroidetes were more dominant in the microbiota prepared with homogenates from lean subjects with an average abundance of 22% compared with the microbiota prepared with homogenates from obese subjects (3.6%). This study brings evidence that different fermentable carbohydrates are fermented differently by lean and obese microbiotas, which contributes to the understanding of the role of diet and the microbiota in

  3. In vitro characterization of the impact of different substrates on metabolite production, energy extraction and composition of gut microbiota from lean and obese subjects.

    Marisol Aguirre

    Full Text Available The aim of this study was to investigate the effect of galacto-oligosaccharides, lactulose, apple fiber and sugar beet pectin on the composition and activity of human colonic microbiota of lean and obese healthy subjects using an in vitro model of the proximal colon: TIM-2. Substrate fermentation was assessed by measuring the production of short-chain and branched-chain fatty acids, lactate and ammonia and by studying the composition of the bacterial communities over time. The results suggest that energy harvest (in terms of metabolites of lean and obese microbiotas is different and may depend on the fermentable substrate. For galacto-oligosaccharides and lactulose, the cumulative amount of short-chain fatty acids plus lactate produced in TIM-2 was lower in the fermentation experiments with the lean microbiota (123 and 155 mmol, respectively compared to the obese (162 and 173 mmol, respectively. This was reversed for the pectin and the fiber. The absolute amount produced of short-chain fatty acids including lactate was higher after 72 h in the fermentation experiments with apple fiber-L (108 mmol than with apple fiber-O (92 mmol. Sugar beet-L was also higher (130 mmol compared to sugar beet-O (103 mmol. Galacto-oligosaccharides and lactulose boosted the balance of health-promoting over toxic metabolites produced by the microbiota from obese subjects. Firmicutes were more predominant in the inoculum prepared from feces of obese subjects compared to lean subjects. The average abundance at time zero was 92% and 74%, respectively. On the other hand, Bacteroidetes were more dominant in the microbiota prepared with homogenates from lean subjects with an average abundance of 22% compared with the microbiota prepared with homogenates from obese subjects (3.6%. This study brings evidence that different fermentable carbohydrates are fermented differently by lean and obese microbiotas, which contributes to the understanding of the role of diet and the

  4. Blood serum metabolites and meat quality in crossbred pigs experiencing different lairage time

    Ivan Juric

    2010-01-01

    Full Text Available Pigs of two crosses: A (Duroc x Swedish Landrace x Pietrain (n=24 and B (Swedish Landrace x Large White x Pietrain (n=26 were used to investigate the effects of different lairage time (2 and 24 hours on levels of stress and meat quality traits. No direct effect of lairage time on cortisol, lactate, electrolytes and meat quality parameters was observed. However, after long lairage time, pigs showed lower level of glucose and higher CK, AST and ALT activity. Crossbred B pigs exposed to short lairage time, showed higher blood lactate, sodium, and potassium level, higher drip loss and lower pHi, whereas there were no significant differences between the crossbreeds in the long lairage group. The results indicate that long lairage time decreases blood glucose level and produces signs of muscle damage. In the short lairage period, the crossbreed B showed a higher response to pre-slaughter handling affecting the meat quality.

  5. Hematologic, Metabolite and Hormone Responses to Weaning-Induced Stress in Foals of Different Breeds

    Anas Sarwar Qureshi*, Fazeela Yaqoob1 and Heinrich Enbergs2

    2013-11-01

    Full Text Available Eighty-four foals of different breeds (Thoroughbred, Standardbred, German Warmblood, aged 5-6 months, were used in a study to evaluate the effects of weaning, sex, breed on haematological, metabolic and hormonal parameters. The values of leukocytes, neutrophils, red blood cells, haemoglobin, packed cell volume, platelets, activity of -GT and concentrations of cholesterol, cortisol and thyroxin rose on day 1 after weaning, while the percentages of eosinophils, lymphocytes and serum concentration of triglycerides decreased one day following weaning. These parameters returned to pre-weaning values on day 14 post-weaning except serum cholesterol, which fell to a significantly lower level on day 14 post-weaning than pre-weaning value. Serum alkaline phosphatase declined markedly on day 14 post-weaning. The most pronounced rise was observed for cortisol (51% and thyroxin (40% values. Females presented higher mean corpuscular haemoglobin concentration and cortisol concentration than males (P<0.05. German Warmblood foals presented a less-altered picture following weaning as compared with Thoroughbreds and Standardbreds. It is concluded that foals respond immediately to weaning, which may lead to suppression of the activities of bone cells i.e., osteoblasts. In addition, serum concentrations of cortisol and thyroxin influence one another in weanling foals. The Thoroughbred foals appear to be the most sensitive to weaning.

  6. Responses to mild water deficit and rewatering differ among secondary metabolites but are similar among provenances within Eucalyptus species.

    McKiernan, Adam B; Potts, Brad M; Brodribb, Timothy J; Hovenden, Mark J; Davies, Noel W; McAdam, Scott A M; Ross, John J; Rodemann, Thomas; O'Reilly-Wapstra, Julianne M

    2016-02-01

    Water deficit associated with drought can severely affect plants and influence ecological interactions involving plant secondary metabolites. We tested the effect of mild water deficit and rewatering on physiological, morphological and chemical traits of juvenile Eucalyptus globulus Labill. and Eucalyptus viminalis Labill. We also tested if responses of juvenile eucalypts to water deficit and rewatering varied within species using provenances across a rainfall gradient. Both species and all provenances were similarly affected by mild water deficit and rewatering, as only foliar abscisic acid levels differed among provenances during water deficit. Across species and provenances, water deficit decreased leaf water potential, above-ground biomass and formylated phloroglucinol compound concentrations, and increased condensed tannin concentrations. Rewatering reduced leaf carbon : nitrogen, and total phenolic and chlorogenic acid concentrations. Water deficit and rewatering had no effect on total oil or individual terpene concentrations. Levels of trait plasticity due to water deficit and rewatering were less than levels of constitutive trait variation among provenances. The overall uniformity of responses to the treatments regardless of native provenance indicates limited diversification of plastic responses when compared with the larger quantitative variation of constitutive traits within these species. These responses to mild water deficit may differ from responses to more extreme water deficit or to responses of juvenile/mature eucalypts growing at each locality. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Differences of Urinary Arsenic Metabolites and Methylation Capacity between Individuals with and without Skin Lesions in Inner Mongolia, Northern China

    Qiang Zhang

    2014-07-01

    Full Text Available Incomplete arsenic (As methylation has been considered a risk factor of As-related diseases. This study aimed to examine the difference of urinary As metabolites and the methylation capacity between subjects with and without skin lesions. Urinary inorganic arsenic (iAs, monomethylarsonic acid (MMA, and dimethylarsinic acid (DMA were analyzed. The percentage of each As species (iAs%, MMA%, and DMA%, the primary methylation index (PMI and secondary methylation index (SMI were calculated. The results showed that subjects with skin lesions have higher levels of urinary iAs (99.08 vs. 70.63 μg/g Cr, p = 0.006 and MMA (69.34 vs. 42.85 μg/g Cr, p = 0.016 than subjects without skin lesions after adjustment for several confounders. Significant differences of urianry MMA% (15.49 vs. 12.11, p = 0.036 and SMI (0.74 vs. 0.81, p = 0.025 were found between the two groups. The findings of the present study suggest that subjects with skin lesions may have a lower As methylation capacity than subjects without skin lesions.

  8. Differences of urinary arsenic metabolites and methylation capacity between individuals with and without skin lesions in Inner Mongolia, Northern China.

    Zhang, Qiang; Li, Yongfang; Liu, Juan; Wang, Da; Zheng, Quanmei; Sun, Guifan

    2014-07-18

    Incomplete arsenic (As) methylation has been considered a risk factor of As-related diseases. This study aimed to examine the difference of urinary As metabolites and the methylation capacity between subjects with and without skin lesions. Urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were analyzed. The percentage of each As species (iAs%, MMA%, and DMA%), the primary methylation index (PMI) and secondary methylation index (SMI) were calculated. The results showed that subjects with skin lesions have higher levels of urinary iAs (99.08 vs. 70.63 μg/g Cr, p = 0.006) and MMA (69.34 vs. 42.85 μg/g Cr, p = 0.016) than subjects without skin lesions after adjustment for several confounders. Significant differences of urianry MMA% (15.49 vs. 12.11, p = 0.036) and SMI (0.74 vs. 0.81, p = 0.025) were found between the two groups. The findings of the present study suggest that subjects with skin lesions may have a lower As methylation capacity than subjects without skin lesions.

  9. Plant secondary metabolites in alfalfa, birdsfoot trefoil, reed canarygrass, and tall fescue unaffected by two different nitrogen sources

    Plant secondary metabolites (PSM) may increase the sustainability of agriculture systems by reducing inputs, as PSM protect plants against herbivores and pathogens, act as pesticides, insecticides, and anthelmintics, while also attracting pollinators and seed dispersers. Therefore, it is important t...

  10. Inflamm-aging and arachadonic acid metabolite differences with stage of tendon disease.

    Stephanie Georgina Dakin

    Full Text Available The contribution of inflammation to the pathogenesis of tendinopathy and high prevalence of re-injury is not well established, although recent evidence suggests involvement of prostaglandins. We investigated the roles of prostaglandins and inflammation-resolving mediators in naturally occurring equine tendon injury with disease stage and age. Levels of prostaglandins E(2 (PGE(2, F(2α (PGF(2α, lipoxin A(4 (LXA(4 and its receptor FPR2/ALX were analysed in extracts of normal, sub-acute and chronic injured tendons. To assess whether potential changes were associated with altered PGE(2 metabolism, microsomal prostaglandin E synthase-1 (mPGES-1, prostaglandin dehydrogenase (PGDH, COX-2 and EP(4 receptor expression were investigated. The ability of tendons to resolve inflammation was determined by assessing FPR2/ALX expression in natural injury and IL-1β stimulated tendon explants.Alterations in the profile of lipid mediators during sub-acute injury included low PGE(2 and elevated LXA(4 levels compared to normal and chronic injuries. In contrast, PGF(2α levels remained unchanged and were three-fold lower than PGE(2. The synthetic capacity of PGE(2 as measured by the ratio of mPGES-1:PGDH was elevated in sub-acute injury, suggesting aberrations in tendon prostaglandin metabolism, whilst COX-2 and EP(4 receptor were unchanged. Paradoxically low tendon PGE(2 levels in early injury may be attributed to increased local clearance via PGDH or the class switching of lipid mediators from the prostaglandin to the lipoxin axis. PGE(2 is therefore implicated in the development of tendon inflammation and its ensuing resolution. Whilst there was no relationship between age and tendon LXA(4 levels, there was an age-associated decline in FPR2/ALX receptor expression with concurrent increased PGE(2 levels in injury. Furthermore, uninjured tendon explants from younger (<10 years but not older horses (≥10 years treated with IL-1β responded by increasing FPR2/ALX

  11. Detection of Amide and Aromatic Proton Resonances of Human Brain Metabolites Using Localized Correlated Spectroscopy Combined with Two Different Water Suppression Schemes

    Rajakumar Nagarajan

    2010-01-01

    Full Text Available The purpose of the study was to demonstrate the J-coupling connectivity network between the amide, aliphatic, and aromatic proton resonances of metabolites in human brain using two-dimensional (2D localized correlated spectroscopy (L-COSY. Two different global water suppression techniques were combined with L-COSY, one before and another after localizing the volume of interest (VOI. Phantom solutions containing several cerebral metabolites at physiological concentrations were evaluated initially for sequence optimization. Nine healthy volunteers were scanned using a 3T whole body MRI scanner. The VOI for 2D L-COSY was placed in the right occipital white/gray matter region. The 2D cross and diagonal peak volumes were measured for several metabolites such as N-acetyl aspartate (NAA, creatine (Cr, free choline (Ch, glutamate/glutamine (Glx, aspartate (Asp, myo-inositol (mI, GABA, glutathione (GSH, phosphocholine (PCh, phosphoethanolamine (PE, tyrosine (Tyr, lactate (Lac, macromolecules (MM and homocarnosine (Car. Using the pre-water suppression technique with L-COSY, the above mentioned metabolites were clearly identifiable and the relative ratios of metabolites were calculated. In addition to detecting multitude of aliphatic resonances in the high field region, we have demonstrated that the amide and aromatic resonances can also be detected using 2D L-COSY by pre water suppression more reliably than the post-water suppression.

  12. NAD+ metabolite levels as a function of vitamins and calorie restriction: evidence for different mechanisms of longevity

    Song Peng

    2010-02-01

    Full Text Available Abstract Background NAD+ is a coenzyme for hydride transfer enzymes and a substrate for sirtuins and other NAD+-dependent ADPribose transfer enzymes. In wild-type Saccharomyces cerevisiae, calorie restriction accomplished by glucose limitation extends replicative lifespan in a manner that depends on Sir2 and the NAD+ salvage enzymes, nicotinic acid phosphoribosyl transferase and nicotinamidase. Though alterations in the NAD+ to nicotinamide ratio and the NAD+ to NADH ratio are anticipated by models to account for the effects of calorie restriction, the nature of a putative change in NAD+ metabolism requires analytical definition and quantification of the key metabolites. Results Hydrophilic interaction chromatography followed by tandem electrospray mass spectrometry were used to identify the 12 compounds that constitute the core NAD+ metabolome and 6 related nucleosides and nucleotides. Whereas yeast extract and nicotinic acid increase net NAD+ synthesis in a manner that can account for extended lifespan, glucose restriction does not alter NAD+ or nicotinamide levels in ways that would increase Sir2 activity. Conclusions The results constrain the possible mechanisms by which calorie restriction may regulate Sir2 and suggest that provision of vitamins and calorie restriction extend lifespan by different mechanisms.

  13. Relationship between cobalamin-dependent metabolites and both serum albumin and alpha1 -proteinase inhibitor concentrations in hypocobalaminemic dogs of 7 different breeds.

    Grützner, Niels; Suchodolski, Jan S; Steiner, Jörg M

    2014-12-01

    Increased serum concentrations of homocysteine (HCY) and methylmalonic acid (MMA), the 2 main cobalamin-dependent metabolites, as well as decreased serum albumin and canine alpha1 -proteinase inhibitor (cα1 -PI) concentrations have previously been described in hypocobalaminemic dogs with gastrointestinal disease. However, no studies have been conducted to evaluate potential relationships between these serum biomarkers. The aim of this study was to evaluate the relationship between HCY and MMA, 2 cobalamin-dependent metabolites, and both serum albumin and cα1 -PI concentrations in hypocobalaminemic dogs. Serum samples from 285 dogs including 7 different breeds (Beagle, Boxer, Cocker Spaniel, German Shepherd, Labrador Retriever, Chinese Shar-Pei, and Yorkshire Terrier) with hypocobalaminemia were used. Serum HCY, MMA, albumin, and cα1 -PI concentrations were determined. There was a significant correlation between serum HCY and albumin concentrations, as well as serum HCY and cα1 -PI concentrations (ρ = 0.62 and ρ = 0.37, respectively; P  .05). In addition, significant breed-specific correlations were observed between serum MMA and albumin concentrations in German Shepherds, and serum HCY and MMA concentrations in Chinese Shar-Peis with hypocobalaminemia. This study shows a correlation between serum albumin and cα1 -PI and HCY concentrations, but not with serum MMA concentration in dogs with hypocobalaminemia. In addition, significant breed-specific correlations were observed between serum MMA and albumin concentrations in German Shepherds, as well as serum HCY and MMA concentrations in Chinese Shar-Peis, emphasizing the unique metabolic interactions in those dog breeds affected by hypocobalaminemia. © 2014 American Society for Veterinary Clinical Pathology.

  14. The effect of different concentrations of water soluble azadirachtin (neem metabolite on Streptococcus mutans compared with chlorhexidine

    Amit R Kankariya

    2016-01-01

    Full Text Available Despite advances in the development of anticaries chemotherapy, the newer agents are unable to control the initiation of dental caries. Research and development of natural antibacterial agents that are safe for the host as well as specific for oral pathogens is awaited. Neem tree extracts have been used for thousands of years for maintaining overall well-being. Chewing neem sticks in the morning is the most common indigenous method of cleaning the mouth in rural population. This has generated the interest of the dentists for the use of neem for controlling dental diseases. Aims: This study aims to evaluate the quantitative and qualitative effect of different concentrations of water soluble azadirachtin (neem metabolite on Streptococcus mutans (S. mutans against chlorhexidine. Materials and Methods: Plaque was collected from 30 children aged 8-12 years reporting to the Department of Pediatric and Preventive Dentistry, Bharti Vidyapeeth Dental College, Pune and transported to the laboratory. After incubation of the plates the inhibitory zones were noted and the diameter of the zone of inhibition was measured and recorded to check the inhibition of growth of S. mutans. For testing the bacterial survival, the biofilms were prepared and colony forming units (CFU was enumerated using a digital colony counter. Statistical Analysis Used: Two-way analysis of variance (ANOVA and Tukey′s test. Results: The results show that there was no statistically significant difference in the inhibition of S. mutans between 40% concentration of water soluble azadirachtin and chlorhexidine. Conclusions: This study concluded that 40% water soluble azadirachtin is as effective as 0.2% chlorhexidine mouthrinse in reducing the S. mutans count in dental plaque. Hence, a water soluble formulation of azadirachtin may provide the maximum benefit to mankind to prevent dental caries.

  15. The effect of different concentrations of water soluble azadirachtin (neem metabolite) on Streptococcus mutans compared with chlorhexidine.

    Kankariya, Amit R; Patel, Alok R; Kunte, Sanket S

    2016-01-01

    Despite advances in the development of anticaries chemotherapy, the newer agents are unable to control the initiation of dental caries. Research and development of natural antibacterial agents that are safe for the host as well as specific for oral pathogens is awaited. Neem tree extracts have been used for thousands of years for maintaining overall well-being. Chewing neem sticks in the morning is the most common indigenous method of cleaning the mouth in rural population. This has generated the interest of the dentists for the use of neem for controlling dental diseases. This study aims to evaluate the quantitative and qualitative effect of different concentrations of water soluble azadirachtin (neem metabolite) on Streptococcus mutans (S. mutans) against chlorhexidine. Plaque was collected from 30 children aged 8-12 years reporting to the Department of Pediatric and Preventive Dentistry, Bharti Vidyapeeth Dental College, Pune and transported to the laboratory. After incubation of the plates the inhibitory zones were noted and the diameter of the zone of inhibition was measured and recorded to check the inhibition of growth of S. mutans. For testing the bacterial survival, the biofilms were prepared and colony forming units (CFU) was enumerated using a digital colony counter. Two-way analysis of variance (ANOVA) and Tukey's test. The results show that there was no statistically significant difference in the inhibition of S. mutans between 40% concentration of water soluble azadirachtin and chlorhexidine. This study concluded that 40% water soluble azadirachtin is as effective as 0.2% chlorhexidine mouthrinse in reducing the S. mutans count in dental plaque. Hence, a water soluble formulation of azadirachtin may provide the maximum benefit to mankind to prevent dental caries.

  16. Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells--possible relevance to autism spectrum disorders.

    Bistra B Nankova

    Full Text Available Alterations in gut microbiome composition have an emerging role in health and disease including brain function and behavior. Short chain fatty acids (SCFA like propionic (PPA, and butyric acid (BA, which are present in diet and are fermentation products of many gastrointestinal bacteria, are showing increasing importance in host health, but also may be environmental contributors in neurodevelopmental disorders including autism spectrum disorders (ASD. Further to this we have shown SCFA administration to rodents over a variety of routes (intracerebroventricular, subcutaneous, intraperitoneal or developmental time periods can elicit behavioral, electrophysiological, neuropathological and biochemical effects consistent with findings in ASD patients. SCFA are capable of altering host gene expression, partly due to their histone deacetylase inhibitor activity. We have previously shown BA can regulate tyrosine hydroxylase (TH mRNA levels in a PC12 cell model. Since monoamine concentration is known to be elevated in the brain and blood of ASD patients and in many ASD animal models, we hypothesized that SCFA may directly influence brain monoaminergic pathways. When PC12 cells were transiently transfected with plasmids having a luciferase reporter gene under the control of the TH promoter, PPA was found to induce reporter gene activity over a wide concentration range. CREB transcription factor(s was necessary for the transcriptional activation of TH gene by PPA. At lower concentrations PPA also caused accumulation of TH mRNA and protein, indicative of increased cell capacity to produce catecholamines. PPA and BA induced broad alterations in gene expression including neurotransmitter systems, neuronal cell adhesion molecules, inflammation, oxidative stress, lipid metabolism and mitochondrial function, all of which have been implicated in ASD. In conclusion, our data are consistent with a molecular mechanism through which gut related environmental signals

  17. Influence of different proteolytic strains of Streptococcus thermophilus in co-culture with Lactobacillus delbrueckii subsp. bulgaricus on the metabolite profile of set-yoghurt.

    Settachaimongkon, Sarn; Nout, M J Robert; Antunes Fernandes, Elsa C; Hettinga, Kasper A; Vervoort, Jacques M; van Hooijdonk, Toon C M; Zwietering, Marcel H; Smid, Eddy J; van Valenberg, Hein J F

    2014-05-02

    Proto-cooperation between Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus is one of the key factors that determine the fermentation process and final quality of yoghurt. In this study, the interaction between different proteolytic strains of S. thermophilus and L. delbrueckii subsp. bulgaricus was investigated in terms of microbial growth, acidification and changes in the biochemical composition of milk during set-yoghurt fermentation. A complementary metabolomics approach was applied for global characterization of volatile and non-volatile polar metabolite profiles of yoghurt associated with proteolytic activity of the individual strains in the starter cultures. The results demonstrated that only non-proteolytic S. thermophilus (Prt-) strain performed proto-cooperation with L. delbrueckii subsp. bulgaricus. The proto-cooperation resulted in significant higher populations of the two species, faster milk acidification, significant abundance of aroma volatiles and non-volatile metabolites desirable for a good organoleptic quality of yoghurt. Headspace SPME-GC/MS and (1)H NMR resulted in the identification of 35 volatiles and 43 non-volatile polar metabolites, respectively. Furthermore, multivariate statistical analysis allows discriminating set-yoghurts fermented by different types of starter cultures according to their metabolite profiles. Our finding underlines that selection of suitable strain combinations in yoghurt starters is important for achieving the best technological performance regarding the quality of product. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Detecting beer intake by unique metabolite patterns

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian

    2016-01-01

    Evaluation of health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern...... representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1) 18 participants were given one at a time four different test beverages: strong, regular and non-alcoholic beers and a soft drink. Four participants were...... assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e. N-methyl tyramine sulfate and the sum...

  19. In vitro effectiveness of Castellani solution including various ingredients against different microorganisms

    Şükran Çopur

    2013-09-01

    Full Text Available Objective: As the external auditory canal is a moisturearea, it facilitates the growth of bacteria and fungi. Infectionsand inflammation due to Staphylococcus aureus,Pseudomonas aeruginosa, Aspergillus spp. and Candidaalbicans can develop in this area. Classical Castellanisolution including boric acid, fenol, fucsin, resorcinol, acetone,and alcohol is used for external ear tract infectionsdue to fungi and bacteria, and also for the superficial dermatophytoses,and eczematous dermatitis of the externalear tract infections.The purpose of this study is to investigate of the in vitroeffectiveness of classical Castellani solution and its differentformulations with different dilutions against the standardyeast and bacteria strains.Methods: C. albicans ATCC 10231, C. krusei ATCC6258, C. dubliniensis CD 36, C. guilliermondii ATCC6260, C. parapsilosis ATCC22019, E. coli ATCC 25922,P. aeruginosa ATCC 27853, MRSA ATCC 43300, Staphylococcusaureus ATCC 25923, and S. epidermidis ATCC12228 strains were included in the study. Broth microdilutionmethod was used for each microorganism and Castellaniformulation. The tests are repeated at least twice.Results: The inhibitory concentration of classical Castellanisolution against bacteria and fungi is 1/64-1/256,1/32-1/64 for fuchsin free solution, 1/32-1/128 for boricacid-free solution and, 1/64-1/128 for resorcinol-free solution.Conclusions: As a conclusion we think that the classicalCastellani solution and its different formulations at variousdilutions may be effective antimicrobial agents for differentpatient populations. J Clin Exp Invest 2013; 4 (3:302-305Key words: Castellani solution, antimicrobial activity, in vitro

  20. Difference in target definition using three different methods to include respiratory motion in radiotherapy of lung cancer.

    Sloth Møller, Ditte; Knap, Marianne Marquard; Nyeng, Tine Bisballe; Khalil, Azza Ahmed; Holt, Marianne Ingerslev; Kandi, Maria; Hoffmann, Lone

    2017-11-01

    Minimizing the planning target volume (PTV) while ensuring sufficient target coverage during the entire respiratory cycle is essential for free-breathing radiotherapy of lung cancer. Different methods are used to incorporate the respiratory motion into the PTV. Fifteen patients were analyzed. Respiration can be included in the target delineation process creating a respiratory GTV, denoted iGTV. Alternatively, the respiratory amplitude (A) can be measured based on the 4D-CT and A can be incorporated in the margin expansion. The GTV expanded by A yielded GTV + resp, which was compared to iGTV in terms of overlap. Three methods for PTV generation were compared. PTV del (delineated iGTV expanded to CTV plus PTV margin), PTV σ (GTV expanded to CTV and A was included as a random uncertainty in the CTV to PTV margin) and PTV ∑ (GTV expanded to CTV, succeeded by CTV linear expansion by A to CTV + resp, which was finally expanded to PTV ∑ ). Deformation of tumor and lymph nodes during respiration resulted in volume changes between the respiratory phases. The overlap between iGTV and GTV + resp showed that on average 7% of iGTV was outside the GTV + resp implying that GTV + resp did not capture the tumor during the full deformable respiration cycle. A comparison of the PTV volumes showed that PTV σ was smallest and PTV Σ largest for all patients. PTV σ was in mean 14% (31 cm 3 ) smaller than PTV del , while PTV del was 7% (20 cm 3 ) smaller than PTV Σ . PTV σ yields the smallest volumes but does not ensure coverage of tumor during the full respiratory motion due to tumor deformation. Incorporating the respiratory motion in the delineation (PTV del ) takes into account the entire respiratory cycle including deformation, but at the cost, however, of larger treatment volumes. PTV Σ should not be used, since it incorporates the disadvantages of both PTV del and PTV σ .

  1. Primary, Secondary Metabolites, H2O2, Malondialdehyde and Photosynthetic Responses of Orthosiphon stimaneus Benth. to Different Irradiance Levels

    Mohd Hafiz Ibrahim

    2012-01-01

    Full Text Available The resource availability hypothesis predicts an increase in the allocation to secondary metabolites when carbon gain is improved relative to nutrient availability, which normally occurs during periods of low irradiance. The present work was carried out to confirm this hypothesis by investigating the effects of decreasing irradiance on the production of plant secondary metabolites (flavonoids and phenolics in the herbal plant Orthosiphon stamineus, and to characterize this production by carbohydrate, H2O2, and malondialdehyde (MDA levels, net photosynthesis, leaf chlorophyll content and carbon to nitrogen ratio (C/N. Four levels of irradiance (225, 500, 625 and 900 µmol/m2/s were imposed onto two-week old seedlings for 12 weeks in a randomized complete block design experiment. Peak production of total flavonoids, phenolics, soluble sugar, starch and total non-structural carbohydrate ocurred under low irradiance of 225 µmol/m2/s, and decreased with increasing irradiance. The up-regulation of secondary metabolites could be explained by the concomitant increases in H2O2 and MDA activities under low irradiance. This condition also resulted in enhanced C/N ratio signifying a reduction in nitrogen levels, which had established significant negative correlations with net photosynthesis, total biomass and total chlorophyll content, indicating the possible existence of a trade-off between growth and secondary metabolism under low irradiance with reduced nitrogen content. The competition between total chlorophyll and secondary metabolites production, as exhibited by the negative correlation coefficient under low irradiance, also suggests a sign of gradual switch of investment from chlorophyll to polyphenols production.

  2. Comparison of different methods to include recycling in LCAs of aluminium cans and disposable polystyrene cups.

    van der Harst, Eugenie; Potting, José; Kroeze, Carolien

    2016-02-01

    Many methods have been reported and used to include recycling in life cycle assessments (LCAs). This paper evaluates six widely used methods: three substitution methods (i.e. substitution based on equal quality, a correction factor, and alternative material), allocation based on the number of recycling loops, the recycled-content method, and the equal-share method. These six methods were first compared, with an assumed hypothetical 100% recycling rate, for an aluminium can and a disposable polystyrene (PS) cup. The substitution and recycled-content method were next applied with actual rates for recycling, incineration and landfilling for both product systems in selected countries. The six methods differ in their approaches to credit recycling. The three substitution methods stimulate the recyclability of the product and assign credits for the obtained recycled material. The choice to either apply a correction factor, or to account for alternative substituted material has a considerable influence on the LCA results, and is debatable. Nevertheless, we prefer incorporating quality reduction of the recycled material by either a correction factor or an alternative substituted material over simply ignoring quality loss. The allocation-on-number-of-recycling-loops method focusses on the life expectancy of material itself, rather than on a specific separate product. The recycled-content method stimulates the use of recycled material, i.e. credits the use of recycled material in products and ignores the recyclability of the products. The equal-share method is a compromise between the substitution methods and the recycled-content method. The results for the aluminium can follow the underlying philosophies of the methods. The results for the PS cup are additionally influenced by the correction factor or credits for the alternative material accounting for the drop in PS quality, the waste treatment management (recycling rate, incineration rate, landfilling rate), and the

  3. Comparison of different methods to include recycling in LCAs of aluminium cans and disposable polystyrene cups

    Harst-Wintraecken, van der Eugenie; Potting, José; Kroeze, Carolien

    2016-01-01

    Many methods have been reported and used to include recycling in life cycle assessments (LCAs). This paper evaluates six widely used methods: three substitution methods (i.e. substitution based on equal quality, a correction factor, and alternative material), allocation based on the number of

  4. Difference in target definition using three different methods to include respiratory motion in radiotherapy of lung cancer

    Sloth Møller, Ditte; Knap, Marianne Marquard; Nyeng, Tine Bisballe

    2017-01-01

    : PTVσ yields the smallest volumes but does not ensure coverage of tumor during the full respiratory motion due to tumor deformation. Incorporating the respiratory motion in the delineation (PTVdel) takes into account the entire respiratory cycle including deformation, but at the cost, however, of larger...

  5. Including the Tukey Mean-Difference (Bland-Altman) Plot in a Statistics Course

    Kozak, Marcin; Wnuk, Agnieszka

    2014-01-01

    The Tukey mean-difference plot, also called the Bland-Altman plot, is a recognized graphical tool in the exploration of biometrical data. We show that this technique deserves a place on an introductory statistics course by encouraging students to think about the kind of graph they wish to create, rather than just creating the default graph for the…

  6. DETERMINATION OF AGE AND GENDER DIFFERENCES IN BIOCHEMICAL PROCESSES AFFECTING THE DISPOSITION OF 2-BUTOXYETHANOL AND ITS METABOLITES IN MICE AND RATS TO IMPROVE PBPK MODELING

    Corley, Rick A.; Grant, Donna M.; Farris, Elizabeth; Weitz, Karl K.; Soelberg, Jolen J.; Thrall, K D.; Poet, Torka S.

    2005-03-28

    2-Butoxyethanol (BE) is the most widely used glycol ether solvent. BE's major metabolite, butoxyacetic acid (BAA), causes hemolysis with significant species differences in sensitivity. Several PBPK models have been developed over the past two decades to describe the disposition of BE and BAA in male rats and humans to refine health risk assessments. More recent efforts by Lee et al. (1998) to describe the kinetics of BE and BAA in the National Toxicology Program (NTP) chronic inhalation studies required the use of several assumptions to extrapolate model parameters from earlier PBPK models developed for young male rats to include female F344 and both sexes of B6C3F1 mice and the effects of aging. To replace these assumptions, studies were conducted to determine the impact of age, gender and species on the metabolism of BE, and the tissue partitioning, renal acid transport and plasma protein binding of BAA. In the current study, the Lee et al. PBPK model was updated and expanded to include the further metabolism of BAA and the salivary excretion of BE and BAA which may contribute to the forestomach irritation observed in mice in the NTP study. The revised model predicted that peak blood concentrations of BAA achieved following 6-hr inhalation exposures are greatest in young adult female rats at concentrations up to 300 ppm. This is not the case predicted for old (>18 months) animals, where peak blood concentrations of BAA in male and female mice were similar to or greater than female rats. The revised model serves as a quantitative tool for integrating an extensive pharmacokinetic and mechanistic database into a format that can readily be used to compare internal dosimetry across dose, route of exposure and species.

  7. Environmental performance of gasified willow from different lands including land-use changes

    Saez de Bikuna Salinas, Koldo; Hauschild, Michael Zwicky; Pilegaard, Kim

    2017-01-01

    A life-cycle assessment (LCA) of a low-input, short rotation coppice (SRC) willow grown on different Danish lands was performed. Woodchips are gasified, producer gas is used for co-generation of heat and power (CHP) and the ash-char output is applied as soil amendment in the field. A hybrid model...... for abandoned farmland, as a relative C stock loss compared to natural regeneration. ILUC results show that area related GHG emissions are dominant (93% of iLUCfood and 80% of iLUCfeed), transformation being more important (82% of iLUCfood) than occupation (11%) impacts. LCA results show that CHP from willow...

  8. Gender differences in episodic memory and visual working memory including the effects of age.

    Pauls, Franz; Petermann, Franz; Lepach, Anja Christina

    2013-01-01

    Analysing the relationship between gender and memory, and examining the effects of age on the overall memory-related functioning, are the ongoing goals of psychological research. The present study examined gender and age group differences in episodic memory with respect to the type of task. In addition, these subgroup differences were also analysed in visual working memory. A sample of 366 women and 330 men, aged between 16 and 69 years of age, participated in the current study. Results indicate that women outperformed men on auditory memory tasks, whereas male adolescents and older male adults showed higher level performances on visual episodic and visual working memory measures. However, the size of gender-linked effects varied somewhat across age groups. Furthermore, results partly support a declining performance on episodic memory and visual working memory measures with increasing age. Although age-related losses in episodic memory could not be explained by a decreasing verbal and visuospatial ability with age, women's advantage in auditory episodic memory could be explained by their advantage in verbal ability. Men's higher level visual episodic memory performance was found to result from their advantage in visuospatial ability. Finally, possible methodological, biological, and cognitive explanations for the current findings are discussed.

  9. Comparison of different interpolation operators including nonlinear subdivision schemes in the simulation of particle trajectories

    Bensiali, Bouchra; Bodi, Kowsik; Ciraolo, Guido; Ghendrih, Philippe; Liandrat, Jacques

    2013-01-01

    In this work, we compare different interpolation operators in the context of particle tracking with an emphasis on situations involving velocity field with steep gradients. Since, in this case, most classical methods give rise to the Gibbs phenomenon (generation of oscillations near discontinuities), we present new methods for particle tracking based on subdivision schemes and especially on the Piecewise Parabolic Harmonic (PPH) scheme which has shown its advantage in image processing in presence of strong contrasts. First an analytic univariate case with a discontinuous velocity field is considered in order to highlight the effect of the Gibbs phenomenon on trajectory calculation. Theoretical results are provided. Then, we show, regardless of the interpolation method, the need to use a conservative approach when integrating a conservative problem with a velocity field deriving from a potential. Finally, the PPH scheme is applied in a more realistic case of a time-dependent potential encountered in the edge turbulence of magnetically confined plasmas, to compare the propagation of density structures (turbulence bursts) with the dynamics of test particles. This study highlights the difference between particle transport and density transport in turbulent fields

  10. Radiation-included brachial plexus injury; Follow-up of two different fractionation schedules

    Powell, S.; Cooke, J.; Parsons, C. (Royal Marsden Hospital, London (UK))

    1990-07-01

    All 449 breast cancer patients treated with post-operative radiotherapy to the breast and lymph nodes between 1982 and 1984 have been followed for 3-5.5 years. In this group two different fractionation schedules were used, one five times a fortnight and one daily, both over 6 weeks. The calculated dose to the brachial plexus was 45 Gy in 15 fractions or 5e Gy in 30 fractions. These schedules are equivalent doses using the standard NSD formula. The diagnosis of a brachial plexus injury was made clinically and computed tomography from recurrent disease. The actuarial incidence of a radiation-induced brachial plexus injury for the whole group was 4.9% at 5.5 years. No cases were seen in the first 10 months following radiotherapy. The incidence rises between 1 and 4 years and then starts to plateau. When the large fraction size group is compared with the small fraction size group the incidence at 5.5 years is 5.9% and 1.0%, respectively (p 0.09). Two different treatment techniques were used in this group but were not found to contribute to the probability of developing a brachial plexud injury. It is suggested that radiation using large doses per fraction are less well tolerated by the brachial plexus than small doses per fraction; a commonly used fractionation schedule such as 45 Gy in 15 fractions may give unacceptably high brachial plexus morbidity; and the of small doses per fraction or avoiding lymphatic irradiation is advocated. (author). 13 refs.; 6 figs.; 1 tab.

  11. Dosimetry in CBCT with different protocols: emphasis on small FOVs including exams for TMJ

    Nascimento, Helena Aguiar Ribeiro; Nascimento, Eduarda Helena Leandro; Freitas, Deborah Queiroz, E-mail: eduarda.hln@gmail.com [Universidade de Campinas (UNICAMP), Piracicaba, SP (Brazil). Departmento de Diagnose Oral; Andrade, Marcos Ely Almeida [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Departmento de Energia Nuclear; Frazão, Marco Antonio Gomes [Faculdade de Odontologia de Recife (FOR), Recife, PE (Brazil). Divisao de Radiologia Oral; Ramos-Perez, Flavia Maria Moraes [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Departmento de Clinica e Odontologica Preventiva

    2017-07-15

    This study aimed to estimate the absorbed dose in cone beam computed tomography (CBCT) exams according to different exposure parameters and size and position of the field of view (FOV). In addition was compared the absorbed dose of two smaller FOV scans with that of a larger FOV scan for evaluation of temporomandibular joint (TMJ), as it is a bilateral structure. CBCT scans were obtained on OP300 Maxio unit varying scanning mode (standard, high and endo) as well as size (5 x 5, 6 x 8 and 8 x 15 cm) and positioning of FOV. With a small FOV, different areas were scanned (maxilla or mandible, anterior or posterior and TMJ). Absorbed doses were determined using thermoluminescent dosimeters on the skin surface of sensitive organs of an anthropomorphic phantom. Endo mode showed the highest dose, followed by the high and standard modes in all FOV positions. With small FOV, doses were higher in the posterior region, especially in the mandible. Dose reduction occurred when small FOVs were used, but it was not proportional to FOV size reduction. For TMJ, the dose in a single acquisition with large FOV was greater than two acquisitions with small FOV, but lower than two acquisitions with medium FOV (6x8 cm). In conclusion, scanning mode, size and FOV position have great influence on the absorbed dose. Small FOV decreases the dose, but there is no linear relation between FOV size and dose. For bilateral exams of TMJ, double acquisition with small FOVs produces decrease in absorbed dose relative to a large FOV. (author)

  12. Morphine metabolites

    Christrup, Lona Louring

    1997-01-01

    , morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule...... are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after...... systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain. Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear...

  13. Occurance of Staphylococcus nepalensis strains in different sources including human clinical material.

    Nováková, Dana; Pantůcek, Roman; Petrás, Petr; Koukalová, Dagmar; Sedlácek, Ivo

    2006-10-01

    Five isolates of coagulase-negative staphylococci were obtained from human urine, the gastrointestinal tract of squirrel monkeys, pig skin and from the environment. All key biochemical characteristics of the tested strains corresponded with the description of Staphylococcus xylosus species. However, partial 16S rRNA gene sequences obtained from analysed strains corresponded with those of Staphylococcus nepalensis reference strains, except for two strains which differed in one residue. Ribotyping with EcoRI and HindIII restriction enzymes, whole cell protein profile analysis performed by SDS-PAGE and SmaI macrorestriction analysis were used for more precise characterization and identification of the analysed strains. Obtained results showed that EcoRI and HindIII ribotyping and whole cell protein fingerprinting are suitable and reliable methods for the differentiation of S. nepalensis strains from the other novobiocin resistant staphylococci, whereas macrorestriction analysis was found to be a good tool for strain typing. The isolation of S. nepalensis is sporadic, and according to our best knowledge this study is the first report of the occurrence of this species in human clinical material as well as in other sources.

  14. Detecting Beer Intake by Unique Metabolite Patterns.

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian; Bech, Lene; Lund, Erik; Dragsted, Lars Ove

    2016-12-02

    Evaluation of the health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1), 18 participants were given, one at a time, four different test beverages: strong, regular, and nonalcoholic beers and a soft drink. Four participants were assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort, and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e., N-methyl tyramine sulfate and the sum of iso-α-acids and tricyclohumols) and the production process (i.e., pyro-glutamyl proline and 2-ethyl malate), was selected to establish a compliance biomarker model for detection of beer intake based on MSt1. The model predicted the MSt2 samples collected before and up to 12 h after beer intake correctly (AUC = 1). A biomarker model including four metabolites representing both beer raw materials and production steps provided a specific and accurate tool for measurement of beer consumption.

  15. Production of metabolites from chloro biphenyls by resting cells of Pseudomonas strain LB400 after growth on different carbon sources

    Billingsley, K.A.; Ward, O.P.

    1999-01-01

    The transformation of polychlorinated biphenyl (PCB), when exposed to microorganisms, into chlorobenzoic acid metabolites was studied. PCBs are widely used in electrical transformers and have become widely dispersed in the environment. A proposed system for clean up of PCBs involves the combined use of anaerobic reductive dehalogenation of highly chlorinated congeners followed by aerobic degradation of moderately chlorinated PCBs, mediated by oxidative ring attack. Much of this work focused on biphenyl-grown cells, in particular Pseudomonas strain LB400 grown on biphenyl, which contains a multicomponent enzyme system. It was shown that resting cells of Pseudomonas strain LB400, grown on glycerol or glucose, could also transform purified PCB congeners and mixtures of PCBs in Aroclors, however, transformation rates were less than those observed with biphenyl-grown cells. 29 refs., 2 tabs., 2 figs

  16. Transcriptomics and metabolite analysis reveals the molecular mechanism of anthocyanin biosynthesis branch pathway in different Senecio cruentus cultivars

    Xuehua Jin

    2016-09-01

    Full Text Available The cyanidin (Cy, pelargonidin (Pg and delphinidin (Dp pathways are the three major branching anthocyanin biosynthesis pathways that regulate flavonoid metabolic flux and are responsible for red, orange and blue flower colors, respectively. Different species have evolved to develop multiple regulation mechanisms that form the branched pathways. In the current study, five Senecio cruentus cultivars with different colors were investigated. We found that the white and yellow cultivars do not accumulate anthocyanin and that the blue, pink and carmine cultivars mainly accumulate Dp, Pg and Cy in differing densities. Subsequent transcriptome analysis determined that there were 43 unigenes encoding anthocyanin biosynthesis genes in the blue cultivar. We also combined chemical and transcriptomic analyses to investigate the major metabolic pathways that are related to the observed differences in flower pigmentation in the series of S. cruentus. The results showed that mutations of the ScbHLH17 and ScCHI1/2 coding regions abolish anthocyanin formation in the white and the yellow cultivars; the competition of the ScF3’H1, ScF3’5’H and ScDFR1/2 genes for naringenin determines the differences in branching metabolic flux of the Cy, Dp and Pg pathways. Our findings provide new insights into the regulation of anthocyanin branching and also supplement gene resources (including ScF3’5’H, ScF3’H and ScDFRs for flower color modification of ornamentals.

  17. Effects of Different Level and Source of Sulfur Supplement in Close-up diets of Dairy Cows on Blood Metabolites, Colostrums Composition and Liver Performance

    E Manidari

    2012-01-01

    Full Text Available The 24 maltiparous Holstein dairy cows were allocated in a completely randomized design to study the effects of different level and source of sulfur supplement in close-up diets on blood metabolites, colostrums composition and liver performance. The mean body weight of the cows was 687.9 kg and the mean days until expected calving date was 21.8 d. The first treatment (T1 has contained 0.21% sulfur (DM basis, the second treatment (T2 has contained 0.41% sulfur which supplied entirely through magnesium sulfate and the third treatment (T3 has contained 0.41% sulfur which supplied through a combination of magnesium sulfate and an organic source of sulfur (Mepran. The DMI for pre-calving (P < 0.001 was affected by treatments and T2 showed the lowest DMI among treatments. Colostrums yield, protein, DM and ash significantly decreased in inorganic sulfur supplemented treatment (P < 0.05. Among the blood metabolites, calcium, copper and glucose were decreased in T2 compared with two other treatments (P < 0.05. However, BHBA, NEFA and urea were increased in T2 (P < 0.05. Urine pH was affected with different treatments (P < 0.0001. The both liver enzymes (i.e. AST and CPK were increased supplementing inorganic sulfur showing that inorganic sulfur has potential to decrease liver performance in dairy cows. The results of the present study indicate that although magnesium sulfate (inorganic source has negative effect on dairy cow health and performance, a combination of magnesium sulfate and organic source of sulfur could have positive effects on dry matter intake, blood metabolites and liver health in dairy cows.

  18. Sprague-Dawley rats display sex-linked differences in the pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA)

    Fonsart, Julien; Menet, Marie-Claude; Debray, Marcel; Hirt, Deborah; Noble, Florence; Scherrmann, Jean-Michel; Decleves, Xavier

    2009-01-01

    The use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has increased in recent years; it can lead to life-threatening hyperthermia and serotonin syndrome. Human and rodent males appear to be more sensitive to acute toxicity than are females. MDMA is metabolized to five main metabolites by the enzymes CYP1A2, CYP2D and COMT. Little is presently known about sex-dependent differences in the pharmacokinetics of MDMA and its metabolites. We therefore analyzed MDMA disposition in male and female rats by measuring the plasma and urine concentrations of MDMA and its metabolites using a validated LC-MS method. MDA AUC last and C max were 1.6- to 1.7-fold higher in males than in females given MDMA (5 mg/kg sc), while HMMA C max and AUC last were 3.2- and 3.5-fold higher, respectively. MDMA renal clearance was 1.26-fold higher in males, and that of MDA was 2.2-fold higher. MDMA AUC last and t 1/2 were 50% higher in females given MDMA (1 mg/kg iv). MDA C max and AUC last were 75-82% higher in males, with a 2.8-fold higher metabolic index. Finally, the AUC last of MDA was 0.73-fold lower in males given 1 mg/kg iv MDA. The volumes of distribution of MDMA and MDA at steady-state were similar in the two sexes. These data strongly suggest that differences in the N-demethylation of MDMA to MDA are major influences on the MDMA and MDA pharmacokinetics in male and female rats. Hence, males are exposed to significantly more toxic MDA, which could explain previously reported sexual dysmorphism in the acute effects and toxicity of MDMA in rats.

  19. Different effects of scopolamine on learning, memory, and nitric oxide metabolite levels in hippocampal tissues of ovariectomized and Sham-operated rats

    Hamid Azizi-Malekabadi

    2012-06-01

    Full Text Available Different effects of scopolamine on learning, memory, and nitric oxide (NO metabolites in hippocampal tissues of ovariectomized (OVX and sham-operated rats were investigated. The animals in the Sham-Scopolamine (Sham-Sco and OVX-Scopolamine (OVX-Sco Groups were treated with 2 mg/kg scopolamine before undergoing the Morris water maze, while the animals in the Sham and OVX Groups received saline. The time latency and path length were significantly higher in both the Sham-Sco and the OVX-Sco Groups, in comparison with the Sham and OVX Groups, respectively (p<0.001. Significantly lower NO metabolite levels in the hippocampi of the Sham-Sco Group were observed, compared with the Sham Group (p<0.001, while there was no significant difference between the OVX-Sco and OVX Groups. The decreased NO level in the hippocampus may play a role in the learning and memory deficits induced by scopolamine. However, it seems that the effect of scopolamine on hippocampal NO differs between situations of presence and absence of ovarian hormones.

  20. Determination and identification of synthetic cannabinoids and their metabolites in different matrices by modern analytical techniques – a review

    Znaleziona, Joanna; Ginterová, Pavlína; Petr, Jan [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacký University, 17. Listopadu 12, Olomouc CZ-77146 (Czech Republic); Ondra, Peter; Válka, Ivo [Department of Forensic Medicine and Medical Law Faculty Hospital, Hněvotínská 3, Olomouc CZ-77146 (Czech Republic); Ševčík, Juraj [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacký University, 17. Listopadu 12, Olomouc CZ-77146 (Czech Republic); Chrastina, Jan [Institute of Special Education Studies, Faculty of Education, Palacký University, Žižkovo náměsti 5, Olomouc CZ-77146 (Czech Republic); Maier, Vítězslav, E-mail: vitezslav.maier@upol.cz [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacký University, 17. Listopadu 12, Olomouc CZ-77146 (Czech Republic)

    2015-05-18

    Highlights: • Synthetic cannabinoids from analytical point of view. • Determination and identification methods of synthetic cannabinoids in different matrices. • Analytical techniques used from thin layer chromatography to high resolution mass spectrometry. • Detailed survey of gas and liquid chromatography methods for synthetic cannabinoids analysis. - Abstract: Synthetic cannabinoids have gained popularity due to their easy accessibility and psychoactive effects. Furthermore, they cannot be detected in urine by routine drug monitoring. The wide range of active ingredients in analyzed matrices hinders the development of a standard analytical method for their determination. Moreover, their possible side effects are not well known which increases the danger. This review is focused on the sample preparation and the determination of synthetic cannabinoids in different matrices (serum, urine, herbal blends, oral fluid, hair) published since 2004. The review includes separation and identification techniques, such as thin layer chromatography, gas and liquid chromatography and capillary electrophoresis, mostly coupled with mass spectrometry. The review also includes results by spectral methods like infrared spectroscopy, nuclear magnetic resonance or direct-injection mass spectrometry.

  1. Determination and identification of synthetic cannabinoids and their metabolites in different matrices by modern analytical techniques – a review

    Znaleziona, Joanna; Ginterová, Pavlína; Petr, Jan; Ondra, Peter; Válka, Ivo; Ševčík, Juraj; Chrastina, Jan; Maier, Vítězslav

    2015-01-01

    Highlights: • Synthetic cannabinoids from analytical point of view. • Determination and identification methods of synthetic cannabinoids in different matrices. • Analytical techniques used from thin layer chromatography to high resolution mass spectrometry. • Detailed survey of gas and liquid chromatography methods for synthetic cannabinoids analysis. - Abstract: Synthetic cannabinoids have gained popularity due to their easy accessibility and psychoactive effects. Furthermore, they cannot be detected in urine by routine drug monitoring. The wide range of active ingredients in analyzed matrices hinders the development of a standard analytical method for their determination. Moreover, their possible side effects are not well known which increases the danger. This review is focused on the sample preparation and the determination of synthetic cannabinoids in different matrices (serum, urine, herbal blends, oral fluid, hair) published since 2004. The review includes separation and identification techniques, such as thin layer chromatography, gas and liquid chromatography and capillary electrophoresis, mostly coupled with mass spectrometry. The review also includes results by spectral methods like infrared spectroscopy, nuclear magnetic resonance or direct-injection mass spectrometry

  2. Volatile metabolites associated with one aflatoxigenic and one nontoxigenic Aspergillus flavus strain grown on two different substrates

    Z. Jurjevic

    2009-01-01

    Full Text Available Aflatoxigenic and non-toxigenic Aspergillus flavus strains were grown on corn and on peanut substrates. Microbial volatile organic compounds (MVOCS were collected by trapping headspace volatiles using thermal desorption tubes (TDT packed with Tenax® TA and Carbotrap™ B. Samples were collected at various fungal growth stages. Trapped compounds were thermally desorbed from the adsorbent tubes, separated by gas chromatography, and identified by mass spectrometry. The fungal stage did not have many differences in the MVOCs but the concentrations of some volatiles changed over time depending on the substrate. Volatiles that were associated with both the aflatoxigenic A. flavus strain and the nontoxigenic strain on both substrates included: ethanol, 1-propanol, butanal, 2-methyl-1-propanol, 3-methylfuran, ethyl acetate, 1-butanol, 3-methylbutanal, 3-methyl-1-butanol, propanoic acid-2-methyl-ethyl-ester, 2-methyl-1-butanol, 1-pentanol, 2-pentanol, 3-methyl-3-buten-1-ol, benzaldehyde, 3-octanone, 2-ethyl-1-hexanol and octane. Volatiles that were associated only with the aflatoxigenic A. flavus strain included: dimethyl disulfide and nonanal. Volatiles that were associated only with the nontoxigenic A. fl avus strain included: hexanal, 1-hexanol, 1-octene-3-ol, 1-octen-3-one and 2-pentyl furan.

  3. Species-specific differences in the accumulation features of organohalogen contaminants and their metabolites in the blood of Japanese terrestrial mammals

    Mizukawa, Hazuki; Nomiyama, Kei; Nakatsu, Susumu; Yachimori, Shuuji; Hayashi, Terutake; Tashiro, Yutaka; Nagano, Yasuko; Tanabe, Shinsuke

    2013-01-01

    Residue levels and patterns of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), their hydroxylated metabolites (OH-PCBs, OH-PBDEs), and methoxylated PBDEs (MeO-PBDEs) in the blood of various terrestrial mammals in Japan, including cats, raccoon dogs, dogs, masked palm civets, foxes, raccoons, badgers, and mongooses were determined. Tri- through penta-chlorinated OH-PCBs were predominant in cat blood, whereas hexa- through octa-chlorinated OH-PCBs were found in other species. High proportion of BDE209 was found in all species, suggesting exposure to municipal waste and soil containing higher levels of deca-BDE products. 6OH-/MeO-BDE47 and 2′OH-/MeO-BDE68 were dominant in all terrestrial mammals. This is first report on the detection of OH-/MeO-PBDEs in the blood of terrestrial mammals. High concentrations of OH-/MeO-PBDEs were found in cats, suggesting the intake of these compounds from seafood. Cats exhibited higher accumulation and specific patterns of OH-PCBs, OH-PBDEs, and MeO-PBDEs, they may be at a high risk from these metabolites. -- Highlights: ► Analysis of organohalogen metabolites in the blood of Japanese terrestrial mammals. ► First study on analysis of OH-/MeO-PBDEs in terrestrial mammals. ► Cats showed specific residue pattern of OH-PCBs compare to other species. ► Metabolic capacities of PCBs in carnivore were higher than marine mammals. ► Marine natural occurrence OH-/MeO-PBDEs were found in terrestrial mammals. -- Cats showed specific residue pattern of OH-PCBs compare to other species and marine natural occurrence OH-/MeO-PBDEs were detected in terrestrial mammals

  4. iNOS expression and biosynthesis of nitric oxide metabolites in the course of tumor growth of different histogenesis

    V. P. Deryagina

    2016-01-01

    Full Text Available The dynamics of the production of nitric oxide (NO metabolites: nitrites, nitrates, volatile nitrosamines and iNOS expression was studied in mice with subcutaneous transplanted, spontaneous and chemical- induced tumors. Tumor growth was accompanied by increased production of nitrites + nitrates in tumors or their release with urine that not dependent on tumor histotype. The total concentration of nitrites and nitrates in tumors reached micromolar levels characteristic of nitrosative stress. The ability of peritoneal macrophages + monocytes to generates nitrites was suppressed at the stage of intensive growth of the Lewis lung carcinoma, which may indicate a decrease in the cytotoxic properties of immune cells. The possibility of formation in the Erlich carcinoma of volative N-nitrosodimethylamine and N-nitrosodiethylamine compounds with pronounced carcinogenic properties was demonstrated. A positive expression of iNOS was revealed in some areas of lung carcinoma at all investigated time points using the immunohistochemical method. The lungs metastases were not stain or weakly stained. This may indicate selection of the cells with a low activity of iNOS migrating in the lungs.

  5. Correlation of different spectral lights with biomass accumulation and production of antioxidant secondary metabolites in callus cultures of medicinally important Prunella vulgaris L.

    Fazal, Hina; Abbasi, Bilal Haider; Ahmad, Nisar; Ali, Syed Shujait; Akbar, Fazal; Kanwal, Farina

    2016-06-01

    Light is one of the key elicitors that directly fluctuates plant developmental processes and biosynthesis of secondary metabolites. In this study, the effects of various spectral lights on biomass accumulation and production of antioxidant secondary metabolites in callus cultures of Prunella vulgaris were investigated. Among different spectral lights, green light induced the maximum callogenic response (95%). Enhanced fresh biomass accumulation was observed in log phases on day-35, when callus cultures were exposed to yellow and violet lights. Yellow light induced maximum biomass accumulation (3.67g/100ml) from leaf explants as compared to control (1.27g/100ml). In contrast, violet lights enhanced biomass accumulation (3.49g/100ml) from petiole explant. Maximum total phenolics content (TPC; 23.9mg/g-DW) and total flavonoids content (TFC; 1.65mg/g-DW) were observed when cultures were grown under blue lights. In contrast, green and yellow lights enhanced total phenolics production (TPP; 112.52g/100ml) and total flavonoids production (TFP; 9.64g/100ml) as compared to control. The calli grown under green, red and blue lights enhanced DPPH-free radical scavenging activity (DFRSA; 91.3%, 93.1% and 93%) than control (56.44%) respectively. The DFRSA was correlated either with TPC and TFC or TPP and TFP. Furthermore, yellow lights enhanced superoxide dismutase (SOD), peroxidase (POD) and protease activities, however, the content of total protein (CTP) was higher in control cultures (186μg BSAE/mg FW) as compared to spectral lights. These results suggest that the exposure of callus cultures to various spectral lights have shown a key role in biomass accumulation and production of antioxidant secondary metabolites. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Nitrogen balance, microbial protein synthesis and blood metabolites in fattening of male Bali cattle fed ration with different protein levels in smallholder farms

    P. K. Tahuk

    2018-03-01

    Full Text Available Research was aimed to determine nitrogen balance, microbial protein synthesis, and blood metabolites of male Bali cattle fattening fed ration with different protein level in smallholder farms North Central Timor, Province of East Timor Tenggara, Indonesia. The cattle used were 18 heads aged 2 to 2.5 years with initial body weight of 229.86±12.46 kg. The cattle were randomly divided into three treatment groups. The T0 group was given feed the same as traditional fattening cattle practices by farmers,T1 group fed ration containing 12% crude protein (CP and 72% total digestible nutrients (TDN, andT2 group fedration containing 15% CP and 72%TDN. Cattle were fed individually for 90 days and drinkingwater ad libitum. The data were analyzedby analysis of variance.Results of research indicated the nitrogen balance, and blood urea nitrogen between T1 and T2 were relatively similar, but those were higher (P<0.05 than T0 . In contrast, microbial proteins synthesis, and blood glucose at 0, 4, and 6 hours before and after feeding were relatively similar between the groups. Blood glucose of T2 at 2 hours after intake were higher (P <0.05 than T0, but was not different with T1 . It can be concluded, that the fattening maleBali cattle fed ration containing 12% CP and 72% TDNimprovedthe nitrogen balance and blood metabolites, butit was no positive effect on the microbial proteins and N synthesis.

  7. Diversity in Secondary Metabolites Including Mycotoxins from Strains of Aspergillus Section Nigri Isolated from Raw Cashew Nuts from Benin, West Africa

    Lamboni, Leo Yendouban; Nielsen, Kristian Fog; Linnemann, Anita R.

    2016-01-01

    metabolites and their isomers were identified. Aurasperone and pyranonigrin A, produced by all species excluding A. aculeatus and A. aculeatinus, were most prevalent and were encountered in 146 (97.3%) and 145 (95.7%) isolates, respectively. Three mycotoxins groups were detected: fumonisins (B2 and B4) (2...

  8. Graphene-based biomimetic materials targeting urine metabolite as potential cancer biomarker: application over different conductive materials for potentiometric transduction

    Truta, Liliana A.A.N.A.; Ferreira, Nádia S.; Sales, M. Goreti F.

    2015-01-01

    This works presents a novel surface Smart Polymer Antibody Material (SPAM) for Carnitine (CRT, a potential biomarker of ovarian cancer), tested for the first time as ionophore in potentiometric electrodes of unconventional configuration. The SPAM material consisted of a 3D polymeric network created by surface imprinting on graphene layers. The polymer was obtained by radical polymerization of (vinylbenzyl)trimethylammonium chloride and 4-styrenesulfonic acid (signaling the binding sites), and vinyl pivalate and ethylene glycol dimethacrylate (surroundings). Non-imprinted material (NIM) was prepared as control, by excluding the template from the procedure. These materials were then used to produce several plasticized PVC membranes, testing the relevance of including the SPAM as ionophore, and the need for a charged lipophilic additive. The membranes were casted over solid conductive supports of graphite or ITO/FTO. The effect of pH upon the potentiometric response was evaluated for different pHs (2-9) with different buffer compositions. Overall, the best performance was achieved for membranes with SPAM ionophore, having a cationic lipophilic additive and tested in HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer, pH 5.1. Better slopes were achieved when the membrane was casted on conductive glass (−57.4mV/decade), while the best detection limits were obtained for graphite-based conductive supports (3.6×10−5mol/L). Good selectivity was observed against BSA, ascorbic acid, glucose, creatinine and urea, tested for concentrations up to their normal physiologic levels in urine. The application of the devices to the analysis of spiked samples showed recoveries ranging from 91% (± 6.8%) to 118% (± 11.2%). Overall, the combination of the SPAM sensory material with a suitable selective membrane composition and electrode design has lead to a promising tool for point-of-care applications. PMID:26456975

  9. Direct detection of glucuronide metabolites of lidocaine in sheep urine.

    Doran, Gregory S; Smith, Alistair K; Rothwell, Jim T; Edwards, Scott H

    2018-02-15

    The anaesthetic lidocaine is metabolised quickly to produce a series of metabolites, including several hydroxylated metabolites, which are further metabolised by addition of a glucuronic acid moiety. Analysis of these glucuronide metabolites in urine is performed indirectly by cleaving the glucuronic acid group using β-glucuronidase. However, direct analysis of intact glucuronide conjugates is a more straightforward approach as it negates the need for long hydrolysis incubations, and minimises the oxidation of sensitive hydrolysis products, while also distinguishing between the two forms of hydroxylated metabolites. A method was developed to identify three intact glucuronides of lidocaine in sheep urine using LC-MS/MS, which was further confirmed by the synthesis of glucuronide derivatives of 3OH-MEGX and 4OH-LIDO. Direct analysis of urine allowed the detection of the glucuronide metabolites of hydroxylidocaine (OH-LIDO), hydroxyl-monoethylglycinexylidide (OH-MEGX), and hydroxy-2,6-xylidine (OH-XYL). Analysis of urine before and after β-glucuronidase digestion showed that the efficiency of hydrolysis of these glucuronide metabolites may be underestimated in some studies. Analysis of urine in the current study from three different sheep with similar glucuronide metabolite concentrations resulted in different hydrolysis efficiencies, which may have been a result of different levels of substrate binding by matrix components, preventing enzyme cleavage. The use of direct analysis of intact glucuronides has the benefit of being less influenced by these matrix effects, while also allowing analysis of unstable metabolites like 4OH-XYL, which rapidly oxidises after hydrolysis. Additionally, direct analysis is less expensive and less time consuming, while providing more information about the status of hydroxylated metabolites in urine. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  10. 1H NMR-based metabolomic fingerprinting to determine metabolite levels in serrano peppers (Capsicum annum L.) grown in two different regions.

    Becerra-Martínez, Elvia; Florentino-Ramos, Elideth; Pérez-Hernández, Nury; Gerardo Zepeda-Vallejo, L; Villa-Ruano, Nemesio; Velázquez-Ponce, Manuel; García-Mendoza, Felipe; Bañuelos-Hernández, Angel E

    2017-12-01

    Chili pepper (Capsicum annuum) is the most important and emblematic condiment in Mexican food. Serrano pepper is a variety of C. annuum that is traditionally cultivated in Mexico and commercialized in local markets. The aim of this study was to describe the 1 H NMR metabolomic profiling of the aqueous phase of serrano peppers harvested from two distinct regions, in the states of Veracruz and Oaxaca, Mexico. According to the current results, aspartate citrate, lactate, leucine and sucrose were found at higher amount in the serrano peppers from Veracruz. On the other hand, acetate, formate, fumarate, malonate, phosphocholine, pyruvate and succinate showed the highest abundance in this product from Oaxaca. These are the main metabolites that distinguish one group from the other. The spectrometric method reported presently is characterized by great simplicity, robustness and reproducibility. Thus, this technique can be used for establishing reliable metabolomic fingerprints of serrano peppers grown under different environmental conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Short-echo 3D H-1 Magnetic Resonance Spectroscopic Imaging of patients with glioma at 7T for characterization of differences in metabolite levels

    Li, Yan; Larson, Peder; Chen, Albert P.; Lupo, Janine M.; Ozhinsky, Eugene; Kelley, Douglas; Chang, Susan M.; Nelson, Sarah J.

    2014-01-01

    Purpose The purpose of this study was to evaluate the feasibility of using a short echo time, 3D H-1 magnetic resonance spectroscopic imaging (MRSI) sequence at 7T to assess the metabolic signature of lesions for patients with glioma. Materials and Methods 29 patients with glioma were studied. MRSI data were obtained using CHESS water suppression, spectrally-selective adiabatic inversion-recovery pulses and automatically prescribed outer-volume-suppression for lipid suppression, and spin echo slice selection (TE=30ms). An interleaved flyback echo-planar trajectory was applied to shorten the total acquisition time (~10min). Relative metabolite ratios were estimated in tumor and in normal-appearing white and gray matter (NAWM, GM). Results Levels of glutamine, myo-inositol, glycine and glutathione relative to total creatine (tCr) were significantly increased in the T2 lesions for all tumor grades compared to those in the NAWM (p < 0.05), while N-acetyl aspartate to tCr were significantly decreased (p < 0.05). In grade 2 gliomas, level of total choline-containing-compounds to tCr was significantly increased (p = 0.0137), while glutamate to tCr was significantly reduced (p = 0.0012). Conclusion The improved sensitivity of MRSI and the increased number of metabolites that can be evaluated using 7T MR scanners is of interest for evaluating patients with glioma. This study has successfully demonstrated the application of a short-echo spin-echo MRSI sequence to detect characteristic differences in regions of tumor versus normal appearing brain. PMID:24935758

  12. Differences among five amaranth varieties (Amaranthus spp.) regarding secondary metabolites and foliar herbivory by chewing insects in the field

    Niveyro, Selene L.; Mortensen, Anne G.; Fomsgaard, Inge S.

    2013-01-01

    and isoquercitin), nine phenolic compounds (coumaric, vanillic, caffeic, syringic, ferulic, sinapic, protocatechuic, salicylic and 4-hydroxybenzoic acid) and three betalains (amaranthine, iso-amaranthine and betanin) were found to be present in amaranth leaves. Flavonoids appeared in of all varieties analyzed......, with rutin being the most important. Betalains occurred only in some varieties and at different proportions, and nine phenolic acids were observed in all the varieties, with the exception of sinapic acid. Significant differences in the chemical composition of the varieties were noted. A total of 17 species...

  13. Identification of Volatile Secondary Metabolites from an Endophytic Microfungus Aspergillus Nomius KUB105

    Lateef Adebola Azeez; Lateef Adebola Azeez; Sepiah Muid; Bolhassan Mohamad Hasnul

    2016-01-01

    Microfungi are a highly diverse group of micro-organisms and important components of the ecosystem with great potential for diverse metabolite production. During a survey of microfungi on leaves in a National Park in Sarawak, an uncommon endophytic microfungus Aspergillus nomius was encountered. The metabolite production of this microfungus was investigated by growing it in a liquid basal medium for 2 weeks. Gas Chromatography - Mass Spectrometry (GC-MS) and Fourier Transform Infrared (FTIR) profiling of the secondary metabolites produced by this microfungus in the liquid medium revealed the presence of 46 different secondary metabolites. The metabolites include saturated hydrocarbons, alkyl halides, alcohols and an unsaturated hydrocarbon. Majority of the metabolites produced were saturated hydrocarbons. Tetracosane, Icosane and 10-Methylicosane were the most abundant metabolites identified while heptadecane and 2,4-dimethylundecane were the least abundant respectively. This study is the first GC-MS and FTIR report of secondary metabolites from A. nomius. The results from this study confirm the ability of microfungi to produce diverse metabolites, including saturated hydrocarbons. (author)

  14. Urinary composition and postprandial blood changes in H-secoisolariciresinol diglycoside (SDG) metabolites in rats do not differ between acute and chronic SDG treatments.

    Rickard, S E; Thompson, L U

    2000-09-01

    Although chronic exposure to secoisolariciresinol diglycoside (SDG) was shown to alter (3)H-SDG metabolite disposition in rats, the proportion of measured radioactivity attributed to known or unknown SDG metabolites was not determined. Using HPLC and GC-MS, two experiments were conducted to determine the effect of acute (1 d) vs. chronic (10 d) SDG treatment on major urinary metabolites of (3)H-SDG in female, Sprague-Dawley rats (70-72-d-old) over a 48-h period and if new urinary metabolites were detectable in rats fed nonradioactive flaxseed or SDG. A third experiment was conducted to determine changes in postprandial blood levels of (3)H-SDG metabolites over a 24-h period with acute or chronic SDG treatment. Regardless of treatment, enterodiol, enterolactone and secoisolariciresinol accounted for 75-80% of urine radioactivity. Four potential new lignan metabolites, two of which were detected in the urine of rats fed nonradioactive flaxseed or SDG, were found. Type of treatment had no effect on levels of individual urinary metabolites of (3)H-SDG. As observed for plasma lignans in women fed flaxseed, blood radioactivity peaked at 9 h and remained high until 24 h in both treatment groups, suggesting that blood lignan kinetics might be similar with flaxseed or SDG consumption and that they were comparable between humans and rats. In conclusion, the main urinary lignan metabolites were enterodiol, enterolactone and secoisolariciresinol. Urinary composition or blood levels of radioactive lignans were not affected by the duration of SDG exposure. Thus, while chronic SDG exposure alters lignan disposition in rats, it does not change the metabolite profile.

  15. Relationships between luteal activity, fertility, blood metabolites and body condition score in multiparous Estonian Holstein dairy cows under different management.

    Samarütel, Jaak; Waldmann, Andres; Ling, Katri; Jaakson, Hanno; Kaart, Tanel; Leesmäe, Andres; Kärt, Olav

    2008-11-01

    The objective was to compare the relationships between luteal activity and fertility, and relate these parameters to metabolic indices and body condition changes in multiparous Estonian Holstein cows on two commercial dairy farms under different management and levels of production and nutrition (higher, H, n=54 (71 lactations) and lower, L, n=39 (39 lactations)). For statistical analysis cows were categorized according to their milk progesterone (P4) profiles as follows: normal ovarian function; delayed start of cyclicity (DC) (interval from calving to first luteal response (P45 ng/ml up to and more than 50 d respectively, followed by regular cyclicity); cessation of luteal activity (prolonged interluteal interval, P4bodies, non-esterified fatty acids, total cholesterol) and aspartate aminotransferase, body condition scores (BCS) and fertility parameters between the two farms, and also fertility parameters between the farms within P4 categories. Differences in milk fat/protein ratio, ketone body levels and BCS indicated a deeper negative energy balance (NEB) during the first month after calving on farm L. On both farms nearly 50% of the recently calved dairy cows suffered from ovarian dysfunction during the post-partum period. Delayed start of cyclicity was the most prevalent abnormal P4 profile, 25% and 28% on farms H and L, respectively. Prolonged luteal activity accounted for one-third of atypical ovarian patterns on farm H, and cessation of luteal activity on farm L. On farm L, DC cows had lower BCS values from day 10 to day 90 after calving compared with normal cows (Pcows lost more BCS (1.2 units) during the 40 d after calving than normal resumption cows (0.75 units; P<0.05). On farm H with moderate NEB the delayed start of ovulation post partum did not impair subsequent reproductive performance.

  16. Roles of different forms of cytochrome P450 in the activation of the promutagen 6-aminochrysene to genotoxic metabolites in human liver microsomes.

    Yamazaki, H; Mimura, M; Oda, Y; Inui, Y; Shiraga, T; Iwasaki, K; Guengerich, F P; Shimada, T

    1993-07-01

    We reported previously that the potent mutagen 6-aminochrysene is catalyzed principally by rat liver microsomal P4501A and P4502B enzymes to reactive metabolites that induce umu gene expression in O-acetyltransferase-over-expressing strain Salmonella typhimurium NM2009; the proposal was made that there are different mechanisms in the formation of reactive N-hydroxylated and diolepoxide metabolites by P450 enzymes (Yamazaki, H. and Shimada, T., Biochem. Pharmacol., 44, 913-920, 1992). Here we further examined the roles of human liver P450 enzymes and the mechanism of activation of 6-aminochrysene by rat and human P450 enzymes in the Salmonella tester strains. Liver microsomes from 18 different human samples catalyzed activation of 6-aminochrysene more efficiently in S. typhimurium NM2009 than in the original strain of S. typhimurium TA1535/pSK1002. The rates of 6-aminochrysene activation in 18 human liver samples showed good correlation to the contents of P4502B6 as well as contents of P4503A4 and the respective mono-oxygenase activities catalyzed by P4503A4. Among purified P450 enzymes examined, P4501A2 as well as P4503A4 were highly active in transforming 6-amino-chrysene to reactive metabolites, suggesting the involvement of different human P450 enzymes in the reaction. Four human samples that contained relatively high levels of particular P450 enzymes in their microsomes were selected and used for further characterization. Liver microsomes from human samples HL-13 and HL-4 that contained the highest levels of P4502B6 and P4503A4 respectively, were sensitive to the respective antibodies raised against monkey P4502B and human P4503A4; the activity in sample HL-16 having the highest level of P4501A2 was inhibited by anti-P4501A2 IgG. alpha-Naphthoflavone enhanced the activation of 6-aminochrysene very significantly in human liver microsomes enriched in P4503A4 and P4502B6 enzymes. Pentachlorophenol, an inhibitor of acetyltransferase activity, suppressed the

  17. Live performance, carcass characteristic and blood metabolite responses of broilers to two distinct corn types with different extent of grinding.

    Zhao, J P; Cui, D P; Zhang, Z Y; Jiao, H C; Song, Z G; Lin, H

    2017-04-01

    The major objective of this research was to establish the main and interactive effects of corn type and extent of grinding on broiler performance including carcass characteristics. A completely randomized experimental design with a 2 (corn type) × 2 (fine and coarse) factorial arrangement, each with six replicates of 45 male Ross chicks, was applied. Experimental diets, containing dent or hard corn, were formulated with two extents of grinding (3.00 or 6.00 mm screens) for three growing phases. In comparison with dent corn, the hard corn increased body weight (BW) gain and thigh muscle yield (p grinding. Coarser grinding increased the weight of proventriculus (p < 0.01), gizzard (p < 0.05) and small + large intestine (p < 0.10) relative to BW, particularly towards market size. These results suggest that feeding hard corn or large-particle-size corn have some favourable effects on growth performance or gastrointestinal development for finishing broilers. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  18. Effects of different forage sources as a free-choice provision on the performance, nutrient digestibility, selected blood metabolites and structural growth of Holstein dairy calves.

    Movahedi, B; Foroozandeh, A D; Shakeri, P

    2017-04-01

    The objective of this study was to determine the effects of different forage sources on the growth performance, nutrient digestibility and blood metabolites of dairy calves. Individually housed calves (n = 40; body weight = 41.2 ± 3.5 kg) were randomly allocated (n = 10 calves per treatment: five males and five females) to one of the following four treatments: (i) starter without forage provision (CON), (ii) starter plus chopped alfalfa hay (AH), (iii) starter plus chopped wheat straw (WS) and 4) starter plus dried sugar beet pulp (BP) flakes. Calves fed AH diets had lowest (p Digestibility of NDF and ADF was greater (p digestibility of DM and OM than those fed CON diets and similar to those fed AH and WS diets. Calves in the AH treatment had greater (p digestibility than CON, but similar to WS and BP calves. Blood beta-hydroxybutyrate concentration was lower in forage-offered calves than CON one. Body measurements (with the exception of body barrel) did not differ across treatments. It was concluded that BP improves final body weight, ADG and nutrient digestibility of calves than starter without forage provision during weaning transition. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  19. Rapid and simultaneous determination of polychlorinated biphenyls and their main metabolites (hydroxylated and methyl sulfonyl) by gas chromatography coupled to mass spectrometry: Comparison of different ionisation modes

    Castro-Puyana, M.; Herrero, L.; González, M.J.; Gómara, B.

    2013-01-01

    Graphical abstract: -- Highlights: •Simultaneous determination of PCB, OH-PCBs and MeSO 2 -PCBs in a single GC–MS run. •Two different ionisation modes (EI and ECNI) are studied and compared. •The analytical characterisation of both methods is satisfactory. •Better LODs are achieved using ECNI-MS as ionisation mode. •The developed methodology is successfully applied to fish liver oil. -- Abstract: Instrumental methods based on gas chromatography coupled to mass spectrometry (GC–MS) have been developed and compared using two different MS ionisation modes, electron impact (EI) and electron capture negative ionisation (ECNI), for the fast, quantitative and simultaneous determination of polychlorinated biphenyls (PCBs) and their main metabolites (hydroxylated PCBs, OH-PCBs, and methyl sulfone PCBs, MeSO 2 -PCBs). Parameters affecting chromatographic separation and MS detection were evaluated in order to achieve the highest selectivity and sensitivity for both operation modes. The analytical characteristics of the developed methods were studied and compared in terms of linear range, limits of detection (LODs), limits of quantification (LOQs), and instrumental precision (repeatability and intermediate precision). Both ionisation methods showed similar precision, being relative standard deviations (RSD, %) lower than 9% and 14% for repeatability and intermediate precision, respectively. However, better LODs (from 0.01 to 0.14 pg injected for the three families of congeners studied) were achieved using ECNI-MS as ionisation mode. The suitability of the developed method was demonstrated through their application to fish liver oil samples

  20. Secondary metabolites from marine microorganisms.

    Kelecom, Alphonse

    2002-03-01

    After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

  1. Secondary metabolites from marine microorganisms

    KELECOM ALPHONSE

    2002-01-01

    Full Text Available After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

  2. Unbiased Scanning Method and Data Banking Approach Using Ultra-High Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry for Quantitative Comparison of Metabolite Exposure in Plasma across Species Analyzed at Different Dates.

    Gao, Hongying; Deng, Shibing; Obach, R Scott

    2015-12-01

    An unbiased scanning methodology using ultra high-performance liquid chromatography coupled with high-resolution mass spectrometry was used to bank data and plasma samples for comparing the data generated at different dates. This method was applied to bank the data generated earlier in animal samples and then to compare the exposure to metabolites in animal versus human for safety assessment. With neither authentic standards nor prior knowledge of the identities and structures of metabolites, full scans for precursor ions and all ion fragments (AIF) were employed with a generic gradient LC method to analyze plasma samples at positive and negative polarity, respectively. In a total of 22 tested drugs and metabolites, 21 analytes were detected using this unbiased scanning method except that naproxen was not detected due to low sensitivity at negative polarity and interference at positive polarity; and 4'- or 5-hydroxy diclofenac was not separated by a generic UPLC method. Statistical analysis of the peak area ratios of the analytes versus the internal standard in five repetitive analyses over approximately 1 year demonstrated that the analysis variation was significantly different from sample instability. The confidence limits for comparing the exposure using peak area ratio of metabolites in animal plasma versus human plasma measured over approximately 1 year apart were comparable to the analysis undertaken side by side on the same days. These statistical analysis results showed it was feasible to compare data generated at different dates with neither authentic standards nor prior knowledge of the analytes.

  3. Bioactive Metabolites from Pathogenic and Endophytic Fungi of Forest Trees.

    Masi, Marco; Maddau, Lucia; Linaldeddu, Benedetto Teodoro; Scanu, Bruno; Evidente, Antonio; Cimmino, Alessio

    2018-01-01

    Fungi play an important role in terrestrial ecosystems interacting positively or negatively with plants. These interactions are complex and the outcomes are different depending on the fungal lifestyles, saprotrophic, mutualistic or pathogenic. Furthermore, fungi are well known for producing secondary metabolites, originating from different biosynthetic pathways, which possess biological properties of considerable biotechnological interest. Among the terrestrial ecosystems, temperate forests represent an enormous reservoir of fungal diversity. This review will highlight the goldmine of secondary metabolites produced by pathogenic and endophytic fungi of forest trees with focus on their biological activities. A structured search of bibliographic databases for peer-reviewed research literature was undertaken using a research discovery application providing access to a large and authoritative source of references. The papers selected were examined and the main results were reported and discussed. Two hundred forthy-one papers were included in the review, outlined a large number of secondary metabolites produced by pathogenic and endophiltic fungi and their biological activities, including phytotoxic, antifungal, antioomycetes, antibacterial, brine shrimp lethality, mosquito biting deterrence and larvicidal, cytotoxic, antiproliferative and many other bioactivities. The findings of this review confirm the importance of secondary metabolites produced by pathogenic and endophytic fungi from forest plants growing in temperate regions as an excellent prospects to discover compounds with new bioactivities and mode of actions. In addition, the potential of some metabolites as a source of new drugs and biopesticides is underlined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Age-related differences in metabolites in the posterior cingulate cortex and hippocampus of normal ageing brain: A 1H-MRS study

    Reyngoudt, Harmen; Claeys, Tom; Vlerick, Leslie; Verleden, Stijn; Acou, Marjan; Deblaere, Karel; De Deene, Yves; Audenaert, Kurt; Goethals, Ingeborg; Achten, Eric

    2012-01-01

    Objective: To study age-related metabolic changes in N-acetylaspartate (NAA), total creatine (tCr), choline (Cho) and myo-inositol (Ins). Materials and methods: Proton magnetic resonance spectroscopy ( 1 H-MRS) was performed in the posterior cingulate cortex (PCC) and the left hippocampus (HC) of 90 healthy subjects (42 women and 48 men aged 18–76 years, mean ± SD, 48.4 ± 16.8 years). Both metabolite ratios and absolute metabolite concentrations were evaluated. Analysis of covariance (ANCOVA) and linear regression were used for statistical analysis. Results: Metabolite ratios Ins/tCr and Ins/H 2 O were found significantly increased with age in the PCC (P 2 O was only observed in the PCC (P 1 H-MRS results in these specific brain regions can be important to differentiate normal ageing from age-related pathologies such as mild cognitive impairment (MCI) and Alzheimer's disease.

  5. Deposition of diazepam and its metabolites in hair following a single dose of diazepam

    Wang, Xin; Johansen, Sys Stybe; Zhang, Yurong

    2017-01-01

    Only sporadic data are available on hair concentrations of diazepam and some of its metabolites (nordazepam, oxazepam, and temazepam) following a single controlled dose. The aim of this study was to investigate the deposition of diazepam and its metabolites in human hair after eight healthy...... volunteers (four women and four men, ages 24-26, East Asian) consumed 10 mg of diazepam. Hair was collected from all volunteers 1 month after exposure, and also 2 months post-exposure from men and 10 months post-exposure from women. Diazepam and the complete metabolite profile, including oxazepam glucuronide...... no differences by gender in the amounts of diazepam or metabolites found. The concentration of the main metabolite nordazepam was consistently higher than that of diazepam at both 1 and 2 months after consumption. Oxazepam and temazepam traces were found in some volunteers' hair, but the glucuronides were...

  6. A new paradigm for known metabolite identification in metabonomics/metabolomics: metabolite identification efficiency.

    Everett, Jeremy R

    2015-01-01

    A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE) and metabolite identification carbon efficiency (MICE), both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field.

  7. A New Paradigm for Known Metabolite Identification in Metabonomics/Metabolomics: Metabolite Identification Efficiency

    Jeremy R. Everett

    2015-01-01

    Full Text Available A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE and metabolite identification carbon efficiency (MICE, both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field.

  8. Adipogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice - including relationship of sex differences

    Ogawa, Rei; Mizuno, Hiroshi; Watanabe, Atsushi; Migita, Makoto; Hyakusoku, Hiko; Shimada, Takashi

    2004-01-01

    We have previously demonstrated that adipose-derived stromal cells (ASCs) as well as bone marrow-derived stromal cells (BSCs) differentiate into a variety of cell lineages both in vitro and in vivo. Both types are considered to include mesenchymal stem cells. Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have also previously reported the plasticity of BSCs and ASCs. In this study, we focused on adipogenic differentiation in vitro by ASCs harvested from GFP transgenic mice. Moreover, preadipocytes and mature adipocytes were harvested at the same time, and the cells were cultured to compare them with ASCs. Inguinal fat pads from GFP transgenic mice were used for the isolation of ASCs, preadipocytes, and mature adipocytes. After expansion to three passages of ASCs, the cells were incubated in an adipogenic medium for two weeks. Adipogenic differentiation of ASCs was assessed by Oil Red O staining and the expression of the adipocyte specific peroxisome proliferative activated receptor γ2 (PPAR-γ2) gene. These ASCs stained positively, and expression of PPAR-γ2 was detected. Moreover, we also tried to characterize the influence of sex differences on the adipogenic differentiation of ASCs harvested from both male and female mice. This was assessed by the expression levels of the PPAR-γ2 gene using real-time PCR. The results showed that the expression levels of ASCs harvested from female mice were a maximum of 2.89 times greater than those harvested from male mice. This suggests that the adipogenic differentiation of ASCs is closely related to sex differences

  9. Species differences in the biotransformation of an alpha 4 beta 2 nicotinic acetylcholine receptor partial agonist: the effects of distinct glucuronide metabolites on overall compound disposition.

    Shaffer, Christopher L; Gunduz, Mithat; Ryder, Tim F; O'Connell, Thomas N

    2010-02-01

    The metabolism and disposition of (1R,5S)-2,3,4,5-tetrahydro-7-(trifluoromethyl)-1,5-methano-1H-3-benzazepine (1), an alpha(4)beta(2) nicotinic acetylcholine receptor partial agonist, was investigated in Sprague-Dawley rats and cynomolgus monkeys receiving (1R,5S)-2,3,4,5-tetrahydro-7-(trifluoromethyl)-1,5-methano-1H-4[(14)C]-3- benzazepine hydrochloride ([(14)C]1) orally. Although both species chiefly (>or=62%) cleared 1 metabolically, species-specific dispositional profiles were observed for both 1 and total radioactivity. Radioactivity was excreted equally in the urine and feces of intact rats but largely (72%) in bile in bile duct-cannulated animals. In monkeys, radioactivity recoveries were 50-fold greater in urine than feces and minimal (<5%) in bile. Both species metabolized 1 similarly: four-electron oxidation to one of four amino acids or two lactams (minor) and glucuronide formation (major). In rats, the latter pathway predominantly formed an N-carbamoyl glucuronide (M6), exclusively present in bile (69% of dose), whereas in monkeys it afforded an N-O-glucuronide (M5), a minor biliary component (4%) but the major plasma (62%) and urinary (42%) entity. In rats, first-pass hepatic conversion of 1 to M6, which was confirmed in rat hepatocytes, and its biliary secretion resulted in the indirect enterohepatic cycling of 1 via M6 and manifested in double-humped plasma concentration-time curves and long t(1/2) for both 1 and total radioactivity. In monkeys, in which only M5 was formed, double-humped plasma concentration-time curves were absent, and moderate t(1/2) for both 1 and total radioactivity were observed. A seemingly subtle, yet critical, difference in the chemical structures of these two glucuronide metabolites considerably affected the overall disposition of 1 in rats versus monkeys.

  10. Secondary metabolites constituents and antioxidant, anticancer and antibacterial activities of Etlingera elatior (Jack) R.M.Sm grown in different locations of Malaysia.

    Ghasemzadeh, Ali; Jaafar, Hawa Z E; Rahmat, Asmah; Ashkani, Sadegh

    2015-09-23

    Etlingera elatior is a well-known herb in Malaysia with various pharmaceutical properties. E. elatior flowers grown in three different locations of Malaysia (Kelantan, Pahang and Johor), were investigated for differences in their content of secondary metabolites (total phenolics [TPC], total flavonoids [TFC], and total tannin content [TTC]) as well as for their antioxidant, anticancer, and antibacterial properties. Phenolic acids and flavonoids were isolated and identified using ultra-high performance liquid chromatography (UHPLC). Ferric reducing antioxidant potential (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays were used to evaluate the antioxidant activities. The anticancer activity of extracts was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. When extracted with various solvents (aqueous and ethanolic), samples from the different locations yielded significantly different results for TPC, TFC, and TTC as well as antioxidant activity. Aqueous extracts of E. elatior flowers collected from Kelantan exhibited the highest values: TPC (618.9 mg/100 g DM), TFC (354.2 mg/100 g DM), TTC (129.5 mg/100 g DM), DPPH (76.4 %), and FRAP (6.88 mM of Fe (II)/g) activity with a half-maximal inhibitory concentration (IC50) of 34.5 μg/mL compared with extracts of flowers collected from the other two locations. The most important phenolic compounds isolated in this study, based on concentration, were: gallic acid > caffeic acid > tannic acid > chlorogenic acid; and the most important flavonoids were: quercetin > apigenin > kaempferol > luteolin > myricetin. Extracts of flowers from Kelantan exhibited potent anticancer activity with a IC50of 173.1 and 196.2 μg/mL against the tumor cell lines MCF-7 and MDA-MB-231 respectively, compared with extracts from Pahang (IC50 = 204.5 and 246.2 μg/mL) and Johor samples (IC50 = 277.1 and 296.7 μg/mL). Extracts of E. elatior flowers also showed

  11. Ethnic differences in metabolite signatures and type 2 diabetes: a nested case-control analysis among people of South Asian, African and European origin

    van Valkengoed, Irene G. M.; Argmann, Carmen; Ghauharali-van der Vlugt, Karen; Aerts, Johannes M. F. G.; Brewster, Lizzy M.; Peters, R. J. G.; Vaz, Frédéric M.; Houtkooper, Riekelt H.

    2017-01-01

    Accumulation of metabolites may mark or contribute to the development of type 2 diabetes mellitus (T2D), but there is a lack of data from ethnic groups at high risk. We examined sphingolipids, acylcarnitines and amino acids, and their association with T2D in a nested case-control study among 54

  12. Ethnic differences in metabolite signatures and type 2 diabetes : a nested case-control analysis among people of South Asian, African and European origin

    Valkengoed, van I.G.M.; Argmann, C.; Ghauharali-van, der Vlugt K.; Aerts, J.M.F.G.; Brewster, L.M.; Peters, R.J.G.; Vaz, F.M.; Houtkooper, R.H.

    2017-01-01

    Accumulation of metabolites may mark or contribute to the development of type 2 diabetes mellitus (T2D), but there is a lack of data from ethnic groups at high risk. We examined sphingolipids, acylcarnitines and amino acids, and their association with T2D in a nested case-control study among 54

  13. Metabolic fingerprinting of high-fat plasma samples processed by centrifugation- and filtration-based protein precipitation delineates significant differences in metabolite information coverage.

    Barri, Thaer; Holmer-Jensen, Jens; Hermansen, Kjeld; Dragsted, Lars O

    2012-03-09

    Metabolomics and metabolic fingerprinting are being extensively employed for improved understanding of biological changes induced by endogenous or exogenous factors. Blood serum or plasma samples are often employed for metabolomics studies. Plasma protein precipitation (PPP) is currently performed in most laboratories before LC-MS analysis. However, the impact of fat content in plasma samples on metabolite coverage has not previously been investigated. Here, we have studied whether PPP procedures influence coverage of plasma metabolites from high-fat plasma samples. An optimized UPLC-QTOF/MS metabolic fingerprinting approach and multivariate modeling (PCA and OPLS-DA) were utilized for finding characteristic metabolite changes induced by two PPP procedures; centrifugation and filtration. We used 12-h fasting samples and postprandial samples collected at 2h after a standardized high-fat protein-rich meal in obese non-diabetic subjects recruited in a dietary intervention. The two PPP procedures as well as external and internal standards (ISs) were used to track errors in response normalization and quantification. Remarkably and sometimes uniquely, the fPPP, but not the cPPP approach, recovered not only high molecular weight (HMW) lipophilic metabolites, but also small molecular weight (SMW) relatively polar metabolites. Characteristic SMW markers of postprandial samples were aromatic and branched-chain amino acids that were elevated (p<0.001) as a consequence of the protein challenge. In contrast, some HMW lipophilic species, e.g. acylcarnitines, were moderately lower (p<0.001) in postprandial samples. LysoPCs were largely unaffected. In conclusion, the fPPP procedure is recommended for processing high-fat plasma samples in metabolomics studies. While method improvements presented here were clear, use of several ISs revealed substantial challenges to untargeted metabolomics due to large and variable matrix effects. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Dietary adherence and acceptability of five different diets, including vegan and vegetarian diets, for weight loss: The New DIETs study.

    Moore, Wendy J; McGrievy, Michael E; Turner-McGrievy, Gabrielle M

    2015-12-01

    The goal of the present study was to examine dietary adherence and acceptability among participants from the New DIETs study who were randomized to one of four plant-based diets (vegan, vegetarian, pesco-vegetarian, semi-vegetarian) or an omnivore diet. Primary outcomes at two- and six months included dietary adherence (24-hour dietary recalls), weight loss and changes in animal product intake (mg cholesterol) by adherence status, Three-Factor Eating Questionnaire (TFEQ), Power of Food Scale (PFS), dietary acceptability (Food Acceptability Questionnaire), and impact of diet preference on adherence. No differences were found in dietary adherence or changes in FAQ, TFEQ, or PFS among the groups. At six months, non-adherent vegan and vegetarian participants (n=16) had a significantly greater decrease in cholesterol intake (-190.2 ± 199.2 mg) than non-adherent pesco-vegetarian/semi-vegetarian (n=15, -2.3 ± 200.3 mg, P=0.02) or omnivore participants (n=7, 17.0 ± 36.0, P=0.04). Non-adherent vegan/vegetarian participants lost significantly more weight at six months (-6.0 ± 6.7%) than non-adherent omnivore participants (-0.4 ± 0.6%, P=0.04). Dietary preference had no impact on adherence at six months. Due to equal rates of adherence and acceptability among the diet groups, instructing participants to follow vegan or vegetarian diets may have a greater impact on weight loss and animal product intake than providing instruction in more moderate approaches even among non-adherent participants. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Secondary metabolites from Eremostachys laciniata

    Calis, Ihsan; Güvenc, Aysegül; Armagan, Metin

    2008-01-01

    ), and forsythoside B (18), and five flavone derivatives, luteolin (19), luteolin 7-O-β-D-glucopyranoside (20), luteolin 7-O-(6''-O-β-D-apiofuranosyl)-β-D-glucopyranoside (21), apigenin 7-O-β-D-glucopyranoside (22), and apigenin 7-O-(6''-O-p-coumaroyl)-β-D-glucopyranoside (23). The structures of the metabolites were...... elucidated from spectroscopic (UV, IR, 1D- and 2D-NMR) and ESI-MS evidence, as well as from their specific optical rotation. The presence of these metabolites of three different classes strongly supports the close relationship of the genera Eremostachys and Phlomis....

  16. Metabolite Profiling of Red Sea Corals

    Ortega, Jovhana Alejandra

    2016-12-01

    Looking at the metabolite profile of an organism provides insights into the metabolomic state of a cell and hence also into pathways employed. Little is known about the metabolites produced by corals and their algal symbionts. In particular, corals from the central Red Sea are understudied, but interesting study objects, as they live in one of the warmest and most saline environments and can provide clues as to the adjustment of corals to environmental change. In this study, we applied gas chromatography – mass spectrometry (GC–MS) metabolite profiling to analyze the metabolic profile of four coral species and their associated symbionts: Fungia granulosa, Acropora hemprichii, Porites lutea, and Pocillopora verrucosa. We identified and quantified 102 compounds among primary and secondary metabolites across all samples. F. granulosa and its symbiont showed a total of 59 metabolites which were similar to the 51 displayed by P. verrucosa. P. lutea and A. hemprichii both harbored 40 compounds in conjunction with their respective isolated algae. Comparing across species, 28 metabolites were exclusively present in algae, while 38 were exclusive to corals. A principal component and cluster analyses revealed that metabolite profiles clustered between corals and algae, but each species harbored a distinct catalog of metabolites. The major classes of compounds were carbohydrates and amino acids. Taken together, this study provides a first description of metabolites of Red Sea corals and their associated symbionts. As expected, the metabolites of coral hosts differ from their algal symbionts, but each host and algal species harbor a unique set of metabolites. This corroborates that host-symbiont species pairs display a fine-tuned complementary metabolism that provide insights into the specific nature of the symbiosis. Our analysis also revealed aquatic pollutants, which suggests that metabolite profiling might be used for monitoring pollution levels and assessing

  17. An update on organohalogen metabolites produced by basidiomycetes

    Field, J.A.; Wijnberg, J.B.P.A.

    2003-01-01

    Basidiomycetes are an ecologically important group of higher fungi known for their widespread capacity to produce organohalogen metabolites. To date, 100 different organohalogen metabolites (mostly chlorinated) have been identified from strains in 70 genera of Basidiomycetes. This manuscript

  18. Metabolite profiling of Alzheimer's disease cerebrospinal fluid.

    Christian Czech

    Full Text Available Alzheimer's disease (AD is a neurodegenerative disorder characterized by progressive loss of cognitive functions. Today the diagnosis of AD relies on clinical evaluations and is only late in the disease. Biomarkers for early detection of the underlying neuropathological changes are still lacking and the biochemical pathways leading to the disease are still not completely understood. The aim of this study was to identify the metabolic changes resulting from the disease phenotype by a thorough and systematic metabolite profiling approach. For this purpose CSF samples from 79 AD patients and 51 healthy controls were analyzed by gas and liquid chromatography-tandem mass spectrometry (GC-MS and LC-MS/MS in conjunction with univariate and multivariate statistical analyses. In total 343 different analytes have been identified. Significant changes in the metabolite profile of AD patients compared to healthy controls have been identified. Increased cortisol levels seemed to be related to the progression of AD and have been detected in more severe forms of AD. Increased cysteine associated with decreased uridine was the best paired combination to identify light AD (MMSE>22 with specificity and sensitivity above 75%. In this group of patients, sensitivity and specificity above 80% were obtained for several combinations of three to five metabolites, including cortisol and various amino acids, in addition to cysteine and uridine.

  19. Comparative Study on Reagents Involved in Grape Bud Break and Their Effects on Different Metabolites and Related Gene Expression during Winter

    Muhammad Khalil-Ur-Rehman

    2017-08-01

    Full Text Available To elucidate promoting and inhibiting effects of hydrogen cynamide (HC and abscisic acid (ABA on quiescence release of grape buds, physiological and molecular approaches were used to explore the mechanisms of quiescence based on metabolic and gene expression analysis. Physiological and molecular mechanisms involved in bud quiescence of grape were studied before and after application of HC, ABA, and ABA-HC. The data showed that ABA inhibited proclamation of quiescence in grape buds and attenuated the influence of HC. Bud quiescence was promoted and regulated by HC and ABA pre-treatment on buds of grape cultivar “Shine Muscat” with 5% HC, 100 μM ABA and combination of ABA-HC (5% HC+100 μM ABA during quiescence under forcing condition. Exogenous application of ABA elevated superoxide dismutase (SOD, peroxidase (POD and ascorbate peroxidase (APX related specific activities, while catalase (CAT activity was increased during initial period of forcing and then decreased. The concentration of plant growth hormones including gibberellins (GA and indole acetic acid increased by HC application but decreased the ABA contents under forcing condition. ABA increased the fructose content during quiescence under forcing condition while sucrose and total soluble sugars peaked in HC treated buds as compared to control. Genes related to ABA pathway, protein phosphatase 2C (PP2C family were down regulated in the buds treated with HC, ABA and ABA-HC as compared to control while two genes related to GA pathway (GID1 family, out of which one gene showed down regulation during initial period of forcing while other gene was up regulated in response to HC and ABA-HC treatments as compared to control. Exogenous ABA application up regulated genes related to antioxidant enzymes as compared to control. The gene probable fructose-bisphosphate aldolase 1, chloroplastic-like, was up regulated in response to ABA treatment as compared to control. Analysis of metabolites and

  20. Biomimetic trapping cocktail to screen reactive metabolites: use of an amino acid and DNA motif mixture as light/heavy isotope pairs differing in mass shift.

    Hosaka, Shuto; Honda, Takuto; Lee, Seon Hwa; Oe, Tomoyuki

    2018-06-01

    Candidate drugs that can be metabolically transformed into reactive electrophilic products, such as epoxides, quinones, and nitroso compounds, are of special concern because subsequent covalent binding to bio-macromolecules can cause adverse drug reactions, such as allergic reactions, hepatotoxicity, and genotoxicity. Several strategies have been reported for screening reactive metabolites, such as a covalent binding assay with radioisotope-labeled drugs and a trapping method followed by LC-MS/MS analyses. Of these, a trapping method using glutathione is the most common, especially at the early stage of drug development. However, the cysteine of glutathione is not the only nucleophilic site in vivo; lysine, histidine, arginine, and DNA bases are also nucleophilic. Indeed, the glutathione trapping method tends to overlook several types of reactive metabolites, such as aldehydes, acylglucuronides, and nitroso compounds. Here, we introduce an alternate way for screening reactive metabolites as follows: A mixture of the light and heavy isotopes of simplified amino acid motifs and a DNA motif is used as a biomimetic trapping cocktail. This mixture consists of [ 2 H 0 ]/[ 2 H 3 ]-1-methylguanidine (arginine motif, Δ 3 Da), [ 2 H 0 ]/[ 2 H 4 ]-2-mercaptoethanol (cysteine motif, Δ 4 Da), [ 2 H 0 ]/[ 2 H 5 ]-4-methylimidazole (histidine motif, Δ 5 Da), [ 2 H 0 ]/[ 2 H 9 ]-n-butylamine (lysine motif, Δ 9 Da), and [ 13 C 0 , 15 N 0 ]/[ 13 C 1 , 15 N 2 ]-2'-deoxyguanosine (DNA motif, Δ 3 Da). Mass tag triggered data-dependent acquisition is used to find the characteristic doublet peaks, followed by specific identification of the light isotope peak using MS/MS. Forty-two model drugs were examined using an in vitro microsome experiment to validate the strategy. Graphical abstract Biomimetic trapping cocktail to screen reactive metabolites.

  1. The use of secondary metabolite profiling in chemotaxonomy of filamentous fungi

    Frisvad, Jens Christian; Andersen, Birgitte; Thrane, Ulf

    2008-01-01

    A secondary metabolite is a chemical compound produced by a limited number of fungal species in a genus, an order, or even phylum. A profile of secondary metabolites consists of all the different compounds a fungus can produce on a given substratum and includes toxins, antibiotics and other outwa......, Xylaria and in few basidiomycete genera, but not in Zygomycota and Chytridiomycota. (C) 2007 The British Mycological Society. Published by Elsevier Ltd. All rights reserved....

  2. A comparison of different ways of including baseline counts in negative binomial models for data from falls prevention trials.

    Zheng, Han; Kimber, Alan; Goodwin, Victoria A; Pickering, Ruth M

    2018-01-01

    A common design for a falls prevention trial is to assess falling at baseline, randomize participants into an intervention or control group, and ask them to record the number of falls they experience during a follow-up period of time. This paper addresses how best to include the baseline count in the analysis of the follow-up count of falls in negative binomial (NB) regression. We examine the performance of various approaches in simulated datasets where both counts are generated from a mixed Poisson distribution with shared random subject effect. Including the baseline count after log-transformation as a regressor in NB regression (NB-logged) or as an offset (NB-offset) resulted in greater power than including the untransformed baseline count (NB-unlogged). Cook and Wei's conditional negative binomial (CNB) model replicates the underlying process generating the data. In our motivating dataset, a statistically significant intervention effect resulted from the NB-logged, NB-offset, and CNB models, but not from NB-unlogged, and large, outlying baseline counts were overly influential in NB-unlogged but not in NB-logged. We conclude that there is little to lose by including the log-transformed baseline count in standard NB regression compared to CNB for moderate to larger sized datasets. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. A survey of bacterial, fungal and plant metabolites against Aedes aegypti (Diptera: Culicidae), the vector of yellow and dengue fevers and Zika virus

    Aedes aegypti L. is the major vector of the arboviruses responsible for dengue fever, one of the most devastating human diseases. Some bacterial, fungal and plant metabolites including Amaryllidaceae alkaloids belonging to different chemical subgroups, including anthracenes, azoxymethoxytetrahydropy...

  4. A review of sex differences in sexual jealousy, including self-report data, psychophysiological responses, interpersonal violence, and morbid jealousy.

    Harris, Christine R

    2003-01-01

    The specific innate modular theory of jealousy hypothesizes that natural selection shaped sexual jealousy as a mechanism to prevent cuckoldry, and emotional jealousy as a mechanism to prevent resource loss. Therefore, men should be primarily jealous over a mate's sexual infidelity and women over a mate's emotional infidelity. Five lines of evidence have been offered as support: self-report responses, psychophysiological data, domestic violence (including spousal abuse and homicide), and morbid jealousy cases. This article reviews each line of evidence and finds only one hypothetical measure consistent with the hypothesis. This, however, is contradicted by a variety of other measures (including reported reactions to real infidelity). A meta-analysis of jealousy-inspired homicides, taking into account base rates for murder, found no evidence that jealousy disproportionately motivates men to kill. The findings are discussed from a social-cognitive theoretical perspective.

  5. Effect of different provisional cement remnant cleaning procedures including Er:YAG laser on shear bond strength of ceramics

    Zortuk, Mustafa; Gumus, Hasan Onder; Kilinc, Halil Ibrahim; Tuncdemir, Ali Riza

    2012-01-01

    PURPOSE The purpose of this study was to evaluate the effect of provisional cement removal by different dentin cleaning protocols (dental explorer, pumice, cleaning bur, Er:YAG laser) on the shear bond strength between ceramic and dentin. MATERIALS AND METHODS In total, 36 caries-free unrestored human third molars were selected as tooth specimens. Provisional restorations were fabricated and cemented with eugenol-free provisional cement. Then, disc-shaped ceramic specimens were fabricated and...

  6. Differences in Tribological Behaviors upon Switching Fixed and Moving Materials of Tribo-pairs including Metal and Polymer.

    Xu, Aijie; Tian, Pengyi; Wen, Shizhu; Guo, Fei; Hu, Yueqiang; Jia, Wenpeng; Dong, Conglin; Tian, Yu

    2017-10-12

    The coefficient of friction (COF) between two materials is usually believed to be an intrinsic property of the materials themselves. In this study, metals of stainless steel (304) and brass (H62), and polymers of polypropylene (PP) and polytetrafluoroethylene (PTFE) were tested on a standard ball-on-three-plates test machine. Significantly different tribological behaviors were observed when fixed and moving materials of tribo-pairs (metal/polymer) were switched. As an example, under the same applied load and rotating speed, the COF (0.49) between a rotating PP ball and three fixed H62 plates was approximately 2.3 times higher than that between switched materials of tribo-pairs. Meanwhile, the COF between H62 and PTFE was relatively stable. The unexpected tribological behaviors were ascribed to the thermal and mechanical properties of tribo-pairs. Theoretical analysis revealed that the differences in the maximum local temperature between switching the fixed and moving materials of tribo-pairs were consistent with the differences in the tested COF. This result indicated the precise prediction of the COF of two materials is complexcity, and that thermal and mechanical properties should be properly considered in designing tribo-pairs, because these properties may significantly affect tribological performance.

  7. A Decade in the MIST: Learnings from Investigations of Drug Metabolites in Drug Development under the "Metabolites in Safety Testing" Regulatory Guidance.

    Schadt, Simone; Bister, Bojan; Chowdhury, Swapan K; Funk, Christoph; Hop, Cornelis E C A; Humphreys, W Griffith; Igarashi, Fumihiko; James, Alexander D; Kagan, Mark; Khojasteh, S Cyrus; Nedderman, Angus N R; Prakash, Chandra; Runge, Frank; Scheible, Holger; Spracklin, Douglas K; Swart, Piet; Tse, Susanna; Yuan, Josh; Obach, R Scott

    2018-06-01

    Since the introduction of metabolites in safety testing (MIST) guidance by the Food and Drug Administration in 2008, major changes have occurred in the experimental methods for the identification and quantification of metabolites, ways to evaluate coverage of metabolites, and the timing of critical clinical and nonclinical studies to generate this information. In this cross-industry review, we discuss how the increased focus on human drug metabolites and their potential contribution to safety and drug-drug interactions has influenced the approaches taken by industry for the identification and quantitation of human drug metabolites. Before the MIST guidance was issued, the method of choice for generating comprehensive metabolite profile was radio chromatography. The MIST guidance increased the focus on human drug metabolites and their potential contribution to safety and drug-drug interactions and led to changes in the practices of drug metabolism scientists. In addition, the guidance suggested that human metabolism studies should also be accelerated, which has led to more frequent determination of human metabolite profiles from multiple ascending-dose clinical studies. Generating a comprehensive and quantitative profile of human metabolites has become a more urgent task. Together with technological advances, these events have led to a general shift of focus toward earlier human metabolism studies using high-resolution mass spectrometry and to a reduction in animal radiolabel absorption/distribution/metabolism/excretion studies. The changes induced by the MIST guidance are highlighted by six case studies included herein, reflecting different stages of implementation of the MIST guidance within the pharmaceutical industry. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Spectral element modelling of wave propagation in isotropic and anisotropic shell-structures including different types of damage

    Schulte, R T; Fritzen, C-P; Moll, J

    2010-01-01

    During the last decades, guided waves have shown great potential for Structural Health Monitoring (SHM) applications. These waves can be excited and sensed by piezoelectric elements that can be permanently attached onto a structure offering online monitoring capability. However, the setup of wave based SHM systems for complex structures may be very difficult and time consuming. For that reason there is a growing demand for efficient simulation tools providing the opportunity to design wave based SHM systems in a virtual environment. As usually high frequency waves are used, the associated short wavelength leads to the necessity of a very dense mesh, which makes conventional finite elements not well suited for this purpose. Therefore in this contribution a flat shell spectral element approach is presented. By including electromechanical coupling a SHM system can be simulated entirely from actuator voltage to sensor voltage. Besides a comparison to measured data for anisotropic materials including delamination, a numerical example of a more complex, stiffened shell structure with debonding is presented.

  9. PREVALENCE OF SOME HELMINTHS IN RODENTS CAPTURED FROM DIFFERENT CITY STRUCTURES INCLUDING POULTRY FARMS AND HUMAN POPULATION OF FAISALABAD, PAKISTAN

    A. RAFIQUE, S. A. RANA, H. A. KHAN AND A. SOHAIL1

    2009-07-01

    Full Text Available The aim of the present study was to investigate prevalence of zoonotic helminths from human, Rattus rattus (R. rattus, Rattus norvegicus (R. norvegicus and Mus musculus of eight different structures, namely grain shops in grain market, departmental stores, railway godowns, food processing plants (bakeries, poultry farms, houses in kachi-abadies, houses in departmental colonies and posh residences and banglows in Faisalabad city. All the structures were sampled for 2 months each and completed in 16 months. Highest prevalence (70% of Vsmpirolepis spp. was observed in R. rattus sampled from poultry farms, which was significantly higher (P<0.05 than the prevalence of all the helminths recovered from other structures. Hymenolepis nana (H. nana was observed in 60% of the sampled Mus musculus collected from kachi-abadies, which was significantly higher (P<0.05 than all other structures studies for H. nana, except R. rattus from kachi-abadies (55% and R. norvegicus from grain shops in grain market (55%. The rodent’s endo-parasites viz., Hymenolepis nana, Teania taenaeformis, Entrobius spps and Trichuiris spps observed in R. rattus, R. norvegicus and M. musculus at different percentages were also recorded in human stool samples with an incidence of 48, 21, 76 and 10%, respectively.

  10. Effect of different provisional cement remnant cleaning procedures including Er:YAG laser on shear bond strength of ceramics.

    Zortuk, Mustafa; Gumus, Hasan Onder; Kilinc, Halil Ibrahim; Tuncdemir, Ali Riza

    2012-11-01

    The purpose of this study was to evaluate the effect of provisional cement removal by different dentin cleaning protocols (dental explorer, pumice, cleaning bur, Er:YAG laser) on the shear bond strength between ceramic and dentin. In total, 36 caries-free unrestored human third molars were selected as tooth specimens. Provisional restorations were fabricated and cemented with eugenol-free provisional cement. Then, disc-shaped ceramic specimens were fabricated and randomly assigned to four groups of dentin cleaning protocols (n = 9). Group 1 (control): Provisional cements were mechanically removed with a dental explorer. Group 2: The dentin surfaces were treated with a cleaning brush with pumice Group 3: The dentin surfaces were treated with a cleaning bur. Group 4: The provisional cements were removed by an Er:YAG laser. Self-adhesive luting cement was used to bond ceramic discs to dentin surfaces. Shear bond strength (SBS) was measured using a universal testing machine at a 0.05 mm/min crosshead speed. The data were analyzed using a Kolmogorov Smirnov, One-way ANOVA and Tukey HSD tests to perform multiple comparisons (α=0.05). THE DENTIN CLEANING METHODS DID NOT SIGNIFICANTLY AFFECT THE SBS OF CERAMIC DISCS TO DENTIN AS FOLLOWS: dental explorer, pumice, cleaning bur, and Er:YAG laser. The use of different cleaning protocols did not affect the SBS between dentin and ceramic surfaces.

  11. A Novel Fungal Metabolite with Beneficial Properties for Agricultural Applications

    Francesco Vinale

    2014-07-01

    Full Text Available Trichoderma are ubiquitous soil fungi that include species widely used as biocontrol agents in agriculture. Many isolates are known to secrete several secondary metabolites with different biological activities towards plants and other microbes. Harzianic acid (HA is a T. harzianum metabolite able to promote plant growth and strongly bind iron. In this work, we isolated from the culture filtrate of a T. harzianum strain a new metabolite, named isoharzianic acid (iso-HA, a stereoisomer of HA. The structure and absolute configuration of this compound has been determined by spectroscopic methods, including UV-Vis, MS, 1D and 2D NMR analyses. In vitro applications of iso-HA inhibited the mycelium radial growth of Sclerotinia sclerotiorum and Rhizoctonia solani. Moreover, iso HA improved the germination of tomato seeds and induced disease resistance. HPLC-DAD experiments showed that the production of HA and iso HA was affected by the presence of plant tissue in the liquid medium. In particular, tomato tissue elicited the production of HA but negatively modulated the biosynthesis of its analogue iso-HA, suggesting that different forms of the same Trichoderma secondary metabolite have specific roles in the molecular mechanism regulating the Trichoderma plant interaction.

  12. A novel fungal metabolite with beneficial properties for agricultural applications.

    Vinale, Francesco; Manganiello, Gelsomina; Nigro, Marco; Mazzei, Pierluigi; Piccolo, Alessandro; Pascale, Alberto; Ruocco, Michelina; Marra, Roberta; Lombardi, Nadia; Lanzuise, Stefania; Varlese, Rosaria; Cavallo, Pierpaolo; Lorito, Matteo; Woo, Sheridan L

    2014-07-08

    Trichoderma are ubiquitous soil fungi that include species widely used as biocontrol agents in agriculture. Many isolates are known to secrete several secondary metabolites with different biological activities towards plants and other microbes. Harzianic acid (HA) is a T. harzianum metabolite able to promote plant growth and strongly bind iron. In this work, we isolated from the culture filtrate of a T. harzianum strain a new metabolite, named isoharzianic acid (iso-HA), a stereoisomer of HA. The structure and absolute configuration of this compound has been determined by spectroscopic methods, including UV-Vis, MS, 1D and 2D NMR analyses. In vitro applications of iso-HA inhibited the mycelium radial growth of Sclerotinia sclerotiorum and Rhizoctonia solani. Moreover, iso HA improved the germination of tomato seeds and induced disease resistance. HPLC-DAD experiments showed that the production of HA and iso HA was affected by the presence of plant tissue in the liquid medium. In particular, tomato tissue elicited the production of HA but negatively modulated the biosynthesis of its analogue iso-HA, suggesting that different forms of the same Trichoderma secondary metabolite have specific roles in the molecular mechanism regulating the Trichoderma plant interaction.

  13. Comparison of species ordinations resulting from alternative indices of interspecific association and different numbers of included species

    Goff, F G

    1975-12-19

    Several measures of interspecific association are compared. Dispersion and covariance are limited in value because they respond to the commonness of the species compared. Correlation is not so limited but it responds to discrepancies in commonness among the species. The practical result of these relationships between commonness and association is that only the most common species can occupy peripheral positions in a species ordination. Rare species are relegated to positions near the center not on the basis of their phytosociological pattern but simply because of their rarity. Both Cole's index of association and the tetrachoric correlation overcome the problem imposed by the relationship between ordination position and species commonness and they both produce very similar results. The effect of differing numbers of species on the ordination configuration is examined using both Pearson's correlation and Cole's index. The basic pattern of the ordination is set with the first few species when Cole's index is used, however, since rare species are given more weight in the analysis with this index, the addition of several very rare species can change the configuration of the ordination. (auth)

  14. Staphylococcus aureus strains associated with food poisoning outbreaks in France: comparison of different molecular typing methods, including MLVA

    Roussel, Sophie; Felix, Benjamin; Vingadassalon, Noémie; Grout, Joël; Hennekinne, Jacques-Antoine; Guillier, Laurent; Brisabois, Anne; Auvray, Fréderic

    2015-01-01

    Staphylococcal food poisoning outbreaks (SFPOs) are frequently reported in France. However, most of them remain unconfirmed, highlighting a need for a better characterization of isolated strains. Here we analyzed the genetic diversity of 112 Staphylococcus aureus strains isolated from 76 distinct SFPOs that occurred in France over the last 30 years. We used a recently developed multiple-locus variable-number tandem-repeat analysis (MLVA) protocol and compared this method with pulsed field gel electrophoresis (PFGE), spa-typing and carriage of genes (se genes) coding for 11 staphylococcal enterotoxins (i.e., SEA, SEB, SEC, SED, SEE, SEG, SEH, SEI, SEJ, SEP, SER). The strains known to have an epidemiological association with one another had identical MLVA types, PFGE profiles, spa-types or se gene carriage. MLVA, PFGE and spa-typing divided 103 epidemiologically unrelated strains into 84, 80, and 50 types respectively demonstrating the high genetic diversity of S. aureus strains involved in SFPOs. Each MLVA type shared by more than one strain corresponded to a single spa-type except for one MLVA type represented by four strains that showed two different-but closely related-spa-types. The 87 enterotoxigenic strains were distributed across 68 distinct MLVA types that correlated all with se gene carriage except for four MLVA types. The most frequent se gene detected was sea, followed by seg and sei and the most frequently associated se genes were sea-seh and sea-sed-sej-ser. The discriminatory ability of MLVA was similar to that of PFGE and higher than that of spa-typing. This MLVA protocol was found to be compatible with high throughput analysis, and was also faster and less labor-intensive than PFGE. MLVA holds promise as a suitable method for investigating SFPOs and tracking the source of contamination in food processing facilities in real time. PMID:26441849

  15. Non-target screening to trace ozonation transformation products in a wastewater treatment train including different post-treatments.

    Schollée, Jennifer E; Bourgin, Marc; von Gunten, Urs; McArdell, Christa S; Hollender, Juliane

    2018-05-25

    Ozonation and subsequent post-treatments are increasingly implemented in wastewater treatment plants (WWTPs) for enhanced micropollutant abatement. While this technology is effective, micropollutant oxidation leads to the formation of ozonation transformation products (OTPs). Target and suspect screening provide information about known parent compounds and known OTPs, but for a more comprehensive picture, non-target screening is needed. Here, sampling was conducted at a full-scale WWTP to investigate OTP formation at four ozone doses (2, 3, 4, and 5 mg/L, ranging from 0.3 to 1.0 gO 3 /gDOC) and subsequent changes during five post-treatment steps (i.e., sand filter, fixed bed bioreactor, moving bed bioreactor, and two granular activated carbon (GAC) filters, relatively fresh and pre-loaded). Samples were measured with online solid-phase extraction coupled to liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) using electrospray ionization (ESI) in positive and negative modes. Existing non-target screening workflows were adapted to (1) examine the formation of potential OTPs at four ozone doses and (2) compare the removal of OTPs among five post-treatments. In (1), data processing included principal component analysis (PCA) and chemical knowledge on possible oxidation reactions to prioritize non-target features likely to be OTPs. Between 394 and 1328 unique potential OTPs were detected in positive ESI for the four ozone doses tested; between 12 and 324 unique potential OTPs were detected in negative ESI. At a specific ozone dose of 0.5 gO 3 /gDOC, 27 parent compounds were identified and were related to 69 non-target features selected as potential OTPs. Two OTPs were confirmed with reference standards (venlafaxine N-oxide and chlorothiazide); 34 other potential OTPs were in agreement with literature data and/or reaction mechanisms. In (2), hierarchical cluster analysis (HCA) was applied on profiles detected in positive ESI mode across the

  16. Determination of Microbial Nitrogen Production by Using Urinary Allantoin and Blood Metabolite Concentrate in Growing Brahman Cattle Fed the Different Proportion of Roughage and Concentrate in Diets

    Suthikrai, Wanvipa; Usawang, Sungwon; Kijsamrej, Suriya; Sophon, Sunpetch; Jetana, Thongsuk

    2003-06-01

    Determination of microbial nitrogen synthesis by using urinary allantoin and blood metabolite for evaluating the efficiency of feed utilization, in this study was conducted by using four Brahman bulls (about 1 year old). Animals were fed ad libitum with 4 fixed diets of four combinations of pineapple fibre (P) and concentrate (C) in the proportions, on dry matter basis of 0.8:0.2 (P80:C20), 0.6:0.04(P60:C40), 0.4:0.6(P40:C60) and 0.2:0.8 (P20:C80). The experiment was designed as a 4x4 Latin square design The Results showed that increasing in the proportion of concentrate linearly increased the rumen microbial nitrogen production (p<0.001), the concentrations of Insulin and urea-N in plasma and the concentration of urea-N in the urine, but not affected on the concentrations of glucose and creatinine in plasma. In conclusion, the using of allantoin urinary associated with blood metabolite can evaluate the accuracy in evaluation of feed utilization in Brahman cattle

  17. Determinants of Organophosphorus Pesticide Urinary Metabolite Levels in Young Children Living in an Agricultural Community

    Brenda Eskenazi

    2011-04-01

    Full Text Available Organophosphorus (OP pesticides are used in agriculture and several are registered for home use. As young children age they may experience different pesticide exposures due to varying diet, behavior, and other factors. We measured six OP dialkylphosphate (DAP metabolites (three dimethyl alkylphosphates (DMAP and three diethyl alkylphosphates (DEAP in urine samples collected from ~400 children living in an agricultural community when they were 6, 12, and 24 months old. We examined bivariate associations between DAP metabolite levels and determinants such as age, diet, season, and parent occupation. To evaluate independent impacts, we then used generalized linear mixed multivariable models including interaction terms with age. The final models indicated that DMAP metabolite levels increased with age. DMAP levels were also positively associated with daily servings of produce at 6- and 24-months. Among the 6-month olds, DMAP metabolite levels were higher when samples were collected during the summer/spring versus the winter/fall months. Among the 12-month olds, DMAP and DEAP metabolites were higher when children lived ≤60 meters from an agricultural field. Among the 24-month-olds, DEAP metabolite levels were higher during the summer/spring months. Our findings suggest that there are multiple determinants of OP pesticide exposures, notably dietary intake and temporal and spatial proximity to agricultural use. The impact of these determinants varied by age and class of DAP metabolite.

  18. Removal of uremic retention products by hemodialysis is coupled with indiscriminate loss of vital metabolites.

    Zhang, Zhi-Hao; Mao, Jia-Rong; Chen, Hua; Su, Wei; Zhang, Yuan; Zhang, Li; Chen, Dan-Qian; Zhao, Ying-Yong; Vaziri, Nosratola D

    2017-12-01

    Although dialysis ameliorates uremia and fluid and electrolytes disorders, annual mortality rate remains high in dialysis population reflecting its shortcoming in replacing renal function. Unlike the normal kidney, dialysis causes dramatic shifts in volume and composition of body fluids and indiscriminate removal of vital solutes. Present study was undertaken to determine the impact of hemodialysis on plasma metabolites in end-stage renal disease (ESRD) patients. 80 hemodialysis patients and 80 age/gender-matched healthy controls were enrolled in the study. Using ultra performance liquid chromatography-high-definition mass spectrometry, we measured plasma metabolites before, during, and after hemodialysis procedure and in blood entering and leaving the dialysis filter. Principal component analysis revealed significant difference in concentration of 214 metabolites between healthy control and ESRD patients' pre-dialysis plasma (126 increased and 88 reduced in ESRD group). Comparison of post-dialysis with pre-dialysis data revealed significant changes in the 362 metabolites. Among ESI + metabolites 195 decreased and 55 increased and among ESI - metabolites 82 decreased and 30 increased following hemodialysis. Single blood passage through the dialyzer caused significant changes in 323 metabolites. Comparison of ESRD patients' post-hemodialysis with healthy subjects' data revealed marked differences in metabolic profiles. We identified 55 of the 362 differential metabolites including well known uremic toxins, waste products and vital biological compounds. In addition to uremic toxins and waste products hemodialysis removes large number of identified and as-yet un-identified metabolites. Depletion of vital biological compounds by dialysis may contribute to the high morbidity and annual mortality rate in this population. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  19. Effects of different sources of fructans on body weight, blood metabolites and fecal bacteria in normal and obese non-diabetic and diabetic rats.

    Rendón-Huerta, Juan A; Juárez-Flores, Bertha; Pinos-Rodríguez, Juan M; Aguirre-Rivera, J Rogelio; Delgado-Portales, Rosa E

    2012-03-01

    Fructans contribute significantly to dietary fiber with beneficial effects on gastrointestinal physiology in healthy individuals and offer a promising approach to treating some diseases. Two experiments (Experiment 1 = rats with normal weight; Experiment 2 = obese rats) were developed to compare the effects of three fructan sources (Cichorium intybus L. Asteraceae, Helianthus tuberosus L. Asteraceae and Agave angustifolia ssp. tequilana Haw, Agavaceae) on body weight change, blood metabolites and fecal bacteria in non-diabetic (ND) and diabetic (D) rats. In Experiment 1 total body weight gain and daily feed intake in D and ND rats decreased (P tequilana decreased blood cholesterol and LDL and liver steatosis. For both ND and D rats, fecal Lactobacillus spp. and Bifidobacterium spp. counts were higher (P < 0.05) with fructan supplements.

  20. Metabolites in vertebrate Hedgehog signaling.

    Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

    2014-04-11

    The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Induced sclerotium formation exposes new bioactive metabolites from Aspergillus sclerotiicarbonarius

    Petersen, Lene Maj; Frisvad, Jens Christian; Knudsen, Peter Boldsen

    2015-01-01

    Sclerotia are known to be fungal survival structures, and induction of sclerotia may prompt production of otherwise undiscovered metabolites. Aspergillus sclerotiicarbonarius (IBT 28362) was investigated under sclerotium producing conditions, which revealed a highly altered metabolic profile. Four...... new compounds were isolated from cultivation under sclerotium formation conditions and their structures elucidated using different analytical techniques (HRMS, UV, 1D and 2D NMR). This included sclerolizine, an alkylated and oxidized pyrrolizine, the new emindole analog emindole SC and two new...

  2. Andrastin A and barceloneic acid metabolites, protein farnesyl transferase inhibitors from Penicillium alborcoremium: chemotaxonomic significance and pathological implications

    Overy, David Patrick; Larsen, Thomas Ostenfeld; Dalsgaard, P.W.

    2005-01-01

    A survey of Penicillium albocoremium was undertaken to identify potential taxonomic metabolite markers. One major and four minor metabolites were consistently produced by the 19 strains surveyed on three different media. Following purification and spectral studies, the metabolites were identified...

  3. Renal excretion of iodine-131 labelled meta-iodobenzylguanidine and metabolites after therapeutic doses in patients suffering from different neural crest-derived tumours

    Wafelman, A.R.; Hoefnagel, C.A.; Maessen, H.J.M.; Maes, R.A.A.; Beijnen, J.H.

    1997-01-01

    Iodine-131 labelled meta-iodobenzylguanidine ([ 131 I[MIBG) is used for diagnostic scintigraphy and radionuclide therapy of neural crest-derived tumours. After administration of therapeutic doses of [ 131 I[MIBG (3.1-7.5 GBq) to 17 patients (n=32 courses), aged 2-73 years, 56%±10%, 73%±11%, 80%±10% and 83%±10% of the dose was cumulatively excreted as total radioactivity in urine at t=24 h, 48 h, 72 h and 96 h, respectively. Except for two adult patients, who showed excretion of 14%-18% of [ 131 I[meta-iodohippuric acid ([ 131 I[MIHA), the cumulatively excreted radioactivity consisted of >85% [ 131 I[MIBG, with 6% of the dose excreted as free [ 131 I[iodide, 4% as [ 131 I[MIHA and 2.5% as an unknown iodine-131 labelled metabolite. Cumulative renal excretion rates of total radioactivity and of [ 131 I[MIBG appeared to be higher in neuroblastoma and phaeochromocytoma patients than in carcinoid patients. Based on the excretion of small amounts of [ 131 I[meta-iodobenzoic acid in two patients, a possible metabolic pathway for [ 131 I[MIBG is suggested. The degree of metabolism was not related to the extent of liver uptake of radioactivity. (orig.). With 2 figs., 5 tabs

  4. Methylselenol, a selenium metabolite, plays common and different roles in cancerous colon HCT116 cell and noncancerous NCM460 colon cell proliferation.

    Zeng, Huawei; Briske-Anderson, Mary; Wu, Min; Moyer, Mary P

    2012-01-01

    Methylselenol is hypothesized to be a critical selenium metabolite for anticancer action, and differential chemopreventive effects of methylselenol on cancerous and noncancerous cells may play an important role. In this study, the submicromolar concentrations of methylselenol were generated by incubating methionase with seleno-L methionine, and colon-cancer-derived HCT-116 cells and noncancerous colon NCM460 cells were exposed to methylselenol. Methylselenol exposure inhibited cell growth and led to an increase in G1 and G2 fractions with a concomitant drop in S-phase and an induction of apoptosis in HCT116, but to a much lesser extent in NCM460 colon cells. Similarly, the examination of mitogen-activated protein kinase (MAPK) and cellular myelocytomatosis oncogene (c-Myc) signaling status revealed that methylselenol inhibited the phosphorylation of extracellular-regulated kinase1/2 and p38 mitogen-activated protein kinase and the expression of c-Myc in HCT116 cells, but also to a lesser extent in NCM460 cells. The other finding is that methylselenol inhibits sarcoma kinase phosphorylation in HCT116 cells. In contrast, methylselenol upregulated the phosphorylation of sarcoma and focal adhesion kinase survival signals in the noncancerous NCM460 cells. Collectively, methylselenol's stronger potential of inhibiting cell proliferation/survival signals in the cancerous HCT116 cells when compared with that in noncancerous NCM460 cells may partly explain the potential of methylselenol's anticancer action.

  5. Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols.

    Pinu, Farhana R; Villas-Boas, Silas G; Aggio, Raphael

    2017-10-23

    Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

  6. Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols

    Farhana R. Pinu

    2017-10-01

    Full Text Available Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

  7. New Methodology for Known Metabolite Identification in Metabonomics/Metabolomics: Topological Metabolite Identification Carbon Efficiency (tMICE).

    Sanchon-Lopez, Beatriz; Everett, Jeremy R

    2016-09-02

    A new, simple-to-implement and quantitative approach to assessing the confidence in NMR-based identification of known metabolites is introduced. The approach is based on a topological analysis of metabolite identification information available from NMR spectroscopy studies and is a development of the metabolite identification carbon efficiency (MICE) method. New topological metabolite identification indices are introduced, analyzed, and proposed for general use, including topological metabolite identification carbon efficiency (tMICE). Because known metabolite identification is one of the key bottlenecks in either NMR-spectroscopy- or mass spectrometry-based metabonomics/metabolomics studies, and given the fact that there is no current consensus on how to assess metabolite identification confidence, it is hoped that these new approaches and the topological indices will find utility.

  8. Ecotoxicological effects of selected cyanobacterial secondary metabolites a short review

    Wiegand, C.; Pflugmacher, S.

    2005-01-01

    Cyanobacteria are one of the most diverse groups of gram-negative photosynthetic prokaryotes. Many of them are able to produce a wide range of toxic secondary metabolites. These cyanobacterial toxins can be classified in five different groups: hepatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritant toxins (lipopolysaccharides). Cyanobacterial blooms are hazardous due to this production of secondary metabolites and endotoxins, which could be toxic to animals and plants. Many of the freshwater cyanobacterial blooms include species of the toxigenic genera Microcystis, Anabaena, or Plankthotrix. These compounds differ in mechanisms of uptake, affected organs, and molecular mode of action. In this review, the main focus is the aquatic environment and the effects of these toxins to the organisms living there. Some basic toxic mechanisms will be discussed in comparison to the mammalian system

  9. Transportable hyperpolarized metabolites

    Ji, Xiao; Bornet, Aurélien; Vuichoud, Basile; Milani, Jonas; Gajan, David; Rossini, Aaron J.; Emsley, Lyndon; Bodenhausen, Geoffrey; Jannin, Sami

    2017-01-01

    Nuclear spin hyperpolarization of 13C-labelled metabolites by dissolution dynamic nuclear polarization can enhance the NMR signals of metabolites by several orders of magnitude, which has enabled in vivo metabolic imaging by MRI. However, because of the short lifetime of the hyperpolarized magnetization (typically <1 min), the polarization process must be carried out close to the point of use. Here we introduce a concept that markedly extends hyperpolarization lifetimes and enables the transportation of hyperpolarized metabolites. The hyperpolarized sample can thus be removed from the polarizer and stored or transported for use at remote MRI or NMR sites. We show that hyperpolarization in alanine and glycine survives 16 h storage and transport, maintaining overall polarization enhancements of up to three orders of magnitude. PMID:28072398

  10. Different biosynthesis patterns among flavonoid 3-glycosides with distinct effects on accumulation of other flavonoid metabolites in pears (Pyrus bretschneideri Rehd..

    Rui Zhai

    Full Text Available Flavonoid biosynthesis profile was clarified by fruit bagging and re-exposure treatments in the green Chinese pear 'Zaosu' (Pyrus bretschneideri Rehd. and its red mutant 'Red Zaosu'. Two distinct biosynthesis patterns of flavonoid 3-glycosides were found in 'Zaosu' pear. By comparison with 'Red Zaosu', the biosynthesis of flavonoid 3-galactosides and flavonoid 3-arabinosides were inhibited by bagging and these compounds only re-accumulated to a small degree in the fruit peel of 'Zaosu' after the bags were removed. In contrast, the biosynthesis of flavonoid 3-gluctosides and flavonoid 3-rutinosides was reduced by bagging and then increased when the fruits were re-exposed to sunlight. A combination of correlation, multicollinearity test and partial-correlation analyses among major flavonoid metabolites indicated that biosynthesis of each phenolic compound was independent in 'Zaosu' pear, except for the positive correlation between flavonoid 3-rutincosides and flavanols. In contrast with the green pear cultivar, almost all phenolic compounds in the red mutant had similar biosynthesis patterns except for arbutin. However, only the biosynthesis of flavonoid 3-galactosides was relatively independent and strongly affected the synthesis of the other phenolic compounds. Therefore, we propose a hypothesis that the strong accumulation of flavonoid 3-galactosides stimulated the biosynthesis of other flavonoid compounds in the red mutant and, therefore, caused systemic variation of flavonoid biosynthesis profiles between 'Zaosu' and its red mutant. This hypothesis had been further demonstrated by the enzyme activity of UFGT, and transcript levels of flavonoid biosynthetic genes and been well tested by a stepwise linear regression forecasting model. The gene that encodes flavonoid 3-galacosyltransferase was also identified and isolated from the pear genome.

  11. Physiologically-based pharmacokinetic modeling of tamoxifen and its metabolites in women of different CYP2D6 phenotypes provides new insight into the tamoxifen mass balance

    Kristin eDickschen

    2012-05-01

    Full Text Available Tamoxifen is a first-line endocrine agent in the mechanism-based treatment of estrogen receptor positive (ER+ mammary carcinoma and applied to breast cancer patients all over the world. Endoxifen is a secondary and highly active metabolite of tamoxifen that is formed among others by the polymorphic cytochrome P450 2D6 (CYP2D6. It is widely accepted that CYP2D6 poor metabolizers (PM exert a pronounced decrease in endoxifen steady-state plasma concentrations compared to CYP2D6 extensive metabolizers (EM. Nevertheless, an in-depth understanding of the chain of cause and effect between CYP2D6 genotype, endoxifen steady-state plasma concentration, and subsequent tamoxifen treatment benefit still remains to be evolved.In this context, physiologically-based pharmacokinetic (PBPK-modeling provides a useful tool to mechanistically investigate the impact of CYP2D6 phenotype on endoxifen formation in female breast cancer patients undergoing tamoxifen therapy.It has long been thought that only a minor percentage of endoxifen is formed via 4-hydroxytamoxifen. However, the current investigation supports very recently published data that postulates a contribution of 4-hydroxytamoxifen above 20 % to total endoxifen formation. The developed PBPK-model describes tamoxifen PK in rats and humans. Moreover, tamoxifen metabolism in dependence of CYP2D6 phenotype in populations of European female individuals is well described, thus providing a good basis to further investigate the linkage of PK, mode of action, and treatment outcome in dependence of factors such as phenotype, ethnicity or co-treatment with CYP2D6 inhibitors.

  12. Metabolomics Workbench: An international repository for metabolomics data and metadata, metabolite standards, protocols, tutorials and training, and analysis tools.

    Sud, Manish; Fahy, Eoin; Cotter, Dawn; Azam, Kenan; Vadivelu, Ilango; Burant, Charles; Edison, Arthur; Fiehn, Oliver; Higashi, Richard; Nair, K Sreekumaran; Sumner, Susan; Subramaniam, Shankar

    2016-01-04

    The Metabolomics Workbench, available at www.metabolomicsworkbench.org, is a public repository for metabolomics metadata and experimental data spanning various species and experimental platforms, metabolite standards, metabolite structures, protocols, tutorials, and training material and other educational resources. It provides a computational platform to integrate, analyze, track, deposit and disseminate large volumes of heterogeneous data from a wide variety of metabolomics studies including mass spectrometry (MS) and nuclear magnetic resonance spectrometry (NMR) data spanning over 20 different species covering all the major taxonomic categories including humans and other mammals, plants, insects, invertebrates and microorganisms. Additionally, a number of protocols are provided for a range of metabolite classes, sample types, and both MS and NMR-based studies, along with a metabolite structure database. The metabolites characterized in the studies available on the Metabolomics Workbench are linked to chemical structures in the metabolite structure database to facilitate comparative analysis across studies. The Metabolomics Workbench, part of the data coordinating effort of the National Institute of Health (NIH) Common Fund's Metabolomics Program, provides data from the Common Fund's Metabolomics Resource Cores, metabolite standards, and analysis tools to the wider metabolomics community and seeks data depositions from metabolomics researchers across the world. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Hydrophobicity and charge shape cellular metabolite concentrations.

    Arren Bar-Even

    2011-10-01

    Full Text Available What governs the concentrations of metabolites within living cells? Beyond specific metabolic and enzymatic considerations, are there global trends that affect their values? We hypothesize that the physico-chemical properties of metabolites considerably affect their in-vivo concentrations. The recently achieved experimental capability to measure the concentrations of many metabolites simultaneously has made the testing of this hypothesis possible. Here, we analyze such recently available data sets of metabolite concentrations within E. coli, S. cerevisiae, B. subtilis and human. Overall, these data sets encompass more than twenty conditions, each containing dozens (28-108 of simultaneously measured metabolites. We test for correlations with various physico-chemical properties and find that the number of charged atoms, non-polar surface area, lipophilicity and solubility consistently correlate with concentration. In most data sets, a change in one of these properties elicits a ~100 fold increase in metabolite concentrations. We find that the non-polar surface area and number of charged atoms account for almost half of the variation in concentrations in the most reliable and comprehensive data set. Analyzing specific groups of metabolites, such as amino-acids or phosphorylated nucleotides, reveals even a higher dependence of concentration on hydrophobicity. We suggest that these findings can be explained by evolutionary constraints imposed on metabolite concentrations and discuss possible selective pressures that can account for them. These include the reduction of solute leakage through the lipid membrane, avoidance of deleterious aggregates and reduction of non-specific hydrophobic binding. By highlighting the global constraints imposed on metabolic pathways, future research could shed light onto aspects of biochemical evolution and the chemical constraints that bound metabolic engineering efforts.

  14. Metabolites of cannabidiol identified in human urine.

    Harvey, D J; Mechoulam, R

    1990-03-01

    1. Urine from a dystonic patient treated with cannabidiol (CBD) was examined by g.l.c.-mass spectrometry for CBD metabolites. Metabolites were identified as their trimethylsilyl (TMS), [2H9]TMS, and methyl ester/TMS derivatives and as the TMS derivatives of the product of lithium aluminium deuteride reduction. 2. Thirty-three metabolites were identified in addition to unmetabolized CBD, and a further four metabolites were partially characterized. 3. The major metabolic route was hydroxylation and oxidation at C-7 followed by further hydroxylation in the pentyl and propenyl groups to give 1"-, 2"-, 3"-, 4"- and 10-hydroxy derivatives of CBD-7-oic acid. Other metabolites, mainly acids, were formed by beta-oxidation and related biotransformations from the pentyl side-chain and these were also hydroxylated at C-6 or C-7. The major oxidized metabolite was CBD-7-oic acid containing a hydroxyethyl side-chain. 4. Two 8,9-dihydroxy compounds, presumably derived from the corresponding epoxide were identified. 5. Also present were several cyclized cannabinoids including delta-6- and delta-1-tetrahydrocannabinol and cannabinol. 6. This is the first metabolic study of CBD in humans; most observed metabolic routes were typical of those found for CBD and related cannabinoids in other species.

  15. Farmed and wild sea bass (Dicentrarchus labrax) volatile metabolites: a comparative study by SPME-GC/MS.

    Vidal, Natalia P; Manzanos, María J; Goicoechea, Encarnación; Guillén, María D

    2016-03-15

    Farmed and wild European sea bass (Dicentrarchus labrax) could be distinguished by its volatile metabolites, an issue not addressed until now. The aim of this work was to study these metabolites by solid-phase microextraction followed by gas chromatography/mass spectrometry (SPME-GC/MS). Both farmed and wild sea bass have a great number of volatile metabolites, most of them being in low concentrations. These include alcohols, aldehydes, ketones, alkylfurans, acids, aliphatic and aromatic hydrocarbons, terpenes, sulfur and nitrogen derivatives, 2,6-di-tert-butyl-4-methylphenol and one derived compound, as well as 2,4,7,9-tetramethyl-5-decyne-4,7-diol, this latter compound presumably resulting from environmental contamination. Important differences have been detected between both types of sea bass, and also among individuals inside each group. Farmed specimens are richer in volatile metabolites than the wild counterparts; however, these latter, in general, contain a high number and abundance of metabolites resulting from microbial and enzymatic non-oxidative activity than the former. Clear differences in the volatile metabolites of wild and farmed sea bass have been found. A great deal of valuable information on sea bass volatile metabolites has been obtained, which can be useful in understanding certain aspects of the quality and safety of raw and processed sea bass. © 2015 Society of Chemical Industry.

  16. Live animal measurements, carcass composition and plasma hormone and metabolite concentrations in male progeny of sires differing in genetic merit for beef production.

    Clarke, A M; Drennan, M J; McGee, M; Kenny, D A; Evans, R D; Berry, D P

    2009-07-01

    In genetic improvement programmes for beef cattle, the effect of selecting for a given trait or index on other economically important traits, or their predictors, must be quantified to ensure no deleterious consequential effects go unnoticed. The objective was to compare live animal measurements, carcass composition and plasma hormone and metabolite concentrations of male progeny of sires selected on an economic index in Ireland. This beef carcass index (BCI) is expressed in euros and based on weaning weight, feed intake, carcass weight and carcass conformation and fat scores. The index is used to aid in the genetic comparison of animals for the expected profitability of their progeny at slaughter. A total of 107 progeny from beef sires of high (n = 11) or low (n = 11) genetic merit for the BCI were compared in either a bull (slaughtered at 16 months of age) or steer (slaughtered at 24 months of age) production system, following purchase after weaning (8 months of age) from commercial beef herds. Data were analysed as a 2 × 2 factorial design (two levels of genetic merit by two production systems). Progeny of high BCI sires had heavier carcasses, greater (P animal value (obtained by multiplying carcass weight by carcass value, which was based on the weight of meat in each cut by its commercial value) than progeny of low BCI sires. Regression of progeny performance on sire genetic merit was also undertaken across the entire data set. In steers, the effect of BCI on carcass meat proportion, calculated carcass value (c/kg) and animal value was positive (P carcass fat proportion (P carcass weight followed the same trends as BCI. Muscularity scores, carcass meat proportion and calculated carcass value increased, whereas scanned fat depth, carcass fat and bone proportions decreased with increasing sire EPD for conformation score. The opposite association was observed for sire EPD for fat score. Results from this study show that selection using the BCI had positive

  17. Effects of 14-day oral low dose selenium nanoparticles and selenite in rat—as determined by metabolite pattern determination

    Niels Hadrup

    2016-10-01

    Full Text Available Selenium (Se is an essential element with a small difference between physiological and toxic doses. To provide more effective and safe Se dosing regimens, as compared to dosing with ionic selenium, nanoparticle formulations have been developed. However, due to the nano-formulation, unexpected toxic effects may occur. We used metabolite pattern determination in urine to investigate biological and/or toxic effects in rats administered nanoparticles and for comparison included ionic selenium at an equimolar dose in the form of sodium selenite. Low doses of 10 and 100 fold the recommended human high level were employed to study the effects at borderline toxicity. Evaluations of all significantly changed putative metabolites, showed that Se nanoparticles and sodium selenite induced similar dose dependent changes of the metabolite pattern. Putative identified metabolites included increased decenedioic acid and hydroxydecanedioic acid for both Se formulations whereas dipeptides were only increased for selenite. These effects could reflect altered fatty acid and protein metabolism, respectively.

  18. Secondary metabolites from Ganoderma.

    Baby, Sabulal; Johnson, Anil John; Govindan, Balaji

    2015-06-01

    Ganoderma is a genus of medicinal mushrooms. This review deals with secondary metabolites isolated from Ganoderma and their biological significance. Phytochemical studies over the last 40years led to the isolation of 431 secondary metabolites from various Ganoderma species. The major secondary compounds isolated are (a) C30 lanostanes (ganoderic acids), (b) C30 lanostanes (aldehydes, alcohols, esters, glycosides, lactones, ketones), (c) C27 lanostanes (lucidenic acids), (d) C27 lanostanes (alcohols, lactones, esters), (e) C24, C25 lanostanes (f) C30 pentacyclic triterpenes, (g) meroterpenoids, (h) farnesyl hydroquinones (meroterpenoids), (i) C15 sesquiterpenoids, (j) steroids, (k) alkaloids, (l) prenyl hydroquinone (m) benzofurans, (n) benzopyran-4-one derivatives and (o) benzenoid derivatives. Ganoderma lucidum is the species extensively studied for its secondary metabolites and biological activities. Ganoderma applanatum, Ganoderma colossum, Ganoderma sinense, Ganoderma cochlear, Ganoderma tsugae, Ganoderma amboinense, Ganoderma orbiforme, Ganoderma resinaceum, Ganoderma hainanense, Ganoderma concinna, Ganoderma pfeifferi, Ganoderma neo-japonicum, Ganoderma tropicum, Ganoderma australe, Ganoderma carnosum, Ganoderma fornicatum, Ganoderma lipsiense (synonym G. applanatum), Ganoderma mastoporum, Ganoderma theaecolum, Ganoderma boninense, Ganoderma capense and Ganoderma annulare are the other Ganoderma species subjected to phytochemical studies. Further phytochemical studies on Ganoderma could lead to the discovery of hitherto unknown biologically active secondary metabolites. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Engineering of secondary metabolite production in streptomycetes

    Robertsen, Helene Lunde; Gram, Lone

    Streptomycetes are known for their ability to produce a range of different secondary metabolites, including antibiotics, immunosuppressive, anti-fungals, and anti-cancer compounds. Of these compounds, antibiotics play an important role in the clinics for treatment of both mild and severe bacterial...... the computational prediction of suitable 20 bp protospacers for the single guide RNAs and a USER-cloning method for construction of the CRISPR plasmids. Additional improvement to the system was achieved through the development of an optimised USER assembly workflow for cheaper and faster plasmid construction....... The workflow was verified by manual knock-down of two biosynthetic gene clusters in model organism Streptomyces coelicolor A3(2), which confirmed the applicability of the system. A second part of the thesis was devoted to engineering of Streptomyces collinus Tü 365, which is a known producer of the narrow...

  20. of Several Organophosphorus Insecticide Metabolites

    Russell L. Carr

    2015-01-01

    Full Text Available Paraoxonase (PON1 is a calcium dependent enzyme that is capable of hydrolyzing organophosphate anticholinesterases. PON1 activity is present in most mammals and previous research established that PON1 activity differs depending on the species. These studies mainly used the organophosphate substrate paraoxon, the active metabolite of the insecticide parathion. Using serum PON1 from different mammalian species, we compared the hydrolysis of paraoxon with the hydrolysis of the active metabolites (oxons of two additional organophosphorus insecticides, methyl parathion and chlorpyrifos. Paraoxon hydrolysis was greater than that of methyl paraoxon, but the level of activity between species displayed a similar pattern. Regardless of the species tested, the hydrolysis of chlorpyrifos-oxon was significantly greater than that of paraoxon or methyl paraoxon. These data indicate that chlorpyrifos-oxon is a better substrate for PON1 regardless of the species. The pattern of species differences in PON1 activity varied with the change in substrate to chlorpyrifos-oxon from paraoxon or methyl paraoxon. For example, the sex difference observed here and reported elsewhere in the literature for rat PON1 hydrolysis of paraoxon was not present when chlorpyrifos-oxon was the substrate.

  1. Profiling and Distribution of Metabolites of Procyanidin B2 in Mice by UPLC-DAD-ESI-IT-TOF-MSn Technique

    Ying Xiao

    2017-05-01

    Full Text Available The metabolite profiles and distributions of procyanidin B2 were qualitatively described using UPLC-DAD-ESI-IT-TOF-MSn without help of reference standards, and a possible metabolic pathway was proposed in the present study. Summarily, 53 metabolites (24 new metabolites were detected as metabolites of procyanidin B2, and 45 of them were tentatively identified. Twenty seven metabolites were assigned as similar metabolites of (−-epicatechin by scission of the flavanol interflavanic bond C4–C8, including 16 aromatic metabolites, 5 conjugated metabolites, 3 ring-cleavage metabolites, and 2 phenylvalerolactone metabolites. Additionally, 14 metabolites were conjugates of free procyanidin B2, comprising 9 methylation metabolites, 8 sulfation metabolites, 5 hydration metabolites, 2 hydroxylation metabolites, 1 hydrogenation metabolites, and 1 glucuronidation metabolites. The results of metabolite distributions in organs indicated that the conjugated reaction of free procyanidin B2 mainly occurred in liver and diversified metabolites forms were observed in small intestine. The metabolic components of procyanidin B2 identified in mice provided useful information for further study of the bioactivity and mechanism of its action.

  2. Periodic depuration of anthracene metabolites by rainbow trout

    Linder, G.; Bergman, H.L.

    1984-01-01

    Rainbow trout Salmo gairdneri, statically exposed to 36 μg/liter anthracene (including 9- 14 C-C anthracene), bioconcentrated the polynuclear aromatic hydrocarbon 200 times the exposure concentration over 18 hours. Then, during a 96-hour clearance periods, mass-balance analysis of fish and water samples indicated that anthracene was rapidly converted to polar metabolites(s), then eliminated periodically. Maximum depuration occurred during the dark phase of a 16-hour-light: 8-hour-dark photocycle. Of the 2-3% contribution of 14 C metabolites(s) to the total 14 C residue, nearly half came from the bile. This periodic depuration may be circadian, although this requires confirmation by further work; to the extent it affects metabolic fate of bioconcentrated organics, periodic depuration undoubtedly contributes to differences between predicted and observed bioconcentration factors

  3. Trophic transfer of pyrene metabolites between aquatic invertebrates

    Carrasco Navarro, V.; Leppänen, M.T.; Kukkonen, J.V.K.; Godoy Olmos, S.

    2013-01-01

    The trophic transfer of pyrene metabolites was studied using Gammarus setosus as a predator and the invertebrates Lumbriculus variegatus and Chironomus riparius as prey. The results obtained by liquid scintillation counting confirmed that the pyrene metabolites produced by the aquatic invertebrates L. variegatus and C. riparius were transferred to G. setosus through the diet. More detailed analyses by liquid chromatography discovered that two of the metabolites produced by C. riparius appeared in the chromatograms of G. setosus tissue extracts, proving their trophic transfer. These metabolites were not present in chromatograms of G. setosus exclusively exposed to pyrene. The present study supports the trophic transfer of PAH metabolites between benthic macroinvertebrates and common species of an arctic amphipod. As some PAH metabolites are more toxic than the parent compounds, the present study raises concerns about the consequences of their trophic transfer and the fate and effects of PAHs in natural environments. - Highlights: ► The trophic transfer of pyrene metabolites between invertebrates was evaluated. ► Biotransformation of pyrene by L. variegatus and C. riparius is different. ► Metabolites produced by L. variegatus and C. riparius are transferred to G. setosus. ► Specifically, two metabolites produced by C. riparius were transferred. - Some of the pyrene metabolites produced by the model invertebrates L. variegatus and C. riparius are transferred to G. setosus through the diet, proving their trophic transfer.

  4. Prospective study of blood metabolites associated with colorectal cancer risk.

    Shu, Xiang; Xiang, Yong-Bing; Rothman, Nathaniel; Yu, Danxia; Li, Hong-Lan; Yang, Gong; Cai, Hui; Ma, Xiao; Lan, Qing; Gao, Yu-Tang; Jia, Wei; Shu, Xiao-Ou; Zheng, Wei

    2018-02-26

    Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In this study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios per standard deviation increase of transformed metabolites: 0.31-1.98; p values: 0.002-1.25 × 10 -10 ]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. © 2018 UICC.

  5. 3D base: a geometrical data base system for the analysis and visualisation of 3D-shapes obtained from parallel serial sections including three different geometrical representations

    Verbeek, F. J.; de Groot, M. M.; Huijsmans, D. P.; Lamers, W. H.; Young, I. T.

    1993-01-01

    In this paper we discuss a geometrical data base that includes three different geometrical representations of one and the same reconstructed 3D shape: the contour-pile, the voxel enumeration, and the triangulation of a surface. The data base is tailored for 3D shapes obtained from plan-parallel

  6. Metabolite Damage and Metabolite Damage Control in Plants

    Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,

    2016-04-29

    It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

  7. [Identification of saponins from Panax notoginseng in metabolites of rats].

    Shen, Wen-Wen; Zhang, Yin; Qiu, Shou-Bei; Zhu, Fen-Xia; Jia, Xiao-Bin; Tang, Dao-Quan; Chen, Bin

    2017-10-01

    UPLC-QTOF-MS/MS was used to identify metabolites in rat blood, urine and feces after the administration of n-butanol extract derived from steamed notoginseng. The metabolic process of saponins came from steamed notoginseng was analyzed. The metabolites were processed by PeakView software, and identified according to the structural characteristics of prototype compounds and the accurate qualitative and quantitative changes of common metabolic pathways. Four saponins metabolites were identified based on MS/MS information of metabolites, namely ginsenoside Rh₄, Rk₃, Rk₁, Rg₅,and their 15 metabolites were verified. The metabolic pathways of the four ginsenosides in n-butanol extract included glucuronidation, desugar, sulfation, dehydromethylation, and branch loss. The metabolites of main active saponin components derived from steamed Panax notoginseng were analyzed from the perspective of qualitative analysis. And the material basis for the efficacy of steamed notoginseng was further clarified. Copyright© by the Chinese Pharmaceutical Association.

  8. LC-MS based analysis of secondary metabolites from Chaetomium and Stachybotrys growth in indoor environments

    Dosen, Ina

    of causing negative health impact. With this in mind, a prime goal of this PhD study was to develop and optimize methods for qualitative and semi-quantitative analysis of secondary metabolites and bioactive compounds produced by Stachybotrys spp. and Chaetomium spp. The main analytical technique used...... and not included in the library, as well as tentatively identified compounds. Metabolite profiling of Stachybotrys spp. and Chaetomium spp. was performed in pure agar cultures. Thereafter, mapped secondary metabolites were screened for in extracts of artificially inoculated building materials and materials from...... analytical tools were applied to the analysis of naturally contaminated building materials, where presence of all previously mapped metabolites was confirmed. Work done on Stachybotrys spp showed no significant difference in metabolite profiles obtained in vitro and in vivo. Concurrently the study...

  9. Acclimatization of mice to different cage types and social groupings with respect to fecal secretion of IgA and corticosterone metabolites

    Bundgaard, Cathrine Juel; Kalliokoski, Otto; Abelson, Klas Sp

    2012-01-01

    genders were housed either in groups of eight in different cage types in open conventional cages, in Individual Ventilated Cages (IVC), in open conventional cages inside a plastic isolator, or in different group sizes (8, 4, 8, 10 or 12 mice in each group) in open conventional cages. Feces were collected...

  10. Differential metabolite profiles during fruit development in high-yielding oil palm mesocarp.

    Huey Fang Teh

    Full Text Available To better understand lipid biosynthesis in oil palm mesocarp, in particular the differences in gene regulation leading to and including de novo fatty acid biosynthesis, a multi-platform metabolomics technology was used to profile mesocarp metabolites during six critical stages of fruit development in comparatively high- and low-yielding oil palm populations. Significantly higher amino acid levels preceding lipid biosynthesis and nucleosides during lipid biosynthesis were observed in a higher yielding commercial palm population. Levels of metabolites involved in glycolysis revealed interesting divergence of flux towards glycerol-3-phosphate, while carbon utilization differences in the TCA cycle were proven by an increase in malic acid/citric acid ratio. Apart from insights into the regulation of enhanced lipid production in oil palm, these results provide potentially useful metabolite yield markers and genes of interest for use in breeding programmes.

  11. A Derivative Method with Free Radical Oxidation to Predict Resveratrol Metabolites by Tandem Mass Spectrometry.

    Liu, Wangta; Shiue, Yow-Ling; Lin, Yi-Reng; Lin, Hugo You-Hsien; Liang, Shih-Shin

    2015-10-01

    In this study, we demonstrated an oxidative method with free radical to generate 3,5,4'-trihydroxy- trans -stilbene ( trans -resveratrol) metabolites and detect sequentially by an autosampler coupling with liquid chromatography electrospray ionization tandem mass spectrometer (LC-ESI-MS/MS). In this oxidative method, the free radical initiator, ammonium persulfate (APS), was placed in a sample bottle containing resveratrol to produce oxidative derivatives, and the reaction progress was tracked by autosampler sequencing. Resveratrol, a natural product with purported cancer preventative qualities, produces metabolites including dihydroresveratrol, 3,4'-dihydroxy- trans -stilbene, lunularin, resveratrol monosulfate, and dihydroresveratrol monosulfate by free radical oxidation. Using APS free radical, the concentrations of resveratrol derivatives differ as a function of time. Besides simple, convenient and time- and labor saving, the advantages of free radical oxidative method of its in situ generation of oxidative derivatives followed by LC-ESI-MS/MS can be utilized to evaluate different metabolites in various conditions.

  12. NMR Spectroscopy Identifies Metabolites Translocated from Powdery Mildew Resistant Rootstocks to Susceptible Watermelon Scions.

    Mahmud, Iqbal; Kousik, Chandrasekar; Hassell, Richard; Chowdhury, Kamal; Boroujerdi, Arezue F

    2015-09-16

    Powdery mildew (PM) disease causes significant loss in watermelon. Due to the unavailability of a commercial watermelon variety that is resistant to PM, grafting susceptible cultivars on wild resistant rootstocks is being explored as a short-term management strategy to combat this disease. Nuclear magnetic resonance-based metabolic profiles of susceptible and resistant rootstocks of watermelon and their corresponding susceptible scions (Mickey Lee) were compared to screen for potential metabolites related to PM resistance using multivariate principal component analysis. Significant score plot differences between the susceptible and resistant groups were revealed through Mahalanobis distance analysis. Significantly different spectral buckets and their corresponding metabolites (including choline, fumarate, 5-hydroxyindole-3-acetate, and melatonin) have been identified quantitatively using multivariate loading plots and verified by volcano plot analyses. The data suggest that these metabolites were translocated from the powdery mildew resistant rootstocks to their corresponding powdery mildew susceptible scions and can be related to PM disease resistance.

  13. Metabolomic profiling and stable isotope labelling of Trichomonas vaginalis and Tritrichomonas foetus reveal major differences in amino acid metabolism including the production of 2-hydroxyisocaproic acid, cystathionine and S-methylcysteine.

    Westrop, Gareth D; Wang, Lijie; Blackburn, Gavin J; Zhang, Tong; Zheng, Liang; Watson, David G; Coombs, Graham H

    2017-01-01

    Trichomonas vaginalis and Tritrichomonas foetus are pathogens that parasitise, respectively, human and bovine urogenital tracts causing disease. Using LC-MS, reference metabolomic profiles were obtained for both species and stable isotope labelling with D-[U-13C6] glucose was used to analyse central carbon metabolism. This facilitated a comparison of the metabolic pathways of T. vaginalis and T. foetus, extending earlier targeted biochemical studies. 43 metabolites, whose identities were confirmed by comparison of their retention times with authentic standards, occurred at more than 3-fold difference in peak intensity between T. vaginalis and T. foetus. 18 metabolites that were removed from or released into the medium during growth also showed more than 3-fold difference between the species. Major differences were observed in cysteine and methionine metabolism in which homocysteine, produced as a bi-product of trans-methylation, is catabolised by methionine γ-lyase in T. vaginalis but converted to cystathionine in T. foetus. Both species synthesise methylthioadenosine by an unusual mechanism, but it is not used as a substrate for methionine recycling. T. vaginalis also produces and exports high levels of S-methylcysteine, whereas only negligible levels were found in T. foetus which maintains significantly higher intracellular levels of cysteine. 13C-labeling confirmed that both cysteine and S-methylcysteine are synthesised by T. vaginalis; S-methylcysteine can be generated by recombinant T. vaginalis cysteine synthase using phosphoserine and methanethiol. T. foetus contained higher levels of ornithine and citrulline than T. vaginalis and exported increased levels of putrescine, suggesting greater flux through the arginine dihydrolase pathway. T. vaginalis produced and exported hydroxy acid derivatives of certain amino acids, particularly 2-hydroxyisocaproic acid derived from leucine, whereas negligible levels of these metabolites occurred in T. foetus.

  14. Metabolomic profiling and stable isotope labelling of Trichomonas vaginalis and Tritrichomonas foetus reveal major differences in amino acid metabolism including the production of 2-hydroxyisocaproic acid, cystathionine and S-methylcysteine.

    Gareth D Westrop

    Full Text Available Trichomonas vaginalis and Tritrichomonas foetus are pathogens that parasitise, respectively, human and bovine urogenital tracts causing disease. Using LC-MS, reference metabolomic profiles were obtained for both species and stable isotope labelling with D-[U-13C6] glucose was used to analyse central carbon metabolism. This facilitated a comparison of the metabolic pathways of T. vaginalis and T. foetus, extending earlier targeted biochemical studies. 43 metabolites, whose identities were confirmed by comparison of their retention times with authentic standards, occurred at more than 3-fold difference in peak intensity between T. vaginalis and T. foetus. 18 metabolites that were removed from or released into the medium during growth also showed more than 3-fold difference between the species. Major differences were observed in cysteine and methionine metabolism in which homocysteine, produced as a bi-product of trans-methylation, is catabolised by methionine γ-lyase in T. vaginalis but converted to cystathionine in T. foetus. Both species synthesise methylthioadenosine by an unusual mechanism, but it is not used as a substrate for methionine recycling. T. vaginalis also produces and exports high levels of S-methylcysteine, whereas only negligible levels were found in T. foetus which maintains significantly higher intracellular levels of cysteine. 13C-labeling confirmed that both cysteine and S-methylcysteine are synthesised by T. vaginalis; S-methylcysteine can be generated by recombinant T. vaginalis cysteine synthase using phosphoserine and methanethiol. T. foetus contained higher levels of ornithine and citrulline than T. vaginalis and exported increased levels of putrescine, suggesting greater flux through the arginine dihydrolase pathway. T. vaginalis produced and exported hydroxy acid derivatives of certain amino acids, particularly 2-hydroxyisocaproic acid derived from leucine, whereas negligible levels of these metabolites occurred in T

  15. Effect of Two Different Levels of Fiber on Feed Intake, Average Daily Gain, Feed Efficiency and Ruminal Metabolites of Holstein Calves

    A. Salary Neya

    2013-03-01

    Full Text Available This experiment was conducted to determine the effect of feeding alfalfa hay and starter fiber level on feed intake and performance of Holstein dairy calves, using thirty two male calves in a completely randomized design assigned to four diets in a 2×2 factorial arrangement. The experimental treatments were as follow: T1: starter with low fiber and without alfalfa hay, T2: starter with low fiber along with alfalfa hay, T3: starter with high fiber and without alfalfa hay and T4: starter with high fiber along with alfalfa hay. Results showed feed intake was not significantly different in pre-weaning and throughout the study but after weaning there was significant difference among treatments. Average daily gain of calves was not significantly different during pre-weaning period but during post-weaning and throughout the study there was significant difference among treatments for this trait. Feed efficiency was not significantly different among treatments in pre-weaning and post-weaning periods but it was significantly different during throughout the study. The results of this experiment showed adding fiber to dairy calves ration through both starter concentrate and alfalfa hay may reduce their performance.

  16. Identification of metabolites of the tryptase inhibitor CRA-9249: observation of a metabolite derived from an unexpected hydroxylation pathway.

    Yu, Walter; Dener, Jeffrey M; Dickman, Daniel A; Grothaus, Paul; Ling, Yun; Liu, Liang; Havel, Chris; Malesky, Kimberly; Mahajan, Tania; O'Brian, Colin; Shelton, Emma J; Sperandio, David; Tong, Zhiwei; Yee, Robert; Mordenti, Joyce J

    2006-08-01

    The metabolites of the tryptase inhibitor CRA-9249 were identified after exposure to liver microsomes. CRA-9249 was found to be degraded rapidly in liver microsomes from rabbit, dog, cynomolgus monkey, and human, and less rapidly in microsomes from rat. The key metabolites included cleavage of an aryl ether, in addition to an unexpected hydroxylation of the amide side chain adjacent to the amide nitrogen. The chemical structures of both metabolites were confirmed by synthesis and comparison to material isolated from the liver microsomes. Several suspected hydroxylated metabolites were also synthesized and analyzed as part of the structure identification process.

  17. Epigenome targeting by probiotic metabolites

    Licciardi Paul V

    2010-12-01

    Full Text Available Abstract Background The intestinal microbiota plays an important role in immune development and homeostasis. A disturbed microbiota during early infancy is associated with an increased risk of developing inflammatory and allergic diseases later in life. The mechanisms underlying these effects are poorly understood but are likely to involve alterations in microbial production of fermentation-derived metabolites, which have potent immune modulating properties and are required for maintenance of healthy mucosal immune responses. Probiotics are beneficial bacteria that have the capacity to alter the composition of bacterial species in the intestine that can in turn influence the production of fermentation-derived metabolites. Principal among these metabolites are the short-chain fatty acids butyrate and acetate that have potent anti-inflammatory activities important in regulating immune function at the intestinal mucosal surface. Therefore strategies aimed at restoring the microbiota profile may be effective in the prevention or treatment of allergic and inflammatory diseases. Presentation of the hypothesis Probiotic bacteria have diverse effects including altering microbiota composition, regulating epithelial cell barrier function and modulating of immune responses. The precise molecular mechanisms mediating these probiotic effects are not well understood. Short-chain fatty acids such as butyrate are a class of histone deacetylase inhibitors important in the epigenetic control of host cell responses. It is hypothesized that the biological function of probiotics may be a result of epigenetic modifications that may explain the wide range of effects observed. Studies delineating the effects of probiotics on short-chain fatty acid production and the epigenetic actions of short-chain fatty acids will assist in understanding the association between microbiota and allergic or autoimmune disorders. Testing the hypothesis We propose that treatment with

  18. Pharmaceutically active secondary metabolites of marine actinobacteria.

    Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

    2014-04-01

    Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future. Copyright © 2013 Elsevier GmbH. All rights reserved.

  19. Effect of different NADH oxidase levels on glucose metabolism by Lactococus lactis : kinetics of intracellular metabolite pools determined by in vivo nuclear magnetic resonance

    Neves, A.R.; Ramos, A.; Costa, H.; Swam, van I.I.; Hugenholtz, J.; Kleerebezem, M.; Vos, de W.M.; Santos, H.

    2002-01-01

    Three isogenic strains of Lactococcus lactis with different levels of H2O-forming NADH oxidase activity were used to study the effect of oxygen on glucose metabolism: the parent strain L. lactis MG1363, a NOX- strain harboring a deletion of the gene coding for H2O-forming NADH oxidase, and a NOX

  20. Influence of different proteolytic strains of Streptococcus thermophilus in co-culture with Lactobacillus delbrueckii subsp. bulgaricus on the metabolite profile of set-yoghurt

    Settachaimongkon, S.; Nout, M.J.R.; Antunes Fernandes, E.C.; Hettinga, K.A.; Vervoort, J.J.M.; Hooijdonk, van A.C.M.; Zwietering, M.H.; Smid, E.J.; Valenberg, van H.J.F.

    2014-01-01

    Proto-cooperation between Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus is one of the key factors that determine the fermentation process and final quality of yoghurt. In this study, the interaction between different proteolytic strains of S. thermophilus and L.

  1. Simvastatin (SV) metabolites in mouse tissues

    Duncan, C.A.; Vickers, S.

    1990-01-01

    SV, a semisynthetic analog of lovastatin, is hydrolyzed in vivo to its hydroxy acid (SVA), a potent inhibitor of HMG CoA reductase (HR). Thus SV lowers plasma cholesterol. SV is a substrate for mixed function oxidases whereas SVA undergoes lactonization and β-oxidation. Male CD-1 mice were dosed orally with a combination of ( 14 C)SV and ( 3 H)SVA at 25 mg/kg of each, bled and killed at 0.5, 2 and 4 hours. Labeled SV, SVA, 6'exomethylene SV (I), 6'CH 2 OH-SV (II), 6'COOH-SV (III) and a β-oxidized metabolite (IV) were assayed in liver, bile, kidneys, testes and plasma by RIDA. Levels of potential and active HR inhibitors in liver were 10 to 40 fold higher than in other tissues. II and III, in which the configuration at 6' is inverted, may be 2 metabolites of I. Metabolites I-III are inhibitors of HR in their hydroxy acid forms. Qualitatively ( 14 C)SV and ( 3 H)SVA were metabolized similarly (consistent with their proposed interconversion). However 3 H-SVA, I-III (including hydroxy acid forms) achieved higher concentrations than corresponding 14 C compounds (except in gall bladder bile). Major radioactive metabolites in liver were II-IV (including hydroxy acid forms). These metabolites have also been reported in rat tissues. In bile a large fraction of either label was unidentified polar metabolites. The presence of IV indicated that mice (like rats) are not good models for SV metabolism in man

  2. Characterization of Urinary Phthalate Metabolites Among Custodians

    Cavallari, Jennifer M.; Simcox, Nancy J.; Wakai, Sara; Lu, Chensheng; Garza, Jennifer L.; Cherniack, Martin

    2015-01-01

    Phthalates, a ubiquitous class of chemicals found in consumer, personal care, and cleaning products, have been linked to adverse health effects. Our goal was to characterize urinary phthalate metabolite concentrations and to identify work and nonwork sources among custodians using traditional cleaning chemicals and ‘green’ or environmentally preferable products (EPP). Sixty-eight custodians provided four urine samples on a workday (first void, before shift, end of shift, and before bedtime) and trained observers recorded cleaning tasks and types of products used (traditional, EPP, or disinfectant) hourly over the work shifts. Questionnaires were used to assess personal care product use. Four different phthalate metabolites [monoethyl phthalate (MEP), monomethyl phthalate (MMP), mono (2-ethylhexyl) phthalate (MEHP), and monobenzyl phthalate (MBzP)] were quantified using liquid chromatography mass spectrometry. Geometric means (GM) and 95% confidence intervals (95% CI) were calculated for creatinine-adjusted urinary phthalate concentrations. Mixed effects univariate and multivariate modeling, using a random intercept for each individual, was performed to identify predictors of phthalate metabolites including demographics, workplace factors, and personal care product use. Creatinine-adjusted urinary concentrations [GM (95% CI)] of MEP, MMP, MEHP, and MBzP were 107 (91.0–126), 2.69 (2.18–3.30), 6.93 (6.00–7.99), 8.79 (7.84–9.86) µg g−1, respectively. An increasing trend in phthalate concentrations from before to after shift was not observed. Creatinine-adjusted urinary MEP was significantly associated with frequency of traditional cleaning chemical intensity in the multivariate model after adjusting for potential confounding by demographics, workplace factors, and personal care product use. While numerous demographics, workplace factors, and personal care products were statistically significant univariate predictors of MMP, MEHP, and MBzP, few

  3. Applying 1H NMR Spectroscopy to Detect Changes in the Urinary Metabolite Levels of Chinese Half-Pipe Snowboarders after Different Exercises

    Fuqiu Wang

    2015-01-01

    Full Text Available Monitoring physical training is important for the health and performance of athletes, and real-time assessment of fatigue is crucial to improve training efficiency. The relationship between key biomarkers and exercise has been reported. The aim of this study was to determine the effects of different levels of training exercises on the urine metabolome. 1H NMR-based metabolomics analysis was performed on urine samples from half-pipe snowboarders, and spectral profiles were subjected to PCA and PLS-DA. Our results show that metabolic profiles varied during different stages of exercises. Lactate, alanine, trimethylamine, malonate, taurine, and glycine levels decreased while TMAO and phenylalanine levels increased in the stage with higher amount and intensity of exercise. Although the amount of exercise was reduced in subsequent stage, no significant variations of metabolic profile were found. Metabolic changes induced by training level were analyzed with related metabolic pathway. Studying metabolome changes can provide a better understanding of the physiology of athletes and could aid in adjusting training.

  4. Production of Metabolites

    2011-01-01

    A recombinant micro-organism such as Saccharomyces cerevisiae which produces and excretes into culture medium a stilbenoid metabolite product when grown under stilbenoid production conditions, which expresses in above native levels a ABC transporter which transports said stilbenoid out of said...... micro-organism cells to the culture medium. The genome of the Saccharomyces cerevisiae produces an auxotrophic phenotype which is compensated by a plasmid which also expresses one or more of said enzymes constituting said metabolic pathway producing said stilbenoid, an expression product of the plasmid...

  5. Production of Secondary Metabolites in Extreme Environments: Food- and Airborne Wallemia spp. Produce Toxic Metabolites at Hypersaline Conditions

    Jančič, Sašo; Frisvad, Jens Christian; Kocev, Dragi

    2016-01-01

    the genome data analysis of W. mellicola (previously W. sebi sensu lato) and W. ichthyophaga revealed a low number of secondary metabolites clusters, a substantial number of secondary metabolites were detected at different conditions. Machine learning analysis of the obtained dataset showed that NaCl has...... of salt or sugar. In relation to food safety, the effect of high salt and sugar concentrations on the production of secondary metabolites by this toxigenic fungus was investigated. The secondary metabolite profiles of 30 strains of the listed species were examined using general growth media, known...... to support the production of secondary metabolites, supplemented with different concentrations of NaCl, glucose and MgCl2. In more than two hundred extracts approximately one hundred different compounds were detected using high-performance liquid chromatography-diode array detection (HPLC-DAD). Although...

  6. Mutagenic azide metabolite is azidoalanine

    Owais, W.M.; Rosichan, J.L.; Ronald, R.C.; Kleinhofs, A.; Nilan, R.A.

    1981-01-01

    Sodium axide produces high mutation rates in a number of species. Azide mutagenicity is mediated through a metabolite in barley and bacteria. Many studies showed that azide affects the L-cysteine biosynthesis pathway. Cell-free extracts of Salmonella typhimurium convert azide and O-acetylserine to the mutagenic metabolite. O-acetylserine sulfhydrylase was identified as the enzyme responsible for the metabolite biosynthesis. To confirm the conclusion that the azide metabolite is formed through the β-substitution pathway of L-cysteine, we radioactively labeled the azide metabolite using 14 C-labeled precursors. Moreover, the mutagenic azide metabolite was purified and identified as azidoalanine based on mass spectroscopy and elemental analysis. 26 refs., 3 figs., 1 tab

  7. In vivo estimation of transverse relaxation time constant (T2 ) of 17 human brain metabolites at 3T.

    Wyss, Patrik O; Bianchini, Claudio; Scheidegger, Milan; Giapitzakis, Ioannis A; Hock, Andreas; Fuchs, Alexander; Henning, Anke

    2018-08-01

    The transverse relaxation times T 2 of 17 metabolites in vivo at 3T is reported and region specific differences are addressed. An echo-time series protocol was applied to one, two, or three volumes of interest with different fraction of white and gray matter including a total number of 106 healthy volunteers and acquiring a total number of 128 spectra. The data were fitted with the 2D fitting tool ProFit2, which included individual line shape modeling for all metabolites and allowed the T 2 calculation of 28 moieties of 17 metabolites. The T 2 of 10 metabolites and their moieties have been reported for the first time. Region specific T 2 differences in white and gray matter enriched tissue occur in 16 of 17 metabolites examined including single resonance lines and coupled spin systems. The relaxation time T 2 is regions specific and has to be considered when applying tissue composition correction for internal water referencing. Magn Reson Med 80:452-461, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

  8. Interspecies differences in the accumulation of tributyltin and its metabolites under dietary exposure in sea perch, Lateolabrax japonicus, and red sea bream, Pagrus major.

    Uno, Seiichi; Murakami, Masayo; Kokushi, Emiko; Koyama, Jiro

    2011-02-01

    Interspecies differences in the accumulation of dietary tributyltin (TBT) between sea perch, Lateolabrax japonicus, and red sea bream, Pagrus major, were studied. Although TBTs in both species reached steady-state condition in low-concentration group (L-group, 200 ng/g nominal concentration) by 1 week, it increased up to the end of exposure in high-concentration group (H-group, 3000 ng/g nominal concentration). In H-group, the accumulation rate of TBT in sea perch from 1 to 2 weeks was much higher than in red sea bream, which were 2.4-fold for sea perch and 1.7-fold for red sea bream, although TBT concentrations were similar between sea perch and red sea bream in L-group. Furthermore, in the H-group, the concentrations of TBT at 1 and 2 weeks were about 1.3- and 1.9-fold, respectively, higher in the sea perch than in the red sea bream. On the other hand, DBT residue in red sea bream was about 1.4-fold higher in sea perch for the L-group but concentrations were similar in both fishes for the H-group. These results suggest that red sea bream could metabolize faster the TBT to DBT than sea perch. This study also reveals that fish probably could absorb TBT through the food chain. The uptake of TBT by fish should be regarded in the real environment, because TBT concentration in seawater has been decreasing and now already at significantly low level. Copyright © 2009 Wiley Periodicals, Inc.

  9. SBRT of lung tumours: Monte Carlo simulation with PENELOPE of dose distributions including respiratory motion and comparison with different treatment planning systems

    Panettieri, Vanessa; Wennberg, Berit; Gagliardi, Giovanna; Amor Duch, Maria; Ginjaume, Mercè; Lax, Ingmar

    2007-07-01

    The purpose of this work was to simulate with the Monte Carlo (MC) code PENELOPE the dose distribution in lung tumours including breathing motion in stereotactic body radiation therapy (SBRT). Two phantoms were modelled to simulate a pentagonal cross section with chestwall (unit density), lung (density 0.3 g cm-3) and two spherical tumours (unit density) of diameters respectively of 2 cm and 5 cm. The phase-space files (PSF) of four different SBRT field sizes of 6 MV from a Varian accelerator were calculated and used as beam sources to obtain both dose profiles and dose-volume histograms (DVHs) in different volumes of interest. Dose distributions were simulated for five beams impinging on the phantom. The simulations were conducted both for the static case and including the influence of respiratory motion. To reproduce the effect of breathing motion different simulations were performed keeping the beam fixed and displacing the phantom geometry in chosen positions in the cranial and caudal and left-right directions. The final result was obtained by combining the different position with two motion patterns. The MC results were compared with those obtained with three commercial treatment planning systems (TPSs), two based on the pencil beam (PB) algorithm, the TMS-HELAX (Nucletron, Sweden) and Eclipse (Varian Medical System, Palo Alto, CA), and one based on the collapsed cone algorithm (CC), Pinnacle3 (Philips). Some calculations were also carried out with the analytical anisotropic algorithm (AAA) in the Eclipse system. All calculations with the TPSs were performed without simulated breathing motion, according to clinical practice. In order to compare all the TPSs and MC an absolute dose calibration in Gy/MU was performed. The analysis shows that the dose (Gy/MU) in the central part of the gross tumour volume (GTV) is calculated for both tumour sizes with an accuracy of 2-3% with PB and CC algorithms, compared to MC. At the periphery of the GTV the TPSs overestimate

  10. Identification of differential metabolites in liquid diet fermented with Bacillus subtilis using gas chromatography time of flight mass spectrometry

    Yuyong He

    2016-12-01

    Full Text Available Growth and health responses of pigs fed fermented liquid diet are not always consistent and causes for this issue are still not very clear. Metabolites produced at different fermentation time points should be one of the most important contributors. However, currently no literatures about differential metabolites of fermented liquid diet are reported. The aim of this experiment was to explore the difference of metabolites in a fermented liquid diet between different fermentation time intervals. A total of eighteen samples that collected from Bacillus subtilis fermented liquid diet on days 7, 21 and 35 respectively were used for the identification of metabolites by gas chromatography time of flight mass spectrometry (GC-TOF-MS. Fifteen differential metabolites including melibiose, sortitol, ribose, cellobiose, maltotriose, sorbose, isomaltose, maltose, fructose, d-glycerol-1-phosphate, 4-aminobutyric acid, beta-alanine, tyrosine, pyruvic acid and pantothenic acid were identified between 7-d samples and 21-d samples. The relative level of melibiose, ribose, maltotriose, d-glycerol-1-phosphate, tyrosine and pyruvic acid in samples collected on day 21 was significantly higher than that in samples collected on day 7 (P < 0.01, respectively. Eight differential metabolites including ribose, sorbose, galactinol, cellobiose, pyruvic acid, galactonic acid, pantothenic acid and guanosine were found between 21-d samples and 35-d samples. Samples collected on day 35 had a higher relative level of ribose than that in samples collected on day 21 (P < 0.01. In conclusion, many differential metabolites which have important effects on the growth and health of pigs are identified and findings contribute to explain the difference in feeding response of fermented liquid diet.

  11. Levels of potential bioactive compounds including carotenoids, vitamin C and phenolic compounds, and expression of their cognate biosynthetic genes vary significantly in different varieties of potato (Solanum tuberosum L.) grown under uniform cultural conditions.

    Valcarcel, Jesus; Reilly, Kim; Gaffney, Michael; O'Brien, Nora M

    2016-02-01

    In addition to their high carbohydrate content, potatoes are also an important dietary source of vitamin C and bioactive secondary metabolites, including phenolic compounds and carotenoids, which have been suggested to play a role in human health. The expression of genes encoding key enzymes involved in the synthesis of these compounds was assessed by reverse transcription-quantitative polymerase chain reaction and compared to the accumulation of the corresponding product in seven potato varieties showing contrasting levels of metabolite accumulation. Strong positive correlations were found between phenolic content in the flesh of tubers and transcript levels of phenylalanine ammonia lyase (PAL) and chalcone synthase (CHS) genes. The expression of PAL and CHS was also related to that of AN1, a transcription factor involved in the synthesis of anthocyanins, suggesting that these genes are regulated in a coordinated manner. No clear relationship was found between transcript levels of phytoene synthase (PSY) or L-galactono-1,4-lactone dehydrogenase (GLDH) genes and total carotenoid or vitamin C accumulation, respectively. Data indicate that levels of total phenolic and flavonoid compounds in potato are controlled primarily by PAL and CHS gene expression. Transcript levels of PSY and GLDH did not control accumulation of carotenoids or vitamin C. © 2015 Society of Chemical Industry.

  12. Antimycobacterial Metabolites from Marine Invertebrates.

    Daletos, Georgios; Ancheeva, Elena; Chaidir, Chaidir; Kalscheuer, Rainer; Proksch, Peter

    2016-10-01

    Marine organisms play an important role in natural product-based drug research due to accumulation of structurally unique and bioactive metabolites. The exploration of marine-derived compounds may significantly extend the scientific knowledge of potential scaffolds for antibiotic drug discovery. Development of novel antitubercular agents is especially significant as the emergence of drug-resistant Mycobacterium tuberculosis strains remains threateningly high. Marine invertebrates (i.e., sponges, corals, gorgonians) as a source of new chemical entities are the center of research for several scientific groups, and the wide spectrum of biological activities of marine-derived compounds encourages scientists to carry out investigations in the field of antibiotic research, including tuberculosis treatment. The present review covers published data on antitubercular natural products from marine invertebrates grouped according to their biogenetic origin. Studies on the structure-activity relationships of these important leads are highlighted as well. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Structural Elucidation of Metabolites of Synthetic Cannabinoid UR-144 by Cunninghamella elegans Using Nuclear Magnetic Resonance (NMR) Spectroscopy.

    Watanabe, Shimpei; Kuzhiumparambil, Unnikrishnan; Fu, Shanlin

    2018-03-08

    The number of new psychoactive substances keeps on rising despite the controlling efforts by law enforcement. Although metabolism of the newly emerging drugs is continuously studied to keep up with the new additions, the exact structures of the metabolites are often not identified due to the insufficient sample quantities for techniques such as nuclear magnetic resonance (NMR) spectroscopy. The aim of the study was to characterise several metabolites of the synthetic cannabinoid (1-pentyl-1H-indol-3-yl) (2,2,3,3-tetramethylcyclopropyl) methanone (UR-144) by NMR spectroscopy after the incubation with the fungus Cunninghamella elegans. UR-144 was incubated with C. elegans for 72 h, and the resulting metabolites were chromatographically separated. Six fractions were collected and analysed by NMR spectroscopy. UR-144 was also incubated with human liver microsomes (HLM), and the liquid chromatography-high resolution mass spectrometry analysis was performed on the HLM metabolites with the characterised fungal metabolites as reference standards. Ten metabolites were characterised by NMR analysis including dihydroxy metabolites, carboxy and hydroxy metabolites, a hydroxy and ketone metabolite, and a carboxy and ketone metabolite. Of these metabolites, dihydroxy metabolite, carboxy and hydroxy metabolites, and a hydroxy and ketone metabolite were identified in HLM incubation. The results indicate that the fungus is capable of producing human-relevant metabolites including the exact isomers. The capacity of the fungus C. elegans to allow for NMR structural characterisation by enabling production of large amounts of metabolites makes it an ideal model to complement metabolism studies.

  14. Assessment of five different guideline indication criteria for spirometry, including modified GOLD criteria, in order to detect COPD: data from 5,315 subjects in the PLATINO study.

    Luize, Ana P; Menezes, Ana Maria B; Perez-Padilla, Rogelio; Muiño, Adriana; López, Maria Victorina; Valdivia, Gonzalo; Lisboa, Carmem; Montes de Oca, Maria; Tálamo, Carlos; Celli, Bartolomé; Nascimento, Oliver A; Gazzotti, Mariana R; Jardim, José R

    2014-10-30

    Spirometry is the gold standard for diagnosing chronic obstructive pulmonary disease (COPD). Although there are a number of different guideline criteria for deciding who should be selected for spirometric screening, to date it is not known which criteria are the best based on sensitivity and specificity. Firstly, to evaluate the proportion of subjects in the PLATINO Study that would be recommended for spirometry testing according to Global initiative for Obstructive Lung Disease (GOLD)-modified, American College of Chest Physicians (ACCP), National Lung Health Education Program (NLHEP), GOLD and American Thoracic Society/European Respiratory Society (ATS/ERS) criteria. Secondly, we aimed to compare the sensitivity, specificity, and positive predictive and negative predictive values, of these five different criteria. Data from the PLATINO study included information on respiratory symptoms, smoking and previous spirometry testing. The GOLD-modified spirometry indication criteria are based on three positive answers out of five questions: the presence of cough, phlegm in the morning, dyspnoea, age over 40 years and smoking status. Data from 5,315 subjects were reviewed. Fewer people had an indication for spirometry (41.3%) according to the GOLD-modified criteria, and more people had an indication for spirometry (80.4%) by the GOLD and ATS/ERS criteria. A low percentage had previously had spirometry performed: GOLD-modified (14.5%); ACCP (13.2%); NLHEP (12.6%); and GOLD and ATS/ERS (12.3%). The GOLD-modified criteria showed the least sensitivity (54.9) and the highest specificity (61.0) for detecting COPD, whereas GOLD and ATS/ERS criteria showed the highest sensitivity (87.9) and the least specificity (20.8). There is a considerable difference in the indication for spirometry according to the five different guideline criteria. The GOLD-modified criteria recruit less people with the greatest sum of sensitivity and specificity.

  15. Evaluation of the vibration attenuation properties of an air-inflated cushion with two different heavy machinery seats in multi-axis vibration environments including jolts.

    Ji, Xiaoxu; Eger, Tammy R; Dickey, James P

    2017-03-01

    Seats and cushions can attenuate whole-body vibration (WBV) exposures and minimize health risks for heavy machine operators. We successfully developed neural network (NN) algorithms to identify the vibration attenuation properties for four different seating conditions (seat/cushion combinations), and implemented each of the NN models to predict the equivalent daily exposure A(8) values for various vehicles in the forestry and mining environments. We also evaluated the performance of the new prototype No-Jolt™ air-inflated cushion and the original cushion of each seat with jolt exposures. We observed that the air cushion significantly improved the vibration attenuation properties of the seat that initially had good performance, but not for the seat that had relatively poor vibration attenuation properties. In addition, operator's anthropometrics and sex influenced the performance of the air-inflated cushion when the vibration environment included jolt exposures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Comparison of different magnetic resonance cholangiography techniques in living liver donors including Gd-EOB-DTPA enhanced T1-weighted sequences.

    Sonja Kinner

    Full Text Available Preoperative evaluation of potential living liver donors (PLLDs includes the assessment of the biliary anatomy to avoid postoperative complications. Aim of this study was to compare T2-weighted (T2w and Gd-EOB-DTPA enhanced T1-weighted (T1w magnetic resonance cholangiography (MRC techniques in the evaluation of PLLDs.30 PLLDs underwent MRC on a 1.5 T Magnetom Avanto (Siemens, Erlangen, Germany using (A 2D T2w HASTE (Half Fourier Acquisition Single Shot Turbo Spin Echo fat saturated (fs in axial plane, (B 2D T2w HASTE fs thick slices in coronal plane, (C free breathing 3D T2w TSE (turbo spin echo RESTORE (high-resolution navigator corrected plus (D maximum intensity projections (MIPs, (E T2w SPACE (sampling perfection with application optimized contrasts using different flip angle evolutions plus (F MIPs and (G T2w TSE BLADE as well as Gd-EOB-DTPA T1w images without (G and with (H inversion recovery. Contrast enhanced CT cholangiography served as reference imaging modality. Two independent reviewers evaluated the biliary tract anatomy on a 5-point scale subjectively and objectively. Data sets were compared using a Mann-Whitney-U-test. Kappa values were also calculated.Source images and maximum intensity projections of 3D T2w TSE sequences (RESTORE and SPACE proved to be best for subjective and objective evaluation directly followed by 2D HASTE sequences. Interobserver variabilities were good to excellent (k = 0.622-0.804.3D T2w sequences are essential for preoperative biliary tract evaluation in potential living liver donors. Furthermore, our results underline the value of different MRCP sequence types for the evaluation of the biliary anatomy in PLLDs including Gd-EOB-DTPA enhanced T1w MRC.

  17. Quantitative Isotope-Dilution High-Resolution-Mass-Spectrometry Analysis of Multiple Intracellular Metabolites in Clostridium autoethanogenum with Uniformly 13C-Labeled Standards Derived from Spirulina.

    Schatschneider, Sarah; Abdelrazig, Salah; Safo, Laudina; Henstra, Anne M; Millat, Thomas; Kim, Dong-Hyun; Winzer, Klaus; Minton, Nigel P; Barrett, David A

    2018-04-03

    We have investigated the applicability of commercially available lyophilized spirulina ( Arthrospira platensis), a microorganism uniformly labeled with 13 C, as a readily accessible source of multiple 13 C-labeled metabolites suitable as internal standards for the quantitative determination of intracellular bacterial metabolites. Metabolites of interest were analyzed by hydrophilic-interaction liquid chromatography coupled with high-resolution mass spectrometry. Multiple internal standards obtained from uniformly (U)- 13 C-labeled extracts from spirulina were used to enable isotope-dilution mass spectrometry (IDMS) in the identification and quantification of intracellular metabolites. Extraction of the intracellular metabolites of Clostridium autoethanogenum using 2:1:1 chloroform/methanol/water was found to be the optimal method in comparison with freeze-thaw, homogenization, and sonication methods. The limits of quantification were ≤1 μM with excellent linearity for all of the calibration curves ( R 2 ≥ 0.99) for 74 metabolites. The precision and accuracy were found to be within relative standard deviations (RSDs) of 15% for 49 of the metabolites and within RSDs of 20% for all of the metabolites. The method was applied to study the effects of feeding different levels of carbon monoxide (as a carbon source) on the central metabolism and Wood-Ljungdahl pathway of C. autoethanogenum grown in continuous culture over 35 days. Using LC-IDMS with U- 13 C spirulina allowed the successful quantification of 52 metabolites in the samples, including amino acids, carboxylic acids, sugar phosphates, purines, and pyrimidines. The method provided absolute quantitative data on intracellular metabolites that was suitable for computational modeling to understand and optimize the C. autoethanogenum metabolic pathways active in gas fermentation.

  18. The effects of concentrate added to pineapple (Ananas comosus Linn. Mer.) waste silage in differing ratios to form complete diets, on digestion, excretion of urinary purine derivatives and blood metabolites in growing, male, Thai swamp buffaloes.

    Jetana, T; Suthikrai, W; Usawang, S; Vongpipatana, C; Sophon, S; Liang, J B

    2009-04-01

    Four, male, growing Thai swamp buffaloes (197 +/- 5.3 kg and all 1 year old) were used to evaluate the effects of concentrate added to pineapple waste silage in differing ratios, to form a complete diet, studying in vivo digestion, the rate of passage, microbial protein synthesis and blood metabolites. Animals were fed ad libitum with 4 diets, using four combinations of pineapple waste silage (P) and concentrate (C), in the proportions (on a dry matter basis) of 0.8:0.2 (P80:C20), 0.6:0.4 (P60:C40), 0.4:0.6 (P40:C60) and 0.2:0.8 (P20:C80). The results showed that the intakes of dry matter (DM), organic matter (OM), nitrogen (N), the N-balance, urinary purine derivatives (PD) excretion, the ratios of allantoin to creatinine (CR), PD to CR, the plasma urea-N (PUN) and insulin increased in the animals, but the intake of neutral detergent fiber (NDF), the coefficient of whole tract, apparent digestibility of NDF, the transit time (TT) and the mean retention time (TMRT) decreased, when the proportion of concentrate in the diet increased. This study indicated that the proportion of P40:C60 in the diet produced the best efficiency of urinary PD excretion (mmol) per digestible OM intake (kg DOMI).

  19. [Geographical differences in clinical characteristics and management of stable outpatients with coronary artery disease: comparison between the Italian and international population included in the Worldwide CLARIFY registry].

    Pozzoli, Massimo; Tavazzi, Luigi

    2014-04-01

    Limited data are available regarding specific differences among countries in demographic and clinical characteristics and treatment of patients with stable coronary artery disease. CLARIFY is an international, prospective and longitudinal registry including more than 33 000 patients with stable coronary artery disease enrolled in 45 countries worldwide. Data were used to compare the characteristics of patients enrolled in Italy with those enrolled in Europe and in the rest of the world. Baseline data were available for 33 283 patients, 2112 of whom from Italy and 12 614 from the remaining western European countries. Italian patients were found to be older, more frequently smoker, hypertensive and with sedentary habits. In addition, they presented more frequently a history of myocardial infarction, carotid arterial disease and chronic obstructive pulmonary disease. In addition, when compared with patients of both European and international cohorts, more Italian patients had undergone coronary angiography and angioplasty. As far as treatment was concerned, a greater number of Italian patients were taking ivabradine, angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers, nitrates, thienopyridines, while those taking beta-blockers, calcium antagonists and other antianginal medications were fewer. Among ambulatory patients with stable coronary artery disease, there are important geographic differences in terms of risk factors, clinical characteristics, surgical and pharmacological treatment.

  20. Novel urinary metabolite of d-delta-tocopherol in rats

    Chiku, S.; Hamamura, K.; Nakamura, T.

    1984-01-01

    A novel metabolite of d-delta-tocopherol was isolated from the urine of rats given d-3,4-[ 3 H 2 ]-delta-tocopherol intravenously. The metabolite was collected from the urine of rats given d-delta-tocopherol in the same manner as that of the labeled compound. It was found that the metabolites consisted of sulfate conjugates. The portion of the major metabolite released with sulfatase was determined to be 2,8-dimethyl-2-(2'-carboxyethyl)-6-chromanol by infrared spectra, nuclear magnetic resonance spectra, and mass spectra. The proposed structure was confirmed by comparing the analytical results with those of a synthetically derived compound. As a result of the structural elucidation of this novel metabolite, a pathway for the biological transformation of delta-tocopherol is proposed which is different from that of alpha-tocopherol. A characteristic feature of the pathway is the absence of any opening of the chroman ring throughout the sequence

  1. Metabolite extraction from adherently growing mammalian cells for metabolomics studies: optimization of harvesting and extraction protocols.

    Dettmer, Katja; Nürnberger, Nadine; Kaspar, Hannelore; Gruber, Michael A; Almstetter, Martin F; Oefner, Peter J

    2011-01-01

    Trypsin/ethylenediaminetetraacetic acid (EDTA) treatment and cell scraping in a buffer solution were compared for harvesting adherently growing mammalian SW480 cells for metabolomics studies. In addition, direct scraping with a solvent was tested. Trypsinated and scraped cell pellets were extracted using seven different extraction protocols including pure methanol, methanol/water, pure acetone, acetone/water, methanol/chloroform/water, methanol/isopropanol/water, and acid-base methanol. The extracts were analyzed by GC-MS after methoximation/silylation and derivatization with propyl chloroformate, respectively. The metabolic fingerprints were compared and 25 selected metabolites including amino acids and intermediates of energy metabolism were quantitatively determined. Moreover, the influence of freeze/thaw cycles, ultrasonication and homogenization using ceramic beads on extraction yield was tested. Pure acetone yielded the lowest extraction efficiency while methanol, methanol/water, methanol/isopropanol/water, and acid-base methanol recovered similar metabolite amounts with good reproducibility. Based on overall performance, methanol/water was chosen as a suitable extraction solvent. Repeated freeze/thaw cycles, ultrasonication and homogenization did not improve overall metabolite yield of the methanol/water extraction. Trypsin/EDTA treatment caused substantial metabolite leakage proving it inadequate for metabolomics studies. Gentle scraping of the cells in a buffer solution and subsequent extraction with methanol/water resulted on average in a sevenfold lower recovery of quantified metabolites compared with direct scraping using methanol/water, making the latter one the method of choice to harvest and extract metabolites from adherently growing mammalian SW480 cells.

  2. Immune regulation by microbiome metabolites.

    Kim, Chang H

    2018-03-22

    Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite-specific receptors such as P2X 7 , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets. Microbial metabolites and their receptors form an extensive array of signals to respond to changes in nutrition, health and immunological status. As a consequence, microbial metabolite signals contribute to nutrient harvest from diet, and regulate host metabolism and the immune system. Importantly, microbial metabolites bidirectionally function to promote both tolerance and immunity to effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects of microbial metabolites have been observed as well. Key immune-regulatory functions of the metabolites, generated from carbohydrates, proteins and bile acids, are reviewed in this article. © 2018 John Wiley & Sons Ltd.

  3. Ecosystem, location, and climate effects on foliar secondary metabolites of lodgepole pine populations from central British Columbia.

    Wallis, Christopher M; Huber, Dezene P W; Lewis, Kathy J

    2011-06-01

    Lodgepole pines, Pinus contorta Douglas ex Louden var. latifolia Engelm. ex S. Watson, are encountering increased abiotic stress and pest activity due to recent increases in temperature and changes in precipitation throughout their range. This tree species counters these threats by producing secondary metabolites, including phenolics and terpenoids. We examined foliar levels of lignin, soluble phenolics, monoterpenoids, sesquiterpenoids, and diterpenoids in 12 stands in British Columbia, Canada. We used these data to assess associations among foliar secondary metabolite levels and ecosystem, geographic, and climatic variables. Regressions were also performed to observe which combinations of variables best explained secondary metabolite variance. Stands of P. c. latifolia in the Coastal Western Hemlock and Interior Cedar/Hemlock biogeoclimatic zones had consistently greater foliar levels of almost all measured secondary metabolites than did other stands. Lignin was present in greater amounts in Boreal White/Black Spruce ecosystem (i.e., northern) stands than in southern stands, suggesting a role for this metabolite in pine survival in the boreal forest. Attempts to develop regression models with geographic and climatic variables to explain foliar secondary metabolite levels resulted in multiple models with similar predictive capability. Since foliar secondary metabolite levels appeared to vary most between stand ecosystem types and not as much due to geographic and climatic variables, metabolic profiles appeared best matched to the stress levels within local environments. It is unknown if differences in secondary metabolite levels are the result of genetic adaptation or phenotypic plasticity, but results from this and other studies suggest that both are important. These results are interpreted in light of ongoing efforts to assist in the migration of certain populations of P. c. latifolia northward in an effort to counter predicted effects of climate change.

  4. The flavonoid pathway in tomato seedlings: transcript abundance and the modeling of metabolite dynamics.

    Marian Groenenboom

    Full Text Available Flavonoids are secondary metabolites present in all terrestrial plants. The flavonoid pathway has been extensively studied, and many of the involved genes and metabolites have been described in the literature. Despite this extensive knowledge, the functioning of the pathway in vivo is still poorly understood. Here, we study the flavonoid pathway using both experiments and mathematical models. We measured flavonoid metabolite dynamics in two tissues, hypocotyls and cotyledons, during tomato seedling development. Interestingly, the same backbone of interactions leads to very different accumulation patterns in the different tissues. Initially, we developed a mathematical model with constant enzyme concentrations that described the metabolic networks separately in both tissues. This model was unable to fit the measured flavonoid dynamics in the hypocotyls, even if we allowed unrealistic parameter values. This suggested us to investigate the effect of transcript abundance on flavonoid accumulation. We found that the expression of candidate flavonoid genes varies considerably with time. Variation in transcript abundance results in enzymatic variation, which could have a large effect on metabolite accumulation. Candidate transcript abundance was included in the mathematical model as representative for enzyme concentration. We fitted the resulting model to the flavonoid dynamics in the cotyledons, and tested it by applying it to the data from hypocotyls. When transcript abundance is included, we are indeed able to explain flavonoid dynamics in both tissues. Importantly, this is possible under the biologically relevant restriction that the enzymatic properties estimated by the model are conserved between the tissues.

  5. Synthesis of deuterium labeled ketamine metabolite dehydronorketamine-d₄.

    Sulake, Rohidas S; Chen, Chinpiao; Lin, Huei-Ru; Lua, Ahai-Chang

    2011-10-01

    A convenient synthesis of ketamine metabolite dehydronorketamine-d(4), starting from commercially available deuterium labeled bromochlorobenzene, was achieved. Key steps include Grignard reaction, regioselective hydroxybromination, Staudinger reduction, and dehydrohalogenation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Secondary Metabolites from Higher Fungi: Discovery, Bioactivity, and Bioproduction

    Zhong, Jian-Jiang; Xiao, Jian-Hui

    Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin.

  7. Strains of Sarcocystis neurona exhibit differences in their surface antigens, including the absence of the major surface antigen SnSAG1.

    Howe, Daniel K; Gaji, Rajshekhar Y; Marsh, Antoinette E; Patil, Bhagyashree A; Saville, William J; Lindsay, David S; Dubey, J P; Granstrom, David E

    2008-05-01

    A gene family of surface antigens is expressed by merozoites of Sarcocystis neurona, the primary cause of equine protozoal myeloencephalitis (EPM). These surface proteins, designated SnSAGs, are immunodominant and therefore excellent candidates for development of EPM diagnostics or vaccines. Prior work had identified an EPM isolate lacking the major surface antigen SnSAG1, thus suggesting there may be some diversity in the SnSAGs expressed by different S. neurona isolates. Therefore, a bioinformatic, molecular and immunological study was conducted to assess conservation of the SnSAGs. Examination of an expressed sequence tag (EST) database revealed several notable SnSAG polymorphisms. In particular, the EST information implied that the EPM strain SN4 lacked the major surface antigen SnSAG1. The absence of this surface antigen from the SN4 strain was confirmed by both Western blot and Southern blot. To evaluate SnSAG polymorphisms in the S. neurona population, 14 strains were examined by Western blots using monospecific polyclonal antibodies against the four described SnSAGs. The results of these analyses demonstrated that SnSAG2, SnSAG3, and SnSAG4 are present in all 14 S. neurona strains tested, although some variance in SnSAG4 was observed. Importantly, SnSAG1 was not detected in seven of the strains, which included isolates from four cases of EPM and a case of fatal meningoencephalitis in a sea otter. Genetic analyses by PCR using gene-specific primers confirmed the absence of the SnSAG1 locus in six of these seven strains. Collectively, the data indicated that there is heterogeneity in the surface antigen composition of different S. neurona isolates, which is an important consideration for development of serological tests and prospective vaccines for EPM. Furthermore, the diversity reported herein likely extends to other phenotypes, such as strain virulence, and may have implications for the phylogeny of the various Sarcocystis spp. that undergo sexual stages

  8. Obstacles to implementing evidence-based practice in Belgium: a context-specific qualitative evidence synthesis including findings from different health care disciplines.

    Hannes, K; Goedhuys, J; Aertgeerts, B

    2012-01-01

    A number of barriers to the implementation of evidence-based practice have already been inventoried. However, little attention has been given to their context-specific nature. This qualitative evidence synthesis examines commonalities in the obstacles perceived by different groups of health care practitioners working in the Belgian health care system and sets out to discuss potential strategies to bridge some of these barriers. We actively searched for primary studies addressing our topic of interest in international and national databases (1990 to May 2008), consulted experts and screened references of retrieved studies. We opted for the meta-aggregative approach, developed by the Joanna Briggs Institute, to analyse our findings. The findings indicate that (1) evidence might have a limited role in decision-making processes; (2) aspects other than quality of care steer the evidence-based practice agenda; (3) some health care providers benefit less from evidence-based practice than others and (4) there is a lack of competences to put the evidence-based principles in practice. Belgian policy makers might consider health care system characteristics from and strategies developed or suggested by others to respond to country-specific obstacles. Examples include but are not limited to; (a) providing incentives for patient-centred care coordination and patient communication, (b) supporting practitioners interested in applying research-related activities, (c) considering direct access systems and interprofessional learning to respond to the demand for autonomous decision-making from satellite professional groups, (d) systematically involving allied health professionals in important governmental advisory boards, (e) considering pharmaceutical companies perceived as 'the enemy' an ally in filling in research gaps, (f) embedding the evaluation of evidence-based knowledge and skills in examinations (g) moving from (in)formative learning to transformative learning and (h

  9. Production of secondary metabolites by some terverticillate penicillia on carbohydrate-rich and meat substrates.

    Núñez, Félix; Westphal, Carmen D; Bermúdez, Elena; Asensio, Miguel A

    2007-12-01

    Most terverticillate penicillia isolated from dry-cured meat products are toxigenic, but their ability to produce hazardous metabolites on meat-based substrates is not well known. The production of extrolites by selected terverticillate penicillia isolated from dry-cured ham has been studied on carbohydrate-rich media (malt extract agar, Czapek yeast autolysate agar, rice extract agar, and rice), meat extract triolein salt agar, and ham slices. Chloroform extracts from the selected strains grown on malt extract agar were toxic for the brine shrimp (Artemia salina) larvae and VERO cells at a concentration of 2 mg/ml, but 0.02 mg/ml produced no toxic effect. Analysis by high-pressure liquid chromatography (HPLC) coupled with photodiode array detection (DAD) or with mass spectrometry (MS) and an atmospheric pressure chemical ionization (APCI) source revealed different biologically active metabolites: cyclopiazonic acid and rugulovasine A from Penicillium commune; verrucosidin, anacine, puberuline, verrucofortine, and viridicatols from Penicillium polonicum; arisugacin and viridicatols from Penicillium echinulatum; and compactin and viridicatols from Penicillium solitum. Most of these metabolites, including the amino acid-derived compounds, were produced in the media containing high levels of carbohydrates. High concentrations of nitrogen compounds in the medium does not imply a greater production of the metabolites studied, not even those derived from the amino acids. However, molds growing on dry-cured ham are able to synthesize limited amounts of some secondary metabolites, a fact not previously reported. The combination of HPLC coupled with DAD and MS-APCI was useful for identification of closely related terverticillate Penicillium species from dry-cured ham. These techniques could be used to characterize the risk associated with the potential production of secondary metabolites in cured meats.

  10. Bignoniaceae Metabolites as Semiochemicals

    Lucía Castillo

    2010-10-01

    Full Text Available Members of the family Bignoniaceae are mostly found in tropical and neo-tropical regions in America, Asia and Africa, although some of them are cultivated in other regions as ornamentals. Species belonging to this family have been extensively studied in regard to their pharmacological properties (as extracts and isolated compounds. The aim of this review is to summarize the reported scientific evidence about the chemical properties as well as that of the extracts and isolated compounds from species of this family, focusing mainly in insect-plant interactions. As it is known, this family is recognized for the presence of iridoids which are markers of oviposition and feeding preference to species which have became specialist feeders. Some herbivore species have also evolved to the point of been able to sequester iridoids and use them as defenses against their predators. However, iridoids also exhibit anti-insect properties, and therefore they may be good lead molecules to develop botanical pesticides. Other secondary metabolites, such as quinones, and whole extracts have also shown potential as anti-insect agents.

  11. Biologically Active Metabolites Synthesized by Microalgae

    Michele Greque de Morais

    2015-01-01

    Full Text Available Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences.

  12. Brain metabolite alterations in Eisenmenger syndrome: Evaluation with MR proton spectroscopy

    Dokumacı, Dilek Şen; Doğan, Ferit; Yıldırım, Ali; Boyacı, Fatıma Nurefşan; Bozdoğan, Erol; Koca, Bülent

    2017-01-01

    Objective: Eisenmenger syndrome (ES) is a life-threatening disease characterized by pulmonary hypertension and cyanosis in patients with congenital heart diseases. The aim of this study was to determine the brain metabolite changes in Eisenmenger syndrome compared with a control group using MR proton spectroscopy. Methods and Materials: The study included 10 children (3 male, 7 female) with congenital heart diseases and a diagnosis of Eisenmenger syndrome. The control group consisted of 10 healthy volunteer children. All were examined with a 1.5 T MRI scanner and single voxel spectroscopy was performed to obtain spectra from three different regions; left frontal subcortical white matter, left lentiform nucleus and left thalamus. Peak integral values obtained from the spectra were used as quantitative data. Results: The ages of the children with ES were between 5 and 16 years, and between 5 and 15 years in the control group. Periventricular white matter hyperintensities were observed in 3 patients. On MR spectroscopy study, significantly lower levels of Choline metabolite (Cho) were detected in the frontal subcortical region and thalamus regions of the patients compared with the control group. There was no statistically significant difference between the levels of other metabolites (NAA, Cr, mI and Glx). In the lentiform nucleus, although the average value of Cho in ES patients was lower than that of the control group, it was not statistically significant. Conclusion: Cho metabolite was determined to have an important role in brain metabolism in Eisenmenger syndrome patients. Oral Cho treatment may help to extend survival.

  13. Brain metabolite alterations in Eisenmenger syndrome: Evaluation with MR proton spectroscopy

    Dokumacı, Dilek Şen, E-mail: dileksendokumaci@yahoo.com [Harran University School of Medicine, Department of Radiology, Sanliurfa (Turkey); Doğan, Ferit [Children Hospital, Department of Radiology, Sanliurfa (Turkey); Yıldırım, Ali [Children Hospital, Department of Pediatric Cardiology, Sanliurfa (Turkey); Boyacı, Fatıma Nurefşan; Bozdoğan, Erol [Harran University School of Medicine, Department of Radiology, Sanliurfa (Turkey); Koca, Bülent [Harran University School of Medicine, Department of Pediatric Cardiology, Sanliurfa (Turkey)

    2017-01-15

    Objective: Eisenmenger syndrome (ES) is a life-threatening disease characterized by pulmonary hypertension and cyanosis in patients with congenital heart diseases. The aim of this study was to determine the brain metabolite changes in Eisenmenger syndrome compared with a control group using MR proton spectroscopy. Methods and Materials: The study included 10 children (3 male, 7 female) with congenital heart diseases and a diagnosis of Eisenmenger syndrome. The control group consisted of 10 healthy volunteer children. All were examined with a 1.5 T MRI scanner and single voxel spectroscopy was performed to obtain spectra from three different regions; left frontal subcortical white matter, left lentiform nucleus and left thalamus. Peak integral values obtained from the spectra were used as quantitative data. Results: The ages of the children with ES were between 5 and 16 years, and between 5 and 15 years in the control group. Periventricular white matter hyperintensities were observed in 3 patients. On MR spectroscopy study, significantly lower levels of Choline metabolite (Cho) were detected in the frontal subcortical region and thalamus regions of the patients compared with the control group. There was no statistically significant difference between the levels of other metabolites (NAA, Cr, mI and Glx). In the lentiform nucleus, although the average value of Cho in ES patients was lower than that of the control group, it was not statistically significant. Conclusion: Cho metabolite was determined to have an important role in brain metabolism in Eisenmenger syndrome patients. Oral Cho treatment may help to extend survival.

  14. Benzene: a case study in parent chemical and metabolite interactions.

    Medinsky, M A; Kenyon, E M; Schlosser, P M

    1995-12-28

    Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene in humans are well documented and include aplastic anemia and pancytopenia, and acute myelogenous leukemia. A combination of metabolites (hydroquinone and phenol for example) is apparently necessary to duplicate the hematotoxic effect of benzene, perhaps due in part to the synergistic effect of phenol on myeloperoxidase-mediated oxidation of hydroquinone to the reactive metabolite benzoquinone. Since benzene and its hydroxylated metabolites (phenol, hydroquinone and catechol) are substrates for the same cytochrome P450 enzymes, competitive interactions among the metabolites are possible. In vivo data on metabolite formation by mice exposed to various benzene concentrations are consistent with competitive inhibition of phenol oxidation by benzene. In vitro studies of the metabolic oxidation of benzene, phenol and hydroquinone are consistent with the mechanism of competitive interaction among the metabolites. The dosimetry of benzene and its metabolites in the target tissue, bone marrow, depends on the balance of activation processes such as enzymatic oxidation and deactivation processes such as conjugation and excretion. Phenol, the primary benzene metabolite, can undergo both oxidation and conjugation. Thus, the potential exists for competition among various enzymes for phenol. However, zonal localization of Phase I and Phase II enzymes in various regions of the liver acinus regulates this competition. Biologically-based dosimetry models that incorporate the important determinants of benzene flux, including interactions with other chemicals, will enable prediction of target tissue doses of benzene and metabolites at low exposure concentrations relevant for humans.

  15. Extraction and applications of cyanotoxins and other cyanobacterial secondary metabolites.

    Haque, Fatima; Banayan, Sara; Yee, Josephine; Chiang, Yi Wai

    2017-09-01

    The rapid proliferation of cyanobacteria in bodies of water has caused cyanobacterial blooms, which have become an increasing cause of concern, largely due to the presence of toxic secondary metabolites (or cyanotoxins). Cyanotoxins are the toxins produced by cyanobacteria that may be harmful to surrounding wildlife. They include hepatotoxins, neurotoxins and dermatotoxins, and are classified based on the organs they affect. There are also non-toxic secondary metabolites that include chelators and UV-absorbing compounds. This paper summarizes the optimal techniques for secondary metabolite extraction and the possible useful products that can be obtained from cyanobacteria, with additional focus given to products derived from secondary metabolites. It becomes evident that the potential for their use as biocides, chelators, biofuels, biofertilizers, pharmaceuticals, food and feed, and cosmetics has not yet been comprehensively studied or extensively implemented. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Metabolomics and Cheminformatics Analysis of Antifungal Function of Plant Metabolites.

    Cuperlovic-Culf, Miroslava; Rajagopalan, NandhaKishore; Tulpan, Dan; Loewen, Michele C

    2016-09-30

    Fusarium head blight (FHB), primarily caused by Fusarium graminearum , is a devastating disease of wheat. Partial resistance to FHB of several wheat cultivars includes specific metabolic responses to inoculation. Previously published studies have determined major metabolic changes induced by pathogens in resistant and susceptible plants. Functionality of the majority of these metabolites in resistance remains unknown. In this work we have made a compilation of all metabolites determined as selectively accumulated following FHB inoculation in resistant plants. Characteristics, as well as possible functions and targets of these metabolites, are investigated using cheminformatics approaches with focus on the likelihood of these metabolites acting as drug-like molecules against fungal pathogens. Results of computational analyses of binding properties of several representative metabolites to homology models of fungal proteins are presented. Theoretical analysis highlights the possibility for strong inhibitory activity of several metabolites against some major proteins in Fusarium graminearum , such as carbonic anhydrases and cytochrome P450s. Activity of several of these compounds has been experimentally confirmed in fungal growth inhibition assays. Analysis of anti-fungal properties of plant metabolites can lead to the development of more resistant wheat varieties while showing novel application of cheminformatics approaches in the analysis of plant/pathogen interactions.

  17. Different types of stainless steel used in equipment in meat plants do not affect the initial microbial transfer, including pathogens, from pork skin.

    Larivière-Gauthier, Guillaume; Quessy, Sylvain; Fournaise, Sylvain; Letellier, Ann; Fravalo, Philippe

    2015-07-01

    This study describes and measures the impact of different compositions and finishes of stainless steel used in equipment in the meat industry on the transfer of natural flora and selected pathogens from artificially contaminated pork skin. It is known that the adhesion to surfaces of Listeria monocytogenes and Salmonella, 2 pathogens frequently found in contaminated pork meat, depends on the nature and roughness of the surface. Our results show no statistically significant differences in microbial transfer regardless of the types of stainless steel considered, with the highest measured transfer difference being 0.18 log colony-forming units (CFUs)/800 cm(2). Moreover, no differences in total microbial community were observed after transfer on the 5 types of stainless steel using single-strand conformation polymorphism (SSCP). It was concluded that the different characteristics of the stainless steel tested did not affect the initial bacterial transfer in this study.

  18. Metabolite Profiling of Candidatus Liberibacter Infection in Hamlin Sweet Oranges.

    Hung, Wei-Lun; Wang, Yu

    2018-04-18

    Huanglongbing (HLB), also known as citrus greening disease, caused by Candidatus Liberibacter asiaticus (CLas), is considered the most serious citrus disease in the world. CLas infection has been shown to greatly affect metabolite profiles in citrus fruits. However, because of uneven distribution of CLas throughout the tree and a minimum bacterial titer requirement for polymerase chain reaction (PCR) detection, the infected trees may test false negative. To prevent this, metabolites of healthy Hamlin oranges (CLas-) obtained from the citrus undercover protection systems (CUPS) were investigated. Comparison of the metabolite profile of juice obtained from CLas- and CLas+ (asymptomatic and symptomatic) trees revealed significant differences in both volatile and nonvolatile metabolites. However, no consistent pattern could be observed in alcohols, esters, sesquiterpenes, sugars, flavanones, and limonoids as compared to previous studies. These results suggest that CLas may affect metabolite profiles of citrus fruits earlier than detecting infection by PCR. Citric acid, nobiletin, malic acid, and phenylalanine were identified as the metabolic biomarkers associated with the progression of HLB. Thus, the differential metabolites found in this study may serve as the biomarkers of HLB in its early stage, and the metabolite signature of CLas infection may provide useful information for developing a potential treatment strategy.

  19. Investigation of tritium incorporation by means of excreted metabolites

    Biro, T.; Szilagyi, M.

    1978-01-01

    The commonly accepted urine analysis by liquid scintillation method was applied for whole body dose estimating. After the separation of metabolite fractions the organically bound tritium in urine could be measured. Urine samples from workers repeatedly exposed to tritium incorporation during the chemical processing of various labeled compounds have been collected and analyzed. The time dependence of tritium activity in certain metabolites was found to be characteristic, significantly differing from the 3 H concentration curve of the native or treated urine sample. (Auth.)

  20. Glucuronidation of deoxynivalenol (DON) by different animal species: identification of iso-DON glucuronides and iso-deepoxy-DON glucuronides as novel DON metabolites in pigs, rats, mice, and cows.

    Schwartz-Zimmermann, Heidi E; Hametner, Christian; Nagl, Veronika; Fiby, Iris; Macheiner, Lukas; Winkler, Janine; Dänicke, Sven; Clark, Erica; Pestka, James J; Berthiller, Franz

    2017-12-01

    The Fusarium mycotoxin deoxynivalenol (DON) is a frequent contaminant of cereal-based food and feed. Mammals metabolize DON by conjugation to glucuronic acid (GlcAc), the extent and regioselectivity of which is species-dependent. So far, only DON-3-glucuronide (DON-3-GlcAc) and DON-15-GlcAc have been unequivocally identified as mammalian DON glucuronides, and DON-7-GlcAc has been proposed as further DON metabolite. In the present work, qualitative HPLC-MS/MS analysis of urine samples of animals treated with DON (rats: 2 mg/kg bw, single bolus, gavage; mice: 1 mg/kg bw, single i.p. injection; pigs: 74 µg/kg bw, single bolus, gavage; cows: 5.2 mg DON/kg dry mass, oral for 13 weeks) revealed additional DON and deepoxy-DON (DOM) glucuronides. To elucidate their structures, DON and DOM were incubated with human (HLM) and rat liver microsomes (RLM). Besides the expected DON/DOM-3- and 15-GlcAc, minor amounts of four DON- and four DOM glucuronides were formed. Isolation and enzymatic hydrolysis of four of these compounds yielded iso-DON and iso-DOM, the identities of which were eventually confirmed by NMR. Incubation of iso-DON and iso-DOM with RLM and HLM yielded two main glucuronides for each parent compound, which were isolated and identified as iso-DON/DOM-3-GlcAc and iso-DON/DOM-8-GlcAc by NMR. Iso-DON-3-GlcAc, most likely misidentified as DON-7-GlcAc in the literature, proved to be a major DON metabolite in rats and a minor metabolite in pigs. In addition, iso-DON-8-GlcAc turned out to be one of the major DON metabolites in mice. DOM-3-GlcAc was the dominant DON metabolite in urine of cows and an important DON metabolite in rat urine. Iso-DOM-3-GlcAc was detected in urine of DON-treated rats and cows. Finally, DON-8,15-hemiketal-8-glucuronide, a previously described by-product of DON-3-GlcAc production by RLM, was identified in urine of DON-exposed mice and rats. The discovery of several novel DON-derived glucuronides in animal urine requires adaptation of

  1. Effect of excess iodine intake on thyroid diseases in different populations: A systematic review and meta-analyses including observational studies.

    Ryoko Katagiri

    Full Text Available Although several reports concerning the association of iodine excess and thyroid disease have appeared, no systematic review of the association between iodine excess intake and thyroid diseases, especially hyperthyroidism and hypothyroidism, has yet been reported.We conducted a systematic search of Ovid MEDLINE, PubMed, Cochrane Central Register of Controlled Trials databases, Ichushi-Web and CiNii database for intervention trials and observational studies. Search terms were constructed from related words for excess AND iodine intake or excretion AND thyroid hormones or diseases AND study designs. After considering the qualitative heterogeneity among studies, a meta-analysis was conducted and odds ratios and 95% confidence intervals (CI were estimated in random-effects models. A protocol was registered with PROSPERO (No. CRD42015028081.50 articles were included, including three intervention trials, six case-control studies, six follow-up studies and 35 cross-sectional studies. Three cross-sectional studies in adults included in meta-analysis. Odds ratio of overt and subclinical hypothyroidism between excess and adequate populations were 2.78 (CI:1.47 to 5.27 and 2.03 (CI:1.58 to 2.62 in adults, respectively. Source of excess iodine status was mainly iodized salt or water in included studies.Although universal salt iodization has improved goiter rates, chronic exposure to excess iodine from water or poorly monitored salt are risk factors for hypothyroidism in free-living populations. Monitoring of both iodine concentration in salt as well as the iodine concentration in local drinking water are essential to preventing thyroid diseases. Hypothyroidism should be also carefully monitored in areas with excess iodine. Because of the low quality and limited number of included studies, further evidence and review are required.

  2. Evaluation of Medical Metabolites in Boraginaceae Family

    Golnaz Taravati

    2014-05-01

    Full Text Available Boraginaceae family is known as a medicinal plant classified in dicotyledons.  It is originated from Asia (Middle East. The aim of this study was to evaluate ingredient between 4 species of Boraginaceae family based on physiological & phytochemical traits as well as seed fatty acid contents.  4 species (E. russicum, E. italicum, E. amoenum, and B. officinalis were evaluated carefully. All seeds were cultivated in identical conditions in a greenhouse in Tehran to assesse parameters such as tannins, phenols, anthocyanin, total protein, seed oil contents, Superoxide Dismutase (SOD, and Catalase (CAT activity. Analysis of oil from seeds of EchiumL. determined 7 different fatty acids including Linolenic acid (35.1%, Linoleic acid (16.8%, Oleic acid (16.6% and Arachidonic acid (15.5% as major fatty acids, while stearic acid (4.42%, Palmitic acid (6.22%, Gama-Linolenic acid (6.04% were the minor fatty acids extracted from seeds. Low protein content was observed in E. russicum(70 mg/g and maximum level of protein was in B. officinalis(91mg/g. E. amoenum had maximum phenols (38mg/g whereas E. russicum had minimum (26 mg/g. For total phenol, B. officinalis had maxium phenols (8.1mg/g whereas E. italicum had minimum (3.9mg/g. Anthocyanins: E. russicum had maximum anthocyanins (65 mg/g whereas B. officinalis had minimum (41 mg/g. In conclusion, it can be said that different species had different amounts of secondary metabolites so that no regular relation would be detected among plant species that we studied

  3. A survey of bacterial, fungal and plant metabolites against Aedes aegypti (Diptera: Culicidae), the vector of yellow and dengue fevers and Zika virus

    Masi Marco; Cimmino Alessio; Tabanca Nurhayat; Becnel James J.; Bloomquist Jeffrey R.; Evidente Antonio

    2017-01-01

    Aedes aegypti L. is the major vector of the arboviruses responsible for dengue fever, one of the most devastating human diseases. Some bacterial, fungal and plant metabolites belonging to different chemical subgroups, including Amaryllidaceae alkaloids, anthracenes, azoxymethoxytetrahydropyrans, cytochalasans, 2,5-diketopiperazines, isochromanones, naphthoquinones, organic small acids and their methyl esters, sterols and terpenes including sesquiterpenes and diterpenes, were tested for their ...

  4. Metabolite profiling identifies candidate markers reflecting the clinical adaptations associated with Roux-en-Y gastric bypass surgery.

    David M Mutch

    Full Text Available BACKGROUND: Roux-en-Y gastric bypass (RYGB surgery is associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. To generate further insight into the numerous metabolic adaptations associated with RYGB surgery, we profiled serum metabolites before and after gastric bypass surgery and integrated metabolite changes with clinical data. METHODOLOGY AND PRINCIPAL FINDINGS: Serum metabolites were detected by gas and liquid chromatography-coupled mass spectrometry before, and 3 and 6 months after RYGB in morbidly obese female subjects (n = 14; BMI = 46.2+/-1.7. Subjects showed decreases in weight-related parameters and improvements in insulin sensitivity post surgery. The abundance of 48% (83 of 172 of the measured metabolites changed significantly within the first 3 months post RYGB (p<0.05, including sphingosines, unsaturated fatty acids, and branched chain amino acids. Dividing subjects into obese (n = 9 and obese/diabetic (n = 5 groups identified 8 metabolites that differed consistently at all time points and whose serum levels changed following RYGB: asparagine, lysophosphatidylcholine (C18:2, nervonic (C24:1 acid, p-Cresol sulfate, lactate, lycopene, glucose, and mannose. Changes in the aforementioned metabolites were integrated with clinical data for body mass index (BMI and estimates for insulin resistance (HOMA-IR. Of these, nervonic acid was significantly and negatively correlated with HOMA-IR (p = 0.001, R = -0.55. CONCLUSIONS: Global metabolite profiling in morbidly obese subjects after RYGB has provided new information regarding the considerable metabolic alterations associated with this surgical procedure. Integrating clinical measurements with metabolomics data is capable of identifying markers that reflect the metabolic adaptations following RYGB.

  5. Ion and metabolite transport in the chloroplast of algae: lessons from land plants.

    Marchand, Justine; Heydarizadeh, Parisa; Schoefs, Benoît; Spetea, Cornelia

    2018-06-01

    Chloroplasts are endosymbiotic organelles and play crucial roles in energy supply and metabolism of eukaryotic photosynthetic organisms (algae and land plants). They harbor channels and transporters in the envelope and thylakoid membranes, mediating the exchange of ions and metabolites with the cytosol and the chloroplast stroma and between the different chloroplast subcompartments. In secondarily evolved algae, three or four envelope membranes surround the chloroplast, making more complex the exchange of ions and metabolites. Despite the importance of transport proteins for the optimal functioning of the chloroplast in algae, and that many land plant homologues have been predicted, experimental evidence and molecular characterization are missing in most cases. Here, we provide an overview of the current knowledge about ion and metabolite transport in the chloroplast from algae. The main aspects reviewed are localization and activity of the transport proteins from algae and/or of homologues from other organisms including land plants. Most chloroplast transporters were identified in the green alga Chlamydomonas reinhardtii, reside in the envelope and participate in carbon acquisition and metabolism. Only a few identified algal transporters are located in the thylakoid membrane and play role in ion transport. The presence of genes for putative transporters in green algae, red algae, diatoms, glaucophytes and cryptophytes is discussed, and roles in the chloroplast are suggested. A deep knowledge in this field is required because algae represent a potential source of biomass and valuable metabolites for industry, medicine and agriculture.

  6. Urinary excretion of phthalate metabolites in 129 healthy Danish children and adolescents: Estimation of daily phthalate intake

    Frederiksen, Hanne; Aksglaede, Lise; Sørensen, Kaspar

    2011-01-01

    Background Phthalates are a group of chemicals with widespread use in the industrial production of numerous consumer products. They are suspected to be involved in male reproductive health problems and have also been associated with several other health problems in children including obesity...... and asthma. Objectives To study the urinary excretion of phthalate metabolites in Danish children recruited from the general population, and to estimate the daily intake of phthalates in this segment of the population. Method One 24 h urine sample and to consecutive first morning urine samples were collected...... from 129 healthy Danish children and adolescents (range 6–21 yrs). The concentrations of 11 phthalate metabolites of 5 different phthalate diesters were analyzed by liquid chromatography–tandem mass spectrometry. Results The analyzed metabolites were detectable in almost all 24 h urine samples...

  7. Metabolomic Analysis and Mode of Action of Metabolites of Tea Tree Oil Involved in the Suppression of Botrytis cinerea

    Jiayu Xu

    2017-06-01

    Full Text Available Tea tree oil (TTO, a volatile essential oil, has been widely used as an antimicrobial agent. However, the mechanism underlying TTO antifungal activity is not fully understood. In this study, a comprehensive metabolomics survey was undertaken to identify changes in metabolite production in Botrytis cinerea cells treated with TTO. Significant differences in 91 metabolites were observed, including 8 upregulated and 83 downregulated metabolites in TTO-treated cells. The results indicate that TTO inhibits primary metabolic pathways through the suppression of the tricarboxylic acid (TCA cycle and fatty acid metabolism. Further experiments show that TTO treatment decreases the activities of key enzymes in the TCA cycle and increases the level of hydrogen peroxide (H2O2. Membrane damage is also induced by TTO treatment. We hypothesize that the effect of TTO on B. cinerea is achieved mainly by disruption of the TCA cycle and fatty acid metabolism, resulting in mitochondrial dysfunction and oxidative stress.

  8. Possible endocrine disrupting effects of parabens and their metabolites

    Boberg, Julie; Taxvig, Camilla; Christiansen, Sofie

    2010-01-01

    Parabens are preservatives used in a wide range of cosmetic products, including products for children, and some are permitted in foods. However, there is concern for endocrine disrupting effects. This paper critically discusses the conclusions of recent reviews and original research papers...... and provides an overview of studies on toxicokinetics. After dermal uptake, parabens are hydrolyzed and conjugated and excreted in urine. Despite high total dermal uptake of paraben and metabolites,little intact paraben can be recovered in blood and urine. Paraben metabolites may play a role in the endocrine...... disruption seen in experimental animals and studies are needed to determine human levels of parabens and metabolites. Overall, the estrogenic burden of parabens and their metabolites in blood may exceed the action of endogenous estradiol in childhood and the safety margin for propylparaben is very low when...

  9. Analysis of the impact of climate change on groundwater related hydrological fluxes: a multi-model approach including different downscaling methods

    S. Stoll

    2011-01-01

    Full Text Available Climate change related modifications in the spatio-temporal distribution of precipitation and evapotranspiration will have an impact on groundwater resources. This study presents a modelling approach exploiting the advantages of integrated hydrological modelling and a broad climate model basis. We applied the integrated MIKE SHE model on a perialpine, small catchment in northern Switzerland near Zurich. To examine the impact of climate change we forced the hydrological model with data from eight GCM-RCM combinations showing systematic biases which are corrected by three different statistical downscaling methods, not only for precipitation but also for the variables that govern potential evapotranspiration. The downscaling methods are evaluated in a split sample test and the sensitivity of the downscaling procedure on the hydrological fluxes is analyzed. The RCMs resulted in very different projections of potential evapotranspiration and, especially, precipitation. All three downscaling methods reduced the differences between the predictions of the RCMs and all corrected predictions showed no future groundwater stress which can be related to an expected increase in precipitation during winter. It turned out that especially the timing of the precipitation and thus recharge is very important for the future development of the groundwater levels. However, the simulation experiments revealed the weaknesses of the downscaling methods which directly influence the predicted hydrological fluxes, and thus also the predicted groundwater levels. The downscaling process is identified as an important source of uncertainty in hydrological impact studies, which has to be accounted for. Therefore it is strongly recommended to test different downscaling methods by using verification data before applying them to climate model data.

  10. Influence of different salting processes on the evolution of the volatile metabolites of vacuum-packed fillets of farmed and wild sea bass (Dicentrarchus labrax) stored under refrigeration conditions: a study by SPME-GC/MS.

    Vidal, Natalia P; Manzanos, María J; Goicoechea, Encarnación; Guillén, María D

    2017-02-01

    Fish shelf-life extension is a topic of great interest. In this study the behaviour of salted and unsalted farmed and wild European sea bass (Dicentrarchus labrax) fillets during storage was analysed through the evolution of their volatile metabolites. Farmed and wild sea bass fillets were brine-salted for 15 or 75 min, or dry-salted, vacuum-packed and stored at 4 °C for up to 1 month, and their headspaces were studied by Solid Phase Micro extraction-Gas Chromatography/Mass Spectrometry (SPME-GC/MS). At the same storage time, unsalted wild fillets contained, in general, a higher number and abundance of volatile compounds coming from microbiological or endogenous enzymatic activity than unsalted farmed ones. The more intense the salting, the lower the number and abundance of microbiological spoilage metabolites, especially in wild samples. The appearance of oxidation metabolites only in dry-salted wild samples evidences that this kind of salting provokes a certain oxidation in these samples. The better performance of farmed than wild fillets suggests that salted farmed fillets, vacuum-packed and stored under refrigeration conditions, could be a successful alternative to diversify the presence of sea bass in the market. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  11. Identification of Unique Metabolites of the Designer Opioid Furanyl Fentanyl.

    Goggin, Melissa M; Nguyen, An; Janis, Gregory C

    2017-06-01

    The illicit drug market has seen an increase in designer opioids, including fentanyl and methadone analogs, and other structurally unrelated opioid agonists. The designer opioid, furanyl fentanyl, is one of many fentanyl analogs clandestinely synthesized for recreational use and contributing to the fentanyl and opioid crisis. A method has been developed and validated for the analysis of furanyl fentanyl and furanyl norfentanyl in urine specimens from pain management programs. Approximately 10% of samples from a set of 500 presumptive heroin-positive urine specimens were found to contain furanyl fentanyl, with an average concentration of 33.8 ng/mL, and ranging from 0.26 to 390 ng/mL. Little to no furanyl norfentanyl was observed; therefore, the furanyl fentanyl specimens were further analyzed by untargeted high-resolution mass spectrometry to identify other metabolites. Multiple metabolites, including a dihydrodiol metabolite, 4-anilino-N-phenethyl-piperidine (4-ANPP) and a sulfate metabolite were identified. The aim of the presented study was to identify the major metabolite(s) of furanyl fentanyl and estimate their concentrations for the purpose of toxicological monitoring. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Detection of Volatile Metabolites Derived from Garlic (Allium sativum in Human Urine

    Laura Scheffler

    2016-12-01

    Full Text Available The metabolism and excretion of flavor constituents of garlic, a common plant used in flavoring foods and attributed with several health benefits, in humans is not fully understood. Likewise, the physiologically active principles of garlic have not been fully clarified to date. It is possible that not only the parent compounds present in garlic but also its metabolites are responsible for the specific physiological properties of garlic, including its influence on the characteristic body odor signature of humans after garlic consumption. Accordingly, the aim of this study was to investigate potential garlic-derived metabolites in human urine. To this aim, 14 sets of urine samples were obtained from 12 volunteers, whereby each set comprised one sample that was collected prior to consumption of food-relevant concentrations of garlic, followed by five to eight subsequent samples after garlic consumption that covered a time interval of up to 26 h. The samples were analyzed chemo-analytically using gas chromatography-mass spectrometry/olfactometry (GC-MS/O, as well as sensorially by a trained human panel. The analyses revealed three different garlic-derived metabolites in urine, namely allyl methyl sulfide (AMS, allyl methyl sulfoxide (AMSO and allyl methyl sulfone (AMSO2, confirming our previous findings on human milk metabolite composition. The excretion rates of these metabolites into urine were strongly time-dependent with distinct inter-individual differences. These findings indicate that the volatile odorant fraction of garlic is heavily biotransformed in humans, opening up a window into substance circulation within the human body with potential wider ramifications in view of physiological effects of this aromatic plant that is appreciated by humans in their daily diet.

  13. Ruta graveolens Extracts and Metabolites against Spodoptera frugiperda.

    Ayil-Gutiérrez, Benjamin A; Villegas-Mendoza, Jesús M; Santes-Hernndez, Zuridai; Paz-González, Alma D; Mireles-Martínez, Maribel; Rosas-García, Ninfa M; Rivera, Gildardo

    2015-11-01

    The biological activity of Ruta graveolens leaf tissue extracts obtained with different solvents (ethyl acetate, ethanol, and water) and metabolites (psoralen, 2- undecanone and rutin) against Spodoptera frugiperda was evaluated. Metabolites levels in extracts were quantified by HPLC and GC. Ethyl acetate and ethanol extracts showed 94% and 78% mortality, respectively. Additionally, psoralen metabolite showed a high mortality as cypermethrin. Metabolite quantification in extracts shows the presence of 2-undecanone (87.9 µmoles mg(-1) DW), psoralen (3.6 µmoles mg(-1) DW) and rutin (0.001 pmoles mg(-1) DW). We suggest that these concentrations of 2-undecanone and psoralen in R. graveolens leaf tissue extracts could be responsible for S. frugiperda mortality.

  14. Metabolome analysis - mass spectrometry and microbial primary metabolites

    Højer-Pedersen, Jesper Juul

    2008-01-01

    , and therefore sample preparation is critical for metabolome analysis. The three major steps in sample preparation for metabolite analysis are sampling, extraction and concentration. These three steps were evaluated for the yeast Saccharomyces cerevisiae with primary focus on analysis of a large number...... of metabolites by one method. The results highlighted that there were discrepancies between different methods. To increase the throughput of cultivation, S. cerevisiae was grown in microtitier plates (MTPs), and the growth was found to be comparable with cultivations in shake flasks. The carbon source was either...... a theoretical metabolome. This showed that in combination with the specificity of MS up to 84% of the metabolites can be identified in a high-accuracy ESI-spectrum. A total of 66 metabolites were systematically analyzed by positive and negative ESI-MS/MS with the aim of initiating a spectral library for ESI...

  15. Comparison of Glycomacropeptide with Phenylalanine Free-Synthetic Amino Acids in Test Meals to PKU Patients: No Significant Differences in Biomarkers, Including Plasma Phe Levels

    Kirsten K. Ahring

    2018-01-01

    Full Text Available Introduction. Management of phenylketonuria (PKU is achieved through low-phenylalanine (Phe diet, supplemented with low-protein food and mixture of free-synthetic (FS amino acid (AA. Casein glycomacropeptide (CGMP is a natural peptide released in whey during cheese-making and does not contain Phe. Lacprodan® CGMP-20 used in this study contained a small amount of Phe due to minor presence of other proteins/peptides. Objective. The purpose of this study was to compare absorption of CGMP-20 to FSAA with the aim of evaluating short-term effects on plasma AAs as well as biomarkers related to food intake. Methods. This study included 8 patients, who had four visits and tested four drink mixtures (DM1–4, consisting of CGMP, FSAA, or a combination. Plasma blood samples were collected at baseline, 15, 30, 60, 120, and 240 minutes (min after the meal. AA profiles and ghrelin were determined 6 times, while surrogate biomarkers were determined at baseline and 240 min. A visual analogue scale (VAS was used for evaluation of taste and satiety. Results. The surrogate biomarker concentrations and VAS scores for satiety and taste were nonsignificant between the four DMs, and there were only few significant results for AA profiles (not Phe. Conclusion. CGMP and FSAA had the overall same nonsignificant short-term effect on biomarkers, including Phe. This combination of FSAA and CGMP is a suitable supplement for PKU patients.

  16. Co-operation of the CMEA member countries in the development of different reactor types, including certain aspects of their nuclear fuel cycle

    Panasenkov, A.; Barbur, I.; Barchenkov, A.; Molnar, L.; Tolpygo, V.; Khake, V.; Shcherbinin, B.

    1977-01-01

    The report gives an account of the problems of the projected development of atomic power and evaluates its role in the fuel and power complex and long-range development of interconnected power systems of the CMEA member countries. The report emphasizes the importance of scientific and technical co-operation in the creation of thermal and fast-neutron power reactors with 1000-1500MW(e) units, and in the elaboration of nuclear plants for heating services. The positive experience of the international scientific and research group of scientists of the CMEA member countries carrying out reactor-physics studies on critical assemblies is mentioned. The report contains basic conclusions from the forecasts for nuclear power in the CMEA member countries up to 1990, including forecasting methodology; the role of nuclear power plants in saving natural and enriched uranium for a projected period; and the impact of nuclear power development rates on its structure (thermal and fast reactor ratio). It lists the impacts of scientific and technical co-operation of the CMEA member countries on the fuel cycle, including the transport of spent nuclear fuel, its recovery, reprocessing and radioactive waste disposal. Particular effects of co-operation of the CMEA member countries on the radiation safety of nuclear power plants and environmental protection are analysed. The report notes the role of the international economic associations Interatomenergo and Interatominstrument in the accelerated development of nuclear power. (author)

  17. Cultivar-Specific Changes in Primary and Secondary Metabolites in Pak Choi (Brassica Rapa, Chinensis Group by Methyl Jasmonate

    Moo Jung Kim

    2017-05-01

    Full Text Available Glucosinolates, their hydrolysis products and primary metabolites were analyzed in five pak choi cultivars to determine the effect of methyl jasmonate (MeJA on metabolite flux from primary metabolites to glucosinolates and their hydrolysis products. Among detected glucosinolates (total 14 glucosinolates; 9 aliphatic, 4 indole and 1 aromatic glucosinolates, indole glucosinolate concentrations (153–229% and their hydrolysis products increased with MeJA treatment. Changes in the total isothiocyanates by MeJA were associated with epithiospecifier protein activity estimated as nitrile formation. Goitrin, a goitrogenic compound, significantly decreased by MeJA treatment in all cultivars. Changes in glucosinolates, especially aliphatic, significantly differed among cultivars. Primary metabolites including amino acids, organic acids and sugars also changed with MeJA treatment in a cultivar-specific manner. A decreased sugar level suggests that they might be a carbon source for secondary metabolite biosynthesis in MeJA-treated pak choi. The result of the present study suggests that MeJA can be an effective agent to elevate indole glucosinolates and their hydrolysis products and to reduce a goitrogenic compound in pak choi. The total glucosinolate concentration was the highest in “Chinese cabbage” in the control group (32.5 µmol/g DW, but indole glucosinolates increased the greatest in “Asian” when treated with MeJA.

  18. Evaluation of elemental profiling methods, including laser-induced breakdown spectroscopy (LIBS), for the differentiation of Cannabis plant material grown in different nutrient solutions.

    El-Deftar, Moteaa M; Robertson, James; Foster, Simon; Lennard, Chris

    2015-06-01

    Laser-induced breakdown spectroscopy (LIBS) is an emerging atomic emission based solid sampling technique that has many potential forensic applications. In this study, the analytical performance of LIBS, as well as that of inductively coupled plasma mass spectrometry (ICP-MS), laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and X-ray microfluorescence (μXRF), was evaluated for the ability to conduct elemental analyses on Cannabis plant material, with a specific investigation of the possible links between hydroponic nutrients and elemental profiles from associated plant material. No such study has been previously published in the literature. Good correlation among the four techniques was observed when the concentrations or peak areas of the elements of interest were monitored. For Cannabis samples collected at the same growth time, the elemental profiles could be related to the use of particular commercial nutrients. In addition, the study demonstrated that ICP-MS, LA-ICP-MS and LIBS are suitable techniques for the comparison of Cannabis samples from different sources, with high discriminating powers being achieved. On the other hand, μXRF method was not suitable for the discrimination of Cannabis samples originating from different growth nutrients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Do metabolites that are produced during resistance exercise enhance muscle hypertrophy?

    Dankel, Scott J; Mattocks, Kevin T; Jessee, Matthew B; Buckner, Samuel L; Mouser, J Grant; Loenneke, Jeremy P

    2017-11-01

    Many reviews conclude that metabolites play an important role with respect to muscle hypertrophy during resistance exercise, but their actual physiologic contribution remains unknown. Some have suggested that metabolites may work independently of muscle contraction, while others have suggested that metabolites may play a secondary role in their ability to augment muscle activation via inducing fatigue. Interestingly, the studies used as support for an anabolic role of metabolites use protocols that are not actually designed to test the importance of metabolites independent of muscle contraction. While there is some evidence in vitro that metabolites may induce muscle hypertrophy, the only study attempting to answer this question in humans found no added benefit of pooling metabolites within the muscle post-exercise. As load-induced muscle hypertrophy is thought to work via mechanotransduction (as opposed to being metabolically driven), it seems likely that metabolites simply augment muscle activation and cause the mechanotransduction cascade in a larger proportion of muscle fibers, thereby producing greater muscle growth. A sufficient time under tension also appears necessary, as measurable muscle growth is not observed after repeated maximal testing. Based on current evidence, it is our opinion that metabolites produced during resistance exercise do not have anabolic properties per se, but may be anabolic in their ability to augment muscle activation. Future studies are needed to compare protocols which produce similar levels of muscle activation, but differ in the magnitude of metabolites produced, or duration in which the exercised muscles are exposed to metabolites.

  20. Spatial Distribution of Lactococcus lactis Colonies Modulates the Production of Major Metabolites during the Ripening of a Model Cheese.

    Le Boucher, Clémentine; Gagnaire, Valérie; Briard-Bion, Valérie; Jardin, Julien; Maillard, Marie-Bernadette; Dervilly-Pinel, Gaud; Le Bizec, Bruno; Lortal, Sylvie; Jeanson, Sophie; Thierry, Anne

    2016-01-01

    In cheese, lactic acid bacteria are immobilized at the coagulation step and grow as colonies. The spatial distribution of bacterial colonies is characterized by the size and number of colonies for a given bacterial population within cheese. Our objective was to demonstrate that different spatial distributions, which lead to differences in the exchange surface between the colonies and the cheese matrix, can influence the ripening process. The strategy was to generate cheeses with the same growth and acidification of a Lactococcus lactis strain with two different spatial distributions, big and small colonies, to monitor the production of the major ripening metabolites, including sugars, organic acids, peptides, free amino acids, and volatile metabolites, over 1 month of ripening. The monitored metabolites were qualitatively the same for both cheeses, but many of them were more abundant in the small-colony cheeses than in the big-colony cheeses over 1 month of ripening. Therefore, the results obtained showed that two different spatial distributions of L. lactis modulated the ripening time course by generating moderate but significant differences in the rates of production or consumption for many of the metabolites commonly monitored throughout ripening. The present work further explores the immobilization of bacteria as colonies within cheese and highlights the consequences of this immobilization on cheese ripening. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. Oxidative defense metabolites induced by salinity stress in roots of Salicornia herbacea.

    Lee, Seung Jae; Jeong, Eun-Mi; Ki, Ah Young; Oh, Kyung-Seo; Kwon, Joseph; Jeong, Jae-Hyuk; Chung, Nam-Jin

    2016-11-01

    High salinity is a major abiotic stress that affects the growth and development of plants. This type of stress can influence flowering, the production of crops, defense mechanisms and other physiological processes. Previous studies have attempted to elucidate salt-tolerance mechanisms to improve plant growth and productivity in the presence of sodium chloride. One such plant that has been studied in detail is Salicornia, a well-known halophyte, which has adapted to grow in the presence of high salt. To further the understanding of how Salicornia grows and develops under high saline conditions, Salicornia herbacea (S. herbacea) was grown under varying saline concentrations (0, 50, 100, 200, 300, and 400mM), and the resulting phenotype, ion levels, and metabolites were investigated. The optimal condition for the growth of S. herbacea was determined to be 100mM NaCl, and increased salt concentrations directly decreased the internal concentrations of other inorganic ions including Ca 2+ , K + , and Mg 2+ . Metabolomics were performed on the roots of the plant as a systematic metabolomics study has not yet been reported for Salicornia roots. Using ethylacetate and methanol extraction followed by high resolution ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS), 1793 metabolites were identified at different NaCl levels. Structural and functional analyses demonstrated that the concentration of 53 metabolites increased as the concentration of NaCl increased. These metabolites have been linked to stress responses, primarily oxidative stress responses, which increase under saline stress. Most metabolites can be classified as polyols, alkaloids, and steroids. Functional studies of these metabolites show that shikimic acid, vitamin K1, and indole-3-carboxylic acid are generated as a result of defense mechanisms, including the shikimate pathway, to protect against reactive oxygen species (ROS) generated by salt stress. This metabolite profiling

  2. Plasma and serum from nonfasting men and women differ in their lipidomic profiles.

    Ishikawa, Masaki; Tajima, Yoko; Murayama, Mayumi; Senoo, Yuya; Maekawa, Keiko; Saito, Yoshiro

    2013-01-01

    Biomarkers will play important roles in disease diagnosis, drug development, and the proper use of drugs. Blood is considered the best biofluid for biomarker research because it is easy to access and a wealth of data are available. However, previous studies revealed that several ionic metabolites showed different levels (including presence or absence) in plasma and serum. Thus, attention should be paid to selecting the best biofluid for biomarker exploration. Many lipid molecules have biological significance and thus would be candidate biomarkers. However, no comprehensive study revealing differences in lipid metabolite levels between plasma and serum has been undertaken. Furthermore, gender differences have not been reported. To clarify the difference in the levels of lipid metabolites between human plasma and serum from both genders, we performed lipid metabolomic analysis using liquid chromatography-mass spectrometry-based systems for phospholipids (PLs), lysoPLs, sphingomyelins, ceramides and oxidative fatty acids. Our results revealed that most of the lipid metabolites were present at similar levels in plasma and serum and in males and females. However, several oxidative fatty acid metabolites showed differences. Of the metabolites related to clotting processes, three showed higher levels in serum than in plasma, and three were detected only in serum. Furthermore, four metabolites were present at different levels between males and females, and two were detected only in males. Thus, attention should be paid to the selection of plasma or serum when utilizing these lipid metabolites as biomarkers.

  3. Secondary metabolites from the roots of Astragalus maximus

    J. Ghasemian-Yadegari

    2017-04-01

    Full Text Available Background and objectives: Astragalus is one of the most abundant genera of flowering plants in Iran. There are a few reports on phytochemical investigation of this valuable genus. Saponins, flavonoids and polysaccharides have been reported as the most important metabolites in Astragalus species. In the present research, we aimed to identify the foremost constituents of Astragalus maximus. Method: Phytochemical analysis of the ethyl acetate (EtOAc fraction of Astragalus maximus roots was performed using different methods of chromatography such as HPLC, SPE and preparative TLC. The structures of the isolated compounds were elucidated on the basis of extensive spectral evidence from 1D and 2D NMR including DQF-COSY, HSQC, HMBC, and DEPT, in comparison with reported values in the literature. Results: Analysis of the extract yielded three flavonoids namely liquiritigenin, formononetin, isoquercitrin and one acylated cycloartane-type saponin, astragaloside I. Conclusion: According to the results of our study, cycloartane-type saponin and flavonoids were the important metabolites in A. maximus.

  4. Simultaneous fecal microbial and metabolite profiling enables accurate classification of pediatric irritable bowel syndrome

    Shankar, Vijay; Reo, Nicholas V.; Paliy, Oleg

    2015-01-01

    Background We previously showed that stool samples of pre-adolescent and adolescent US children diagnosed with diarrhea-predominant IBS (IBS-D) had different compositions of microbiota and metabolites compared to healthy age-matched controls. Here we explored whether observed fecal microbiota and metabolite differences between these two adolescent populations can be used to discriminate between IBS and health. Findings We constructed individual microbiota- and metabolite-based sample classifi...

  5. The immunoprofile of odontogenic keratocyst (keratocystic odontogenic tumor) that includes expression of PTCH, SMO, GLI-1 and bcl-2 is similar to ameloblastoma but different from odontogenic cysts.

    Vered, M; Peleg, O; Taicher, S; Buchner, A

    2009-08-01

    The aggressive biological behavior of odontogenic keratocysts (OKCs), unlike that of other odontogenic cysts, has argued for its recent re-classification as a neoplasm, 'keratocystic odontogenic tumor'. Identification of mutations in the PTCH gene in some of the OKCs that were expected to produce truncated proteins, resulting in loss of control of the cell cycle, provided additional support for OKCs having a neoplastic nature. We investigated the immunohistochemical expression of the sonic hedgehog (SHH) signaling pathway-related proteins, PTCH, smoothened (SMO) and GLI-1, and of the SHH-induced bcl-2 oncoprotein in a series of primary OKC (pOKC), recurrent OKC (rOKC) and nevoid basal cell carcinoma syndrome-associated OKCs (NBCCS-OKCs), and compared them to solid ameloblastomas (SAMs), unicystic ameloblastomas (UAMs), 'orthokeratinized' OKCs (oOKCs), dentigerous cysts (DCs) and radicular cysts (RCs). All studied lesions expressed the SHH pathway-related proteins in a similar pattern. The expression of bcl-2 in OKCs (pOKCs and NBCCS-OKCs) and SAMs was significantly higher than in oOKCs, DCs and RCs (P < 0.001). The present results of the immunoprofile of OKCs (that includes the expression of the SHH-related proteins and the SHH-induced bcl-2 oncoprotein) further support the notion of OKC having a neoplastic nature. As OKCs vary considerably in their biologic behavior, it is suggested that the quality and quantity of interactions between the SHH and other cell cycle regulatory pathways are likely to work synergistically to define the individual phenotype and corresponding biological behavior of this lesion.

  6. The effects of feeding rations that differ in fiber and fermentable starch within a day on milk production and the daily rhythm of feed intake and plasma hormones and metabolites in dairy cows.

    Niu, M; Ying, Y; Bartell, P A; Harvatine, K J

    2017-01-01

    A daily pattern of feed intake, milk synthesis, and plasma metabolites and hormones occurs in dairy cows fed a total mixed ration once or twice a day. The objective of this study was to determine if feeding multiple rations within a day, complementing these rhythms, would improve milk production. Twelve Holstein cows were used in a replicated 3×3 Latin square design with 21-d periods. Cows were housed in tie stalls with feed tubs, and feed weight was recorded every 10 s for observation of feeding behavior. Rations were a low fiber and high fermentable starch ration [LFHS; 27.4% neutral detergent fiber (NDF) and 31.7% starch based on 55.7% corn silage and 14.1% steam-flaked corn], a high fiber and low fermentable starch ration (HFLS; 31.7% NDF and 22.3% starch based on 44% corn silage, 26.3% alfalfa haylage, and no steam-flaked corn), and a total mixed ration that was a 1:3 ratio of LFHS and HFLS (30.7% NDF, 24.5% starch). The control treatment (CON) cows were fed the total mixed ration at 0700h, the high/low treatment (HL) fed HFLS ration at 0700h and LFHS ration at 2200h, and the low/high (LH) treatment fed LFHS ration at 0700h and HFLS ration at 1100h (LFHS and HFLS rations fed at a 1:3 ratio). No effect was found of treatment on daily milk, but LH decreased milk fat concentration and yield compared with HL (0.2 percentage units and 0.24kg, respectively). Daily dry matter and NDF intake and total-tract digestibility did not differ between treatments. The HL treatment reduced intake at the morning-conditioned meal after feeding and reduced intake before the evening feeding. A treatment by time of day interaction was found for fecal NDF and indigestible NDF concentration, blood urea nitrogen (BUN), plasma insulin, and fatty acid concentration, and body temperature. The CON and LH treatments increased the daily amplitude of fecal NDF by 1.0 and 1.1 percentage units compared with HL. Plasma insulin was higher in HL than CON at 0100 and 0400h, but lower at 1300 and

  7. A combined genetic and multi medium approach revels new secondary metabolites in Aspergillus nidulans

    Klejnstrup, Marie Louise; Nielsen, Morten Thrane; Frisvad, Jens Christian

    Secondary metabolites are a diverse group of metabolites which serve as important natural sources of drugs for treating diseases. The availability of full genome sequences of several filamentous fungi has revealed a large genetic potential for production of secondary metabolites that are not obse......Secondary metabolites are a diverse group of metabolites which serve as important natural sources of drugs for treating diseases. The availability of full genome sequences of several filamentous fungi has revealed a large genetic potential for production of secondary metabolites...... that are not observed under standard laboratory conditions. Genetic approaches have proven a fruitfull strategy towards the production and identification of these unknown metabolites. Examples include deletion of the cclA1 and laeA2 genes in A. nidulans which affects the expression of secondary metabolites including...... monodictyphenone and terrequinone A respectively. We have deleted the cclA gene in A. nidulans and grown the mutants on several complex media to provoke the production of secondary metabolites. This resulted in the production of several metabolites not previously reported from A. nidulans. Some of these have been...

  8. Identification of phenylbutyrate-generated metabolites in Huntington disease patients using parallel liquid chromatography/electrochemical array/mass spectrometry and off-line tandem mass spectrometry.

    Ebbel, Erika N; Leymarie, Nancy; Schiavo, Susan; Sharma, Swati; Gevorkian, Sona; Hersch, Steven; Matson, Wayne R; Costello, Catherine E

    2010-04-15

    Oral sodium phenylbutyrate (SPB) is currently under investigation as a histone deacetylation (HDAC) inhibitor in Huntington disease (HD). Ongoing studies indicate that symptoms related to HD genetic abnormalities decrease with SPB therapy. In a recently reported safety and tolerability study of SPB in HD, we analyzed overall chromatographic patterns from a method that employs gradient liquid chromatography with series electrochemical array, ultraviolet (UV), and fluorescence (LCECA/UV/F) for measuring SPB and its metabolite phenylacetate (PA). We found that plasma and urine from SPB-treated patients yielded individual-specific patterns of approximately 20 metabolites that may provide a means for the selection of subjects for extended trials of SPB. The structural identification of these metabolites is of critical importance because their characterization will facilitate understanding the mechanisms of drug action and possible side effects. We have now developed an iterative process with LCECA, parallel LCECA/LCMS, and high-performance tandem MS for metabolite characterization. Here we report the details of this method and its use for identification of 10 plasma and urinary metabolites in treated subjects, including indole species in urine that are not themselves metabolites of SPB. Thus, this approach contributes to understanding metabolic pathways that differ among HD patients being treated with SPB. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Lichen secondary metabolites affect growth of Physcomitrella patens by allelopathy.

    Goga, Michal; Antreich, Sebastian J; Bačkor, Martin; Weckwerth, Wolfram; Lang, Ingeborg

    2017-05-01

    Lichen secondary metabolites can function as allelochemicals and affect the development and growth of neighboring bryophytes, fungi, vascular plants, microorganisms, and even other lichens. Lichen overgrowth on bryophytes is frequently observed in nature even though mosses grow faster than lichens, but there is still little information on the interactions between lichens and bryophytes.In the present study, we used extracts from six lichen thalli containing secondary metabolites like usnic acid, protocetraric acid, atranorin, lecanoric acid, nortistic acid, and thamnolic acid. To observe the influence of these metabolites on bryophytes, the moss Physcomitrella patens was cultivated for 5 weeks under laboratory conditions and treated with lichen extracts. Toxicity of natural mixtures of secondary metabolites was tested at three selected doses (0.001, 0.01, and 0.1 %). When the mixture contained substantial amounts of usnic acid, we observed growth inhibition of protonemata and reduced development of gametophores. Significant differences in cell lengths and widths were also noticed. Furthermore, usnic acid had a strong effect on cell division in protonemata suggesting a strong impact on the early stages of bryophyte development by allelochemicals contained in the lichen secondary metabolites.Biological activities of lichen secondary metabolites were confirmed in several studies such as antiviral, antibacterial, antitumor, antiherbivore, antioxidant, antipyretic, and analgetic action or photoprotection. This work aimed to expand the knowledge on allelopathic effects on bryophyte growth.

  10. Fully Automated Trimethylsilyl (TMS) Derivatisation Protocol for Metabolite Profiling by GC-MS.

    Zarate, Erica; Boyle, Veronica; Rupprecht, Udo; Green, Saras; Villas-Boas, Silas G; Baker, Philip; Pinu, Farhana R

    2016-12-29

    Gas Chromatography-Mass Spectrometry (GC-MS) has long been used for metabolite profiling of a wide range of biological samples. Many derivatisation protocols are already available and among these, trimethylsilyl (TMS) derivatisation is one of the most widely used in metabolomics. However, most TMS methods rely on off-line derivatisation prior to GC-MS analysis. In the case of manual off-line TMS derivatisation, the derivative created is unstable, so reduction in recoveries occurs over time. Thus, derivatisation is carried out in small batches. Here, we present a fully automated TMS derivatisation protocol using robotic autosamplers and we also evaluate a commercial software, Maestro available from Gerstel GmbH. Because of automation, there was no waiting time of derivatised samples on the autosamplers, thus reducing degradation of unstable metabolites. Moreover, this method allowed us to overlap samples and improved throughputs. We compared data obtained from both manual and automated TMS methods performed on three different matrices, including standard mix, wine, and plasma samples. The automated TMS method showed better reproducibility and higher peak intensity for most of the identified metabolites than the manual derivatisation method. We also validated the automated method using 114 quality control plasma samples. Additionally, we showed that this online method was highly reproducible for most of the metabolites detected and identified (RSD TMS method has been applied to analyse a large number of complex plasma samples. Furthermore, we found that this method was highly applicable for routine metabolite profiling (both targeted and untargeted) in any metabolomics laboratory.

  11. Fully Automated Trimethylsilyl (TMS Derivatisation Protocol for Metabolite Profiling by GC-MS

    Erica Zarate

    2016-12-01

    Full Text Available Gas Chromatography-Mass Spectrometry (GC-MS has long been used for metabolite profiling of a wide range of biological samples. Many derivatisation protocols are already available and among these, trimethylsilyl (TMS derivatisation is one of the most widely used in metabolomics. However, most TMS methods rely on off-line derivatisation prior to GC-MS analysis. In the case of manual off-line TMS derivatisation, the derivative created is unstable, so reduction in recoveries occurs over time. Thus, derivatisation is carried out in small batches. Here, we present a fully automated TMS derivatisation protocol using robotic autosamplers and we also evaluate a commercial software, Maestro available from Gerstel GmbH. Because of automation, there was no waiting time of derivatised samples on the autosamplers, thus reducing degradation of unstable metabolites. Moreover, this method allowed us to overlap samples and improved throughputs. We compared data obtained from both manual and automated TMS methods performed on three different matrices, including standard mix, wine, and plasma samples. The automated TMS method showed better reproducibility and higher peak intensity for most of the identified metabolites than the manual derivatisation method. We also validated the automated method using 114 quality control plasma samples. Additionally, we showed that this online method was highly reproducible for most of the metabolites detected and identified (RSD < 20 and specifically achieved excellent results for sugars, sugar alcohols, and some organic acids. To the very best of our knowledge, this is the first time that the automated TMS method has been applied to analyse a large number of complex plasma samples. Furthermore, we found that this method was highly applicable for routine metabolite profiling (both targeted and untargeted in any metabolomics laboratory.

  12. 67Cu-labelled antibody fragments for RIT: strategies to prevent kidney accumulation of 67Cu-labelled metabolites

    Rutherford, R.A.D.; Zimmermann, K.; Waibel, R.; Ruch, C.; Pasquale, C. de; Novak-Hofer, I.

    1997-01-01

    Two different approaches to reduce accumulation of radiocopper labelled metabolites in the kidney were pursued. The first strategy consisted of pharmacological blockade of reuptake of metabolites by predosing with basic amino acids. The second approach is chemical modification of the DOTA chelator in an attempt to increase clearance of metabolites from the kidneys. (author) 1 fig., 1 ref

  13. Primary expectations of secondary metabolites

    My program examines the plant secondary metabolites (i.e. phenolics) important for human health, and which impart the organoleptic properties that are quality indicators for fresh and processed foods. Consumer expectations such as appearance, taste, or texture influence their purchasing decisions; a...

  14. Associations between urinary metabolites of di(2-ethylhexyl) phthalate and reproductive hormones in fertile men

    Mendiola, J; Jørgensen, N; Andersson, A-M

    2010-01-01

    metabolites were measured in urine and serum samples were analysed for reproductive hormones, including follicle-stimulating hormone, luteinizing hormone, testosterone, inhibin B and oestradiol and sex hormone-binding globulin (SHBG). Pearson correlations and parametric tests were used for unadjusted analyses...... inversely correlated with the urinary concentrations of four DEHP metabolites. After adjustment by appropriate covariates, there was no longer an association between urinary DEHP metabolite concentrations and total testosterone levels; however, FAI was significantly associated with the urinary...

  15. Associations between urinary metabolites of di(2-ethylhexyl) phthalate and reproductive hormones in fertile men

    Mendiola, J; Jørgensen, N; Andersson, A-M

    2011-01-01

    metabolites were measured in urine and serum samples were analysed for reproductive hormones, including follicle-stimulating hormone, luteinizing hormone, testosterone, inhibin B and oestradiol and sex hormone-binding globulin (SHBG). Pearson correlations and parametric tests were used for unadjusted analyses...... inversely correlated with the urinary concentrations of four DEHP metabolites. After adjustment by appropriate covariates, there was no longer an association between urinary DEHP metabolite concentrations and total testosterone levels; however, FAI was significantly associated with the urinary...

  16. Proton NMR-based metabolite analyses of archived serial paired serum and urine samples from myeloma patients at different stages of disease activity identifies acetylcarnitine as a novel marker of active disease.

    Alessia Lodi

    Full Text Available BACKGROUND: Biomarker identification is becoming increasingly important for the development of personalized or stratified therapies. Metabolomics yields biomarkers indicative of phenotype that can be used to characterize transitions between health and disease, disease progression and therapeutic responses. The desire to reproducibly detect ever greater numbers of metabolites at ever diminishing levels has naturally nurtured advances in best practice for sample procurement, storage and analysis. Reciprocally, since many of the available extensive clinical archives were established prior to the metabolomics era and were not processed in such an 'ideal' fashion, considerable scepticism has arisen as to their value for metabolomic analysis. Here we have challenged that paradigm. METHODS: We performed proton nuclear magnetic resonance spectroscopy-based metabolomics on blood serum and urine samples from 32 patients representative of a total cohort of 1970 multiple myeloma patients entered into the United Kingdom Medical Research Council Myeloma IX trial. FINDINGS: Using serial paired blood and urine samples we detected metabolite profiles that associated with diagnosis, post-treatment remission and disease progression. These studies identified carnitine and acetylcarnitine as novel potential biomarkers of active disease both at diagnosis and relapse and as a mediator of disease associated pathologies. CONCLUSIONS: These findings show that samples conventionally processed and archived can provide useful metabolomic information that has important implications for understanding the biology of myeloma, discovering new therapies and identifying biomarkers potentially useful in deciding the choice and application of therapy.

  17. Marine metabolites: The sterols of soft coral

    Sarma, N.S.; Krishna, M.S.; Pasha, Sk.G.; Rao, T.S.P.; Venkateswarlu, Y.; Parameswaran, P.S.

    Sterols constitute a major group of secondary metabolites of soft corals. Several of these compounds have the 'usual' 3 beta-hydroxy, delta sup(5) (or delta sup(0)) cholestane skeleton, a large number of these metabolites are polar sterols...

  18. Familial Resemblance for Serum Metabolite Concentrations

    Draisma, H.H.M.; Beekman, M.; Pool, R.; van Ommen, G.J.B; Vaarhorst, A.A.M.; de Craen, A.J.; Willemsen, G.; Slagboom, P.E.; Boomsma, D.I.

    2013-01-01

    Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of

  19. Plasma Metabolites Predict Severity of Depression and Suicidal Ideation in Psychiatric Patients-A Multicenter Pilot Analysis.

    Setoyama, Daiki; Kato, Takahiro A; Hashimoto, Ryota; Kunugi, Hiroshi; Hattori, Kotaro; Hayakawa, Kohei; Sato-Kasai, Mina; Shimokawa, Norihiro; Kaneko, Sachie; Yoshida, Sumiko; Goto, Yu-Ichi; Yasuda, Yuka; Yamamori, Hidenaga; Ohgidani, Masahiro; Sagata, Noriaki; Miura, Daisuke; Kang, Dongchon; Kanba, Shigenobu

    2016-01-01

    Evaluating the severity of depression (SOD), especially suicidal ideation (SI), is crucial in the treatment of not only patients with mood disorders but also psychiatric patients in general. SOD has been assessed on interviews such as the Hamilton Rating Scale for Depression (HAMD)-17, and/or self-administered questionnaires such as the Patient Health Questionnaire (PHQ)-9. However, these evaluation systems have relied on a person's subjective information, which sometimes lead to difficulties in clinical settings. To resolve this limitation, a more objective SOD evaluation system is needed. Herein, we collected clinical data including HAMD-17/PHQ-9 and blood plasma of psychiatric patients from three independent clinical centers. We performed metabolome analysis of blood plasma using liquid chromatography mass spectrometry (LC-MS), and 123 metabolites were detected. Interestingly, five plasma metabolites (3-hydroxybutyrate (3HB), betaine, citrate, creatinine, and gamma-aminobutyric acid (GABA)) are commonly associated with SOD in all three independent cohort sets regardless of the presence or absence of medication and diagnostic difference. In addition, we have shown several metabolites are independently associated with sub-symptoms of depression including SI. We successfully created a classification model to discriminate depressive patients with or without SI by machine learning technique. Finally, we produced a pilot algorithm to predict a grade of SI with citrate and kynurenine. The above metabolites may have strongly been associated with the underlying novel biological pathophysiology of SOD. We should explore the biological impact of these metabolites on depressive symptoms by utilizing a cross species study model with human and rodents. The present multicenter pilot study offers a potential utility for measuring blood metabolites as a novel objective tool for not only assessing SOD but also evaluating therapeutic efficacy in clinical practice. In addition

  20. Plasma Metabolites Predict Severity of Depression and Suicidal Ideation in Psychiatric Patients-A Multicenter Pilot Analysis.

    Daiki Setoyama

    Full Text Available Evaluating the severity of depression (SOD, especially suicidal ideation (SI, is crucial in the treatment of not only patients with mood disorders but also psychiatric patients in general. SOD has been assessed on interviews such as the Hamilton Rating Scale for Depression (HAMD-17, and/or self-administered questionnaires such as the Patient Health Questionnaire (PHQ-9. However, these evaluation systems have relied on a person's subjective information, which sometimes lead to difficulties in clinical settings. To resolve this limitation, a more objective SOD evaluation system is needed. Herein, we collected clinical data including HAMD-17/PHQ-9 and blood plasma of psychiatric patients from three independent clinical centers. We performed metabolome analysis of blood plasma using liquid chromatography mass spectrometry (LC-MS, and 123 metabolites were detected. Interestingly, five plasma metabolites (3-hydroxybutyrate (3HB, betaine, citrate, creatinine, and gamma-aminobutyric acid (GABA are commonly associated with SOD in all three independent cohort sets regardless of the presence or absence of medication and diagnostic difference. In addition, we have shown several metabolites are independently associated with sub-symptoms of depression including SI. We successfully created a classification model to discriminate depressive patients with or without SI by machine learning technique. Finally, we produced a pilot algorithm to predict a grade of SI with citrate and kynurenine. The above metabolites may have strongly been associated with the underlying novel biological pathophysiology of SOD. We should explore the biological impact of these metabolites on depressive symptoms by utilizing a cross species study model with human and rodents. The present multicenter pilot study offers a potential utility for measuring blood metabolites as a novel objective tool for not only assessing SOD but also evaluating therapeutic efficacy in clinical practice. In

  1. Application of Fourier-transform ion cyclotron resonance mass spectrometry to metabolic profiling and metabolite identification.

    Ohta, Daisaku; Kanaya, Shigehiko; Suzuki, Hideyuki

    2010-02-01

    Metabolomics, as an essential part of genomics studies, intends holistic understanding of metabolic networks through simultaneous analysis of a myriad of both known and unknown metabolites occurring in living organisms. The initial stage of metabolomics was designed for the reproducible analyses of known metabolites based on their comparison to available authentic compounds. Such metabolomics platforms were mostly based on mass spectrometry (MS) technologies enabled by a combination of different ionization methods together with a variety of separation steps including LC, GC, and CE. Among these, Fourier-transform ion cyclotron resonance MS (FT-ICR/MS) is distinguished from other MS technologies by its ultrahigh resolution power in mass to charge ratio (m/z). The potential of FT-ICR/MS as a distinctive metabolomics tool has been demonstrated in nontargeted metabolic profiling and functional characterization of novel genes. Here, we discuss both the advantages and difficulties encountered in the FT-ICR/MS metabolomics studies.

  2. Depression of brain dopamine and its metabolite after mating in European honeybee (Apis mellifera) queens

    Harano, Ken-Ichi; Sasaki, Ken; Nagao, Takashi

    2005-07-01

    To explore neuro-endocrinal changes in the brain of European honeybee (Apis mellifera) queens before and after mating, we measured the amount of several biogenic amines, including dopamine and its metabolite in the brain of 6- and 12-day-old virgins and 12-day-old mated queens. Twelve-day-old mated queens showed significantly lower amounts of dopamine and its metabolite (N-acetyldopamine) than both 6- and 12-day-old virgin queens, whereas significant differences in the amounts of these amines were not detected between 6- and 12-day-old virgin queens. These results are explained by down-regulation of both synthesis and secretion of brain dopamine after mating. It is speculated that higher amounts of brain dopamine in virgin queens might be involved in activation of ovarian follicles arrested in previtellogenic stages, as well as regulation of their characteristic behaviors.

  3. Detection of mastitis pathogens by analysis of volatile bacterial metabolites.

    Hettinga, K A; van Valenberg, H J F; Lam, T J G M; van Hooijdonk, A C M

    2008-10-01

    The ability to detect mastitis pathogens based on their volatile metabolites was studied. Milk samples from cows with clinical mastitis, caused by Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus uberis, Streptococcus dysgalactiae, and Escherichia coli were collected. In addition, samples from cows without clinical mastitis and with low somatic cell count (SCC) were collected for comparison. All mastitis samples were examined by using classical microbiological methods, followed by headspace analysis for volatile metabolites. Milk from culture-negative samples contained a lower number and amount of volatile components compared with cows with clinical mastitis. Because of variability between samples within a group, comparisons between pathogens were not sufficient for classification of the samples by univariate statistics. Therefore, an artificial neural network was trained to classify the pathogen in the milk samples based on the bacterial metabolites. The trained network differentiated milk from uninfected and infected quarters very well. When comparing pathogens, Staph. aureus produced a very different pattern of volatile metabolites compared with the other samples. Samples with coagulase-negative staphylococci and E. coli had enough dissimilarity with the other pathogens, making it possible to separate these 2 pathogens from each other and from the other samples. The 2 streptococcus species did not show significant differences between each other but could be identified as a different group from the other pathogens. Five groups can thus be identified based on the volatile bacterial metabolites: Staph. aureus, coagulase-negative staphylococci, streptococci (Strep. uberis and Strep. dysgalactiae as one group), E. coli, and uninfected quarters.

  4. Lightweight expanded clay aggregates (LECA), a new up-scaleable matrix for production of microfungal metabolites

    Nielsen, Kristian Fog; Larsen, Thomas Ostenfeld; Frisvad, Jens Christian

    2004-01-01

    In order to compare the effects of different growth matrices on secondary metabolite production we compared 16 Penicillium species known to produce several families of bioactive compounds. The isolates were grown in rich complex media formulated as semisolid (agar), liquid (still), shake culture,...... for production of sporulation-associated metabolites, such as cyclopenins and viridicatins, for quick up-scaling from agar based media, and as an alternative for production of metabolites that are not induced under submerse conditions....

  5. Sulfate Metabolites of 4-Monochlorobiphenyl in Whole Poplar Plants

    Zhai, Guangshu; Lehmler, Hans-Joachim; Schnoor, Jerald L.

    2012-01-01

    4-Monochlorobiphenyl (PCB3) has been proven to be transformed into hydroxylated metabolites of PCB3 (OH-PCB3s) in whole poplar plants in our previous work. However, hydroxylated metabolites of PCBs, including OH-PCB3s, as the substrates of sulfotransferases have not been studied in many organisms including plants in vivo. Poplar (Populus deltoides × nigra, DN34) was used to investigate the further metabolism from OH-PCB3s to PCB3 sulfates because it is a model plant and one that is frequently...

  6. Rapid Quantification of Major Volatile Metabolites in Fermented Food and Beverages Using Gas Chromatography-Mass Spectrometry

    Farhana R. Pinu

    2017-07-01

    Full Text Available Here we present a method for the accurate quantification of major volatile metabolites found in different food and beverages, including ethanol, acetic acid and other aroma compounds, using gas chromatography coupled to mass spectrometry (GC-MS. The method is combined with a simple sample preparation procedure using sodium chloride and anhydrous ethyl acetate. The GC-MS analysis was accomplished within 4.75 min, and over 80 features were detected, of which 40 were positively identified using an in-house and a commercialmass spectrometry (MS library. We determined different analytical parameters of these metabolites including the limit of detection (LOD, limit of quantitation (LOQ and range of quantification. In order to validate the method, we also determined detailed analytical characteristics of five major fermentation end products including ethanol, acetic acid, isoamyl alcohol, ethyl-L-lactate and, acetoin. The method showed very low technical variability for the measurements of these metabolites in different matrices (<3% with an excellent accuracy (100% ± 5%, recovery (100% ± 10%, reproducibility and repeatability [Coefficient of variation (CV 1–10%]. To demonstrate the applicability of the method, we analysed different fermented products including balsamic vinegars, sourdough, distilled (whisky and non-distilled beverages (wine and beer.

  7. Rapid Quantification of Major Volatile Metabolites in Fermented Food and Beverages Using Gas Chromatography-Mass Spectrometry.

    Pinu, Farhana R; Villas-Boas, Silas G

    2017-07-26

    Here we present a method for the accurate quantification of major volatile metabolites found in different food and beverages, including ethanol, acetic acid and other aroma compounds, using gas chromatography coupled to mass spectrometry (GC-MS). The method is combined with a simple sample preparation procedure using sodium chloride and anhydrous ethyl acetate. The GC-MS analysis was accomplished within 4.75 min, and over 80 features were detected, of which 40 were positively identified using an in-house and a commercialmass spectrometry (MS) library. We determined different analytical parameters of these metabolites including the limit of detection (LOD), limit of quantitation (LOQ) and range of quantification. In order to validate the method, we also determined detailed analytical characteristics of five major fermentation end products including ethanol, acetic acid, isoamyl alcohol, ethyl-L-lactate and, acetoin. The method showed very low technical variability for the measurements of these metabolites in different matrices (<3%) with an excellent accuracy (100% ± 5%), recovery (100% ± 10%), reproducibility and repeatability [Coefficient of variation (CV) 1-10%)]. To demonstrate the applicability of the method, we analysed different fermented products including balsamic vinegars, sourdough, distilled (whisky) and non-distilled beverages (wine and beer).

  8. Metabolite Biometrics for the Differentiation of Individuals.

    Hair, Mindy E; Mathis, Adrianna I; Brunelle, Erica K; Halámková, Lenka; Halámek, Jan

    2018-04-17

    Sweat is a biological fluid present on the skin surface of every individual and is known to contain amino acids as well as other low molecular weight compounds. (1) Each individual is inherently different from one another based on certain factors including, but not limited to, his/her genetic makeup, environment, and lifestyle. As such, the biochemical composition of each person greatly differs. The concentrations of the biochemical content within an individual's sweat are largely controlled by metabolic processes within the body that fluctuate regularly based on attributes such as age, sex, and activity level. Therefore, the concentrations of these sweat components are person-specific and can be exploited, as presented here, to differentiate individuals based on trace amounts of sweat. For this concept, we analyzed three model compounds-lactate, urea, and glutamate. The average absorbance change from each compound in sweat was determined using three separate bioaffinity-based systems: lactate oxidase coupled with horseradish peroxidase (LOx-HRP), urease coupled with glutamate dehydrogenase (UR-GlDH), and glutamate dehydrogenase alone (GlDH). After optimization of a linear dependence for each assay to its respective analyte, analysis was performed on 50 mimicked sweat samples. Additionally, a collection and extraction method was developed and optimized by our group to evaluate authentic sweat samples from the skin surface of 25 individuals. A multivariate analysis of variance (MANOVA) test was performed to demonstrate that these three single-analyte enzymatic assays were effectively used to identify each person in both sample sets. This novel sweat analysis approach is capable of differentiating individuals, without the use of DNA, based on the collective responses from the chosen metabolic compounds in sweat. Applications for this newly developed, noninvasive analysis can include the field of forensic science in order to differentiate between individuals as well

  9. Analysis, occurrence, fate and risks of proton pump inhibitors, their metabolites and transformation products in aquatic environment: A review

    Kosma, Christina I.; Lambropoulou, Dimitra A.; Albanis, Triantafyllos A.

    2016-01-01

    Proton pump inhibitors (PPIs) which include omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole, are extensively used for the relief of gastro-intestinal disorders. Despite their high worldwide consumption, PPIs are extensively metabolized in human bodies and therefore are not regularly detected in monitoring studies. Very recently, however, it has been shown that some omeprazole metabolites may enter and are likely to persist in aquatic environment. Hence, to fully assess the environmental exposures and risks associated with PPIs, it is important to better understand and evaluate the fate and behavior not only of the parent compound but also of their metabolites and their transformation products arising from biotic and abiotic processes (hydrolysis, photodegradation, biodegradation etc.) in the environment. In this light, the purpose of this review is to summarize the present state of knowledge on the introduction and behavior of these chemicals in natural and engineering systems and highlight research needs and gaps. It draws attention to their transformation, the increase contamination by their metabolites/TPs in different environmental matrices and their potential adverse effects in the environment. Furthermore, existing research on analytical developments with respect to sample treatment, separation and detection of PPIs and their metabolites/TPs is provided. - Highlights: • Occurrence and fate of PPIs and their metabolites/TPs in the aquatic environment • Overview of the analytical methods applied, using LC-MS techniques • Omeprazole attended the most frequent analysis • Determination and behavior of omeprazole's metabolites/TPs in the environment • More ecotoxicological research is needed to assess the risks of PPIs.

  10. Analysis, occurrence, fate and risks of proton pump inhibitors, their metabolites and transformation products in aquatic environment: A review

    Kosma, Christina I. [Department of Chemistry, University of Ioannina, Ioannina, 45110 (Greece); Lambropoulou, Dimitra A., E-mail: dlambro@chem.auth.gr [Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124 (Greece); Albanis, Triantafyllos A. [Department of Chemistry, University of Ioannina, Ioannina, 45110 (Greece)

    2016-11-01

    Proton pump inhibitors (PPIs) which include omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole, are extensively used for the relief of gastro-intestinal disorders. Despite their high worldwide consumption, PPIs are extensively metabolized in human bodies and therefore are not regularly detected in monitoring studies. Very recently, however, it has been shown that some omeprazole metabolites may enter and are likely to persist in aquatic environment. Hence, to fully assess the environmental exposures and risks associated with PPIs, it is important to better understand and evaluate the fate and behavior not only of the parent compound but also of their metabolites and their transformation products arising from biotic and abiotic processes (hydrolysis, photodegradation, biodegradation etc.) in the environment. In this light, the purpose of this review is to summarize the present state of knowledge on the introduction and behavior of these chemicals in natural and engineering systems and highlight research needs and gaps. It draws attention to their transformation, the increase contamination by their metabolites/TPs in different environmental matrices and their potential adverse effects in the environment. Furthermore, existing research on analytical developments with respect to sample treatment, separation and detection of PPIs and their metabolites/TPs is provided. - Highlights: • Occurrence and fate of PPIs and their metabolites/TPs in the aquatic environment • Overview of the analytical methods applied, using LC-MS techniques • Omeprazole attended the most frequent analysis • Determination and behavior of omeprazole's metabolites/TPs in the environment • More ecotoxicological research is needed to assess the risks of PPIs.

  11. NUTRITIVE VALUE, In Vitro FERMENTATION AND SECONDARY METABOLITES OF WEEDS AND MAIZE STRAW USED FOR FEEDING DAIRY CATTLE

    Raquel Martínez-Loperena

    2011-03-01

    Full Text Available In the highlands of Central Mexico a surplus of different forages is observed during the rainy season particularly weeds, which grow in maize fields. Weeds are widely used by farmers to feed dairy cattle. The objective of the present work was to determine the nutritive value of weeds, their content of secondary metabolites, and their effect on in vitro fermentation kinetics when included (at different levels of inclusion in a diet based on maize straw. The present study was carried out in two regions of the Toluca valley from August to October 2007. A split plot design was used to evaluate the variables associated with the nutritive value and a randomized design was employed to evaluate the content of secondary metabolites in the different weed species. Significant differences (P

  12. Effect of competition on the production and activity of secondary metabolites in Aspergillus species

    Losada, L.; Ajayi, O.; Frisvad, Jens Christian

    2009-01-01

    and in the presence of other fungal species. However, it is not known whether secreted secondary metabolites provide a competitive advantage over other fungal species, or whether competition has any effect on the production of those metabolites. Here, we have performed co-cultivation competition assays among......Secondary metabolites are of intense interest to humans due to their pharmaceutical and/or toxic properties. Also, these metabolites are clinically relevant because of their importance in fungal pathogenesis. Aspergillus species secrete secondary metabolites when grown individually...... different species of Aspergillus to determine relative species fitness in culture, and to analyze the presence of possible antifungal activity of secondary metabolites in extracts. The results show that, for the most part, at 30C only one species is able to survive direct competition with a second species...

  13. Metabolite Profiles of Diabetes Risk

    Gerszten, Robert E.

    2013-01-01

    Metabolic diseases present particular difficulty for clinicians because they are often present for years before becoming clinically apparent. We investigated whether metabolite profiles can predict the development of diabetes in the Framingham Heart Study. Five branched-chain and aromatic amino acids had highly-significant associations with future diabetes, while a combination of three amino acids strongly predicted future diabetes by up to 12 years (>5-fold increased risk for individuals in ...

  14. Effect of pistachio consumption on the modulation of urinary gut microbiota-related metabolites in prediabetic subjects.

    Hernández-Alonso, Pablo; Cañueto, Daniel; Giardina, Simona; Salas-Salvadó, Jordi; Cañellas, Nicolau; Correig, Xavier; Bulló, Mònica

    2017-07-01

    The specific nutritional composition of nuts could affect different metabolic pathways involved in a broad range of metabolic diseases. We therefore investigated whether chronic consumption of pistachio nuts modifies the urine metabolome in prediabetic subjects. We designed a randomized crossover clinical trial in 39 prediabetic subjects. They consumed a pistachio-supplemented diet (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2-week wash-out. Nuclear magnetic resonance (NRM) was performed to determine changes in 24-h urine metabolites. Significant changes in urine metabolites according to the different intervention periods were found in uni- and multivariate analysis. Score plot of the first two components of the multilevel partial least squares discriminant analysis (ML-PLS-DA) showed a clear separation of the intervention periods. Three metabolites related with gut microbiota metabolism (i.e., hippurate, p-cresol sulfate and dimethylamine) were found decreased in PD compared with CD (Ppistachio consumption may modulate some urinary metabolites related to gut microbiota metabolism and the TCA cycle; all associated with metabolic derangements associated with insulin resistance and Type 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Some Metabolites Act as Second Messengers in Yeast Chronological Aging

    Karamat Mohammad

    2018-03-01

    Full Text Available The concentrations of some key metabolic intermediates play essential roles in regulating the longevity of the chronologically aging yeast Saccharomyces cerevisiae. These key metabolites are detected by certain ligand-specific protein sensors that respond to concentration changes of the key metabolites by altering the efficiencies of longevity-defining cellular processes. The concentrations of the key metabolites that affect yeast chronological aging are controlled spatially and temporally. Here, we analyze mechanisms through which the spatiotemporal dynamics of changes in the concentrations of the key metabolites influence yeast chronological lifespan. Our analysis indicates that a distinct set of metabolites can act as second messengers that define the pace of yeast chronological aging. Molecules that can operate both as intermediates of yeast metabolism and as second messengers of yeast chronological aging include reduced nicotinamide adenine dinucleotide phosphate (NADPH, glycerol, trehalose, hydrogen peroxide, amino acids, sphingolipids, spermidine, hydrogen sulfide, acetic acid, ethanol, free fatty acids, and diacylglycerol. We discuss several properties that these second messengers of yeast chronological aging have in common with second messengers of signal transduction. We outline how these second messengers of yeast chronological aging elicit changes in cell functionality and viability in response to changes in the nutrient, energy, stress, and proliferation status of the cell.

  16. Biodegradation of clofibric acid and identification of its metabolites

    Salgado, R. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); ESTS-IPS, Escola Superior de Tecnologia de Setubal do Instituto Politecnico de Setubal, Rua Vale de Chaves, Campus do IPS, Estefanilha, 2910-761 Setubal (Portugal); Oehmen, A. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Carvalho, G. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Instituto de Biologia Experimental e Tecnologica (IBET), Av. da Republica (EAN), 2784-505 Oeiras (Portugal); Noronha, J.P. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Reis, M.A.M., E-mail: amr@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal)

    2012-11-30

    Graphical abstract: Metabolites produced during clofibric acid biodegradation. Highlights: Black-Right-Pointing-Pointer Clofibric acid is biodegradable. Black-Right-Pointing-Pointer Mainly heterotrophic bacteria degraded the clofibric acid. Black-Right-Pointing-Pointer Metabolites of clofibric acid biodegradation were identified. Black-Right-Pointing-Pointer The metabolic pathway of clofibric acid biodegradation is proposed. - Abstract: Clofibric acid (CLF) is the pharmaceutically active metabolite of lipid regulators clofibrate, etofibrate and etofyllinclofibrate, and it is considered both environmentally persistent and refractory. This work studied the biotransformation of CLF in aerobic sequencing batch reactors (SBRs) with mixed microbial cultures, monitoring the efficiency of biotransformation of CLF and the production of metabolites. The maximum removal achieved was 51% biodegradation (initial CLF concentration = 2 mg L{sup -1}), where adsorption and abiotic removal mechanisms were shown to be negligible, showing that CLF is indeed biodegradable. Tests showed that the observed CLF biodegradation was mainly carried out by heterotrophic bacteria. Three main metabolites were identified, including {alpha}-hydroxyisobutyric acid, lactic acid and 4-chlorophenol. The latter is known to exhibit higher toxicity than the parent compound, but it did not accumulate in the SBRs. {alpha}-Hydroxyisobutyric acid and lactic acid accumulated for a period, where nitrite accumulation may have been responsible for inhibiting their degradation. A metabolic pathway for the biodegradation of CLF is proposed in this study.

  17. Biodegradation of clofibric acid and identification of its metabolites

    Salgado, R.; Oehmen, A.; Carvalho, G.; Noronha, J.P.; Reis, M.A.M.

    2012-01-01

    Graphical abstract: Metabolites produced during clofibric acid biodegradation. Highlights: ► Clofibric acid is biodegradable. ► Mainly heterotrophic bacteria degraded the clofibric acid. ► Metabolites of clofibric acid biodegradation were identified. ► The metabolic pathway of clofibric acid biodegradation is proposed. - Abstract: Clofibric acid (CLF) is the pharmaceutically active metabolite of lipid regulators clofibrate, etofibrate and etofyllinclofibrate, and it is considered both environmentally persistent and refractory. This work studied the biotransformation of CLF in aerobic sequencing batch reactors (SBRs) with mixed microbial cultures, monitoring the efficiency of biotransformation of CLF and the production of metabolites. The maximum removal achieved was 51% biodegradation (initial CLF concentration = 2 mg L −1 ), where adsorption and abiotic removal mechanisms were shown to be negligible, showing that CLF is indeed biodegradable. Tests showed that the observed CLF biodegradation was mainly carried out by heterotrophic bacteria. Three main metabolites were identified, including α-hydroxyisobutyric acid, lactic acid and 4-chlorophenol. The latter is known to exhibit higher toxicity than the parent compound, but it did not accumulate in the SBRs. α-Hydroxyisobutyric acid and lactic acid accumulated for a period, where nitrite accumulation may have been responsible for inhibiting their degradation. A metabolic pathway for the biodegradation of CLF is proposed in this study.

  18. Fetal Serum Metabolites Are Independently Associated with Gestational Diabetes Mellitus

    Yong-Ping Lu

    2018-01-01

    Full Text Available Background/Aims: Gestational diabetes (GDM might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. Methods: At the time of birth, serum samples from mothers and newborns (cord blood samples were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. Results: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32: 1 and proline still showed an independent association with GDM. Conclusions: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal serum metabolites and maternal GDM. Our findings might suggest a potential effect of the fetal metabolome on maternal GDM.

  19. Genomics-guided discovery of secondary metabolites and their regulation in Pseudomonas protegens Pf-5

    Pseudomonas protegens strain Pf-5 is a well-characterized rhizosphere bacterium known for its production of a diverse spectrum of secondary metabolites and its capacity to suppress plant diseases caused by soilborne fungal, bacterial and oomycete pathogens. Metabolites produced by Pf-5 include 2,4-...

  20. Improved profiling of estrogen metabolites by orbitrap LC/MS

    Li, Xingnan; Franke, Adrian A.

    2015-01-01

    Estrogen metabolites are important biomarkers to evaluate cancer risks and metabolic diseases. Due to their low physiological levels, a sensitive and accurate method is required, especially for the quantitation of unconjugated forms of endogenous steroids and their metabolites in humans. Here, we evaluated various derivatives of estrogens for improved analysis by orbitrap LC/MS in human serum samples. A new chemical derivatization reagent was applied modifying phenolic steroids to form 1-methylimidazole-2-sulfonyl adducts. The method significantly improves the sensitivity 2–100 fold by full scan MS and targeted selected ion monitoring MS over other derivatization methods including, dansyl, picolinoyl, and pyridine-3-sulfonyl products. PMID:25543003

  1. Population variability of phthalate metabolites and bisphenol A concentrations in spot urine samples versus 24- or 48-h collections.

    Christensen, Krista L Yorita; Lorber, Matthew; Koch, Holger M; Kolossa-Gehring, Marike; Morgan, Marsha K

    2012-11-01

    Human exposure to phthalates and bisphenol A (BPA) can be assessed through urinary biomonitoring, but methods to infer daily intakes assume that spot sample concentrations are comparable to daily average concentrations. We evaluate this assumption using human biomonitoring data from Germany and the United States (US). The German data comprised three regional studies with spot samples and one with full-day samples analyzed for phthalate metabolites. The US data included: a study on DEHP metabolites and BPA involving eight persons supplying all urine voids (from which 24-h samples were constructed) for seven consecutive days; NHANES spot sample data on DEHP metabolites and BPA; and a regional study of children with 48-h samples analyzed for BPA. In the German data, measures of central tendency differed, but spot and 24-h samples showed generally comparable variance including 95th percentiles and maxima equidistant from central tendency measures. In contrast, the US adult data from the eight-person study showed similar central tendencies for phthalate metabolites and BPA, but generally greater variability for the spot samples, including higher 95th percentiles and maxima. When comparing children's BPA concentrations in NHANES spot and 48-h samples, distributions showed similar central tendency and variability. Overall, spot urinary concentrations of DEHP metabolites and BPA have variability roughly comparable with corresponding 24-h average concentrations obtained from a comparable population, suggesting that spot samples can be used to characterize population distributions of intakes. However, the analysis also suggests that caution should be exercised when interpreting the high end of spot sample data sets.

  2. Detection of Volatile Metabolites of Garlic in Human Breast Milk

    Scheffler, Laura; Sauermann, Yvonne; Zeh, Gina; Hauf, Katharina; Heinlein, Anja; Sharapa, Constanze; Buettner, Andrea

    2016-01-01

    The odor of human breast milk after ingestion of raw garlic at food-relevant concentrations by breastfeeding mothers was investigated for the first time chemo-analytically using gas chromatography−mass spectrometry/olfactometry (GC-MS/O), as well as sensorially using a trained human sensory panel. Sensory evaluation revealed a clear garlic/cabbage-like odor that appeared in breast milk about 2.5 h after consumption of garlic. GC-MS/O analyses confirmed the occurrence of garlic-derived metabolites in breast milk, namely allyl methyl sulfide (AMS), allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO2). Of these, only AMS had a garlic-like odor whereas the other two metabolites were odorless. This demonstrates that the odor change in human milk is not related to a direct transfer of garlic odorants, as is currently believed, but rather derives from a single metabolite. The formation of these metabolites is not fully understood, but AMSO and AMSO2 are most likely formed by the oxidation of AMS in the human body. The excretion rates of these metabolites into breast milk were strongly time-dependent with large inter-individual differences. PMID:27275838

  3. Bioactive secondary metabolites from marine microbes for drug discovery.

    Nikapitiya, Chamilani

    2012-01-01

    The isolation and extraction of novel bioactive secondary metabolites from marine microorganisms have a biomedical potential for future drug discovery as the oceans cover 70% of the planet's surface and life on earth originates from sea. Wide range of novel bioactive secondary metabolites exhibiting pharmacodynamic properties has been isolated from marine microorganisms and many to be discovered. The compounds isolated from marine organisms (macro and micro) are important in their natural form and also as templates for synthetic modifications for the treatments for variety of deadly to minor diseases. Many technical issues are yet to overcome before wide-scale bioprospecting of marine microorganisms becomes a reality. This chapter focuses on some novel secondary metabolites having antitumor, antivirus, enzyme inhibitor, and other bioactive properties identified and isolated from marine microorganisms including bacteria, actinomycetes, fungi, and cyanobacteria, which could serve as potentials for drug discovery after their clinical trials. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. MSD-MAP: A Network-Based Systems Biology Platform for Predicting Disease-Metabolite Links.

    Wathieu, Henri; Issa, Naiem T; Mohandoss, Manisha; Byers, Stephen W; Dakshanamurthy, Sivanesan

    2017-01-01

    Cancer-associated metabolites result from cell-wide mechanisms of dysregulation. The field of metabolomics has sought to identify these aberrant metabolites as disease biomarkers, clues to understanding disease mechanisms, or even as therapeutic agents. This study was undertaken to reliably predict metabolites associated with colorectal, esophageal, and prostate cancers. Metabolite and disease biological action networks were compared in a computational platform called MSD-MAP (Multi Scale Disease-Metabolite Association Platform). Using differential gene expression analysis with patient-based RNAseq data from The Cancer Genome Atlas, genes up- or down-regulated in cancer compared to normal tissue were identified. Relational databases were used to map biological entities including pathways, functions, and interacting proteins, to those differential disease genes. Similar relational maps were built for metabolites, stemming from known and in silico predicted metabolite-protein associations. The hypergeometric test was used to find statistically significant relationships between disease and metabolite biological signatures at each tier, and metabolites were assessed for multi-scale association with each cancer. Metabolite networks were also directly associated with various other diseases using a disease functional perturbation database. Our platform recapitulated metabolite-disease links that have been empirically verified in the scientific literature, with network-based mapping of jointly-associated biological activity also matching known disease mechanisms. This was true for colorectal, esophageal, and prostate cancers, using metabolite action networks stemming from both predicted and known functional protein associations. By employing systems biology concepts, MSD-MAP reliably predicted known cancermetabolite links, and may serve as a predictive tool to streamline conventional metabolomic profiling methodologies. Copyright© Bentham Science Publishers; For any

  5. Enantioseparation of thalidomide and its hydroxylated metabolites using capillary electrophoresis with various cyclodextrins and their combinations as chiral buffer additives.

    Meyring, M; Chankvetadze, B; Blaschke, G

    1999-09-01

    The separation of thalidomide (TD) and its hydroxylated metabolites including their simultaneous enantioseparation was studied in capillary electrophoresis (CE) using four different randomly substituted charged cyclodextrin (CD) derivatives, the combinations of some of them with each other, and beta-CD. TD, as well as two metabolites recently found in incubations of human liver microsomes and human blood, 5-hydroxythalidomide (5-OH-TD) and one of the diastereomeric 5'-hydroxythalidomides (5'-OH-TD), are neutral compounds. Therefore, they were resolved using charged chiral selectors in CE. Two different separation modes (normal polarity and carrier mode) and two different capillaries (fused-silica and polyacrylamide-coated) were tested. Based on the behavior of the individual CDs, their designed combinations were selected in order to improve the separation selectivity and enantioselectivity. Under optimized conditions all three chiral compounds and their enantiomers were resolved simultaneously.

  6. Determination of two progestin metabolites (17α-hydroxypregnanolone and pregnanediol) and different classes of steroids (androgens, estrogens, corticosteroids, progestins) in rivers and wastewaters by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

    Zhang, Kun; Fent, Karl

    2018-01-01

    A highly sensitive and robust method was developed for routine analysis of two progestin metabolites, 17α-hydroxypregnanolone (17OH-Δ5P) and pregnanediol (PD), and 31 other natural and synthetic steroids and related metabolites (estrogens, androgens, corticosteroids, progestins) in river water, as well as influents and effluents of municipal wastewater treatment plants (WWTP) using HPLC-MS/MS combined with solid-phase extraction. For the various matrixes considered, the optimized method showed satisfactory performance with recoveries of 70-120% for most of target steroids. The method detection limits (MDLs) ranged from 0.01 to 3ng/L for river water, 0.02 to 10ng/L for WWTP effluents, and 0.1 to 40ng/L for influents with good linearity and reproducibility. The developed method was successfully applied for the analysis of steroids in rivers and WWTP influent and effluents. WWTP influents concentrations of 17OH-Δ5P and PD were 51-256ng/L and up to 400ng/L, respectively, along with androstenedione (concentration range: 38-220ng/L), testosterone (11-26ng/L), estrone (2.3-37ng/L), 17β-estradiol (N.D.-8.7ng/L), 17α-hydroxyprogesterone (N.D.-66ng/L), medroxyprogesterone acetate (N.D.-5.3ng/L), and progesterone (2.0-22ng/L), while only androstenedione (ADD), estrone (E1), and estriol (E3) were detected in effluent with concentrations ranging up to 1.7ng/L, 0.90ng/L and 0.8ng/L, respectively. In river water samples, only ADD and E1 were detected with concentrations up to 1.0ng/L and 0.91ng/L. Our procedure represents the first method for analyzing 17OH-Δ5P and PD in environmental samples along with a large series of steroids. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Impact of secondary metabolites and related enzymes in flax ...

    Changes in various physiological defenses including secondary metabolites, proline, total soluble protein and antioxidant enzymes were investigated in leaves and stems of 18 flax lines either resistant or susceptible to powdery mildew. The results showed that the total alkaloids content in flax stems was significantly ...

  8. Secondary metabolites from the unique bamboo, Melocanna baccifera.

    Govindan, Balaji; Johnson, Anil John; Viswanathan, Gayathri; Ramaswamy, Venkataraman; Koshy, Konnath Chacko; Baby, Sabulal

    2018-02-15

    Phytochemistry of fruits and leaves of the unique bamboo Melocanna baccifera resulted in the isolation of 27 secondary metabolites, including 4-Oxabicyclo[3.2.2]nona-1(7),5,8-triene and Verbacine. Biological activity studies of Verbacine revealed it as an inhibitor of acetylcholinesterase and as cytotoxic against C6 cancer cells.

  9. In vivo MRS metabolite quantification using genetic optimization

    Papakostas, G. A.; Karras, D. A.; Mertzios, B. G.; van Ormondt, D.; Graveron-Demilly, D.

    2011-11-01

    The in vivo quantification of metabolites' concentrations, revealed in magnetic resonance spectroscopy (MRS) spectra, constitutes the main subject under investigation in this work. Significant contributions based on artificial intelligence tools, such as neural networks (NNs), with good results have been presented lately but have shown several drawbacks, regarding their quantification accuracy under difficult conditions. A general framework that encounters the quantification procedure as an optimization problem, which is solved using a genetic algorithm (GA), is proposed in this paper. Two different lineshape models are examined, while two GA configurations are applied on artificial data. Moreover, the introduced quantification technique deals with metabolite peaks' overlapping, a considerably difficult situation occurring under real conditions. Appropriate experiments have proved the efficiency of the introduced methodology, in artificial MRS data, by establishing it as a generic metabolite quantification procedure.

  10. In vivo MRS metabolite quantification using genetic optimization

    Papakostas, G A; Mertzios, B G; Karras, D A; Van Ormondt, D; Graveron-Demilly, D

    2011-01-01

    The in vivo quantification of metabolites' concentrations, revealed in magnetic resonance spectroscopy (MRS) spectra, constitutes the main subject under investigation in this work. Significant contributions based on artificial intelligence tools, such as neural networks (NNs), with good results have been presented lately but have shown several drawbacks, regarding their quantification accuracy under difficult conditions. A general framework that encounters the quantification procedure as an optimization problem, which is solved using a genetic algorithm (GA), is proposed in this paper. Two different lineshape models are examined, while two GA configurations are applied on artificial data. Moreover, the introduced quantification technique deals with metabolite peaks' overlapping, a considerably difficult situation occurring under real conditions. Appropriate experiments have proved the efficiency of the introduced methodology, in artificial MRS data, by establishing it as a generic metabolite quantification procedure

  11. Engineering Microbial Metabolite Dynamics and Heterogeneity.

    Schmitz, Alexander C; Hartline, Christopher J; Zhang, Fuzhong

    2017-10-01

    As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Aspergillus Sydowii Marine Fungal Bloom in Australian Coastal Waters, Its Metabolites and Potential Impact on Symbiodinium Dinoflagellates

    Aiko Hayashi

    2016-03-01

    Full Text Available Dust has been widely recognised as an important source of nutrients in the marine environment and as a vector for transporting pathogenic microorganisms. Disturbingly, in the wake of a dust storm event along the eastern Australian coast line in 2009, the Continuous Plankton Recorder collected masses of fungal spores and mycelia (~150,000 spores/m3 forming a floating raft that covered a coastal area equivalent to 25 times the surface of England. Cultured A. sydowii strains exhibited varying metabolite profiles, but all produced sydonic acid, a chemotaxonomic marker for A. sydowii. The Australian marine fungal strains share major metabolites and display comparable metabolic diversity to Australian terrestrial strains and to strains pathogenic to Caribbean coral. Secondary colonisation of the rafts by other fungi, including strains of Cladosporium, Penicillium and other Aspergillus species with distinct secondary metabolite profiles, was also encountered. Our bioassays revealed that the dust-derived marine fungal extracts and known A. sydowii metabolites such as sydowic acid, sydowinol and sydowinin A adversely affect photophysiological performance (Fv/Fm of the coral reef dinoflagellate endosymbiont Symbiodinium. Different Symbiodinium clades exhibited varying sensitivities, mimicking sensitivity to coral bleaching phenomena. The detection of such large amounts of A. sydowii following this dust storm event has potential implications for the health of coral environments such as the Great Barrier Reef.

  13. Arsenate impact on the metabolite profile, production and arsenic loading of xylem sap in cucumbers (Cucumis sativus L.

    Kalle eUroic

    2012-04-01

    Full Text Available Arsenic uptake and translocation studies on xylem sap focus generally on the concentration and speciation of arsenic in the xylem. Arsenic impact on the xylem sap metabolite profile and its production during short term exposure has not been reported in detail. To investigate this, cucumbers were grown hydroponically and arsenate (AsV and DMA were used for plant treatment for 24 h. Total arsenic and arsenic speciation in xylem sap was analysed including a metabolite profiling under arsenate stress. Produced xylem sap was quantified and absolute arsenic transported was determined. AsV exposure has a significant impact on the metabolite profile of xylem sap. Four m/z values corresponding to four compounds were up regulated, one compound down regulated by arsenate exposure. The compound down regulated was identified to be isoleucine. Furthermore, arsenate has a significant influence on sap production, leading to a reduction of up to 96 % sap production when plants are exposed to 1000 μg kg-1 arsenate. No difference to control plants was observed when plants were exposed to 1000 μg kg-1 DMA. Absolute arsenic amount in xylem sap was the lowest at high arsenate exposure. These results show that AsV has a significant impact on the production and metabolite profile of xylem sap. The physiological importance of isoleucine needs further attention.

  14. Arsenate Impact on the Metabolite Profile, Production, and Arsenic Loading of Xylem Sap in Cucumbers (Cucumis sativus L.)

    Uroic, M. Kalle; Salaün, Pascal; Raab, Andrea; Feldmann, Jörg

    2012-01-01

    Arsenic uptake and translocation studies on xylem sap focus generally on the concentration and speciation of arsenic in the xylem. Arsenic impact on the xylem sap metabolite profile and its production during short term exposure has not been reported in detail. To investigate this, cucumbers were grown hydroponically and arsenate (AsV) and DMA were used for plant treatment for 24 h. Total arsenic and arsenic speciation in xylem sap was analyzed including a metabolite profiling under AsV stress. Produced xylem sap was quantified and absolute arsenic transported was determined. AsV exposure had a significant impact on the metabolite profile of xylem sap. Four m/z values corresponding to four compounds were up-regulated, one compound down-regulated by AsV exposure. The compound down-regulated was identified to be isoleucine. Furthermore, AsV exposure had a significant influence on sap production, leading to a reduction of up to 96% sap production when plants were exposed to 1000 μg kg−1 AsV. No difference to control plants was observed when plants were exposed to 1000 μg kg−1 DMA. Absolute arsenic amount in xylem sap was the lowest at high AsV exposure. These results show that AsV has a significant impact on the production and metabolite profile of xylem sap. The physiological importance of isoleucine needs further attention. PMID:22536187

  15. Impact of metal stress on the production of secondary metabolites in Pteris vittata L. and associated rhizosphere bacterial communities.

    Pham, Hoang Nam; Michalet, Serge; Bodillis, Josselin; Nguyen, Tien Dat; Nguyen, Thi Kieu Oanh; Le, Thi Phuong Quynh; Haddad, Mohamed; Nazaret, Sylvie; Dijoux-Franca, Marie-Geneviève

    2017-07-01

    Plants adapt to metal stress by modifying their metabolism including the production of secondary metabolites in plant tissues. Such changes may impact the diversity and functions of plant associated microbial communities. Our study aimed to evaluate the influence of metals on the secondary metabolism of plants and the indirect impact on rhizosphere bacterial communities. We then compared the secondary metabolites of the hyperaccumulator Pteris vittata L. collected from a contaminated mining site to a non-contaminated site in Vietnam and identified the discriminant metabolites. Our data showed a significant increase in chlorogenic acid derivatives and A-type procyanidin in plant roots at the contaminated site. We hypothesized that the intensive production of these compounds could be part of the antioxidant defense mechanism in response to metals. In parallel, the structure and diversity of bulk soil and rhizosphere communities was studied using high-throughput sequencing. The results showed strong differences in bacterial composition, characterized by the dominance of Proteobacteria and Nitrospira in the contaminated bulk soil, and the enrichment of some potential human pathogens, i.e., Acinetobacter, Mycobacterium, and Cupriavidus in P. vittata's rhizosphere at the mining site. Overall, metal pollution modified the production of P. vittata secondary metabolites and altered the diversity and structure of bacterial communities. Further investigations are needed to understand whether the plant recruits specific bacteria to adapt to metal stress.

  16. Analysis, occurrence, fate and risks of proton pump inhibitors, their metabolites and transformation products in aquatic environment: A review.

    Kosma, Christina I; Lambropoulou, Dimitra A; Albanis, Triantafyllos A

    2016-11-01

    Proton pump inhibitors (PPIs) which include omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole, are extensively used for the relief of gastro-intestinal disorders. Despite their high worldwide consumption, PPIs are extensively metabolized in human bodies and therefore are not regularly detected in monitoring studies. Very recently, however, it has been shown that some omeprazole metabolites may enter and are likely to persist in aquatic environment. Hence, to fully assess the environmental exposures and risks associated with PPIs, it is important to better understand and evaluate the fate and behavior not only of the parent compound but also of their metabolites and their transformation products arising from biotic and abiotic processes (hydrolysis, photodegradation, biodegradation etc.) in the environment. In this light, the purpose of this review is to summarize the present state of knowledge on the introduction and behavior of these chemicals in natural and engineering systems and highlight research needs and gaps. It draws attention to their transformation, the increase contamination by their metabolites/TPs in different environmental matrices and their potential adverse effects in the environment. Furthermore, existing research on analytical developments with respect to sample treatment, separation and detection of PPIs and their metabolites/TPs is provided. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. In vivo biochemistry: quantifying ion and metabolite levels in individual cells or cultures of yeast.

    Bermejo, Clara; Ewald, Jennifer C; Lanquar, Viviane; Jones, Alexander M; Frommer, Wolf B

    2011-08-15

    Over the past decade, we have learned that cellular processes, including signalling and metabolism, are highly compartmentalized, and that relevant changes in metabolic state can occur at sub-second timescales. Moreover, we have learned that individual cells in populations, or as part of a tissue, exist in different states. If we want to understand metabolic processes and signalling better, it will be necessary to measure biochemical and biophysical responses of individual cells with high temporal and spatial resolution. Fluorescence imaging has revolutionized all aspects of biology since it has the potential to provide information on the cellular and subcellular distribution of ions and metabolites with sub-second time resolution. In the present review we summarize recent progress in quantifying ions and metabolites in populations of yeast cells as well as in individual yeast cells with the help of quantitative fluorescent indicators, namely FRET metabolite sensors. We discuss the opportunities and potential pitfalls and the controls that help preclude misinterpretation. © The Authors Journal compilation © 2011 Biochemical Society

  18. Metabolite modifications in Solanum lycopersicum roots and leaves ...

    During the treatment, Cd accumulated significantly in the roots compared to stems and leaves. Plant growth (root, stem and leaf) decreased when Cd concentration increased. The analysis of 1H-NMR spectra of polar extracts showed clear differences between metabolites amounts (soluble sugars, organic and amino acids) ...

  19. An evaluation of the use of blood metabolite concentrations as ...

    The aim of this study was to determine whether blood metabolite concentrations in free-ranging indigenous goats are sensitive to expected variations in nutrient supply, and whether they could be used to evaluate different kidding seasons at two locations subject to similar seasonal variations in terms of nutrient supply.

  20. Concentration of fecal corticosterone metabolites in dominant versus ...

    The objective of this work was to evaluate the concentration of fecal metabolites of corticosterone and to verify if there are differences between dominant and subordinate heifers. The feces of 18 buffalo heifers were collected in the estrous period, to quantify the corticosterone concentrations. The heifers were separated into ...

  1. Global metabolite analysis of yeast: evaluation of sample preparation methods

    Villas-Bôas, Silas Granato; Højer-Pedersen, Jesper; Åkesson, Mats Fredrik

    2005-01-01

    Sample preparation is considered one of the limiting steps in microbial metabolome analysis. Eukaryotes and prokaryotes behave very differently during the several steps of classical sample preparation methods for analysis of metabolites. Even within the eukaryote kingdom there is a vast diversity...

  2. Physiological Characteristics of Some Monoamine Metabolites in Cat Cerebrospinal Fluid

    Orešković, Darko; Sanković, Mauricio; Fröbea, Ana; Klarica, Marijan

    1995-01-01

    The concentrations of main metabolites of serotonin and dopamine, 5-hydroxyindoleacetic acid and homovanillic acid, respectively, were measured in cisternal cerebrospinal fluid of cats by high performance liquid chromatography with an electrochemical detector. Higher concentrations of homovanillic acid and a wide interindividual oscillation for both parameters have been found. However, samples collected at four different time intervals showed stabile intraindividual concentrations of the m...

  3. Structural elucidation of in vitro and in vivo metabolites of emodin in rats by LC -ESI-MS/MS

    Wang, D.; Zhu, Q.; Chen, G.; Liu, B.; Chen, L.

    2013-01-01

    Emodin is a widely occurring natural product and has been studied extensively for its varieties of pharmacological activity. In attempt to know more deeply about its metabolism, this paper investigated the metabolites of emodin in rats, including its in vitro conversion product by intestinal microflora and urinary metabolites. The detection of emodin metabolites was performed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) with negative ion mode. By comparing the changes of metabolites in molecular masses (delta M), product ions and retention times with those of the parent drug, six metabolites (8-O-methylemodin, omega-hydroxyemodin, x-hydroxyemodin, emodin glucuronide, hydroxyemodin glucuronide and emodin sulfate) were observed,and what is more, the metabolite hydroxyemodin glucuronide was first reported in this article. For some metabolites, identification of their precise structure needs to be confirmed by other techniques such as the 1H and 13C NMR. (author)

  4. The first insight into the metabolite profiling of grapes from three Vitis vinifera L. cultivars of two controlled appellation (DOC) regions.

    Teixeira, António; Martins, Viviana; Noronha, Henrique; Eiras-Dias, José; Gerós, Hernâni

    2014-03-10

    The characterization of the metabolites accumulated in the grapes of specific cultivars grown in different climates is of particular importance for viticulturists and enologists. In the present study, the metabolite profiling of grapes from the cultivars, Alvarinho, Arinto and Padeiro de Basto, of two Portuguese Controlled Denomination of Origin (DOC) regions (Vinho Verde and Lisboa) was investigated by gas chromatography-coupled time-of-flight mass spectrometry (GC-TOF-MS) and an amino acid analyzer. Primary metabolites, including sugars, organic acids and amino acids, and some secondary metabolites were identified. Tartaric and malic acids and free amino acids accumulated more in grapes from vines of the DOC region of Vinho Verde than DOC Lisboa, but a principal component analysis (PCA) plot showed that besides the DOC region, the grape cultivar also accounted for the variance in the relative abundance of metabolites. Grapes from the cultivar, Alvarinho, were particularly rich in malic acid and tartaric acids in both DOC regions, but sucrose accumulated more in the DOC region of Vinho Verde.

  5. The First Insight into the Metabolite Profiling of Grapes from Three Vitis vinifera L. Cultivars of Two Controlled Appellation (DOC Regions

    António Teixeira

    2014-03-01

    Full Text Available The characterization of the metabolites accumulated in the grapes of specific cultivars grown in different climates is of particular importance for viticulturists and enologists. In the present study, the metabolite profiling of grapes from the cultivars, Alvarinho, Arinto and Padeiro de Basto, of two Portuguese Controlled Denomination of Origin (DOC regions (Vinho Verde and Lisboa was investigated by gas chromatography-coupled time-of-flight mass spectrometry (GC-TOF-MS and an amino acid analyzer. Primary metabolites, including sugars, organic acids and amino acids, and some secondary metabolites were identified. Tartaric and malic acids and free amino acids accumulated more in grapes from vines of the DOC region of Vinho Verde than DOC Lisboa, but a principal component analysis (PCA plot showed that besides the DOC region, the grape cultivar also accounted for the variance in the relative abundance of metabolites. Grapes from the cultivar, Alvarinho, were particularly rich in malic acid and tartaric acids in both DOC regions, but sucrose accumulated more in the DOC region of Vinho Verde.

  6. Involvement of a volatile metabolite during phosphoramide mustard-induced ovotoxicity

    Madden, Jill A. [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Hoyer, Patricia B. [Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States); Devine, Patrick J. [INRS—Institut Armand-Frappier Research Centre, University of Quebec, Laval, QC H7V 1B7 (Canada); Keating, Aileen F., E-mail: akeating@iastate.edu [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States)

    2014-05-15

    The finite ovarian follicle reserve can be negatively impacted by exposure to chemicals including the anti-neoplastic agent, cyclophosphamide (CPA). CPA requires bioactivation to phosphoramide mustard (PM) to elicit its therapeutic effects however; in addition to being the tumor-targeting metabolite, PM is also ovotoxic. In addition, PM can break down to a cytotoxic, volatile metabolite, chloroethylaziridine (CEZ). The aim of this study was initially to characterize PM-induced ovotoxicity in growing follicles. Using PND4 Fisher 344 rats, ovaries were cultured for 4 days before being exposed once to PM (10 or 30 μM). Following eight additional days in culture, relative to control (1% DMSO), PM had no impact on primordial, small primary or large primary follicle number, but both PM concentrations induced secondary follicle depletion (P < 0.05). Interestingly, a reduction in follicle number in the control-treated ovaries was observed. Thus, the involvement of a volatile, cytotoxic PM metabolite (VC) in PM-induced ovotoxicity was explored in cultured rat ovaries, with control ovaries physically separated from PM-treated ovaries during culture. Direct PM (60 μM) exposure destroyed all stage follicles after 4 days (P < 0.05). VC from nearby wells depleted primordial follicles after 4 days (P < 0.05), temporarily reduced secondary follicle number after 2 days, and did not impact other stage follicles at any other time point. VC was determined to spontaneously liberate from PM, which could contribute to degradation of PM during storage. Taken together, this study demonstrates that PM and VC are ovotoxicants, with different follicular targets, and that the VC may be a major player during PM-induced ovotoxicity observed in cancer survivors. - Highlights: • PM depletes all stage ovarian follicles in a temporal pattern. • A volatile ovotoxic compound is liberated from PM. • The volatile metabolite depletes primordial follicles.

  7. Monitoring MDMA metabolites in urban wastewater as novel biomarkers of consumption.

    González-Mariño, Iria; Zuccato, Ettore; Santos, Miquel M; Castiglioni, Sara

    2017-05-15

    Consumption of 3,4-methylendioxymethamphetamine (MDMA) has been always estimated by measuring the parent substance through chemical analysis of wastewater. However, this may result in an overestimation of the use if the substance is directly disposed in sinks or toilets. Using specific urinary metabolites may overcome this limitation. This study investigated for the first time the suitability of a panel of MDMA metabolites as biomarkers of consumption, considering the specific criteria recently proposed, i.e. being detectable and stable in wastewater, being excreted in a known percentage in urine, and having human excretion as the sole source. A new analytical method was developed and validated for the extraction and analysis of MDMA and three of its main metabolites in wastewater. 24-h composite raw wastewater samples from three European cities were analysed and MDMA use was back-calculated. Results from single MDMA loads, 4-hydroxy-3-methoxymethamphetamine (HMMA) loads and from the sum of MDMA, HMMA and 4-hydroxy-3-methoxyamphetamine (HMA) loads were in line with the well-known recreational use of this drug: consumption was higher during the weekend in all cities. HMMA and HMA turned out to be suitable biomarkers of consumption; however, concentrations measured in wastewater did not resemble the expected pharmacokinetic profiles, quite likely due to the very limited information available on excretion profiles. Different options were tested to back-calculate MDMA use, including the sum of MDMA and its metabolites, to balance the biases associated with each single substance. Nevertheless, additional pharmacokinetic studies are urgently needed in order to get more accurate excretion rates and, therefore, improve the estimates of MDMA use. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. The microbiota is essential for the generation of black tea theaflavins-derived metabolites.

    Huadong Chen

    Full Text Available BACKGROUND: Theaflavins including theaflavin (TF, theaflavin-3-gallate (TF3G, theaflavin-3'-gallate (TF3'G, and theaflavin-3,3'-digallate (TFDG, are the most important bioactive polyphenols in black tea. Because of their poor systemic bioavailability, it is still unclear how these compounds can exert their biological functions. The objective of this study is to identify the microbial metabolites of theaflavins in mice and in humans. METHODS AND FINDINGS: In the present study, we gavaged specific pathogen free (SPF mice and germ free (GF mice with 200 mg/kg TFDG and identified TF, TF3G, TF3'G, and gallic acid as the major fecal metabolites of TFDG in SPF mice. These metabolites were absent in TFDG- gavaged GF mice. The microbial bioconversion of TFDG, TF3G, and TF3'G was also investigated in vitro using fecal slurries collected from three healthy human subjects. Our results indicate that TFDG is metabolized to TF, TF3G, TF3'G, gallic acid, and pyrogallol by human microbiota. Moreover, both TF3G and TF3'G are metabolized to TF, gallic acid, and pyrogallol by human microbiota. Importantly, we observed interindividual differences on the metabolism rate of gallic acid to pyrogallol among the three human subjects. In addition, we demonstrated that Lactobacillus plantarum 299v and Bacillus subtilis have the capacity to metabolize TFDG. CONCLUSIONS: The microbiota is important for the metabolism of theaflavins in both mice and humans. The in vivo functional impact of microbiota-generated theaflavins-derived metabolites is worthwhile of further study.

  9. Gene-metabolite profile integration to understand the cause of spaceflight induced immunodeficiency.

    Chakraborty, Nabarun; Cheema, Amrita; Gautam, Aarti; Donohue, Duncan; Hoke, Allison; Conley, Carolynn; Jett, Marti; Hammamieh, Rasha

    2018-01-01

    Spaceflight presents a spectrum of stresses very different from those associated with terrestrial conditions. Our previous study (BMC Genom. 15 : 659, 2014) integrated the expressions of mRNAs, microRNAs, and proteins and results indicated that microgravity induces an immunosuppressive state that can facilitate opportunistic pathogenic attack. However, the existing data are not sufficient for elucidating the molecular drivers of the given immunosuppressed state. To meet this knowledge gap, we focused on the metabolite profile of spaceflown human cells. Independent studies have attributed cellular energy deficiency as a major cause of compromised immunity of the host, and metabolites that are closely associated with energy production could be a robust signature of atypical energy fluctuation. Our protocol involved inoculation of human endothelial cells in cell culture modules in spaceflight and on the ground concurrently. Ten days later, the cells in space and on the ground were exposed to lipopolysaccharide (LPS), a ubiquitous membrane endotoxin of Gram-negative bacteria. Nucleic acids, proteins, and metabolites were collected 4 and 8 h post-LPS exposure. Untargeted profiling of metabolites was followed by targeted identification of amino acids and knowledge integration with gene expression profiles. Consistent with the past reports associating microgravity with increased energy expenditure, we identified several markers linked to energy deficiency, including various amino acids such as tryptophan, creatinine, dopamine, and glycine, and cofactors such as lactate and pyruvate. The present study revealed a molecular architecture linking energy metabolism and immunodeficiency in microgravity. The energy-deficient condition potentially cascaded into dysregulation of protein metabolism and impairment of host immunity. This project is limited by a small sample size. Although a strict statistical screening was carefully implemented, the present results further emphasize

  10. Protein and metabolite composition of xylem sap from field-grown soybeans (Glycine max).

    Krishnan, Hari B; Natarajan, Savithiry S; Bennett, John O; Sicher, Richard C

    2011-05-01

    The xylem, in addition to transporting water, nutrients and metabolites, is also involved in long-distance signaling in response to pathogens, symbionts and environmental stresses. Xylem sap has been shown to contain a number of proteins including metabolic enzymes, stress-related proteins, signal transduction proteins and putative transcription factors. Previous studies on xylem sap have mostly utilized plants grown in controlled environmental chambers. However, plants in the field are subjected to high light and to environmental stress that is not normally found in growth chambers. In this study, we have examined the protein and metabolite composition of xylem sap from field-grown cultivated soybean plants. One-dimensional gel electrophoresis of xylem sap from determinate, indeterminate, nodulating and non-nodulating soybean cultivars revealed similar protein profiles consisting of about 8-10 prominent polypeptides. Two-dimensional gel electrophoresis of soybean xylem sap resulted in the visualization of about 60 distinct protein spots. A total of 38 protein spots were identified using MALDI-TOF MS and LC-MS/MS. The most abundant proteins present in the xylem sap were identified as 31 and 28 kDa vegetative storage proteins. In addition, several proteins that are conserved among different plant species were also identified. Diurnal changes in the metabolite profile of xylem sap collected during a 24-h cycle revealed that asparagine and aspartate were the two predominant amino acids irrespective of the time collected. Pinitol (D-3-O-methyl-chiro-inositol) was the most abundant carbohydrate present. The possible roles of xylem sap proteins and metabolites as nutrient reserves for sink tissue and as an indicator of biotic stress are also discussed.

  11. The application of NMR-based milk metabolite analysis in milk authenticity identification.

    Li, Qiangqiang; Yu, Zunbo; Zhu, Dan; Meng, Xianghe; Pang, Xiumei; Liu, Yue; Frew, Russell; Chen, He; Chen, Gang

    2017-07-01

    Milk is an important food component in the human diet and is a target for fraud, including many unsafe practices. For example, the unscrupulous adulteration of soymilk into bovine and goat milk or of bovine milk into goat milk in order to gain profit without declaration is a health risk, as the adulterant source and sanitary history are unknown. A robust and fit-for-purpose technique is required to enforce market surveillance and hence protect consumer health. Nuclear magnetic resonance (NMR) is a powerful technique for characterization of food products based on measuring the profile of metabolites. In this study, 1D NMR in conjunction with multivariate chemometrics as well as 2D NMR was applied to differentiate milk types and to identify milk adulteration. Ten metabolites were found which differed among milk types, hence providing characteristic markers for identifying the milk. These metabolites were used to establish mathematical models for milk type differentiation. The limit of quantification (LOQ) of adulteration was 2% (v/v) for soymilk in bovine milk, 2% (v/v) for soymilk in goat milk and 5% (v/v) for bovine milk in goat milk, with relative standard deviation (RSD) less than 10%, which can meet the needs of daily inspection. The NMR method described here is effective for milk authenticity identification, and the study demonstrates that the NMR-based milk metabolite analysis approach provides a means of detecting adulteration at expected levels and can be used for dairy quality monitoring. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  12. Urinary Phthalate Metabolites Are Associated with Body Mass Index and Waist Circumference in Chinese School Children

    Wang, Hexing; Zhou, Ying; Tang, Chuanxi; He, Yanhong; Wu, Jingui; Chen, Yue; Jiang, Qingwu

    2013-01-01

    Background Lab studies have suggested that ubiquitous phthalate exposures are related to obesity, but relevant epidemiological studies are scarce, especially for children. Objective To investigate the association of phthalate exposures with body mass index (BMI) and waist circumference (WC) in Chinese school children. Methods A cross-sectional study was conducted in three primary and three middle schools randomly selected from Changning District of Shanghai City of China in 2011–2012. According to the physical examination data in October, 2011, 124 normal weight, 53 overweight, and 82 obese students 8–15 years of age were randomly chosen from these schools on the basis of BMI-based age- and sex-specific criterion. First morning urine was collected in January, 2012, and fourteen urine phthalate metabolites (free plus conjugated) were determined by ultra-performance liquid chromatography coupled to tandem mass spectrometry. Multiple linear regression was used to explore the associations between naturally log-transformed urine phthalate metabolites and BMI or WC. Results The urine specific gravity-corrected concentrations of nine urine phthalate metabolites and five molar sums were positively associated with BMI or WC in Chinese school children after adjustment for age and sex. However, when other urine phthalate metabolites were included in the models together with age and sex as covariables, most of these significant associations disappeared except for mono (2-ethylhexyl) phthalate (MEHP) and monoethyl phthalate (MEP). Additionally, some associations showed sex- or age-specific differences. Conclusions Some phthalate exposures were associated with BMI or WC in Chinese school children. Given the cross-sectional nature of this study and lack of some important obesity-related covariables, further studies are needed to confirm the associations. PMID:23437242

  13. Simultaneous analysis of gemfibrozil, morphine, and its two active metabolites in different mouse brain structures using solid-phase extraction with ultra-high performance liquid chromatography and tandem mass spectrometry with a deuterated internal standard.

    Yang, Zizhao; Wang, Lu; Xu, Mingcheng; Gu, Jingkai; Yu, Lushan; Zeng, Su

    2016-06-01

    A rapid and sensitive bioassay was established and validated to simultaneously determine gemfibrozil, morphine, morphine-3β-glucuronide, and morphine-6β-glucuronide in mouse cerebrum, epencephalon, and hippocampus based on ultra-high performance liquid chromatography and tandem mass spectrometry. The deuterated internal standard, M6G-d3, was mixed with the prepared samples at 10 ng/mL as the final concentration. The samples were transferred into the C18 solid-phase extraction columns with gradient elution for solid-phase extraction. The mobile phase consisted of methanol and 0.05% formic acid (pH 3.2). Multiple reaction monitoring has been applied to analyze gemfibrozil (m/z 249.0 → 121.0) in anion mode, and M6G-d3 (m/z 465.1 → 289.1), morphine (m/z 286.0 → 200.9), and M3G and M6G (m/z 462.1 → 286.1) in the positive ion mode. The method has a linear calibration range from 0.05 to 10 ng for gemfibrozil, morphine, and M3G and M6G with correlation coefficients >0.993. The lower limit of quantitation for all four analytes was 0.05 ng/mL, relative standard deviation of intra- and interday precision was less than 10.5%, and the relative error of accuracy was from -8.2 to 8.3% at low, medium, and high concentrations for all the analytes. In conclusion, gemfibrozil can influence the morphine antinociception after coronary heart disease induced chronic angina by the change in one of morphine metabolites', M3G, distribution in mouse brain. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Racial and ethnic variations in phthalate metabolite concentration changes across full-term pregnancies.

    James-Todd, Tamarra M; Meeker, John D; Huang, Tianyi; Hauser, Russ; Seely, Ellen W; Ferguson, Kelly K; Rich-Edwards, Janet W; McElrath, Thomas F

    2017-03-01

    Higher concentrations of certain phthalate metabolites are associated with adverse reproductive and pregnancy outcomes, as well as poor infant/child health outcomes. In non-pregnant populations, phthalate metabolite concentrations vary by race/ethnicity. Few studies have documented racial/ethnic differences between phthalate metabolite concentrations at multiple time points across the full-course of pregnancy. The objective of the study was to characterize the change in phthalate metabolite concentrations by race/ethnicity across multiple pregnancy time points. Women were participants in a prospectively collected pregnancy cohort who delivered at term (≥37 weeks) and had available urinary phthalate metabolite concentrations for ≥3 time points across full-term pregnancies (n=350 women). We assessed urinary concentrations of eight phthalate metabolites that were log-transformed and specific gravity-adjusted. We evaluated the potential racial/ethnic differences in phthalate metabolite concentrations at baseline (median 10 weeks gestation) using ANOVA and across pregnancy using linear mixed models to calculate the percent change and 95% confidence intervals adjusted for sociodemographic and lifestyle factors. Almost 30% of the population were non-Hispanic black or Hispanic. With the exception of mono-(3-carboxypropyl) (MCPP) and di-ethylhexyl phthalate (DEHP) metabolites, baseline levels of phthalate metabolites were significantly higher in non-whites (Pethnicity, mono-ethyl phthalate (MEP) and MCPP had significant percent changes across pregnancy. MEP was higher in Hispanics at baseline and decreased in mid-pregnancy but increased in late pregnancy for non-Hispanic blacks. MCPP was substantially higher in non-Hispanic blacks at baseline but decreased later in pregnancy. Across pregnancy, non-Hispanic black and Hispanic women had higher concentrations of certain phthalate metabolites. These differences may have implications for racial/ethnic differences in adverse

  15. Occurrence of Ochratoxins, Fumonisin B2 , Aflatoxins (B1 and B2 ), and Other Secondary Fungal Metabolites in Dried Date Palm Fruits from Egypt: A Mini-Survey.

    Abdallah, Mohamed F; Krska, Rudolf; Sulyok, Michael

    2018-02-01

    This study was conducted to investigate the natural co-occurrence of 295 fungal and bacterial metabolites in 28 samples of dried date palm fruits collected from different shops distributed in Assiut Governorate, Upper Egypt in 2016. Extraction and quantification of the target analytes were done using the "dilute and shoot" approach followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. In total, 30 toxic fungal metabolites were detected. Among these metabolites, 4 types of ochratoxins including ochratoxin type A and B were quantified in 3 samples (11%) with a contamination range from 1.48 to 6070 μg/kg for ochratoxin A and from 0.28 to 692 μg/kg for ochratoxin B. In addition, fumonisin B 2 was observed in 2 (7%) samples with contamination levels ranging from 4.99 to 16.2 μg/kg. The simultaneous detection of fumonisin B 2 in the same contaminated samples with ochratoxins indicates the fungal attack by Aspergillus niger species during storage. Only 1 sample was contaminated with aflatoxin B 1 (14.4 μg/kg) and B 2 (2.44 μg/kg). The highest maximum concentration (90400 μg/kg) was for kojic acid that contaminated 43% of the samples. To the best of the authors' knowledge, this is the first report of the natural co-occurrence of fumonisin B 2 and ochratoxin A and B in addition to a wide range of other fungal metabolites in date palm fruits. Mycotoxins are secondary metabolites produced by different fungi. These metabolites pose a potential risk on human health since they contaminate many food commodities. Among these, date palm fruits which are an integral part of diet in several countries. Therefore, detection of mycotoxins is a prerequisite to insure the safety of food. Here, different types of mycotoxins have been detected in levels that may have health hazard. © 2018 Institute of Food Technologists®.

  16. Correcting ligands, metabolites, and pathways

    Vriend Gert

    2006-11-01

    Full Text Available Abstract Background A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases, however, treat chemical structures more as illustrations than as a datafield in its own right. Lack of chemical accuracy impedes progress in the areas mentioned above. We present a database of metabolites called BioMeta that augments the existing pathway databases by explicitly assessing the validity, correctness, and completeness of chemical structure and reaction information. Description The main bulk of the data in BioMeta were obtained from the KEGG Ligand database. We developed a tool for chemical structure validation which assesses the chemical validity and stereochemical completeness of a molecule description. The validation tool was used to examine the compounds in BioMeta, showing that a relatively small number of compounds had an incorrect constitution (connectivity only, not considering stereochemistry and that a considerable number (about one third had incomplete or even incorrect stereochemistry. We made a large effort to correct the errors and to complete the structural descriptions. A total of 1468 structures were corrected and/or completed. We also established the reaction balance of the reactions in BioMeta and corrected 55% of the unbalanced (stoichiometrically incorrect reactions in an automatic procedure. The BioMeta database was implemented in PostgreSQL and provided with a web-based interface. Conclusion We demonstrate that the validation of metabolite structures and reactions is a feasible and worthwhile undertaking, and that the validation results can be used to trigger corrections and improvements to BioMeta, our metabolite database. BioMeta provides some tools for rational drug design, reaction searches, and

  17. Automated pathway and reaction prediction facilitates in silico identification of unknown metabolites in human cohort studies.

    Quell, Jan D; Römisch-Margl, Werner; Colombo, Marco; Krumsiek, Jan; Evans, Anne M; Mohney, Robert; Salomaa, Veikko; de Faire, Ulf; Groop, Leif C; Agakov, Felix; Looker, Helen C; McKeigue, Paul; Colhoun, Helen M; Kastenmüller, Gabi

    2017-12-15

    Identification of metabolites in non-targeted metabolomics continues to be a bottleneck in metabolomics studies in large human cohorts. Unidentified metabolites frequently emerge in the results of association studies linking metabolite levels to, for example, clinical phenotypes. For further analyses these unknown metabolites must be identified. Current approaches utilize chemical information, such as spectral details and fragmentation characteristics to determine components of unknown metabolites. Here, we propose a systems biology model exploiting the internal correlation structure of metabolite levels in combination with existing biochemical and genetic information to characterize properties of unknown molecules. Levels of 758 metabolites (439 known, 319 unknown) in human blood samples of 2279 subjects were measured using a non-targeted metabolomics platform (LC-MS and GC-MS). We reconstructed the structure of biochemical pathways that are imprinted in these metabolomics data by building an empirical network model based on 1040 significant partial correlations between metabolites. We further added associations of these metabolites to 134 genes from genome-wide association studies as well as reactions and functional relations to genes from the public database Recon 2 to the network model. From the local neighborhood in the network, we were able to predict the pathway annotation of 180 unknown metabolites. Furthermore, we classified 100 pairs of known and unknown and 45 pairs of unknown metabolites to 21 types of reactions based on their mass differences. As a proof of concept, we then looked further into the special case of predicted dehydrogenation reactions leading us to the selection of 39 candidate molecules for 5 unknown metabolites. Finally, we could verify 2 of those candidates by applying LC-MS analyses of commercially available candidate substances. The formerly unknown metabolites X-13891 and X-13069 were shown to be 2-dodecendioic acid and 9

  18. Extending metabolome coverage for untargeted metabolite profiling of adherent cultured hepatic cells.

    García-Cañaveras, Juan Carlos; López, Silvia; Castell, José Vicente; Donato, M Teresa; Lahoz, Agustín

    2016-02-01

    MS-based metabolite profiling of adherent mammalian cells comprises several challenging steps such as metabolism quenching, cell detachment, cell disruption, metabolome extraction, and metabolite measurement. In LC-MS, the final metabolome coverage is strongly determined by the separation technique and the MS conditions used. Human liver-derived cell line HepG2 was chosen as adherent mammalian cell model to evaluate the performance of several commonly used procedures in both sample processing and LC-MS analysis. In a first phase, metabolite extraction and sample analysis were optimized in a combined manner. To this end, the extraction abilities of five different solvents (or combinations) were assessed by comparing the number and the levels of the metabolites comprised in each extract. Three different chromatographic methods were selected for metabolites separation. A HILIC-based method which was set to specifically separate polar metabolites and two RP-based methods focused on lipidome and wide-ranging metabolite detection, respectively. With regard to metabolite measurement, a Q-ToF instrument operating in both ESI (+) and ESI (-) was used for unbiased extract analysis. Once metabolite extraction and analysis conditions were set up, the influence of cell harvesting on metabolome coverage was also evaluated. Therefore, different protocols for cell detachment (trypsinization or scraping) and metabolism quenching were compared. This study confirmed the inconvenience of trypsinization as a harvesting technique, and the importance of using complementary extraction solvents to extend metabolome coverage, minimizing interferences and maximizing detection, thanks to the use of dedicated analytical conditions through the combination of HILIC and RP separations. The proposed workflow allowed the detection of over 300 identified metabolites from highly polar compounds to a wide range of lipids.

  19. Neurochemical metabolites in prefrontal cortex in patients with mild/moderate levels in first-episode depression

    Sozeri-Varma G

    2013-08-01

    Full Text Available Gülfizar Sözeri-Varma,1 Nalan Kalkan-Oğuzhanoglu,1 Muharrem Efe,1 Yilmaz Kiroglu,2 Taçlan Duman11Department of Psychiatry, 2Department of Radiology, Faculty of Medicine, Pamukkale University, Denizli, TurkeyBackground: Previous studies have determined the neurochemical metabolite abnormalities in major depressive disorder (MDD. The results of studies are inconsistent. Severity of depression may relate to neurochemical metabolic changes. The aim of this study is to investigate neurochemical metabolite levels in the prefrontal cortex (PFC of patients with mild/moderate MDD.Methods: Twenty-one patients with mild MDD, 18 patients with moderate MDD, and 16 matched control subjects participated in the study. Patients had had their first episode. They had not taken treatment. The severity of depression was assessed by the Hamilton Rating Scale for Depression (HAM-D. Levels of N-acetyl aspartate (NAA, choline-containing compounds (Cho, and creatine-containing compounds (Cr were measured using proton magnetic resonance spectroscopy (1H-MRS at 1.5 T, with an 8-cm3 single voxel placed in the right PFC.Results: The moderate MDD patients had lower NAA/Cr levels than the control group. No differences were found in neurochemical metabolite levels between the mild MDD and control groups. No correlation was found between the patients’ neurochemical metabolite levels and HAM-D scores.Conclusion: Our findings suggest that NAA/Cr levels are low in moderate-level MDD in the PFC. Neurochemical metabolite levels did not change in mild depressive disorder. Our results suggest that the severity of depression may affect neuronal function and viability. Studies are needed to confirm this finding, including studies on severely depressive patients.Keywords: major depressive disorder, magnetic resonance spectroscopy, N-acetyl aspartate, creatine, choline

  20. Cerebrospinal Fluid Levels of Monoamine Metabolites in the Epileptic Baboon

    Szabó, C. Ákos; Patel, Mayuri; Uteshev, Victor V.

    2016-01-01

    The baboon represents a natural model for genetic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). In this retrospective study, cerebrospinal fluid (CSF) monoamine metabolites and scalp electroencephalography (EEG) were evaluated in 263 baboons of a pedigreed colony. CSF monoamine abnormalities have been linked to reduced seizure thresholds, behavioral abnormalities and SUDEP in various animal models of epilepsy. The levels of 3-hydroxy-4-methoxyphenylglycol, 5-hydroxyindolacetic acid and homovanillic acid in CSF samples drawn from the cisterna magna were analyzed using high-performance liquid chromatography. These levels were compared between baboons with seizures (SZ), craniofacial trauma (CFT) and asymptomatic, control (CTL) baboons, between baboons with abnormal and normal EEG studies. We hypothesized that the CSF levels of major monoaminergic metabolites (i.e., dopamine, serotonin and norepinephrine) associate with the baboons’ electroclinical status and thus can be used as clinical biomarkers applicable to seizures/epilepsy. However, despite apparent differences in metabolite levels between the groups, usually lower in SZ and CFT baboons and in baboons with abnormal EEG studies, we did not find any statistically significant differences using a logistic regression analysis. Significant correlations between the metabolite levels, especially between 5-HIAA and HVA, were preserved in all electroclinical groups. While we were not able to demonstrate significant differences in monoamine metabolites in relation to seizures or EEG markers of epilepsy, we cannot exclude the monoaminergic system as a potential source of pathogenesis in epilepsy and SUDEP. A prospective study evaluating serial CSF monoamine levels in baboons with recently witnessed seizures, and evaluation of abnormal expression and function of monoaminergic receptors and transporters within epilepsy-related brain regions, may impact the electroclinical status. PMID:26924854

  1. Duodenal L cell density correlates with features of metabolic syndrome and plasma metabolites

    Annieke C G van Baar

    2018-05-01

    Full Text Available Background: Enteroendocrine cells are essential for the regulation of glucose metabolism, but it is unknown whether they are associated with clinical features of metabolic syndrome (MetS and fasting plasma metabolites. Objective: We aimed to identify fasting plasma metabolites that associate with duodenal L cell, K cell and delta cell densities in subjects with MetS with ranging levels of insulin resistance. Research design and methods: In this cross-sectional study, we evaluated L, K and delta cell density in duodenal biopsies from treatment-naïve males with MetS using machine-learning methodology. Results: We identified specific clinical biomarkers and plasma metabolites associated with L cell and delta cell density. L cell density was associated with increased plasma metabolite levels including symmetrical dimethylarginine, 3-aminoisobutyric acid, kynurenine and glycine. In turn, these L cell-linked fasting plasma metabolites correlated with clinical features of MetS. Conclusions: Our results indicate a link between duodenal L cells, plasma metabolites and clinical characteristics of MetS. We conclude that duodenal L cells associate with plasma metabolites that have been implicated in human glucose metabolism homeostasis. Disentangling the causal relation between L cells and these metabolites might help to improve the (small intestinal-driven pathophysiology behind insulin resistance in human obesity.

  2. The secondary metabolite bioinformatics portal

    Weber, Tilmann; Kim, Hyun Uk

    2016-01-01

    . In this context, this review gives a summary of tools and databases that currently are available to mine, identify and characterize natural product biosynthesis pathways and their producers based on ‘omics data. A web portal called Secondary Metabolite Bioinformatics Portal (SMBP at http...... analytical and chemical methods gave access to this group of compounds, nowadays genomics-based methods offer complementary approaches to find, identify and characterize such molecules. This paradigm shift also resulted in a high demand for computational tools to assist researchers in their daily work......Natural products are among the most important sources of lead molecules for drug discovery. With the development of affordable whole-genome sequencing technologies and other ‘omics tools, the field of natural products research is currently undergoing a shift in paradigms. While, for decades, mainly...

  3. Microsomal metabolism of trenbolone acetate metabolites ...

    Trenbolone acetate (TBA) is a synthetic growth promoter widely used in animal agriculture, and its metabolites are suspected endocrine disrupting compounds in agriculturally impacted receiving waters. However, beyond the three widely recognized TBA metabolites (17-trenbolone, 17-trenbolone and trendione), little is known about other metabolites formed in vivo and subsequently discharged into the environment, with some evidence suggesting these unknown metabolites comprise a majority of the TBA mass dosed to the animal. Here, we explored the metabolism of the three known TBA metabolites using rat liver microsome studies. All TBA metabolites are transformed into a complex mixture of monohydroxylated products. Based on product characterization, the majority are more polar than the parent metabolites but maintain their characteristic trienone backbone. A minor degree of interconversion between known metabolites was also observed, as were higher order hydroxylated products with a greater extent of reaction. Notably, the distribution and yield of products were generally comparable across a series of variably induced rat liver microsomes, as well as during additional studies with human and bovine liver microsomes. Bioassays conducted with mixtures of these transformation products suggest that androgen receptor (AR) binding activity is diminished as a result of the microsomal treatment, suggesting that the transformation products are generally less potent than

  4. SECONDARY METABOLITES FROM MARINE PENICILLIUM BREVICOMPACTUM

    ROVIROSA, JUANA; DIAZ-MARRERO, ANA; DARIAS, JOSE; PAINEMAL, KARIN; SAN MARTIN, AURELIO

    2006-01-01

    In a screening of Basidiomycete cultures isolated from marine invertebrates collected along the Chilean coastline for the production of antibiotics we identified a Penicillium brevicompactum strain as a producer of metabolites inhibiting the growth of bacteria and fungi. Bioactivity guided purification resulted in the isolation of four known metabolites. Their structures were elucidated by spectroscopic methods.

  5. Biochemical and secondary metabolites changes under moisture ...

    The study showed the importance of carbohydrate and nitrogen cycle related metabolites in mediating tolerance in cassava by affecting their phenotypic expression in the plant. Keywords: Hydrothermal stress, bio-chemicals, pigments, secondary metabolites, cassava. African Journal of Biotechnology, Vol 13(31) 3173-3186 ...

  6. MARSI: metabolite analogues for rational strain improvement

    Cardoso, João G. R.; Zeidan, Ahmad A; Jensen, Kristian

    2018-01-01

    reactions in an organism can be used to predict effects of MAs on cellular phenotypes. Here, we present the Metabolite Analogues for Rational Strain Improvement (MARSI) framework. MARSI provides a rational approach to strain improvement by searching for metabolites as targets instead of genes or reactions...

  7. Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells

    Peng Liu

    2018-05-01

    Full Text Available Sulforaphane (SFN exhibits chemopreventive effects through various mechanisms. However, few studies have focused on the bioactivities of its metabolites. Here, three metabolites derived from SFN were studied, known as sulforaphane glutathione, sulforaphane cysteine and sulforaphane-N-acetylcysteine. Their effects on cell viability, DNA damage, tumorigenicity, cell migration and adhesion were measured in human hepatoma HepG2 cells, and their anti-angiogenetic effects were determined in a 3D co-culture model of human umbilical vein endothelial cells (HUVECs and pericytes. Results indicated that these metabolites at high doses decreased cancer cell viability, induced DNA damage and inhibited motility, and impaired endothelial cell migration and tube formation. Additionally, pre-treatment with low doses of SFN metabolites protected against H2O2 challenge. The activation of the nuclear factor E2-related factor 2 (Nrf2-antioxidant response element (ARE pathway and the induction of intracellular glutathione (GSH played an important role in the cytoprotective effects of SFN metabolites. In conclusion, SFN metabolites exhibited similar cytotoxic and cytoprotective effects to SFN, which proves the necessity to study the mechanisms of action of not only SFN but also of its metabolites. Based on the different tissue distribution profiles of these metabolites, the most relevant chemical forms can be selected for targeted chemoprevention.

  8. Effects of short-term feeding of different sources of fatty acids in pre-mating diets on reproductive performance and blood metabolites of fat-tailed Iranian Afshari ewes.

    Mirzaei-Alamouti, H; Mohammadi, Z; Shahir, M H; Vazirigohar, M; Mansouryar, M

    2018-06-01

    The effects of dietary omega-3 and omega-6 fatty acids (FAs) in pre-mating diets on reproductive performances and metabolic status of ewes have not been well investigated. Therefore, this study investigated the effect of supplementing different source of FAs on different aspects of reproductive performance of fat-tailed Iranian Afshari ewes. Thirty-two cycling, multiparous Afshari ewes were divided into four groups and fed one of the isocaloric and isonitrogenous diets supplemented with Sunflower oil (SFO), Fish oil (FO), calcium salt of palm oil (CaPO) and/or an equal mixture of SFO + FO (SFOFO). One day after the start of the flushing, the estrous cycles of all ewes were synchronized using 12-day CIDRs. After detecting signs of estrous, all ewes were mated with rams for 2 days. The examination of ovarian follicles was done by a transrectal ultrasonography. After counting all visible follicles, they were classified into 3 classes based on their diameters: small (≤3 mm), medium (3-4 mm) and large (≥4 mm). The results showed that fat sources had no impact on dry matter intake (DMI) and body condition score (BCS) of animals (P > 0.05). Plasma glucose, total cholesterol, and albumin concentrations also were not significantly affected by supplemental fat sources (P > 0.05). Plasma insulin levels were higher at the end of the flushing (on the day of CIDR removal) and the day of mating for ewes on CaPO diet (P ewes fed FO (P ewes fed FO were higher 30 d after mating (11.02 ng/mL; P ewes fed FO or SFO diets (P ewes on FO diet (P ewes fed FO or SFO, respectively. In conclusion, supplementation of n-3 PUFA rich FA especially FO in pre-mating diets showed beneficial effects on some indices of reproductive performance of Afshari ewes including lambing and twining rate due to higher number of medium sized follicles and size of the ovulatory (large) follicles at the day of oestrus and increased plasma progesterone levels in pregnant ewes. Copyright © 2018

  9. Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study.

    Hauser, Russ; Gaskins, Audrey J; Souter, Irene; Smith, Kristen W; Dodge, Laura E; Ehrlich, Shelley; Meeker, John D; Calafat, Antonia M; Williams, Paige L

    2016-06-01

    Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes. We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART). This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004-2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman. In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, ΣDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of ΣDEHP were -0.19 (-0.29, -0.08) and -0.19 (-0.28, -0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites. Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy, and live birth following ART. Hauser R, Gaskins AJ, Souter I, Smith

  10. Prediction of metabolites of epoxidation reaction in MetaTox.

    Rudik, A V; Dmitriev, A V; Bezhentsev, V M; Lagunin, A A; Filimonov, D A; Poroikov, V V

    2017-10-01

    Biotransformation is a process of the chemical modifications which may lead to the reactive metabolites, in particular the epoxides. Epoxide reactive metabolites may cause the toxic effects. The prediction of such metabolites is important for drug development and ecotoxicology studies. Epoxides are formed by some oxidation reactions, usually catalysed by cytochromes P450, and represent a large class of three-membered cyclic ethers. Identification of molecules, which may be epoxidized, and indication of the specific location of epoxide functional group (which is called SOE - site of epoxidation) are important for prediction of epoxide metabolites. Datasets from 355 molecules and 615 reactions were created for training and validation. The prediction of SOE is based on a combination of LMNA (Labelled Multilevel Neighbourhood of Atom) descriptors and Bayesian-like algorithm implemented in PASS software and MetaTox web-service. The average invariant accuracy of prediction (AUC) calculated in leave-one-out and 20-fold cross-validation procedures is 0.9. Prediction of epoxide formation based on the created SAR model is included as the component of MetaTox web-service ( http://www.way2drug.com/mg ).

  11. The Synthesis of Active Metabolites and Analogues of Vitamin D3

    Yakhimovich, R. I.

    1980-04-01

    The literature date on the synthesis of the active metabolites and analogues of vitamin D3 (cholecalciferol), which play an important role in regulating the homeostatis of calcium in the organism, are reviewed. The bibliography includes 150 references.

  12. Metabolite secretion in microorganisms: the theory of metabolic overflow put to the test

    Pinu, Farhana R.; Granucci, Ninna; Daniell, James

    2018-01-01

    Introduction Microbial cells secrete many metabolites during growth, including important intermediates of the central carbon metabolism. This has not been taken into account by researchers when modeling microbial metabolism for metabolic engineering and systems biology studies. Materials and Meth...

  13. Association between Metabolite Profiles, Metabolic Syndrome and Obesity Status

    Bénédicte Allam-Ndoul

    2016-05-01

    Full Text Available Underlying mechanisms associated with the development of abnormal metabolic phenotypes among obese individuals are not yet clear. Our aim is to investigate differences in plasma metabolomics profiles between normal weight (NW and overweight/obese (Ov/Ob individuals, with or without metabolic syndrome (MetS. Mass spectrometry-based metabolite profiling was used to compare metabolite levels between each group. Three main principal components factors explaining a maximum of variance were retained. Factor 1’s (long chain glycerophospholipids metabolite profile score was higher among Ov/Ob with MetS than among Ov/Ob and NW participants without MetS. This factor was positively correlated to plasma total cholesterol (total-C and triglyceride levels in the three groups, to high density lipoprotein -cholesterol (HDL-C among participants without MetS. Factor 2 (amino acids and short to long chain acylcarnitine was positively correlated to HDL-C and negatively correlated with insulin levels among NW participants. Factor 3’s (medium chain acylcarnitines metabolite profile scores were higher among NW participants than among Ov/Ob with or without MetS. Factor 3 was negatively associated with glucose levels among the Ov/Ob with MetS. Factor 1 seems to be associated with a deteriorated metabolic profile that corresponds to obesity, whereas Factors 2 and 3 seem to be rather associated with a healthy metabolic profile.

  14. Comparison of Expression of Secondary Metabolite Biosynthesis Cluster Genes in Aspergillus flavus, A. parasiticus, and A. oryzae

    Ehrlich, Kenneth C.; Mack, Brian M.

    2014-01-01

    Fifty six secondary metabolite biosynthesis gene clusters are predicted to be in the Aspergillus flavus genome. In spite of this, the biosyntheses of only seven metabolites, including the aflatoxins, kojic acid, cyclopiazonic acid and aflatrem, have been assigned to a particular gene cluster. We used RNA-seq to compare expression of secondary metabolite genes in gene clusters for the closely related fungi A. parasiticus, A. oryzae, and A. flavus S and L sclerotial morphotypes. The data help ...

  15. Use of Vitamin D and Its Metabolites in Broiler Chicken Feed on Performance, Bone Parameters and Meat Quality

    Ana Flávia Quiles Marques Garcia

    2013-03-01

    Full Text Available The objective of this experiment was to assess the use of different vitamin D metabolites in the feed of broiler chickens and the effects of the metabolites on performance, bone parameters and meat quality. A total of 952 one-day-old male broiler chicks were distributed in a completely randomised design, with four treatments, seven replicates and 34 birds per experimental unit. The treatments consisted of four different sources of vitamin D included in the diet, D3, 25(OHD3, 1,25(OH2D3, and 1α(OHD3, providing 2000 and 1600 IU of vitamin D in the starter (1 to 21 d and growth phases (22 to 42 d, respectively. Mean weight, feed:gain and weight gain throughout the rearing period were less in animals fed 1α(OHD3 when compared with the other treatments (p0.05 for various bone parameters. Meat colour differed among the treatments (p>0.05. All of the metabolites used in the diets, with the exception of 1α(OHD3, can be used for broiler chickens without problems for performance and bone quality, however, some aspects of meat quality were affected.

  16. Importance of microbial pest control agents and their metabolites In relation to the natural microbiota on strawberry

    Jensen, Birgit; Knudsen, Inge M. B.; Jensen, Dan Funck

    control. A series of laboratory, growth chamber, semi-field and field experiments using strawberry as a model plant focusing on commercial microbial pest control products (MPCPs) or laboratory MPCAs expected to be on the market within 10 years served as our experimental platform. Initially the background...... level of indigenous microbial communities and their mycotoxins/metabolites on strawberries was examined in a field survey with 4 conventional and 4 organic growers with different production practise and geographic distribution. Culturable bacteria, yeasts and filamentous fungi were isolated...... and identified using both chemotaxonomy (fatty acids and metabolite profiling) and morphological characteristics. Microbial communities on strawberries were complex including potential plant pathogens, opportunistic human pathogens, plant disease biocontrol agents and mycotoxin producers. Bacteria were the most...

  17. Ketamine Metabolites for the Treatment of Depression and Pain | NCI Technology Transfer Center | TTC

    The National Institute on Aging, Laboratory of Clinical Investigation, is seeking parties interested in collaborative research to co-develop ketamine metabolites for the treatment of different forms of depression and for alleviating pain.

  18. Characterization of differential cocaine metabolism in mouse and rat through metabolomics-guided metabolite profiling.

    Yao, Dan; Shi, Xiaolei; Wang, Lei; Gosnell, Blake A; Chen, Chi

    2013-01-01

    Rodent animal models have been widely used for studying neurologic and toxicological events associated with cocaine abuse. It is known that the mouse is more susceptible to cocaine-induced hepatotoxicity (CIH) than the rat. However, the causes behind this species-dependent sensitivity to cocaine have not been elucidated. In this study, cocaine metabolism in the mouse and rat was characterized through LC-MS-based metabolomic analysis of urine samples and were further compared through calculating the relative abundance of individual cocaine metabolites. The results showed that the levels of benzoylecgonine, a major cocaine metabolite from ester hydrolysis, were comparable in the urine from the mice and rats treated with the same dose of cocaine. However, the levels of the cocaine metabolites from oxidative metabolism, such as N-hydroxybenzoylnorecgonine and hydroxybenzoylecgonine, differed dramatically between the two species, indicating species-dependent cocaine metabolism. Subsequent structural analysis through accurate mass analysis and LC-MS/MS fragmentation revealed that N-oxidation reactions, including N-demethylation and N-hydroxylation, are preferred metabolic routes in the mouse, while extensive aryl hydroxylation reactions occur in the rat. Through stable isotope tracing and in vitro enzyme reactions, a mouse-specific α-glucoside of N-hydroxybenzoylnorecgonine and a group of aryl hydroxy glucuronides high in the rat were identified and structurally elucidated. The differences in the in vivo oxidative metabolism of cocaine between the two rodent species were confirmed by the in vitro microsomal incubations. Chemical inhibition of P450 enzymes further revealed that different P450-mediated oxidative reactions in the ecgonine and benzoic acid moieties of cocaine contribute to the species-dependent biotransformation of cocaine.

  19. Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

    2014-01-01

    Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

  20. Drinking-water exposure to a mixture of nitrate and low-dose atrazine metabolites and small-for-gestational age (SGA) babies: a historic cohort study.

    Migeot, V; Albouy-Llaty, M; Carles, C; Limousi, F; Strezlec, S; Dupuis, A; Rabouan, S

    2013-04-01

    Groundwater, surface water and drinking water are contaminated by nitrates and atrazine, an herbicide. They are present as a mixture in drinking water and with their endocrine-disrupting activity, they may alter fetal growth. To study an association between drinking-water atrazine metabolites/nitrate mixture exposure and small-for-gestational-age(SGA). A historic cohort study based on birth records and drinking-water nitrate and pesticide measurements in Deux-Sèvres (France) between 2005 and 2009 was carried out. Exposure to drinking-water atrazine metabolites/nitrate mixture was divided into 6 classes according to the presence or absence of atrazine metabolites and to terciles of nitrate concentrations in each trimester of pregnancy. Regression analysis of SGA by mixture exposure at second trimester was subsequently conducted. We included 11,446 woman-neonate couples of whom 37.0% were exposed to pesticides, while 99.9% of the women were exposed to nitrates. Average nitrate concentration was from 0 to 63.30 mg/L. In the second trimester of pregnancy, the risk of SGA was different with mixture exposure when drinking-water atrazine metabolites, mainly 2 hydroxyatrazine and desethylatrazine, were present and nitrate dose exposure increased: compared to single first tercile of nitrate concentration exposure, single second tercile exposure OR was 1.74 CI 95% [1.10; 2.75] and atrazine metabolites presence in the third tercile of nitrate concentration exposure OR was 0.87 CI 95% [0.45;1.67]. It is possible that the association found at the second trimester of exposure with regard to birth weight may likewise be observed before birth, with regard to the estimated fetal weight, and that it might change in the event that the atrazine metabolites dose were higher or the nitrate dose lower. It would appear necessary to further explore the variability of effects. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  1. Brain Metabolites in Autonomic Regulatory Insular Sites in Heart Failure

    Woo, Mary A.; Yadav, Santosh K.; Macey, Paul M.; Fonarow, Gregg C.; Harper, Ronald M.; Kumar, Rajesh

    2014-01-01

    © 2014 Elsevier B.V. All rights reserved. Autonomic, pain, and neuropsychologic comorbidities appear in heart failure (HF), likely resulting from brain changes, indicated as loss of structural integrity and functional deficits. Among affected brain sites, the anterior insulae are prominent in serving major regulatory roles in many of the disrupted functions commonly seen in HF. Metabolite levels, including N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (MI), could ind...

  2. Characterization of macromolecular baseline of human brain using metabolite cycled semi-LASER at 9.4T.

    Giapitzakis, Ioannis-Angelos; Avdievich, Nikolai; Henning, Anke

    2018-08-01

    Macromolecular resonances (MM) arise mainly from cytosolic proteins and overlap with metabolites, influencing metabolite quantification. Macromolecules can serve as valuable biomarkers for diseases and pathologies. The objectives of this study were to characterize MM at 9.4T in the human brain (occipital and left parietal lobe) and to describe the RF coil setup used for MM acquisition in the two regions. An adiabatic inversion pulse was optimised for metabolite nulling at 9.4T using double inversion recovery and was combined for the first time with metabolite cycled (MC) semi-LASER and appropriate coil configuration. MM spectra (seven volunteers) from two brain locations were averaged and smoothed creating MM templates, which were then parametrized using simulated Voigt-shaped lines within LCModel. Quantification was performed on individual data sets, including corrections for different tissue composition and the T 1 and T 2 relaxation of water. Our coil configuration method resulted in efficient B1+ (>30 T/√kW) for both brain regions. The 15 MM components were detected and quantified in MM baselines of the two brain areas. No significant differences in concentration levels of MM between different regions were found. Two new MM peaks were reported (M7 & M8). Double inversion, which was combined with MC semi-LASER, enabled the acquisition of high spectral resolution MM spectra for both brain regions at 9.4T. The 15 MM components were detected and quantified. Two new MM peaks were reported for the first time (M7 & M8) and preliminarily assigned to β-methylene protons of aspartyl-groups. Magn Reson Med 80:462-473, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

  3. Stable isotope N-phosphoryl amino acids labeling for quantitative profiling of amine-containing metabolites using liquid chromatography mass spectrometry.

    Zhang, Shanshan; Shi, Jinwen; Shan, Changkai; Huang, Chengting; Wu, Yile; Ding, Rong; Xue, Yuhua; Liu, Wen; Zhou, Qiang; Zhao, Yufen; Xu, Pengxiang; Gao, Xiang

    2017-07-25

    Stable isotope chemical labeling liquid chromatography-mass spectrometry (LC-MS) is a powerful strategy for comprehensive metabolomics profiling, which can improve metabolites coverage and quantitative information for exploration of metabolic regulation in complex biological systems. In the current work, a novel stable isotope N-phosphoryl amino acids labeling strategy (SIPAL) has been successful developed for quantitative profiling of amine-containing metabolites in urine based on organic phosphorus chemistry. Two isotopic reagents, 16 O 2 - and 18 O 2 -N-diisopropyl phosphoryl l-alanine N-hydroxysuccinimide esters ( 16 O/ 18 O-DIPP-L-Ala-NHS), were firstly synthesized in high yields for labeling the amine-containing metabolites. The performance of SIPAL strategy was tested by analyzing standard samples including 20 l-amino acids, 10 d-amino acids and small peptides by using LC-MS. We observed highly efficient and selective labeling for SIPAL strategy within 15 min in a one-pot derivatization reaction under aqueous reaction conditions. The introduction of a neutral phosphate group at N-terminus can increase the proton affinity and overall hydrophobicity of targeted metabolites, leading to the better ionization efficiency in electrospray ionization processes and chromatographic separations of hydrophilic metabolites on reversed-phase column. Furthermore, the chiral metabolites, such as d-amino acids, could be converted to diastereomers after SIPAL and successfully separated on regular reversed-phase column. The chirality of labeled enantiomers can be determined by using different detection methods such as 31 P NMR, UV, and MS, demonstrating the potential application of SIPAL strategy. In addition, absolute quantification of chiral metabolites in biological samples can be easily achieved by using SIPAL strategy. For this purpose, urine samples collected from a healthy volunteer were analyzed by using LC-ESI-Orbitrap MS. Over 300 pairs of different amine

  4. Defensive Metabolites from Antarctic Invertebrates: Does Energetic Content Interfere with Feeding Repellence?

    Núñez-Pons, Laura; Avila, Conxita

    2014-01-01

    Many bioactive products from benthic invertebrates mediating ecological interactions have proved to reduce predation, but their mechanisms of action, and their molecular identities, are usually unknown. It was suggested, yet scarcely investigated, that nutritional quality interferes with defensive metabolites. This means that antifeedants would be less effective when combined with energetically rich prey, and that higher amounts of defensive compounds would be needed for predator avoidance. We evaluated the effects of five types of repellents obtained from Antarctic invertebrates, in combination with diets of different energetic values. The compounds came from soft corals, ascidians and hexactinellid sponges; they included wax esters, alkaloids, a meroterpenoid, a steroid, and the recently described organic acid, glassponsine. Feeding repellency was tested through preference assays by preparing diets (alginate pearls) combining different energetic content and inorganic material. Experimental diets contained various concentrations of each repellent product, and were offered along with control compound-free pearls, to the Antarctic omnivore amphipod Cheirimedon femoratus. Meridianin alkaloids were the most active repellents, and wax esters were the least active when combined with foods of distinct energetic content. Our data show that levels of repellency vary for each compound, and that they perform differently when mixed with distinct assay foods. The natural products that interacted the most with energetic content were those occurring in nature at higher concentrations. The bioactivity of the remaining metabolites tested was found to depend on a threshold concentration, enough to elicit feeding repellence, independently from nutritional quality. PMID:24962273

  5. Defensive Metabolites from Antarctic Invertebrates: Does Energetic Content Interfere with Feeding Repellence?

    Laura Núñez-Pons

    2014-06-01

    Full Text Available Many bioactive products from benthic invertebrates mediating ecological interactions have proved to reduce predation, but their mechanisms of action, and their molecular identities, are usually unknown. It was suggested, yet scarcely investigated, that nutritional quality interferes with defensive metabolites. This means that antifeedants would be less effective when combined with energetically rich prey, and that higher amounts of defensive compounds would be needed for predator avoidance. We evaluated the effects of five types of repellents obtained from Antarctic invertebrates, in combination with diets of different energetic values. The compounds came from soft corals, ascidians and hexactinellid sponges; they included wax esters, alkaloids, a meroterpenoid, a steroid, and the recently described organic acid, glassponsine. Feeding repellency was tested through preference assays by preparing diets (alginate pearls combining different energetic content and inorganic material. Experimental diets contained various concentrations of each repellent product, and were offered along with control compound-free pearls, to the Antarctic omnivore amphipod Cheirimedon femoratus. Meridianin alkaloids were the most active repellents, and wax esters were the least active when combined with foods of distinct energetic content. Our data show that levels of repellency vary for each compound, and that they perform differently when mixed with distinct assay foods. The natural products that interacted the most with energetic content were those occurring in nature at higher concentrations. The bioactivity of the remaining metabolites tested was found to depend on a threshold concentration, enough to elicit feeding repellence, independently from nutritional quality.

  6. Gut flora profiling and fecal metabolite composition of colorectal cancer patients and healthy individuals.

    Wang, Xiaoxue; Wang, Jianping; Rao, Benqiang; Deng, Li

    2017-06-01

    Colorectal cancer is one of the most common types of cancer in the world and its morbidity and mortality rates are increasing due to alterations to human lifestyle and dietary habits. The relationship between human gut flora and colorectal cancer has attracted increasing attention. In the present study, a metabolic fingerprinting technique that combined pyrosequencing with gas chromatography-mass spectrometry was utilized to compare the differences in gut flora profiling and fecal metabolites between healthy individuals and patients with colorectal cancer. The results demonstrated that there were no significant differences in the abundance and diversity of gut flora between healthy individuals and patients with colorectal cancer (P>0.05) and the dominant bacterial phyla present in the gut of both groups included Firmicutes , Bacteroidetes and Verrucomicrobia . At the bacterial strain/genus level, significant differences were observed in the relative abundance of 18 species of bacteria (Pflora profiling and metabolite composition. These findings suggest that gut flora disorder results in the alteration of bacterial metabolism, which may be associated with the pathogenesis of colorectal cancer. The results of the present study are useful as a foundation for further studies to elucidate a potential colorectal cancer diagnostic index and therapeutic targets.

  7. Liquid separation techniques coupled with mass spectrometry for chiral analysis of pharmaceuticals compounds and their metabolites in biological fluids.

    Erny, G L; Cifuentes, A

    2006-02-24

    Determination of the chiral composition of drugs is nowadays a key step in order to determine purity, activity, bioavailability, biodegradation, etc., of pharmaceuticals. In this article, works published for the last 5 years on the analysis of chiral drugs by liquid separation techniques coupled with mass spectrometry are reviewed. Namely, chiral analysis of pharmaceuticals including, e.g., antiinflammatories, antihypertensives, relaxants, etc., by liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry are included. The importance and interest of the analysis of the enantiomers of the active compound and its metabolites in different biological fluids (plasma, urine, cerebrospinal fluid, etc.) are also discussed.

  8. A bell pepper cultivar tolerant to chilling enhanced nitrogen allocation and stress-related metabolite accumulation in the roots in response to low root-zone temperature.

    Aidoo, Moses Kwame; Sherman, Tal; Lazarovitch, Naftali; Fait, Aaron; Rachmilevitch, Shimon

    2017-10-01

    Two bell pepper (Capsicum annuum) cultivars, differing in their response to chilling, were exposed to three levels of root-zone temperatures. Gas exchange, shoot and root phenology, and the pattern of change of the central metabolites and secondary metabolites caffeate and benzoate in the leaves and roots were profiled. Low root-zone temperature significantly inhibited gaseous exchange, with a greater effect on the sensitive commercial pepper hybrid (Canon) than on the new hybrid bred to enhance abiotic stress tolerance (S103). The latter was less affected by the treatment with respect to plant height, shoot dry mass, root maximum length, root projected area, number of root tips and root dry mass. More carbon was allocated to the leaves of S103 than nitrogen at 17°C, while in the roots at 17°C, more nitrogen was allocated and the ratio between C/N decreased. Metabolite profiling showed greater increase in the root than in the leaves. Leaf response between the two cultivars differed significantly. The roots accumulated stress-related metabolites including γ-aminobutyric acid (GABA), proline, galactinol and raffinose and at chilling (7°C) resulted in an increase of sugars in both cultivars. Our results suggest that the enhanced tolerance of S103 to root cold stress, reflected in the relative maintenance of shoot and root growth, is likely linked to a more effective regulation of photosynthesis facilitated by the induction of stress-related metabolism. © 2017 Scandinavian Plant Physiology Society.

  9. NMR Profiling of Metabolites in Larval and Juvenile Blue Mussels (Mytilus edulis) under Ambient and Low Salinity Conditions.

    May, Melissa A; Bishop, Karl D; Rawson, Paul D

    2017-07-06

    Blue mussels ( Mytilus edulis ) are ecologically and economically important marine invertebrates whose populations are at risk from climate change-associated variation in their environment, such as decreased coastal salinity. Blue mussels are osmoconfomers and use components of the metabolome (free amino acids) to help maintain osmotic balance and cellular function during low salinity exposure. However, little is known about the capacity of blue mussels during the planktonic larval stages to regulate metabolites during osmotic stress. Metabolite studies in species such as blue mussels can help improve our understanding of the species' physiology, as well as their capacity to respond to environmental stress. We used 1D ¹H nuclear magnetic resonance (NMR) and 2D total correlation spectroscopy (TOCSY) experiments to describe baseline metabolite pools in larval (veliger and pediveliger stages) and juvenile blue mussels (gill, mantle, and adductor tissues) under ambient conditions and to quantify changes in the abundance of common osmolytes in these stages during low salinity exposure. We found evidence for stage- and tissue-specific differences in the baseline metabolic profiles of blue mussels, which reflect variation in the function and morphology of each larval stage or tissue type of juveniles. These differences impacted the utilization of osmolytes during low salinity exposure, likely stemming from innate physiological variation. This study highlights the importance of foundational metabolomic studies that include multiple tissue types and developmental stages to adequately evaluate organismal responses to stress and better place these findings in a broader physiological context.

  10. Linking dynamic phenotyping with metabolite analysis to study natural variation in drought responses of Brachypodium distachyon

    Lorraine H.C. Fisher

    2016-11-01

    Full Text Available Drought is an important environmental stress limiting the productivity of major crops worldwide. Understanding drought tolerance and possible mechanisms for improving drought resistance is therefore a prerequisite to develop drought-tolerant crops that produce significant yields with reduced amounts of water. Brachypodium distachyon (Brachypodium is a key model species for cereals, forage grasses and energy grasses. In this study, initial screening of a Brachypodium germplasm collection consisting of 138 different ecotypes exposed to progressive drought, highlighted the natural variation in morphology, biomass accumulation and responses to drought stress. A core set of ten ecotypes, classified as being either tolerant, susceptible or intermediate, in response to drought stress, were exposed to mild or severe (respectively 15% and 0% soil water content drought stress and phenomic parameters linked to growth and colour changes were assessed. When exposed to severe drought stress, phenotypic data and metabolite profiling combined with multivariate analysis revealed a remarkable consistency in separating the selected ecotypes into their different pre-defined drought tolerance groups. Increases in several metabolites, including for the phytohormones jasmonic acid and salicylic acid, and TCA-cycle intermediates, were positively correlated with biomass yield and with reduced yellow pixel counts; suggestive of delayed senescence, both key target traits for crop improvement to drought stress. While metabolite analysis also separated ecotypes into the distinct tolerance groupings after exposure to mild drought stress, similar analysis of the phenotypic data failed to do so, confirming the value of metabolomics to investigate early responses to drought stress. The results highlight the potential of combining the analyses of phenotypic and metabolic responses to identify key mechanisms and markers associated with drought tolerance in both the Brachypodium

  11. Metabolite profiles of common Stemphylium species

    Andersen, Birgitte; Solfrizzo, Michelle; Visconti, Angelo

    1995-01-01

    and identified by their chromatographic and spectroscopic data (Rf values, reflectance spectrum, retention index and ultraviolet spectrum). These metabolites have been used for the chemotaxonomical characterization of Stemphylium botryosum, S. herbarum, S. alfalfae, S. majusculum, S. sarciniforme, S. vesicarium...

  12. METABOLITE CHARACTERIZATION IN SERUM SAMPLES FROM ...

    Preferred Customer

    Metabonomics offers a distinct advantage over other tests as it can be ... Metabolic profiling in heart disease has also been successfully ... resonances of the small metabolites showing fingerprints of serum metabolomic profile (Figure. 3).

  13. Secondary metabolites of cyanobacteria Nostoc sp.

    Kobayashi, Akio; Kajiyama, Shin-Ichiro

    1998-03-01

    Cyanobacteria attracted much attention recently because of their secondary metabolites with potent biological activities and unusual structures. This paper reviews some recent studies on the isolation, structural, elucidation and biological activities of the bioactive compounds from cyanobacteria Nostoc species.

  14. Metabolite Profiling of Red Sea Corals

    Ortega, Jovhana Alejandra

    2016-01-01

    that provide insights into the specific nature of the symbiosis. Our analysis also revealed aquatic pollutants, which suggests that metabolite profiling might be used for monitoring pollution levels and assessing environmental impact.

  15. Differential responses of human dendritic cells to metabolites from the oral/airway microbiome.

    Whiteson, K; Agrawal, S; Agrawal, A

    2017-06-01

    Small molecule metabolites that are produced or altered by host-associated microbial communities are emerging as significant immune response modifiers. However, there is a key gap in our knowledge of how oral microbial metabolites affect the immune response. Here, we examined the effects of metabolites from five bacterial strains found commonly in the oral/airway microbial communities of humans. The five strains, each isolated from cystic fibrosis patient sputum, were Pseudomonas aeruginosa FLR01 non-mucoid (P1) and FLR02 mucoid (P2) forms, Streptococcus pneumoniae (Sp), S. salivarius (Ss) and Rothia mucilaginosa (Rm). The effect of bacterial metabolites on dendritic cell (DC) activation, T cell priming and cytokine secretion was determined by exposing DCs to bacterial supernatants and individual metabolites of interest. Supernatants from P1 and P2 induced high levels of tumour necrosis factor (TNF)-α, interleukin (IL)-12 and IL-6 from DCs and primed T cells to secrete interferon (IFN)-γ, IL-22 compared to supernatants from Sp, Ss and Rm. Investigations into the composition of supernatants using gas chromatography-mass spectroscopy (GC-MS) revealed signature metabolites for each of the strains. Supernatants from P1 and P2 contained high levels of putrescine and glucose, while Sp and Ss contained high levels of 2,3-butanediol. The individual metabolites replicated the results of whole supernatants, although the magnitudes of their effects were reduced significantly. Altogether, our data demonstrate for the first time that the signature metabolites produced by different bacteria have different effects on DC functions. The identification of signature metabolites and their effects on the host immune system can provide mechanistic insights into diseases and may also be developed as biomarkers. © 2017 British Society for Immunology.

  16. The importance of drug metabolites synthesis: the case-study of cardiotoxic anticancer drugs.

    Hrynchak, Ivanna; Sousa, Emília; Pinto, Madalena; Costa, Vera Marisa

    2017-05-01

    Anticancer drugs are presently guarantying more survivors as a result of more powerful drugs or combinations of drugs used in therapy. Thus, it has become more crucial to study and overcome the side effects of these therapies. Cardiotoxicity is one of the most relevant side effects on the long-term cancer survivors, because of its high social and economic impact. Drug metabolism can result in active metabolites or toxic metabolites that can lead to important side effects. The metabolites of anticancer drugs are possible culprits of cardiotoxicity; however, the cardiotoxicity of many of the metabolites in several drug classes was not yet suitably studied so far. On the other hand, the use of prodrugs that are bioactivated through metabolism can be a good alternative to obtain more cardio safe drugs. In this review, the methods to obtain and study metabolites are summarized and their application to the study of a group of anticancer drugs with acknowledged cardiotoxicity is highlighted. In this group of drugs, doxorubicin (DOX, 1), mitoxantrone (MTX, 2), cyclophosphamide (CTX, 3) and 5-fluorouracil (5-FU, 4) are included, as well as the tyrosine kinase inhibitors, such as imatinib (5), sunitinib (6) and sorafenib (7). Only with the synthesis and purification of considerable amounts of the metabolites can reliable studies be performed, either in vitro or in vivo that allow accurate conclusions regarding the cardiotoxicity of anticancer drug metabolites and then pharmacological prevention or treatment of the cardiac side effects can be done.

  17. Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort

    Eline H. van Roekel

    2018-05-01

    Full Text Available Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit. Data were randomly divided into discovery (2/3 and replication (1/3 sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05 were further tested in the replication set (Bonferroni-corrected p-value < 0.05. Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions.

  18. Fate of cyanobacteria and their metabolites during water treatment sludge management processes.

    Ho, Lionel; Dreyfus, Jennifer; Boyer, Justine; Lowe, Todd; Bustamante, Heriberto; Duker, Phil; Meli, Tass; Newcombe, Gayle

    2012-05-01

    Cyanobacteria and their metabolites are an issue for water authorities; however, little is known as to the fate of coagulated cyanobacterial-laden sludge during waste management processes in water treatment plants (WTPs). This paper provides information on the cell integrity of Anabaena circinalis and Cylindrospermopsis raciborskii during: laboratory-scale coagulation/sedimentation processes; direct filtration and backwashing procedures; and cyanobacterial-laden sludge management practices. In addition, the metabolites produced by A. circinalis (geosmin and saxitoxins) and C. raciborskii (cylindrospermopsin) were investigated with respect to their release (and possible degradation) during each of the studied processes. Where sedimentation was used, coagulation effectively removed cyanobacteria (and intracellular metabolites) without any considerable exertion on coagulant demand. During direct filtration experiments, cyanobacteria released intracellular metabolites through a stagnation period, suggesting that more frequent backwashing of filters may be required to prevent floc build-up and metabolite release. Cyanobacteria appeared to be protected within the flocs, with minimal damage during backwashing of the filters. Within coagulant sludge, cyanobacteria released intracellular metabolites into the supernatant after 3d, even though cells remained viable up to 7d. This work has improved the understanding of cyanobacterial metabolite risks associated with management of backwash water and sludge and is likely to facilitate improvements at WTPs, including increased monitoring and the application of treatment strategies and operational practices, with respect to cyanobacterial-laden sludge and/or supernatant recycle management. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Study of Blood Metabolites Changes of Purebred Ghezel and Crossbred Arkhar Merinos × Ghezel Ewes during Late Pregnancy

    Leila Ahmadzadeh

    2016-11-01

    Full Text Available Introduction As pregnancy progresses, nutrient requirements of fetus and thereby ewe increases and some changes in the levels of blood metabolites including glucose, cholesterol and total protein may occur. During gestation, maternal tissues contribute to supplying energy that required for fetus resulting in changes of ewe blood metabolites; however other factors such as breed, age, feeding type of ewes during gestation and season may influence them. The study of blood metabolic changes in different phases of reproductive cycle can be helpful in detecting abnormal situations of ewes and preventing of metabolic disorders such as pregnancy toxemia and fatty liver syndrome. There is little information about the effect of different genotypes on blood metabolites and the occurrence of metabolic disorders in late pregnancy. Therefore the aim of the present study was to determine changes in blood metabolites of purebred Ghezel and ArkharMerino× Ghezel crossbred ewes during late pregnancy and effect of crossbreeding of Iranian purebred sheep with Merino sheep on metabolite level changes in these two groups of sheep and study of susceptibility to metabolic disease in late pregnancy. Materials and Methods In the present study, fifty five pregnant Ghezel ewes (36 singles and 15 twins and 34 pregnant crossbred ewes (20 singles and 14 twins were used. Estrus synchronization of all ewes was done using CIDR. CIDR were removed 14 days later and all ewes were injected PMSG intramuscularly and then mated with rams. All of the ewes were grazing in the pasture during pregnancy, but in the last two months of pregnancy, feeding of ewes was manually. Blood samples were collected by vacuum tubes during four hours after feeding from the jugular vein of ewes on 15 days prior to mating period and on days 90, 120 and 140 of the pregnancy. Blood samples were centrifuged with 4000 rpm for 12 minutes to extract blood serum and then sera were frozen in -20oC until further

  20. Urinary metabolites of tetrahydronorharman in the rat

    Greiner, B.; Rommelspacher, H.

    1982-01-01

    The metabolism of THN in the rat was studied in vivo by use of /sup 14/C-radiolabelled compound. Structures of major urinary metabolites were determined by exact spectral data. Their concentrations were measured by liquid scintillation counting. It was found that THN is submitted to endogenous transformation, and that the excreted derivatives form three groups of similar concentration: unchanged substance, hydroxylated/conjugated compounds, and aromatic metabolites. Structures and proposed pathways are summed in diagram.

  1. Urinary metabolites of tetrahydronorharman in the rat

    Greiner, B.; Rommelspacher, H.

    1982-01-01

    The metabolism of THN in the rat was studied in vivo by use of 14 C-radiolabelled compound. Structures of major urinary metabolites were determined by exact spectral data. Their concentrations were measured by liquid scintillation counting. It was found that THN is submitted to endogenous transformation, and that the excreted derivatives form three groups of similar concentration: unchanged substance, hydroxylated/conjugated compounds, and aromatic metabolites. Structures and proposed pathways are summed in diagram

  2. GPCR-Mediated Signaling of Metabolites

    Husted, Anna Sofie; Trauelsen, Mette; Rudenko, Olga

    2017-01-01

    microbiota target primarily enteroendocrine, neuronal, and immune cells in the lamina propria of the gut mucosa and the liver and, through these tissues, the rest of the body. In contrast, metabolites from the intermediary metabolism act mainly as metabolic stress-induced autocrine and paracrine signals...... and obesity. The concept of key metabolites as ligands for specific GPCRs has broadened our understanding of metabolic signaling significantly and provides a number of novel potential drug targets....

  3. Determination of flutamide and two major metabolites using HPLC-DAD and HPTLC methods.

    Abdelwahab, Nada S; Elshemy, Heba A H; Farid, Nehal F

    2018-01-25

    Flutamide is a potential antineoplastic drug classified as an anti-androgen. It is a therapy for men with advanced prostate cancer, administered orally after which it undergoes extensively first pass metabolism in the liver with the production of several metabolites. These metabolites are predominantly excreted in urine. One of the important metabolites in plasma is 4-nitro-3-(trifluoromethyl)phenylamine (Flu-1), while the main metabolite in urine is 2-amino-5-nitro-4-(trifluoromethyl)phenol (Flu-3). In this work the two metabolites, Flu-1 and Flu-3, have been synthesized, and then structural confirmation has been carried out by HNMR analysis. Efforts were exerted to develop chromatographic methods for resolving Flutamide and its metabolites with the use of acceptable solvents without affecting the efficiency of the methods. The drug along with its metabolites were quantitatively analyzed in pure form, human urine, and plasma samples using two chromatographic methods, HPTLC and HPLC-DAD methods. FDA guidelines for bio-analytical method validation were followed and USP recommendations were used for analytical method validation. Interference from excipients has been tested by application of the methods to pharmaceutical tablets. No significant difference was found between the proposed methods and the official one when they were statistically compared at p value of 0.05%.

  4. Phthalate metabolites in the European eel (Anguilla anguilla) from Mediterranean coastal lagoons.

    Fourgous, C; Chevreuil, M; Alliot, F; Amilhat, E; Faliex, E; Paris-Palacios, S; Teil, M J; Goutte, A

    2016-11-01

    The levels and fate of phthalate metabolites have been poorly evaluated in fish, despite their potential ecotoxicological impacts. The present study aims to characterize the levels of phthalate metabolites in muscle tissue of yellow eels (Anguilla anguilla) from two coastal Mediterranean lagoons, during three sampling periods. Nine phthalate metabolites were detected in >70% of the samples. Slightly higher levels of phthalate metabolites were detected in March and June compared to October, suggesting possible seasonal variations in environmental release and/or phthalate metabolization process by eels. The large sample size (N=117) made it possible to explore correlations between phthalate metabolites' levels and individual parameters, such as body length, age, body condition and hepatic histo-pathologies. Body length and estimated age poorly correlated with phthalate metabolites, suggesting that eels did not accumulate phthalates during growth, contrary to persistent compounds. Eels presented different grades of hepatic fibrosis and lipidosis. A negative correlation was found between the severity of these pathologies in the liver and the sum of phthalate metabolites levels, supporting the hypothesis that eels with damaged liver are less able to metabolize xenobiotics. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. New metabolites of hongdenafil, homosildenafil and hydroxyhomosildenafil.

    Yeo, Miseon; Park, Yujin; Lee, Heesang; Choe, Sanggil; Baek, Seung-Hoon; Kim, Hye Kyung; Pyo, Jae Sung

    2018-02-05

    Recently, illegal sildenafil analogues have emerged, causing serious social issues. In spite of the importance of sildenafil analogues, their metabolic profiles or clinical effects have not been reported yet. In this study, new metabolites of illegal sildenafil analogues such as hongdenafil, homosildenafil, and hydroxyhomosildenafil were determined using liquid chromatography quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS) and tandem mass spectrometry (LC-Q-TOF-MS/MS). To prepare metabolic samples, in vitro and in vivo studies were performed. For in vivo metabolites analysis, urine and feces samples of rats treated with sildenafil analogues were analyzed. For in vitro metabolites analysis, human liver microsomes incubated with sildenafil analogues were extracted and analyzed. All metabolites were characterized by LC-Q-TOF-MS and LC-Q-TOF-MS/MS. As a result, five, six, and seven metabolites were determined in hongdenafil, homosildenafil, and hydroxyhomosildenafil treated samples, respectively. These results could be applied to forensic science and other analytical fields. Moreover, these newly identified metabolites could be used as fundamental data to determine the side effect and toxicity of illegal sildenafil analogues. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Proteomics Coupled with Metabolite and Cell Wall Profiling Reveal Metabolic Processes of a Developing Rice Stem Internode

    Lin, Fan; Williams, Brad J.; Thangella, Padmavathi A. V.; Ladak, Adam; Schepmoes, Athena A.; Olivos, Hernando J.; Zhao, Kangmei; Callister, Stephen J.; Bartley, Laura E.

    2017-07-13

    Internodes of grass stems function in mechanical support, transport, and, in some species, are a major sink organ for carbon in the form of cell wall polymers. This study reports cell wall composition, proteomic and metabolite analyses of the rice elongating internode. Along eight segments of the second rice internode (internode II) at booting stage, cellulose, lignin, and xylose increase as a percentage of cell wall material from the younger to the older internode segments, indicating active cell wall synthesis. Liquid-chromatography tandem mass spectrometry (LC-MS/MS) of trypsin-digested peptides of size-fractionated proteins extracted from this internode at booting reveals 2547proteins with at least two unique peptides. The dataset includes many glycosyltransferases, acyltransferases, glycosyl hydrolases, cell wall-localized proteins, and protein kinases that have or may have functions in cell wall biosynthesis or remodeling. Phospho-enrichment of the internode II peptides identified 21 unique phosphopeptides belonging to 20 phosphoproteins including an LRR-III family receptor like kinase. GO over-representation and KEGG pathway analyses highlight the abundances of internode proteins involved in biosynthetic processes, especially the synthesis of secondary metabolites such as phenylpropanoids and flavonoids. LC-MS of hot methanol-extracted secondary metabolites from internode II at four stages (elongation, early mature, mature and post mature) indicates that secondary metabolites in stems are distinct from those of roots and leaves, and differ during stem maturation. This work fills a void of knowledge of proteomics and metabolomics data for grass stems, specifically for rice, and provides baseline knowledge for more detailed studies of cell wall synthesis and other biological processes during internode development, toward improving grass agronomic properties.

  7. Production of Metabolites as Bacterial Responses to the Marine Environment

    Pedro Fernandes

    2010-03-01

    Full Text Available Bacteria in marine environments are often under extreme conditions of e.g., pressure, temperature, salinity, and depletion of micronutrients, with survival and proliferation often depending on the ability to produce biologically active compounds. Some marine bacteria produce biosurfactants, which help to transport hydrophobic low water soluble substrates by increasing their bioavailability. However, other functions related to heavy metal binding, quorum sensing and biofilm formation have been described. In the case of metal ions, bacteria developed a strategy involving the release of binding agents to increase their bioavailability. In the particular case of the Fe3+ ion, which is almost insoluble in water, bacteria secrete siderophores that form soluble complexes with the ion, allowing the cells to uptake the iron required for cell functioning. Adaptive changes in the lipid composition of marine bacteria have been observed in response to environmental variations in pressure, temperature and salinity. Some fatty acids, including docosahexaenoic and eicosapentaenoic acids, have only been reported in prokaryotes in deep-sea bacteria. Cell membrane permeability can also be adapted to extreme environmental conditions by the production of hopanoids, which are pentacyclic triterpenoids that have a function similar to cholesterol in eukaryotes. Bacteria can also produce molecules that prevent the attachment, growth and/or survival of challenging organisms in competitive environments. The production of these compounds is particularly important in surface attached strains and in those in biofilms. The wide array of compounds produced by marine bacteria as an adaptive response to demanding conditions makes them suitable candidates for screening of compounds with commercially interesting biological functions. Biosurfactants produced by marine bacteria may be helpful to increase mass transfer in different industrial processes and in the bioremediation of

  8. Metabolite profiling during cold acclimation of Lolium perenne genotypes distinct in the level of frost tolerance.

    Bocian, Aleksandra; Zwierzykowski, Zbigniew; Rapacz, Marcin; Koczyk, Grzegorz; Ciesiołka, Danuta; Kosmala, Arkadiusz

    2015-11-01

    Abiotic stresses, including low temperature, can significantly reduce plant yielding. The knowledge on the molecular basis of stress tolerance could help to improve its level in species of relatively high importance to agriculture. Unfortunately, the complex research performed so far mainly on model species and also, to some extent, on cereals does not fully cover the demands of other agricultural plants of temperate climate, including forage grasses. Two Lolium perenne (perennial ryegrass) genotypes with contrasting levels of frost tolerance, the high frost tolerant (HFT) and the low frost tolerant (LFT) genotypes, were selected for comparative metabolomic research. The work focused on the analysis of leaf metabolite accumulation before and after seven separate time points of cold acclimation. Gas chromatography-mass spectrometry (GC/MS) was used to identify amino acids (alanine, proline, glycine, glutamic and aspartic acid, serine, lysine and asparagine), carbohydrates (fructose, glucose, sucrose, raffinose and trehalose) and their derivatives (mannitol, sorbitol and inositol) accumulated in leaves in low temperature. The observed differences in the level of frost tolerance between the analysed genotypes could be partially due to the time point of cold acclimation at which the accumulation level of crucial metabolite started to increase. In the HFT genotype, earlier accumulation was observed for proline and asparagine. The increased amounts of alanine, glutamic and aspartic acids, and asparagine during cold acclimation could be involved in the regulation of photosynthesis intensity in L. perenne. Among the analysed carbohydrates, only raffinose revealed a significant association with the acclimation process in this species.

  9. Fate of cyanobacteria and their metabolites during water treatment sludge management processes

    Ho, Lionel, E-mail: lionel.ho@sawater.com.au [Australian Water Quality Centre, SA Water Corporation, 250 Victoria Square, Adelaide, SA 5000 (Australia); Centre for Water Management and Reuse, University of South Australia, Mawson Lakes, SA 5095 (Australia); Dreyfus, Jennifer; Boyer, Justine; Lowe, Todd [Australian Water Quality Centre, SA Water Corporation, 250 Victoria Square, Adelaide, SA 5000 (Australia); Bustamante, Heriberto; Duker, Phil [Sydney Water, PO Box 399, Parramatta, NSW 2124 (Australia); Meli, Tass [TRILITY Pty Ltd, PO Box 86, Appin, NSW 2560 (Australia); Newcombe, Gayle [Australian Water Quality Centre, SA Water Corporation, 250 Victoria Square, Adelaide, SA 5000 (Australia); Centre for Water Management and Reuse, University of South Australia, Mawson Lakes, SA 5095 (Australia)

    2012-05-01

    Cyanobacteria and their metabolites are an issue for water authorities; however, little is known as to the fate of coagulated cyanobacterial-laden sludge during waste management processes in water treatment plants (WTPs). This paper provides information on the cell integrity of Anabaena circinalis and Cylindrospermopsis raciborskii during: laboratory-scale coagulation/sedimentation processes; direct filtration and backwashing procedures; and cyanobacterial-laden sludge management practices. In addition, the metabolites produced by A. circinalis (geosmin and saxitoxins) and C. raciborskii (cylindrospermopsin) were investigated with respect to their release (and possible degradation) during each of the studied processes. Where sedimentation was used, coagulation effectively removed cyanobacteria (and intracellular metabolites) without any considerable exertion on coagulant demand. During direct filtration experiments, cyanobacteria released intracellular metabolites through a stagnation period, suggesting that more frequent backwashing of filters may be required to prevent floc build-up and metabolite release. Cyanobacteria appeared to be protected within the flocs, with minimal damage during backwashing of the filters. Within coagulant sludge, cyanobacteria released intracellular metabolites into the supernatant after 3 d, even though cells remained viable up to 7 d. This work has improved the understanding of cyanobacterial metabolite risks associated with management of backwash water and sludge and is likely to facilitate improvements at WTPs, including increased monitoring and the application of treatment strategies and operational practices, with respect to cyanobacterial-laden sludge and/or supernatant recycle management. - Highlights: Black-Right-Pointing-Pointer Coagulation removed cyanobacteria without an additional exertion on coagulant demand. Black-Right-Pointing-Pointer During a stagnation period in direct filtration intracellular metabolites were

  10. Fate of cyanobacteria and their metabolites during water treatment sludge management processes

    Ho, Lionel; Dreyfus, Jennifer; Boyer, Justine; Lowe, Todd; Bustamante, Heriberto; Duker, Phil; Meli, Tass; Newcombe, Gayle

    2012-01-01

    Cyanobacteria and their metabolites are an issue for water authorities; however, little is known as to the fate of coagulated cyanobacterial-laden sludge during waste management processes in water treatment plants (WTPs). This paper provides information on the cell integrity of Anabaena circinalis and Cylindrospermopsis raciborskii during: laboratory-scale coagulation/sedimentation processes; direct filtration and backwashing procedures; and cyanobacterial-laden sludge management practices. In addition, the metabolites produced by A. circinalis (geosmin and saxitoxins) and C. raciborskii (cylindrospermopsin) were investigated with respect to their release (and possible degradation) during each of the studied processes. Where sedimentation was used, coagulation effectively removed cyanobacteria (and intracellular metabolites) without any considerable exertion on coagulant demand. During direct filtration experiments, cyanobacteria released intracellular metabolites through a stagnation period, suggesting that more frequent backwashing of filters may be required to prevent floc build-up and metabolite release. Cyanobacteria appeared to be protected within the flocs, with minimal damage during backwashing of the filters. Within coagulant sludge, cyanobacteria released intracellular metabolites into the supernatant after 3 d, even though cells remained viable up to 7 d. This work has improved the understanding of cyanobacterial metabolite risks associated with management of backwash water and sludge and is likely to facilitate improvements at WTPs, including increased monitoring and the application of treatment strategies and operational practices, with respect to cyanobacterial-laden sludge and/or supernatant recycle management. - Highlights: ► Coagulation removed cyanobacteria without an additional exertion on coagulant demand. ► During a stagnation period in direct filtration intracellular metabolites were released. ► Cyanobacterial cells were not damaged

  11. Dietary Metabolites and Chronic Kidney Disease

    Sho Hasegawa

    2017-04-01

    Full Text Available Dietary contents and their metabolites are closely related to chronic kidney disease (CKD progression. Advanced glycated end products (AGEs are a type of uremic toxin produced by glycation. AGE accumulation is not only the result of elevated glucose levels or reduced renal clearance capacity, but it also promotes CKD progression. Indoxyl sulfate, another uremic toxin derived from amino acid metabolism, accumulates as CKD progresses and induces tubulointerstitial fibrosis and glomerular sclerosis. Specific types of amino acids (d-serine or fatty acids (palmitate are reported to be closely associated with CKD progression. Promising therapeutic targets associated with nutrition include uremic toxin absorbents and inhibitors of AGEs or the receptor for AGEs (RAGE. Probiotics and prebiotics maintain gut flora balance and also prevent CKD progression by enhancing gut barriers and reducing uremic toxin formation. Nrf2 signaling not only ameliorates oxidative stress but also reduces elevated AGE levels. Bardoxolone methyl, an Nrf2 activator and NF-κB suppressor, has been tested as a therapeutic agent, but the phase 3 clinical trial was terminated owing to the high rate of cardiovascular events. However, a phase 2 trial has been initiated in Japan, and the preliminary analysis reveals promising results without an increase in cardiovascular events.

  12. Comparative pharmacokinetics of acetyl salicylic acid and its metabolites in children suffering from autoimmune diseases.

    Juárez Olguín, Hugo; Flores Pérez, Janett; Lares Asseff, Ismael; Loredo Abdalá, Arturo; Carbajal Rodríguez, Luis

    2004-01-01

    The aim of the present study was to compare the effect produced by juvenile rheumatoid arthritis (JRA) or rheumatic fever (RF) on the pharmacokinetics of acetyl salicylic acid (ASA) and its metabolites in children with autoimmune diseases (AD). A prospective, open labelled study was performed in 17 children with JRA and 17 with RF who received a single dose of 25 mg ASA/kg orally. The pharmacokinetics of ASA and its metabolites were determined. The blood and urine levels of each salicylate collected during 24 h were measured by HPLC. A group of 15 healthy teenage volunteers was included as a control group. The maximum plasma concentration, half-life time, area under the curve and the amount of salicylates excreted were statistically different between the JRA and the RF groups, as well as between the RF group and the controls, however, there were no significant differences between the JRA group and the controls. Dosage schemes must be adjusted for JRA patients, since the half life in these patients is longer than in RF patients. However, due to ample variability of pharmacokinetic parameters it is recommended that dose schemes are individualized on the type of autoimmune disease considered. Copyright 2004 John Wiley & Sons, Ltd.

  13. Programming adaptive control to evolve increased metabolite production.

    Chou, Howard H; Keasling, Jay D

    2013-01-01

    The complexity inherent in biological systems challenges efforts to rationally engineer novel phenotypes, especially those not amenable to high-throughput screens and selections. In nature, increased mutation rates generate diversity in a population that can lead to the evolution of new phenotypes. Here we construct an adaptive control system that increases the mutation rate in order to generate diversity in the population, and decreases the mutation rate as the concentration of a target metabolite increases. This system is called feedback-regulated evolution of phenotype (FREP), and is implemented with a sensor to gauge the concentration of a metabolite and an actuator to alter the mutation rate. To evolve certain novel traits that have no known natural sensors, we develop a framework to assemble synthetic transcription factors using metabolic enzymes and construct four different sensors that recognize isopentenyl diphosphate in bacteria and yeast. We verify FREP by evolving increased tyrosine and isoprenoid production.

  14. Assessment of the Human Kynurenine Pathway: Comparisons and Clinical Implications of Ethnic and Gender Differences in Plasma Tryptophan, Kynurenine Metabolites, and Enzyme Expressions at Baseline and after Acute Tryptophan Loading and Depletion

    Abdulla A.-B. Badawy

    2016-01-01

    Full Text Available Tryptophan (Trp metabolism via the kynurenine pathway (KP was assessed in normal healthy US volunteers at baseline and after acute Trp depletion (ATD and acute Trp loading (ATL using amino acid formulations. The hepatic KP accounts for ~90% of overall Trp degradation. Liver Trp 2,3-dioxygenase (TDO contributes ~70% toward Trp oxidation, with the remainder achieved by subsequent rate-limiting enzymes in the KP. TDO is not influenced by a 1.15 g Trp load, but is maximally activated by a 5.15 g dose. We recommend a 30 mg/kg dose for future ATL studies. ATD activates TDO and enhances the Trp flux down the KP via its leucine component. Higher plasma free [Trp] and lower total [Trp] are observed in women, with no gender differences in kynurenines. Kynurenic acid is lower in female Caucasians, which may explain their lower incidence of schizophrenia. African-American and Hispanic women have a lower TDO and Trp oxidation relative to free Trp than the corresponding men. African-American women have a potentially higher 3-hydroxyanthranilic acid/anthranilic acid ratio, which may protect them against osteoporosis. Future studies of the KP in relation to health and disease should focus on gender and ethnic differences.

  15. New seismograph includes filters

    1979-11-02

    The new Nimbus ES-1210 multichannel signal enhancement seismograph from EG and G geometrics has recently been redesigned to include multimode signal fillers on each amplifier. The ES-1210F is a shallow exploration seismograph for near subsurface exploration such as in depth-to-bedrock, geological hazard location, mineral exploration, and landslide investigations.

  16. Metabolic Networks and Metabolites Underlie Associations Between Maternal Glucose During Pregnancy and Newborn Size at Birth.

    Scholtens, Denise M; Bain, James R; Reisetter, Anna C; Muehlbauer, Michael J; Nodzenski, Michael; Stevens, Robert D; Ilkayeva, Olga; Lowe, Lynn P; Metzger, Boyd E; Newgard, Christopher B; Lowe, William L

    2016-07-01

    Maternal metabolites and metabolic networks underlying associations between maternal glucose during pregnancy and newborn birth weight and adiposity demand fuller characterization. We performed targeted and nontargeted gas chromatography/mass spectrometry metabolomics on maternal serum collected at fasting and 1 h following glucose beverage consumption during an oral glucose tolerance test (OGTT) for 400 northern European mothers at ∼28 weeks' gestation in the Hyperglycemia and Adverse Pregnancy Outcome Study. Amino acids, fatty acids, acylcarnitines, and products of lipid metabolism decreased and triglycerides increased during the OGTT. Analyses of individual metabolites indicated limited maternal glucose associations at fasting, but broader associations, including amino acids, fatty acids, carbohydrates, and lipids, were found at 1 h. Network analyses modeling metabolite correlations provided context for individual metabolite associations and elucidated collective associations of multiple classes of metabolic fuels with newborn size and adiposity, including acylcarnitines, fatty acids, carbohydrates, and organic acids. Random forest analyses indicated an improved ability to predict newborn size outcomes by using maternal metabolomics data beyond traditional risk factors, including maternal glucose. Broad-scale association of fuel metabolites with maternal glucose is evident during pregnancy, with unique maternal metabolites potentially contributing specifically to newborn birth weight and adiposity. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  17. Patulin and secondary metabolite production by marine-derived Penicillium strains

    Vansteelandt, Marieke; Kerzaon, Isabelle; Blanchet, Elodie

    2012-01-01

    )–mass spectrometry (MS)/MS. Each strain was grown on six different culture media to enhance the number of observable metabolites.Thirty-two secondary metabolites were detected in crude extracts with twenty first observations for studied species. Patulin, a major mycotoxin, was classically detected in extracts...... of these fungi in shellfish farming areas.Patulin induced acute neurotoxicity on Diptera larvae, indicating the interest of this bioassay as an additional tool for detection of this major mycotoxin in crude extracts....

  18. Evaluation of Extraction Protocols for Simultaneous Polar and Non-Polar Yeast Metabolite Analysis Using Multivariate Projection Methods

    Nicolas P. Tambellini

    2013-07-01

    Full Text Available Metabolomic and lipidomic approaches aim to measure metabolites or lipids in the cell. Metabolite extraction is a key step in obtaining useful and reliable data for successful metabolite studies. Significant efforts have been made to identify the optimal extraction protocol for various platforms and biological systems, for both polar and non-polar metabolites. Here we report an approach utilizing chemoinformatics for systematic comparison of protocols to extract both from a single sample of the model yeast organism Saccharomyces cerevisiae. Three chloroform/methanol/water partitioning based extraction protocols found in literature were evaluated for their effectiveness at reproducibly extracting both polar and non-polar metabolites. Fatty acid methyl esters and methoxyamine/trimethylsilyl derivatized aqueous compounds were analyzed by gas chromatography mass spectrometry to evaluate non-polar or polar metabolite analysis. The comparative breadth and amount of recovered metabolites was evaluated using multivariate projection methods. This approach identified an optimal protocol consisting of 64 identified polar metabolites from 105 ion hits and 12 fatty acids recovered, and will potentially attenuate the error and variation associated with combining metabolite profiles from different samples for untargeted analysis with both polar and non-polar analytes. It also confirmed the value of using multivariate projection methods to compare established extraction protocols.

  19. Dichlorodiphenyltrichloroethane (DDT), DDT Metabolites and Pregnancy Outcomes

    Kezios, Katrina L.; Liu, Xinhua; Cirillo, Piera M.; Cohn, Barbara A.; Kalantzi, Olga I.; Wang, Yunzhu; Petreas, Myrto X.; Park, June-Soo; Factor-Litvak, Pam

    2012-01-01

    Organochlorine pesticides (OCPs) are persistent endocrine disruptors. OCPs cross the placenta; this prenatal exposure has been associated with adverse pregnancy outcomes. We investigated associations between prenatal exposure to OCPs and gestational age and birth weight in 600 infants born between 1960 and 1963. The primary OCP was 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p′-DDT), its primary metabolite, 1,1′-dichloro-2,2'-bis(p-chlorophenyl)ethylene(p,p′-DDE) and the contaminant, 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)-ethane (o,p′-DDT). Regression analysis indicated that for each natural log unit increase in p,p′-DDT, birth weight increased by 274 grams (95% CI 122, 425) when controlling for p,p′-DDE and o,p′-DDT. At a given level of p,p′-DDT exposure, o,p′-DDT and p,p′-DDE were associated with decreased birth weight. p,p′-DDE was negatively associated with length of gestation, controlling for p,p′-DDT and o,p′-DDT. These findings suggest opposing associations between exposure to p,p′-DDT and p,p′-DDE and birth weight. We did not find evidence to support mediation by maternal thyroid hormone status nor that the association differed by sex. PMID:23142753

  20. Glutamine and glutamate as vital metabolites

    Newsholme P.

    2003-01-01

    Full Text Available Glucose is widely accepted as the primary nutrient for the maintenance and promotion of cell function. This metabolite leads to production of ATP, NADPH and precursors for the synthesis of macromolecules such as nucleic acids and phospholipids. We propose that, in addition to glucose, the 5-carbon amino acids glutamine and glutamate should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine/glutamate are many, i.e., they are substrates for protein synthesis, anabolic precursors for muscle growth, they regulate acid-base balance in the kidney, they are substrates for ureagenesis in the liver and for hepatic and renal gluconeogenesis, they act as an oxidative fuel for the intestine and cells of the immune system, provide inter-organ nitrogen transport, and act as precursors of neurotransmitter synthesis, of nucleotide and nucleic acid synthesis and of glutathione production. Many of these functions are interrelated with glucose metabolism. The specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells are discussed in the context of glucose requirements and cell function.

  1. Effects of ambient and elevated CO2 on growth, chlorophyll fluorescence, photosynthetic pigments, antioxidants, and secondary metabolites of Catharanthus roseus (L.) G Don. grown under three different soil N levels.

    Singh, Aradhana; Agrawal, Madhoolika

    2015-03-01

    Catharanthus roseus L. plants were grown under ambient (375 ± 30 ppm) and elevated (560 ± 25 ppm) concentrations of atmospheric CO2 at different rates of N supply (without supplemental N, 0 kg N ha(-1); recommended N, 50 kg N ha(-1); and double recommended N, 100 kg N ha(-1)) in open top chambers under field condition. Elevated CO2 significantly increased photosynthetic pigments, photosynthetic efficiency, and organic carbon content in leaves at recommended (RN) and double recommended N (DRN), while significantly decreased total nitrogen content in without supplemental N (WSN). Activities of superoxide dismutase, catalase, and ascorbate peroxidase were declined, while glutathione reductase, peroxidase, and phenylalanine-ammonia lyase were stimulated under elevated CO2. However, the responses of the above enzymes were modified with different rates of N supply. Elevated CO2 significantly reduced superoxide production rate, hydrogen peroxide, and malondialdehyde contents in RN and DRN. Compared with ambient, total alkaloids content increased maximally at recommended level of N, while total phenolics in WSN under elevated CO2. Elevated CO2 stimulated growth of plants by increasing plant height and numbers of branches and leaves, and the magnitude of increment were maximum in DRN. The study suggests that elevated CO2 has positively affected plants by increasing growth and alkaloids production and reducing the level of oxidative stress. However, the positive effects of elevated CO2 were comparatively lesser in plants grown under limited N availability than in moderate and higher N availability. Furthermore, the excess N supply in DRN has stimulated the growth but not the alkaloids production under elevated CO2.

  2. The Use of Secondary Metabolites Heracleum Sosnowskyi Manden in Agriculture

    S. N. BUDARIN

    2014-06-01

    Full Text Available The composition of secondary metabolites Heracleum sosnowskyi include: tannins, essential oils, furanocoumarin and other agent. The greatest interest is the phenolic compounds coumarin furanocoumarin order which is known for their photosensitizing effect. Coumarins are part of hogweed. The greatest number of different kinds of coumarin was found in fruit. Researchers from the Far Eastern Branch of the RAS have been identified series of angelicin furocoumarins (sfondin, angelicin and psoralenum (bergapten, xanthotoxin, oksikumarina umbeliferon furocoumarins. In our research we have identified the influence of active substances hogweed on growth and development of different groups of plants.So experiment with biotest Heracleum sosnowskyi sap (with concentration are 1:1, 1:4, 1:16, and control - H2O stimulates energy germination of pea seeds (Vicia sativa L. - 6%, wheat (Triticum aestivum L. - 1,2%, barley (Hordeum vulgare L. - 5%, and tutsan (Hypéricum perforátum L. - 3,5% at a concentration of 1:16. The same concentration has an inhibitory effect on radish (Raphanus sativus L., chamomile (Matricaria chamomilla L. and oregano (Oríganum vulgáre L..In the experiment on the effect of active substances contained in the soil under hogweed (the control is the soil where wasn’t Heracleum sosnowskyi we observed a stimulatory effect on plant growth and development of wild camomile. So biometric indicators chamomile plants was grown in the A1 horizon (topsoil differ significantly in all indicators of underlying horizons and from controls.So Heracleum sosnowskyi possessing high photosensitizing effect due to content in the bergapten, psoralen, xanthotoxin can be used for medicine along with Ammi majus as the raw material for the preparation of herbal remedies in dermatology. Also in our studies we have shown the use of active substances hogweed in agriculture as regulators growth of some plant species: camomile, wheat, pea, barley, tutsan.

  3. Optimizing Urine Processing Protocols for Protein and Metabolite Detection.

    Siddiqui, Nazema Y; DuBois, Laura G; St John-Williams, Lisa; Will, Thompson J; Grenier, Carole; Burke, Emily; Fraser, Matthew O; Amundsen, Cindy L; Murphy, Susan K

    In urine, factors such as timing of voids, and duration at room temperature (RT) may affect the quality of recovered protein and metabolite data. Additives may aid with detection, but can add more complexity in sample collection or analysis. We aimed to identify the optimal urine processing protocol for clinically-obtained urine samples that allows for the highest protein and metabolite yields with minimal degradation. Healthy women provided multiple urine samples during the same day. Women collected their first morning (1 st AM) void and another "random void". Random voids were aliquotted with: 1) no additive; 2) boric acid (BA); 3) protease inhibitor (PI); or 4) both BA + PI. Of these aliquots, some were immediately stored at 4°C, and some were left at RT for 4 hours. Proteins and individual metabolites were quantified, normalized to creatinine concentrations, and compared across processing conditions. Sample pools corresponding to each processing condition were analyzed using mass spectrometry to assess protein degradation. Ten Caucasian women between 35-65 years of age provided paired 1 st morning and random voided urine samples. Normalized protein concentrations were slightly higher in 1 st AM compared to random "spot" voids. The addition of BA did not significantly change proteins, while PI significantly improved normalized protein concentrations, regardless of whether samples were immediately cooled or left at RT for 4 hours. In pooled samples, there were minimal differences in protein degradation under the various conditions we tested. In metabolite analyses, there were significant differences in individual amino acids based on the timing of the void. For comparative translational research using urine, information about void timing should be collected and standardized. For urine samples processed in the same day, BA does not appear to be necessary while the addition of PI enhances protein yields, regardless of 4°C or RT storage temperature.

  4. Analytic device including nanostructures

    Di Fabrizio, Enzo M.; Fratalocchi, Andrea; Totero Gongora, Juan Sebastian; Coluccio, Maria Laura; Candeloro, Patrizio; Cuda, Gianni

    2015-01-01

    A device for detecting an analyte in a sample comprising: an array including a plurality of pixels, each pixel including a nanochain comprising: a first nanostructure, a second nanostructure, and a third nanostructure, wherein size of the first nanostructure is larger than that of the second nanostructure, and size of the second nanostructure is larger than that of the third nanostructure, and wherein the first nanostructure, the second nanostructure, and the third nanostructure are positioned on a substrate such that when the nanochain is excited by an energy, an optical field between the second nanostructure and the third nanostructure is stronger than an optical field between the first nanostructure and the second nanostructure, wherein the array is configured to receive a sample; and a detector arranged to collect spectral data from a plurality of pixels of the array.

  5. Saskatchewan resources. [including uranium

    1979-09-01

    The production of chemicals and minerals for the chemical industry in Saskatchewan are featured, with some discussion of resource taxation. The commodities mentioned include potash, fatty amines, uranium, heavy oil, sodium sulfate, chlorine, sodium hydroxide, sodium chlorate and bentonite. Following the successful outcome of the Cluff Lake inquiry, the uranium industry is booming. Some developments and production figures for Gulf Minerals, Amok, Cenex and Eldorado are mentioned.

  6. Allosteric modulation of endogenous metabolites as an avenue for drug discovery.

    Wootten, Denise; Savage, Emilia E; Valant, Celine; May, Lauren T; Sloop, Kyle W; Ficorilli, James; Showalter, Aaron D; Willard, Francis S; Christopoulos, Arthur; Sexton, Patrick M

    2012-08-01

    G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and a key drug target class. Recently, allosteric drugs that can co-bind with and modulate the activity of the endogenous ligand(s) for the receptor have become a major focus of the pharmaceutical and biotechnology industry for the development of novel GPCR therapeutic agents. This class of drugs has distinct properties compared with drugs targeting the endogenous (orthosteric) ligand-binding site that include the ability to sculpt cellular signaling and to respond differently in the presence of discrete orthosteric ligands, a behavior termed "probe dependence." Here, using cell signaling assays combined with ex vivo and in vivo studies of insulin secretion, we demonstrate that allosteric ligands can cause marked potentiation of previously "inert" metabolic products of neurotransmitters and peptide hormones, a novel consequence of the phenomenon of probe dependence. Indeed, at the muscarinic M(2) receptor and glucagon-like peptide 1 (GLP-1) receptor, allosteric potentiation of the metabolites, choline and GLP-1(9-36)NH(2), respectively, was ~100-fold and up to 200-fold greater than that seen with the physiological signaling molecules acetylcholine and GLP-1(7-36)NH(2). Modulation of GLP-1(9-36)NH(2) was also demonstrated in ex vivo and in vivo assays of insulin secretion. This work opens up new avenues for allosteric drug discovery by directly targeting modulation of metabolites, but it also identifies a behavior that could contribute to unexpected clinical outcomes if interaction of allosteric drugs with metabolites is not part of their preclinical assessment.

  7. Reliability of Serum Metabolites over a Two-Year Period: A Targeted Metabolomic Approach in Fasting and Non-Fasting Samples from EPIC

    Achaintre, David; Sacerdote, Carlotta; Vineis, Paolo; Key, Timothy J.; Onland Moret, N. Charlotte; Scalbert, Augustin; Rinaldi, Sabina; Ferrari, Pietro

    2015-01-01

    Objective Although metabolic profiles have been associated with chronic disease risk, lack of temporal stability of metabolite levels could limit their use in epidemiological investigations. The present study aims to evaluate the reliability over a two-year period of 158 metabolites and compare reliability over time in fasting and non-fasting serum samples. Methods Metabolites were measured with the AbsolueIDQp180 kit (Biocrates, Innsbruck, Austria) by mass spectrometry and included acylcarnitines, amino acids, biogenic amines, hexoses, phosphatidylcholines and sphingomyelins. Measurements were performed on repeat serum samples collected two years apart in 27 fasting men from Turin, Italy, and 39 non-fasting women from Utrecht, The Netherlands, all participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Reproducibility was assessed by estimating intraclass correlation coefficients (ICCs) in multivariable mixed models. Results In fasting samples, a median ICC of 0.70 was observed. ICC values were fasting samples, the median ICC was 0.54. ICC values were fasting as compared to fasting samples, with a statistically significant difference for 19–36% of acylcarnitines, phosphatidylcholines and sphingomyelins. Conclusion A single measurement per individual may be sufficient for the study of 73% and 52% of the metabolites showing ICCs >0.50 in fasting and non-fasting samples, respectively. ICCs were higher in fasting samples that are preferable to non-fasting. PMID:26274920

  8. Metabolite Profiling of 14 Wuyi Rock Tea Cultivars Using UPLC-QTOF MS and UPLC-QqQ MS Combined with Chemometrics

    Si Chen

    2018-01-01

    Full Text Available Wuyi Rock tea, well-recognized for rich flavor and long-lasting fragrance, is a premium subcategory of oolong tea mainly produced in Wuyi Mountain and nearby regions of China. The quality of tea is mainly determined by the chemical constituents in the tea leaves. However, this remains underexplored for Wuyi Rock tea cultivars. In this study, we investigated the leaf metabolite profiles of 14 major Wuyi Rock tea cultivars grown in the same producing region using UPLC-QTOF MS and UPLC-QqQ MS with data processing via principal component analysis and cluster analysis. Relative quantitation of 49 major metabolites including flavan-3-ols, proanthocyanidins, flavonol glycosides, flavone glycosides, flavonone glycosides, phenolic acid derivatives, hydrolysable tannins, alkaloids and amino acids revealed clear variations between tea cultivars. In particular, catechins, kaempferol and quercetin derivatives were key metabolites responsible for cultivar discrimination. Information on the varietal differences in the levels of bioactive/functional metabolites, such as methylated catechins, flavonol glycosides and theanine, offers valuable insights to further explore the nutritional values and sensory qualities of Wuyi Rock tea. It also provides potential markers for tea plant fingerprinting and cultivar identification.

  9. Phthalate metabolites in Norwegian mothers and children: Levels, diurnal variation and use of personal care products.

    Sakhi, Amrit Kaur; Sabaredzovic, Azemira; Cequier, Enrique; Thomsen, Cathrine

    2017-12-01

    Exposure to phthalates has been associated with reproductive and developmental toxicity. Data on levels of these compounds in the Norwegian population is limited. In this study, urine samples were collected from 48 mothers and their children in two counties in Norway. Eleven different phthalate metabolites originating from six commonly used phthalates in consumer products were determined. Concentrations of phthalate metabolites were significantly higher in children compared to mothers except for mono-ethyl phthalate (MEP). The mothers provided several urine samples during 24hours (h) and diurnal variation showed that the concentrations in the morning urine samples (24-8h) were significantly higher than at other time-periods for most of the phthalate metabolites. Intraclass correlation coefficients (ICCs) for 24-hour time-period were in the range of 0.49-0.81. These moderate to high ICCs indicate that one spot urine sample can be used to estimate the exposure to phthalates. Since a significant effect of time of day was observed, it is still advisable to standardize the collection time point to reduce the variation. For the mothers, the use of personal care products (PCPs) were less associated with morning urine samples than early day (8-12h) and evening (16-24h) urine samples. The use of perfume and hair products were positively associated with the urinary concentrations of low molecular weight phthalates. Use of shower soap and shampoo were positively associated with urinary concentration of di(2-ethylhexyl) phthalate (DEHP) metabolites. For children, face cream use was positively associated with phthalate metabolites in the morning samples, and hand soap use was negatively associated with concentration of urinary DEHP metabolites in afternoon/evening samples. Since different PCPs were associated with the urinary phthalate metabolites in different time-periods during a day, more than one spot urine sample might be required to study associations between urinary

  10. Comparative metabolite profiling of Solanum tuberosum against six wild Solanum species with Colorado potato beetle resistance.

    Tai, Helen H; Worrall, Kraig; Pelletier, Yvan; De Koeyer, David; Calhoun, Larry A

    2014-09-10

    The Colorado potato beetle Leptinotarsa decemlineata (Say) (CPB) is a coleopteran herbivore that feeds on the foliage on Solanum species, in particular, potato. Six resistant wild Solanum species were identified, and two of these species had low levels of glycoalkaloids. Comparative analysis of the untargeted metabolite profiles of the foliage using UPLC-qTOF-MS was done to find metabolites shared between the wild species but not with Solanum tuberosum (L.) to identify resistance-related metabolites. It was found that only S. tuberosum produced the triose glycoalkaloids solanine and chaconine. Instead, the six wild species produced glycoalkaloids that shared in common tetrose sugar side chains. Additionally, there were non-glycoalkaloid metabolites associated with resistance including hydroxycoumarin and a phenylpropanoid, which were produced in all wild species but not in S. tuberosum.

  11. Comparison of different application systems and CT- assisted treatment planning procedures in primary endometrium cancer: Is it technically possible to include the whole uterus volume in the volume treated by brachytherapy

    Mock, U.; Knocke, Th.; Fellner, C.; Poetter, R.

    1996-01-01

    Purpose: Brachytherapy is regarded as the definitive component of treatment for inoperable patients with endometrium cancer. In published series the whole uterus has been claimed to represent the target volume independently of the individual tumor spread. The purpose of this work is to compare different planning and application procedures and to analyze the target volumes (whole uterus), treatment volumes and their respective relation for the given various conditions. Material and Methods: In ten patients with primary endometrium cancer the correlation between target- and treatment volume was analysed based on standard one-channel applicators or individual Heyman applicators. A comparative analysis of target volumes resulting from two different planning procedures of Heyman applications was performed. CT was carried out after insertion of the Heyman ovoids. Target volume was estimated by measuring the uterus size at different cross sections of the CT images. Dose calculation was performed with (PLATO-system) or without (NPS-system) transferring these data directly to the planning system. We report on the differences in treatment volumes resulting from the two application and planning systems. Results: The mean value of the uterus volume was 180 ccm (range 57 ccm to 316 ccm). Four out of 10 patients had an asymmetric uterus configuration with a side-difference (in longitudinal or transversal direction) of more than 1 cm. On average 70% (range 48-95%) of the uterus volume was included by the treatment volume when Heymann applicators were used compared to 45 % (range 25-89%) when standard one channel applicators were used. This represents an improvement of 25% (range from 11%-35%). By utilizing the more sophisticated way of treatment planning a more adequate coverage of the uterus volume was achieved in five out of ten patients. The treated volume increased on the average by 20 % (range 11 %-32%). In three cases changes in the irradiation volume were less than 5%. In

  12. HPLC analysis of prostaglandin metabolites plasma from irradiated rats

    Walden, T.L. Jr.; Catravas, G.N.

    1985-01-01

    The authors used RP-HPLC to quantitatively and qualitatively evaluate the PG metabolites in the plasma of rats during the first 24 hrs following a 10 Gy whole body dose of cobalt 60 gamma rays. The PGs and other arachidonic acid metabolites in plasma were extracted and then covalently attached to a fluroescent dye to enhance detection. A number of PGs and their metabolites were observed in the irradiated sample, including: 13,14 dihydro -15 keto PGE/sub 2/ and 13,14, dihydro -15 keto PGF/sub 2/, and their respective precursors, PGE/sub 2/ and PGF/sub 2/. The two major compounds present in the plasma samples were 13,14 dihydro -15 keto PFG/sub 2/ and another compound which is as yet unidentified. The levels of the individual PGs within a sample varied with time after irradiation, and the time at which a PG reached a peak level in the plasma depended on the particular PG in question. 13,14 dihdyro -15 keto PGD/sub 2/ was observed to reach a peak plasma concentration at 6 hours postirradiation, and at that time was at least 20 times higher than control levels

  13. Biodegradation of clofibric acid and identification of its metabolites.

    Salgado, R; Oehmen, A; Carvalho, G; Noronha, J P; Reis, M A M

    2012-11-30

    Clofibric acid (CLF) is the pharmaceutically active metabolite of lipid regulators clofibrate, etofibrate and etofyllinclofibrate, and it is considered both environmentally persistent and refractory. This work studied the biotransformation of CLF in aerobic sequencing batch reactors (SBRs) with mixed microbial cultures, monitoring the efficiency of biotransformation of CLF and the production of metabolites. The maximum removal achieved was 51% biodegradation (initial CLF concentration=2 mg L(-1)), where adsorption and abiotic removal mechanisms were shown to be negligible, showing that CLF is indeed biodegradable. Tests showed that the observed CLF biodegradation was mainly carried out by heterotrophic bacteria. Three main metabolites were identified, including α-hydroxyisobutyric acid, lactic acid and 4-chlorophenol. The latter is known to exhibit higher toxicity than the parent compound, but it did not accumulate in the SBRs. α-Hydroxyisobutyric acid and lactic acid accumulated for a period, where nitrite accumulation may have been responsible for inhibiting their degradation. A metabolic pathway for the biodegradation of CLF is proposed in this study. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Importance of Secondary Metabolites for Leaf Beetles (Coleoptera: Chrysomelidae

    A. N. EKİZ

    2014-06-01

    Full Text Available Leaf beetles (Chrysomelidae are one of the most diverse families of herbivorous insects. Many of them are important agricultural pests and cause remarkable loss of crop and money as well. Plant leaves and roots are primary food source of both larva and adults of leaf beetles. Plants produce many secondary metabolites in reaction to herbivore insects. It is a well-known phenomenon that quantity and variety of secondary metabolites in plant leaves may change in response to insect attacks. Herbivore insects have to deal with such defensive secondary chemicals and overcome either by detoxifying or storing them. Accordingly, many specialist herbivores coevolved with their host plant. Certain phenolic glycosides may reduce leaf beetle feeding. Condensed tannins are anti-herbivore defenses against leaf chewing beetles, including leaf beetles. Flavonoid compounds are feeding deterrents for many flea leaf beetles. Cinnamic acid derivatives are other known feeding deterrents for leaf beetles. Secondary metabolites quantity and nutritional quality of host plants are not only important for feeding but also for providing enemy-free space and suitable oviposition sites.

  15. Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies.

    van der Lee, Sven J; Teunissen, Charlotte E; Pool, René; Shipley, Martin J; Teumer, Alexander; Chouraki, Vincent; Melo van Lent, Debora; Tynkkynen, Juho; Fischer, Krista; Hernesniemi, Jussi; Haller, Toomas; Singh-Manoux, Archana; Verhoeven, Aswin; Willemsen, Gonneke; de Leeuw, Francisca A; Wagner, Holger; van Dongen, Jenny; Hertel, Johannes; Budde, Kathrin; Willems van Dijk, Ko; Weinhold, Leonie; Ikram, M Arfan; Pietzner, Maik; Perola, Markus; Wagner, Michael; Friedrich, Nele; Slagboom, P Eline; Scheltens, Philip; Yang, Qiong; Gertzen, Robert E; Egert, Sarah; Li, Shuo; Hankemeier, Thomas; van Beijsterveldt, Catharina E M; Vasan, Ramachandran S; Maier, Wolfgang; Peeters, Carel F W; Jörgen Grabe, Hans; Ramirez, Alfredo; Seshadri, Sudha; Metspalu, Andres; Kivimäki, Mika; Salomaa, Veikko; Demirkan, Ayşe; Boomsma, Dorret I; van der Flier, Wiesje M; Amin, Najaf; van Duijn, Cornelia M

    2018-01-06

    Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined. We discovered and replicated 15 metabolites associated with cognition including subfractions of high-density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (APOE) genotypes. Six of the cognition-associated metabolites were related to the risk of dementia and lifestyle factors. Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia. Copyright © 2018 the Alzheimer's Association. All rights reserved.

  16. Pharmacologically active plant metabolites as survival strategy products.

    Attardo, C; Sartori, F

    2003-01-01

    The fact that plant organisms produce chemical substances that are able to positively or negatively interfere with the processes which regulate human life has been common knowledge since ancient times. One of the numerous possible examples in the infusion of Conium maculatum, better known as Hemlock, a plant belonging to the family umbelliferae, used by the ancient Egyptians to cure skin diseases. The current official pharmacopoeia includes various chemical substances produced by secondary plant metabolisms. For example, the immunosuppressive drugs used to prevent organ transplant rejection and the majority of antibiotics are metabolites produced by fungal organisms, pilocarpin, digitalis, strophantus, salicylic acid and curare are examples of plant organism metabolites. For this reason, there has been an increase in research into plants, based on information on their medicinal use in the areas where they grow. The study of plants in relation to local culture and traditions is known as "ethnobotany". Careful study of the behaviour of sick animals has also led to the discovery of medicinal plants. The study of this subject is known as "zoopharmacognosy". The aim of this article is to discuss the fact that "ad hoc" production of such chemical substances, defined as "secondary metabolites", is one of the modes in which plant organisms respond to unfavourable environmental stimuli, such as an attack by predatory phytophagous animals or an excessive number of plant individuals, even of the same species, in a terrain. In the latter case, the plant organisms produce toxic substances, called "allelopathic" which limit the growth of other individuals. "Secondary metabolites" are produced by metabolic systems that are shunts of the primary systems which, when required, may be activated from the beginning, or increased to the detriment of others. The study of the manner in which such substances are produced is the subject of a new branch of learning called "ecological

  17. Plant metabolites and nutritional quality of vegetables.

    Hounsome, N; Hounsome, B; Tomos, D; Edwards-Jones, G

    2008-05-01

    Vegetables are an important part of the human diet and a major source of biologically active substances such as vitamins, dietary fiber, antioxidants, and cholesterol-lowering compounds. Despite a large amount of information on this topic, the nutritional quality of vegetables has not been defined. Historically, the value of many plant nutrients and health-promoting compounds was discovered by trial and error. By the turn of the century, the application of chromatography, mass spectrometry, infrared spectrometry, and nuclear magnetic resonance allowed quantitative and qualitative measurements of a large number of plant metabolites. Approximately 50000 metabolites have been elucidated in plants, and it is predicted that the final number will exceed 200000. Most of them have unknown function. Metabolites such as carbohydrates, organic and amino acids, vitamins, hormones, flavonoids, phenolics, and glucosinolates are essential for plant growth, development, stress adaptation, and defense. Besides the importance for the plant itself, such metabolites determine the nutritional quality of food, color, taste, smell, antioxidative, anticarcinogenic, antihypertension, anti-inflammatory, antimicrobial, immunostimulating, and cholesterol-lowering properties. This review is focused on major plant metabolites that characterize the nutritional quality of vegetables, and methods of their analysis.

  18. Secondary metabolites in fungus-plant interactions

    Pusztahelyi, Tünde; Holb, Imre J.; Pócsi, István

    2015-01-01

    Fungi and plants are rich sources of thousands of secondary metabolites. The genetically coded possibilities for secondary metabolite production, the stimuli of the production, and the special phytotoxins basically determine the microscopic fungi-host plant interactions and the pathogenic lifestyle of fungi. The review introduces plant secondary metabolites usually with antifungal effect as well as the importance of signaling molecules in induced systemic resistance and systemic acquired resistance processes. The review also concerns the mimicking of plant effector molecules like auxins, gibberellins and abscisic acid by fungal secondary metabolites that modulate plant growth or even can subvert the plant defense responses such as programmed cell death to gain nutrients for fungal growth and colonization. It also looks through the special secondary metabolite production and host selective toxins of some significant fungal pathogens and the plant response in form of phytoalexin production. New results coming from genome and transcriptional analyses in context of selected fungal pathogens and their hosts are also discussed. PMID:26300892

  19. Functional metabolite assemblies—a review

    Aizen, Ruth; Tao, Kai; Rencus-Lazar, Sigal; Gazit, Ehud

    2018-05-01

    Metabolites are essential for the normal operation of cells and fulfill various physiological functions. It was recently found that in several metabolic disorders, the associated metabolites could self-assemble to generate amyloid-like structures, similar to canonical protein amyloids that have a role in neurodegenerative disorders. Yet, assemblies with typical amyloid characteristics are also known to have physiological function. In addition, many non-natural proteins and peptides presenting amyloidal properties have been used for the fabrication of functional nanomaterials. Similarly, functional metabolite assemblies are also found in nature, demonstrating various physiological roles. A notable example is the structural color formed by guanine crystals or fluorescent crystals in feline eyes responsible for enhanced night vision. Moreover, some metabolites have been used for the in vitro fabrication of functional materials, such as glycine crystals presenting remarkable piezoelectric properties or indigo films used to assemble organic semi-conductive electronic devices. Therefore, we believe that the study of metabolite assemblies is not only important in order to understand their role in normal physiology and in pathology, but also paves a new route in exploring the fabrication of organic, bio-compatible materials.

  20. Being Included and Excluded

    Korzenevica, Marina

    2016-01-01

    Following the civil war of 1996–2006, there was a dramatic increase in the labor mobility of young men and the inclusion of young women in formal education, which led to the transformation of the political landscape of rural Nepal. Mobility and schooling represent a level of prestige that rural...... politics. It analyzes how formal education and mobility either challenge or reinforce traditional gendered norms which dictate a lowly position for young married women in the household and their absence from community politics. The article concludes that women are simultaneously excluded and included from...... community politics. On the one hand, their mobility and decision-making powers decrease with the increase in the labor mobility of men and their newly gained education is politically devalued when compared to the informal education that men gain through mobility, but on the other hand, schooling strengthens...

  1. Analysis of Metabolites in Stem Parasitic Plant Interactions: Interaction of Cuscuta–Momordica versus Cassytha–Ipomoea

    Furuhashi, Takeshi; Nakamura, Takemichi; Iwase, Koji

    2016-01-01

    Cuscuta and Cassytha are two well-known stem parasitic plant genera with reduced leaves and roots, inducing haustoria in their stems. Their similar appearance in the field has been recognized, but few comparative studies on their respective plant interactions are available. To compare their interactions, we conducted a metabolite analysis of both the Cassytha–Ipomoea and the Cuscuta–Momordica interaction. We investigated the energy charge of the metabolites by UFLC (ultra-high performance liquid chromatography), and conducted GC-MS (gas chromatography-mass spectrometry) analysis for polar metabolites (e.g., saccharides, polyols) and steroids. The energy charge after parasitization changed considerably in Cassytha but not in Cusucta. Cuscuta changed its steroid pattern during the plant interaction, whereas Cassytha did not. In the polar metabolite analysis, the laminaribiose increase after parasitization was conspicuous in Cuscuta, but not in Cassytha. This metabolite profile difference points to different lifestyles and parasitic strategies. PMID:27941603

  2. Analysis of Metabolites in Stem Parasitic Plant Interactions: Interaction of Cuscuta–Momordica versus Cassytha–Ipomoea

    Takeshi Furuhashi

    2016-12-01

    Full Text Available Cuscuta and Cassytha are two well-known stem parasitic plant genera with reduced leaves and roots, inducing haustoria in their stems. Their similar appearance in the field has been recognized, but few comparative studies on their respective plant interactions are available. To compare their interactions, we conducted a metabolite analysis of both the Cassytha–Ipomoea and the Cuscuta–Momordica interaction. We investigated the energy charge of the metabolites by UFLC (ultra-high performance liquid chromatography, and conducted GC-MS (gas chromatography-mass spectrometry analysis for polar metabolites (e.g., saccharides, polyols and steroids. The energy charge after parasitization changed considerably in Cassytha but not in Cusucta. Cuscuta changed its steroid pattern during the plant interaction, whereas Cassytha did not. In the polar metabolite analysis, the laminaribiose increase after parasitization was conspicuous in Cuscuta, but not in Cassytha. This metabolite profile difference points to different lifestyles and parasitic strategies.

  3. Analysis of Metabolites in Stem Parasitic Plant Interactions: Interaction of Cuscuta-Momordica versus Cassytha-Ipomoea.

    Furuhashi, Takeshi; Nakamura, Takemichi; Iwase, Koji

    2016-12-07

    Cuscuta and Cassytha are two well-known stem parasitic plant genera with reduced leaves and roots, inducing haustoria in their stems. Their similar appearance in the field has been recognized, but few comparative studies on their respective plant interactions are available. To compare their interactions, we conducted a metabolite analysis of both the Cassytha-Ipomoea and the Cuscuta-Momordica interaction. We investigated the energy charge of the metabolites by UFLC (ultra-high performance liquid chromatography), and conducted GC-MS (gas chromatography-mass spectrometry) analysis for polar metabolites (e.g., saccharides, polyols) and steroids. The energy charge after parasitization changed considerably in Cassytha but not in Cusucta . Cuscuta changed its steroid pattern during the plant interaction, whereas Cassytha did not. In the polar metabolite analysis, the laminaribiose increase after parasitization was conspicuous in Cuscuta , but not in Cassytha . This metabolite profile difference points to different lifestyles and parasitic strategies.

  4. The radioimmunological determination of glibenclamide and its metabolites in serum

    Glogner, P.; Heni, N.; Nissen, L.

    1977-01-01

    This report describes a sensitive and specific radio-immunological method for determining serum levels of the 1-(p-[2- (5-chloro-2-methoxybenzamido) -ethyl]-benzenesulfonyl) -3-cyclohexylurea (clibenclamide) and its metabolites. The antigen was prepared by coupling a metabolite to bovine serum albumin. Antibodies could be demonstrated in serum after immunisation of rabbits. The separation of free and antibody-bound glibenclamide was achieved by a dextran-charcoal suspension. Presence of serum did not influence the binding characteristics. The limit of detection was 20 ng/ml. The affinity of the metabolites differed only slightly from that of glibenclamide. The presence of related drugs from the sulfonylurea series such as tolbutamide, glibornuride and the sulfonamide sulfamethoxazol did not affect the determination. Only closely related substances showed a variable degree of affinity towards antibodies. As an example of the possible application of this method, the serum concentration of glibenclamide was determined over a period of 8 h after single i.v. injection to a volunteer. The data are in close accordance with the results of authors using radioactive glibenclamide. (orig.) [de

  5. Secondary Metabolites from Leaves of Manilkara subsericea (Mart.) Dubard.

    de Almeida, Fernanda Borges; Fernandes, Caio Pinho; Romao, Wanderson; Vanini, Gabriela; Costa, Helber Barcelos; França, Hildegardo Seibert; Santos, Marcelo Guerra; Carvalho, José Carlos Tavares; Falcão, Deborah Quintanilha; Rocha, Leandro

    2015-10-01

    Manilkara subsericea (Sapotaceae) is a species widely spread in the sandbanks of Restinga de Jurubatiba National Park (Rio de Janeiro, Brazil). It is commonly known as "maçaranduba", "maçarandubinha" and "guracica", being used in this locality as food, and timber. However, M. subsericea remains almost unexplored regarding its chemical constituents, including secondary metabolites from the leaves. Identify the chemical constituents from the leaves of M. subsericea. Leaves were macerated with ethanol (96% v/v), and dried crude ethanolic extract was sequentially washed with the organic solvents in order to obtain an ethyl acetate fraction. Substances from this fraction were identified by different techniques, such as negative-ion electrospray ionization Fourier and (1)H and (13)C nuclear magnetic resonance (NMR). Fresh leaves from M. subsericea were also submitted to hydrodistillation in order to obtain volatile substances, which were identified by gas chromatograph coupled to mass spectrometer. NMR(1)H and (13)C spectra allowed for the identification of the compounds myricetin, quercetin, and kaempferol from the ethyl acetate fraction. The negative-ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry mass spectrum also revealed the presence in this fraction of a polyhydroxytriterpene acid (pomolic acid), and some flavonoids, such as quercitrin, and myricitrin. In all 34 volatile compounds were identified by gas chromatography-mass spectrometry, including monoterpenes, sesquiterpenes, and long chain hydrocarbons. This study describes the first reports concerning the phytochemical information about leaves from M. subsericea. Manilkara subsericea fruits proved to be a rich source of triterpenes. However, no phytochemical studies were carried out with leaves. Thus, we described identification of volatile substances from its essential oils, in addition to non-reported triterpene and flavonoids from this species.

  6. Secondary Metabolites from Leaves of Manilkara subsericea (Mart.) Dubard

    de Almeida, Fernanda Borges; Fernandes, Caio Pinho; Romao, Wanderson; Vanini, Gabriela; Costa, Helber Barcelos; França, Hildegardo Seibert; Santos, Marcelo Guerra; Carvalho, José Carlos Tavares; Falcão, Deborah Quintanilha; Rocha, Leandro

    2015-01-01

    Background: Manilkara subsericea (Sapotaceae) is a species widely spread in the sandbanks of Restinga de Jurubatiba National Park (Rio de Janeiro, Brazil). It is commonly known as “maçaranduba”, “maçarandubinha” and “guracica”, being used in this locality as food, and timber. However, M. subsericea remains almost unexplored regarding its chemical constituents, including secondary metabolites from the leaves. Objective: Identify the chemical constituents from the leaves of M. subsericea. Materials and Methods: Leaves were macerated with ethanol (96% v/v), and dried crude ethanolic extract was sequentially washed with the organic solvents in order to obtain an ethyl acetate fraction. Substances from this fraction were identified by different techniques, such as negative-ion electrospray ionization Fourier and 1H and 13C nuclear magnetic resonance (NMR). Fresh leaves from M. subsericea were also submitted to hydrodistillation in order to obtain volatile substances, which were identified by gas chromatograph coupled to mass spectrometer. Results: NMR1H and 13C spectra allowed for the identification of the compounds myricetin, quercetin, and kaempferol from the ethyl acetate fraction. The negative-ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry mass spectrum also revealed the presence in this fraction of a polyhydroxytriterpene acid (pomolic acid), and some flavonoids, such as quercitrin, and myricitrin. In all 34 volatile compounds were identified by gas chromatography-mass spectrometry, including monoterpenes, sesquiterpenes, and long chain hydrocarbons. Conclusion: This study describes the first reports concerning the phytochemical information about leaves from M. subsericea. SUMMARY Manilkara subsericea fruits proved to be a rich source of triterpenes. However, no phytochemical studies were carried out with leaves. Thus, we described identification of volatile substances from its essential oils, in addition to

  7. A Latex Metabolite Benefits Plant Fitness under Root Herbivore Attack.

    Meret Huber

    2016-01-01

    Full Text Available Plants produce large amounts of secondary metabolites in their shoots and roots and store them in specialized secretory structures. Although secondary metabolites and their secretory structures are commonly assumed to have a defensive function, evidence that they benefit plant fitness under herbivore attack is scarce, especially below ground. Here, we tested whether latex secondary metabolites produced by the common dandelion (Taraxacum officinale agg. decrease the performance of its major native insect root herbivore, the larvae of the common cockchafer (Melolontha melolontha, and benefit plant vegetative and reproductive fitness under M. melolontha attack. Across 17 T. officinale genotypes screened by gas and liquid chromatography, latex concentrations of the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G were negatively associated with M. melolontha larval growth. Adding purified TA-G to artificial diet at ecologically relevant concentrations reduced larval feeding. Silencing the germacrene A synthase ToGAS1, an enzyme that was identified to catalyze the first committed step of TA-G biosynthesis, resulted in a 90% reduction of TA-G levels and a pronounced increase in M. melolontha feeding. Transgenic, TA-G-deficient lines were preferred by M. melolontha and suffered three times more root biomass reduction than control lines. In a common garden experiment involving over 2,000 T. officinale individuals belonging to 17 different genotypes, high TA-G concentrations were associated with the maintenance of high vegetative and reproductive fitness under M. melolontha attack. Taken together, our study demonstrates that a latex secondary metabolite benefits plants under herbivore attack, a result that provides a mechanistic framework for root herbivore driven natural selection and evolution of plant defenses below ground.

  8. A Latex Metabolite Benefits Plant Fitness under Root Herbivore Attack.

    Huber, Meret; Epping, Janina; Schulze Gronover, Christian; Fricke, Julia; Aziz, Zohra; Brillatz, Théo; Swyers, Michael; Köllner, Tobias G; Vogel, Heiko; Hammerbacher, Almuth; Triebwasser-Freese, Daniella; Robert, Christelle A M; Verhoeven, Koen; Preite, Veronica; Gershenzon, Jonathan; Erb, Matthias

    2016-01-01

    Plants produce large amounts of secondary metabolites in their shoots and roots and store them in specialized secretory structures. Although secondary metabolites and their secretory structures are commonly assumed to have a defensive function, evidence that they benefit plant fitness under herbivore attack is scarce, especially below ground. Here, we tested whether latex secondary metabolites produced by the common dandelion (Taraxacum officinale agg.) decrease the performance of its major native insect root herbivore, the larvae of the common cockchafer (Melolontha melolontha), and benefit plant vegetative and reproductive fitness under M. melolontha attack. Across 17 T. officinale genotypes screened by gas and liquid chromatography, latex concentrations of the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G) were negatively associated with M. melolontha larval growth. Adding purified TA-G to artificial diet at ecologically relevant concentrations reduced larval feeding. Silencing the germacrene A synthase ToGAS1, an enzyme that was identified to catalyze the first committed step of TA-G biosynthesis, resulted in a 90% reduction of TA-G levels and a pronounced increase in M. melolontha feeding. Transgenic, TA-G-deficient lines were preferred by M. melolontha and suffered three times more root biomass reduction than control lines. In a common garden experiment involving over 2,000 T. officinale individuals belonging to 17 different genotypes, high TA-G concentrations were associated with the maintenance of high vegetative and reproductive fitness under M. melolontha attack. Taken together, our study demonstrates that a latex secondary metabolite benefits plants under herbivore attack, a result that provides a mechanistic framework for root herbivore driven natural selection and evolution of plant defenses below ground.

  9. NMR-Based Identification of Metabolites in Polar and Non-Polar Extracts of Avian Liver.

    Fathi, Fariba; Brun, Antonio; Rott, Katherine H; Falco Cobra, Paulo; Tonelli, Marco; Eghbalnia, Hamid R; Caviedes-Vidal, Enrique; Karasov, William H; Markley, John L

    2017-11-16

    Metabolites present in liver provide important clues regarding the physiological state of an organism. The aim of this work was to evaluate a protocol for high-throughput NMR-based analysis of polar and non-polar metabolites from a small quantity of liver tissue. We extracted the tissue with a methanol/chloroform/water mixture and isolated the polar metabolites from the methanol/water layer and the non-polar metabolites from the chloroform layer. Following drying, we re-solubilized the fractions for analysis with a 600 MHz NMR spectrometer equipped with a 1.7 mm cryogenic probe. In order to evaluate the feasibility of this protocol for metabolomics studies, we analyzed the metabolic profile of livers from house sparrow ( Passer domesticus ) nestlings raised on two different diets: livers from 10 nestlings raised on a high protein diet (HP) for 4 d and livers from 12 nestlings raised on the HP diet for 3 d and then switched to a high carbohydrate diet (HC) for 1 d. The protocol enabled the detection of 52 polar and nine non-polar metabolites in ¹H NMR spectra of the extracts. We analyzed the lipophilic metabolites by one-way ANOVA to assess statistically significant concentration differences between the two groups. The results of our studies demonstrate that the protocol described here can be exploited for high-throughput screening of small quantities of liver tissue (approx. 100 mg wet mass) obtainable from small animals.

  10. MSM, an Efficient Workflow for Metabolite Identification Using Hybrid Linear Ion Trap Orbitrap Mass Spectrometer

    Cho, Robert; Huang, Yingying; Schwartz, Jae C.; Chen, Yan; Carlson, Timothy J.; Ma, Ji

    2012-05-01

    Identification of drug metabolites can often yield important information regarding clearance mechanism, pharmacologic activity, or toxicity for drug candidate molecules. Additionally, the identification of metabolites can provide beneficial structure-activity insight to help guide lead optimization efforts towards molecules with optimal metabolic profiles. There are challenges associated with detecting and identifying metabolites in the presence of complex biological matrices, and new LC-MS technologies have been developed to meet these challenges. In this report, we describe the development of an experimental approach that applies unique features of the hybrid linear ion trap Orbitrap mass spectrometer to streamline in vitro and in vivo metabolite identification experiments. The approach, referred to as MSM, utilizes multiple collision cells, dissociation methods, mass analyzers, and detectors. With multiple scan types and different dissociation modes built into one experimental method, along with flexible post-acquisition analysis options, the MSM workflow offers an attractive option to fast and reliable identification of metabolites in different kinds of in vitro and in vivo samples. The MSM workflow was successfully applied to metabolite identification analysis of verapamil in both in vitro rat hepatocyte incubations and in vivo rat bile samples.

  11. Monitoring of thiopurine metabolites in patients with inflammatory bowel disease-what is actually measured?

    Vikingsson, Svante; Carlsson, Björn; Almer, Sven H C; Peterson, Curt

    2009-06-01

    Azathioprine and 6-mercaptopurine are often used in the treatment of patients with inflammatory bowel disease (IBD). They are prodrugs and undergo a complex metabolism to active and inactive metabolites. Thiopurine treatment is monitored in many laboratories by measuring metabolite concentrations in erythrocytes (red blood cells). The metabolites of interest are not measured directly but as hydrolysis products, which can be produced from several metabolites. The aim of this study was to examine which metabolites are actually measured during routine monitoring. Samples from 18 patients treated with a thiopurine were analyzed by a typical routine high-performance liquid chromatography method for therapeutic drug monitoring and by a newly developed specific method measuring thioguanosine monophosphate (TGMP), thioguanosine diphosphate (TGDP), and thioguanosine triphosphate (TGTP), as well as methylthioinosine monophosphate (meTIMP), and the results were compared. 6-Thioguanine nucleotide (TGN) values detected by the routine method were 69% (range 40%-90%) of the sum of TGMP, TGDP, and TGTP measured by the specific method. TGTP and TGDP contributed 85% (range 78%-90%) and 14% (range 10%-21%) of the TGN total, respectively. Thioguanosine was not found in any patient sample. The concentration of meTIMP obtained by the routine method was 548% of the value obtained by the specific method (range 340%-718%). The difference in TGN measurements between the routine and specific methods can be explained by low hydrolysis efficiency in the routine method, although the most likely explanation for the difference in meTIMP values is that not yet identified metabolites are codetermined in the routine high-performance liquid chromatography method. Concentrations reported as TGN during therapeutic drug monitoring of thiopurine metabolites consist of TGDP and TGTP with a minor contribution of the TGMP. Concentrations reported as meTIMP or methyl mercaptopurine consist in part of me

  12. Effects of 14-day oral low dose selenium nanoparticles and selenite in rat—as determined by metabolite pattern determination

    Hadrup, Niels; Löschner, Katrin; Skov, Kasper

    2016-01-01

    Selenium (Se) is an essential element with a small difference between physiological and toxic doses. To provide more effective and safe Se dosing regimens, as compared to dosing with ionic selenium, nanoparticle formulations have been developed. However, due to the nano-formulation, unexpected...... toxic effects may occur. We used metabolite pattern determination in urine to investigate biological and/or toxic effects in rats administered nanoparticles and for comparison included ionic selenium at an equimolar dose in the form of sodium selenite. Low doses of 10 and 100 fold the recommended human...

  13. Untargeted metabolomics of colonic digests reveals kynurenine pathway metabolites, dityrosine and 3-dehydroxycarnitine as red versus white meat discriminating metabolites

    Rombouts, Caroline; Hemeryck, Lieselot Y.; Van Hecke, Thomas; De Smet, Stefaan; De Vos, Winnok H.; Vanhaecke, Lynn

    2017-01-01

    Epidemiological research has demonstrated that the consumption of red meat is an important risk factor for the development of colorectal cancer (CRC), diabetes mellitus and cardiovascular diseases. However, there is no holistic insight in the (by-) products of meat digestion that may contribute to disease development. To address this hiatus, an untargeted mass spectrometry (MS)-based metabolomics approach was used to create red versus white meat associated metabolic fingerprints following in vitro colonic digestion using the fecal inocula of ten healthy volunteers. Twenty-two metabolites were unequivocally associated with simulated colonic digestion of red meat. Several of these metabolites could mechanistically be linked to red meat-associated pathways including N’-formylkynurenine, kynurenine and kynurenic acid (all involved in tryptophan metabolism), the oxidative stress marker dityrosine, and 3-dehydroxycarnitine. In conclusion, the used MS-based metabolomics platform proved to be a powerful platform for detection of specific metabolites that improve the understanding of the causal relationship between red meat consumption and associated diseases. PMID:28195169

  14. Isolasi dan Identifikasi Senyawa Metabolit Sekunder Ekstrak n-Heksan dari Umbi Lobak (Raphanus Sativus Lamk

    Ummi Zahra

    2013-01-01

    Full Text Available Isolation and identification of secondary metabolite compound in extract of n-Hexane in Umbi Lobak (Raphanus sativus Lamk have been carried out. The purpose of this research is to know secondary metabolite compound which is contained in Umbi Lobak (Raphanus sativus Lamk which obtained from Gowa. The compound was obtained by isolation process that consists of several steps including extraction, fractination, purification, and identification. Extraction was carried out using maceration with n- hexane. The identification has done by phytochemistry test, melting point, solubility, TLC, and IR spectroscopy. The result of research found out that the obtained compound was the steroid compound, with melt point 133-133,5 oC and had positive  reaction toward Lieberman Burchad reagents, where the Lieberman Burchad reagent resulting is green which perfectly solved in n-hexane, bit solved in methanol, and could not be solved in aceton. TLC analysis showed a stain in three scales different solvent and the result of elucidation structure in IR spectrophotometer showed that compound which get is β sitosterol.

  15. Correlative analysis of metabolite profiling of Danggui Buxue Tang in rat biological fluids by rapid resolution LC-TOF/MS.

    Li, Chang-Yin; Qi, Lian-Wen; Li, Ping

    2011-04-28

    In this work, the metabolite profiles of Danggui Buxue Tang (DBT) in rat bile and plasma were qualitatively described, and the possible metabolic pathways of DBT were subsequently proposed. Emphasis was put on correlative analysis of metabolite profiling in different biological fluids. After oral administration of DBT, bile and plasma samples were collected and pretreated by solid phase extraction. Rapid resolution liquid chromatography coupled to time-of-flight mass spectrometry (RRLC-TOFMS) was used for characterization of DBT-related compounds (parent compounds and metabolites) in biological matrices. A total of 142 metabolites were detected and tentatively identified from the drug-containing bile and plasma samples. Metabolite profiling shows that rat bile contained relatively more glutathione-derived conjugates, more saponins compounds and more diverse forms of metabolites than urine. The metabolite profile in plasma revealed that glucuronide conjugates of isoflavonoids, dimmers, acetylcysteine conjugates and parent form of phthalides, as well as saponin aglycones were the major circulating forms of DBT. Collectively, the metabolite profile analysis of DBT in different biological matrices provided a comprehensive understanding of the in vivo metabolic fates of constituents in DBT. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Histogram analysis of ADC in rectal cancer: associations with different histopathological findings including expression of EGFR, Hif1-alpha, VEGF, p53, PD1, and KI 67. A preliminary study.

    Meyer, Hans Jonas; Höhn, Annekathrin; Surov, Alexey

    2018-04-06

    Functional imaging modalities like Diffusion-weighted imaging are increasingly used to predict tumor behavior like cellularity and vascularity in different tumors. Histogram analysis is an emergent imaging analysis, in which every voxel is used to obtain a histogram and therefore statistically information about tumors can be provided. The purpose of this study was to elucidate possible associations between ADC histogram parameters and several immunhistochemical features in rectal cancer. Overall, 11 patients with histologically proven rectal cancer were included into the study. There were 2 (18.18%) females and 9 males with a mean age of 67.1 years. KI 67-index, expression of p53, EGFR, VEGF, and Hif1-alpha were semiautomatically estimated. The tumors were divided into PD1-positive and PD1-negative lesions. ADC histogram analysis was performed as a whole lesion measurement using an in-house matlab application. Spearman's correlation analysis revealed a strong correlation between EGFR expression and ADCmax (p=0.72, P=0.02). None of the vascular parameters (VEGF, Hif1-alpha) correlated with ADC parameters. Kurtosis and skewness correlated inversely with p53 expression (p=-0.64, P=0.03 and p=-0.81, P=0.002, respectively). ADCmedian and ADCmode correlated with Ki67 (p=-0.62, P=0.04 and p=-0.65, P=0.03, respectively). PD1-positive tumors showed statistically significant lower ADCmax values in comparison to PD1-negative tumors, 1.93 ± 0.36 vs 2.32 ± 0.47×10 -3 mm 2 /s, p=0.04. Several associations were identified between histogram parameter derived from ADC maps and EGFR, KI 67 and p53 expression in rectal cancer. Furthermore, ADCmax was different between PD1 positive and PD1 negative tumors indicating an important role of ADC parameters for possible future treatment prediction.

  17. Analytical methodologies for broad metabolite coverage of exhaled breath condensate.

    Aksenov, Alexander A; Zamuruyev, Konstantin O; Pasamontes, Alberto; Brown, Joshua F; Schivo, Michael; Foutouhi, Soraya; Weimer, Bart C; Kenyon, Nicholas J; Davis, Cristina E

    2017-09-01

    Breath analysis has been gaining popularity as a non-invasive technique that is amenable to a broad range of medical uses. One of the persistent problems hampering the wide application of the breath analysis method is measurement variability of metabolite abundances stemming from differences in both sampling and analysis methodologies used in various studies. Mass spectrometry has been a method of choice for comprehensive metabolomic analysis. For the first time in the present study, we juxtapose the most commonly employed mass spectrometry-based analysis methodologies and directly compare the resultant coverages of detected compounds in exhaled breath condensate in order to guide methodology choices for exhaled breath condensate analysis studies. Four methods were explored to broaden the range of measured compounds across both the volatile and non-volatile domain. Liquid phase sampling with polyacrylate Solid-Phase MicroExtraction fiber, liquid phase extraction with a polydimethylsiloxane patch, and headspace sampling using Carboxen/Polydimethylsiloxane Solid-Phase MicroExtraction (SPME) followed by gas chromatography mass spectrometry were tested for the analysis of volatile fraction. Hydrophilic interaction liquid chromatography and reversed-phase chromatography high performance liquid chromatography mass spectrometry were used for analysis of non-volatile fraction. We found that liquid phase breath condensate extraction was notably superior compared to headspace extraction and differences in employed sorbents manifested altered metabolite coverages. The most pronounced effect was substantially enhanced metabolite capture for larger, higher-boiling compounds using polyacrylate SPME liquid phase sampling. The analysis of the non-volatile fraction of breath condensate by hydrophilic and reverse phase high performance liquid chromatography mass spectrometry indicated orthogonal metabolite coverage by these chromatography modes. We found that the metabolite coverage

  18. Characteristic differences in metabolite profile in male and female

    Piper betle is a dioecious pan-Asiatic plant having cultural and medicinal uses. It belongs to the family Piperaceae and is a native of the tropics although it is also cultivated in subtropical areas. Flowering in P. betle occurs only in tropical regions. Due to lack of inductive floral cycles the plant remains in its vegetative state in ...

  19. Differences in compassion fatigue, symptoms of posttraumatic stress disorder and relationship satisfaction, including sexual desire and functioning, between male and female detectives who investigate sexual offenses against children: a pilot study.

    Lane, Eric J; Lating, Jeffrey M; Lowry, Jenny L; Martino, Traci P

    2010-01-01

    Law enforcement detectives who work with traumatized individuals, especially children who were victims of sexual abuse or assault, are likely to experience job-related emotional distress. The purpose of this study was to examine the relations among compassion fatigue, probable PTSD symptoms, and personal relationship satisfaction, including communication and sexual satisfaction, in a sample of 47 male and female detectives. Responses to the administered questionnaires indicated a relation between compassion fatigue symptoms and probable PTSD symptoms. There also were compelling gender differences. For example, for male detectives, open communication with their spouse or significant other was negatively correlated with burnout, indicating the more open the communication, the lower the reported burnout. However for female detectives there was a negative correlation between open communication with spouse or significant other and compassion satisfaction, suggesting that more open communication was related to lower levels of satisfaction with their ability to be a professional caregiver Furthermore, although stepwise regression analysis indicated that years of service as a detective is independently associated with sexual desire, female detectives evidenced less sexual desire and more difficulty with sexual functioning than did male detectives. Implications of these preliminary findings are discussed and limitations addressed.

  20. Metabolite production by species of Stemphylium

    Olsen, Kresten Jon Kromphardt; Rossman, Amy; Andersen, Birgitte

    2018-01-01

    metabolites were found to be important for distinguishing species, while some unknown metabolites were also found to have important roles in distinguishing species of Stemphylium. This study is the first of its kind to investigate the chemical potential of Stemphylium across the whole genus.......Morphology and phylogeny has been used to distinguish members of the plant pathogenic fungal genus Stemphylium. A third method for distinguishing species is by chemotaxonomy. The main goal of the present study was to investigate the chemical potential of Stemphylium via HPLC-UV-MS analysis, while...

  1. Animal bioavailability of defined xenobiotic lignin metabolites

    Sandermann, H. Jr.; Arjmand, M.; Gennity, I.; Winkler, R.; Struble, C.B.; Aschbacher, P.W.

    1990-01-01

    Lignin has been recognized as a major component of bound pesticide residues in plants and is thought to be undigestible in animals. Two defined ring-U- 14 C-labeled chloroaniline/lignin metabolites have now been fed to rats, where a release of ∼66% of the bound xenobiotic occurred in the form of simple chloroaniline derivatives. The observed high degree of bioavailability indicates that bound pesticidal residues may possess ecotoxicological significance. In parallel studies, the white-rot fungus Phanerochaete chrysosporium was more efficient, and a soil system was much less efficient, in the degradation of the [ring-U- 14 C]chloroaniline/lignin metabolites

  2. Bacterial dynamics and metabolite changes in solid-state acetic acid fermentation of Shanxi aged vinegar.

    Li, Sha; Li, Pan; Liu, Xiong; Luo, Lixin; Lin, Weifeng

    2016-05-01

    Solid-state acetic acid fermentation (AAF), a natural or semi-controlled fermentation process driven by reproducible microbial communities, is an important technique to produce traditional Chinese cereal vinegars. Highly complex microbial communities and metabolites are involved in traditional Chinese solid-state AAF, but the association between microbiota and metabolites during this process are still poorly understood. In this study, we performed amplicon 16S rRNA gene sequencing on the Illumina MiSeq platform, PCR-denaturing gradient gel electrophoresis, and metabolite analysis to trace the bacterial dynamics and metabolite changes under AAF process. A succession of bacterial assemblages was observed during the AAF process. Lactobacillales dominated all the stages. However, Acetobacter species in Rhodospirillales were considerably accelerated during AAF until the end of fermentation. Quantitative PCR results indicated that the biomass of total bacteria showed a "system microbe self-domestication" process in the first 3 days, and then peaked at the seventh day before gradually decreasing until the end of AAF. Moreover, a total of 88 metabolites, including 8 organic acids, 16 free amino acids, and 66 aroma compounds were detected during AAF. Principal component analysis and cluster analyses revealed the high correlation between the dynamics of bacterial community and metabolites.

  3. Characterization of rhizobacteria associated to maize crop in IAA, siderophores and salicylic acid metabolite production

    Annia Hernández

    2004-01-01

    Full Text Available It has been demonstrated that rhizobacteria are able to produce metabolites having agricultural interest, including salicylic acid, the siderophores and phytohormones. Indol acetic acid (IAA is the most well-known and studied auxin, playing a governing role in culture growth. The object of this work was to characterise rhizobacteria associated with the maize crop in terms of producing IAA, siderophores and salicylic acid metabolites. Burkholderia cepacia and Pseudomonas fluorescens strains previously isolated from maize Francisco variety rhizosphere were used. Colorimetric and chromatographic techniques for detecting these metabolites were studied; multi-variable analysis of hierarchic conglomerate and complete ligament were used for selecting the best strains for producing metabolites of interest. These results demonstrated that all rhizobacteria strains studied produced IAA, siderophores and salicylic acid metabolites. Burkholderia cepacia MBf21, MBp1, MBp2, MBf22, MBp3, MBf20, MBf 15 and Pseudomonas fluorescens MPp4strains have presented the greatest production of these metabolites, showing that these strains could be used in promoting vegetal growth in economically important cultures. Key words: Pseudomonas fluorescens, Burkholderia cepacia, IAA, siderophore, salicylic acid.

  4. Metabolite Profiling of Root Exudates of Common Bean under Phosphorus Deficiency

    Keitaro Tawaraya

    2014-07-01

    Full Text Available Root exudates improve the nutrient acquisition of plants and affect rhizosphere microbial communities. The plant nutrient status affects the composition of root exudates. The purpose of this study was to examine common bean (Phaseolus vulgaris L. root exudates under phosphorus (P deficiency using a metabolite profiling technique. Common bean plants were grown in a culture solution at P concentrations of 0 (P0, 1 (P1 and 8 (P8 mg P L−1 for 1, 10 and 20 days after transplanting (DAT. Root exudates were collected, and their metabolites were determined by capillary electrophoresis time-of-flight mass spectrometry (CE-TOF MS. The shoot P concentration and dry weight of common bean plants grown at P0 were lower than those grown at P8. One hundred and fifty-nine, 203 and 212 metabolites were identified in the root exudates, and 16% (26/159, 13% (26/203 and 9% (20/212 of metabolites showed a P0/P8 ratio higher than 2.0 at 1, 10 and 20 DAT, respectively. The relative peak areas of several metabolites, including organic acids and amino acids, in root exudates were higher at P0 than at P8. These results suggest that more than 10% of primary and secondary metabolites are induced to exude from roots of common bean by P deficiency.

  5. Robust volcano plot: identification of differential metabolites in the presence of outliers.

    Kumar, Nishith; Hoque, Md Aminul; Sugimoto, Masahiro

    2018-04-11

    The identification of differential metabolites in metabolomics is still a big challenge and plays a prominent role in metabolomics data analyses. Metabolomics datasets often contain outliers because of analytical, experimental, and biological ambiguity, but the currently available differential metabolite identification techniques are sensitive to outliers. We propose a kernel weight based outlier-robust volcano plot for identifying differential metabolites from noisy metabolomics datasets. Two numerical experiments are used to evaluate the performance of the proposed technique against nine existing techniques, including the t-test and the Kruskal-Wallis test. Artificially generated data with outliers reveal that the proposed method results in a lower misclassification error rate and a greater area under the receiver operating characteristic curve compared with existing methods. An experimentally measured breast cancer dataset to which outliers were artificially added reveals that our proposed method produces only two non-overlapping differential metabolites whereas the other nine methods produced between seven and 57 non-overlapping differential metabolites. Our data analyses show that the performance of the proposed differential metabolite identification technique is better than that of existing methods. Thus, the proposed method can contribute to analysis of metabolomics data with outliers. The R package and user manual of the proposed method are available at https://github.com/nishithkumarpaul/Rvolcano .

  6. MetaboSearch: tool for mass-based metabolite identification using multiple databases.

    Bin Zhou

    Full Text Available Searching metabolites against databases according to their masses is often the first step in metabolite identification for a mass spectrometry-based untargeted metabolomics study. Major metabolite databases include Human Metabolome DataBase (HMDB, Madison Metabolomics Consortium Database (MMCD, Metlin, and LIPID MAPS. Since each one of these databases covers only a fraction of the metabolome, integration of the search results from these databases is expected to yield a more comprehensive coverage. However, the manual combination of multiple search results is generally difficult when identification of hundreds of metabolites is desired. We have implemented a web-based software tool that enables simultaneous mass-based search against the four major databases, and the integration of the results. In addition, more complete chemical identifier information for the metabolites is retrieved by cross-referencing multiple databases. The search results are merged based on IUPAC International Chemical Identifier (InChI keys. Besides a simple list of m/z values, the software can accept the ion annotation information as input for enhanced metabolite identification. The performance of the software is demonstrated on mass spectrometry data acquired in both positive and negative ionization modes. Compared with search results from individual databases, MetaboSearch provides better coverage of the metabolome and more complete chemical identifier information.The software tool is available at http://omics.georgetown.edu/MetaboSearch.html.

  7. Identification, quantification, spatiotemporal distribution and genetic variation of major latex secondary metabolites in the common dandelion (Taraxacum officinale agg.).

    Huber, Meret; Triebwasser-Freese, Daniella; Reichelt, Michael; Heiling, Sven; Paetz, Christian; Chandran, Jima N; Bartram, Stefan; Schneider, Bernd; Gershenzon, Jonathan; Erb, Matthias

    2015-07-01

    The secondary metabolites in the roots, leaves and flowers of the common dandelion (Taraxacum officinale agg.) have been studied in detail. However, little is known about the specific constituents of the plant's highly specialized laticifer cells. Using a combination of liquid and gas chromatography, mass spectrometry and nuclear magnetic resonance spectrometry, we identified and quantified the major secondary metabolites in the latex of different organs across different growth stages in three genotypes, and tested the activity of the metabolites against the generalist root herbivore Diabrotica balteata. We found that common dandelion latex is dominated by three classes of secondary metabolites: phenolic inositol esters (PIEs), triterpene acetates (TritAc) and the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G). Purification and absolute quantification revealed concentrations in the upper mgg(-1) range for all compound classes with up to 6% PIEs, 5% TritAc and 7% TA-G per gram latex fresh weight. Contrary to typical secondary metabolite patterns, concentrations of all three classes increased with plant age. The highest concentrations were measured in the main root. PIE profiles differed both quantitatively and qualitatively between plant genotypes, whereas TritAc and TA-G differed only quantitatively. Metabolite concentrations were positively correlated within and between the different compound classes, indicating tight biosynthetic co-regulation. Latex metabolite extracts strongly repelled D. balteata larvae, suggesting that the latex constituents are biologically active. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Parâmetros ruminal, sangüíneo e urinário e digestibilidade de nutrientes em novilhas leiteiras recebendo diferentes níveis de monensina Effects of different dietary levels of monensin on nutrient digestibility and on ruminal, blood and urinary metabolites in dairy heifers

    Marcus Vinicius Morais de Oliveira

    2005-12-01

    Full Text Available Objetivou-se verificar a influência da inclusão de diferentes níveis do ionóforo monensina sódica na dieta sobre os parâmetros ruminal, sangüíneo e urinário e a digestibilidade aparente em novilhas leiteiras. Foram coletadas amostras de líquido ruminal (imediatamente antes e duas horas após a alimentação, sangue, urina e fezes de 28 novilhas da raça Holandesa mantidas em regime de confinamento por 84 dias. As dietas possuíam 32,84% de concentrado (grão de milho, farelo de soja, uréia e mistura mineral, 33,58% de silagem de milho e 33,58% de cana-de-açúcar na matéria seca. Os níveis de ionóforo avaliados foram 0, 14, 28 e 42 mg de monensina/kg de matéria seca da dieta. O experimento foi instalado conforme delineamento inteiramente casualizado, com quatro tratamentos e sete repetições, realizando-se estudos de regressão e contrastes ortogonais. Antes da alimentação, a monensina não influenciou o pH ruminal e a concentração de amônia e dos ácidos acético, propiônico e butírico, mas promoveu redução da relação acetato:propionato. Duas horas após a alimentação, verificou-se redução do pH e da relação acetato:propionato; e aumento da concentração de ácido propiônico. O estudo de contrastes revelou que ocorreu diminuição da concentração de amônia antes da alimentação. Não foram verificadas mudanças significativas nas concentrações de glicose e uréia sangüínea. A monensina também não influenciou os consumos de matéria seca (MS, matéria orgânica, proteína bruta, extrato etéreo (EE, carboidratos totais (CHOT e fibra em detergente neutro. As digestibilidades da MS, EE e CHOT e a perda de nitrogênio urinário apresentaram respostas quadráticas.The objective of this trial was to study the effects of different dietary levels of the ionophore monensin on apparent digestibility of nutrients and on ruminal, blood, and urinary metabolites in dairy heifers. Samples of ruminal fluid (pre

  9. Metabolic Profiling and Antioxidant Assay of Metabolites from Three Radish Cultivars (Raphanus sativus

    Chang Ha Park

    2016-01-01

    Full Text Available A total of 13 anthocyanins and 33 metabolites; including organic acids, phenolic acids, amino acids, organic compounds, sugar acids, sugar alcohols, and sugars, were profiled in three radish cultivars by using high-performance liquid chromatography (HPLC and gas chromatography time-of-flight mass spectrometry (GC-TOFMS-based metabolite profiling. Total phenolics and flavonoids and their in vitro antioxidant activities were assessed. Pelargonidins were found to be the major anthocyanin in the cultivars studied. The cultivar Man Tang Hong showed the highest level of anthocyanins (1.89 ± 0.07 mg/g, phenolics (0.0664 ± 0.0033 mg/g and flavonoids (0.0096 ± 0.0004 mg/g. Here; the variation of secondary metabolites in the radishes is described, as well as their association with primary metabolites. The low-molecular-weight hydrophilic metabolite profiles were subjected to principal component analysis (PCA, hierarchical clustering analysis (HCA, Pearson’s correlation analysis. PCA fully distinguished the three radish cultivars tested. The polar metabolites were strongly correlated between metabolites that participate in the TCA cycle. The chemometrics results revealed that TCA cycle intermediates and free phenolic acids as well as anthocyanins were higher in the cultivar Man Tang Hong than in the others. Furthermore; superoxide radical scavenging activities and 1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging were investigated to elucidate the antioxidant activity of secondary metabolites in the cultivars. Man Tang Hong showed the highest superoxide radical scavenging activity (68.87% at 1000 μg/mL, and DPPH activity (20.78%, followed by Seo Ho and then Hong Feng No. 1. The results demonstrate that GC-TOFMS-based metabolite profiling, integrated with chemometrics, is an applicable method for distinguishing phenotypic variation and determining biochemical reactions connecting primary and secondary metabolism. Therefore; this study might

  10. Metabolite analysis of Mycobacterium species under aerobic and hypoxic conditions reveals common metabolic traits.

    Drapal, Margit; Wheeler, Paul R; Fraser, Paul D

    2016-08-01

    A metabolite profiling approach has been implemented to elucidate metabolic adaptation at set culture conditions in five Mycobacterium species (two fast- and three slow-growing) with the potential to act as model organisms for Mycobacterium tuberculosis (Mtb). Analysis has been performed over designated growth phases and under representative environments (nutrient and oxygen depletion) experienced by Mtb during infection. The procedure was useful in determining a range of metabolites (60-120 compounds) covering nucleotides, amino acids, organic acids, saccharides, fatty acids, glycerols, -esters, -phosphates and isoprenoids. Among these classes of compounds, key biomarker metabolites, which can act as indicators of pathway/process activity, were identified. In numerous cases, common metabolite traits were observed for all five species across the experimental conditions (e.g. uracil indicating DNA repair). Amino acid content, especially glutamic acid, highlighted the different properties between the fast- and slow-growing mycobacteria studied (e.g. nitrogen assimilation). The greatest similarities in metabolite composition between fast- and slow-growing mycobacteria were apparent under hypoxic conditions. A comparison to previously reported transcriptomic data revealed a strong correlation between changes in transcription and metabolite content. Collectively, these data validate the changes in the transcription at the metabolite level, suggesting transcription exists as one of the predominant modes of cellular regulation in Mycobacterium. Sectors with restricted correlation between metabolites and transcription (e.g. hypoxic cultivation) warrant further study to elucidate and exploit post-transcriptional modes of regulation. The strong correlation between the laboratory conditions used and data derived from in vivo conditions, indicate that the approach applied is a valuable addition to our understanding of cell regulation in these Mycobacterium species.

  11. The Role of Drug Metabolites in the Inhibition of Cytochrome P450 Enzymes.

    Mikov, Momir; Đanić, Maja; Pavlović, Nebojša; Stanimirov, Bojan; Goločorbin-Kon, Svetlana; Stankov, Karmen; Al-Salami, Hani

    2017-12-01

    Following the drug administration, patients are exposed not only to the parent drug itself, but also to the metabolites generated by drug-metabolizing enzymes. The role of drug metabolites in cytochrome P450 (CYP) inhibition and subsequent drug-drug interactions (DDIs) have recently become a topic of considerable interest and scientific debate. The list of metabolites that were found to significantly contribute to clinically relevant DDIs is constantly being expanded and reported in the literature. New strategies have been developed for better understanding how different metabolites of a drug candidate contribute to its pharmacokinetic properties and pharmacological as well as its toxicological effects. However, the testing of the role of metabolites in CYP inhibition is still not routinely performed during the process of drug development, although the evaluation of time-dependent CYP inhibition during the clinical candidate selection process may provide information on possible effects of metabolites in CYP inhibition. Due to large number of compounds to be tested in the early stages of drug discovery, the experimental approaches for assessment of CYP-mediated metabolic profiles are particularly resource demanding. Consequently, a large number of in silico or computational tools have been developed as useful complement to experimental approaches. In summary, circulating metabolites may be recognized as significant CYP inhibitors. Current data may suggest the need for an optimized effort to characterize the inhibitory potential of parent drugs metabolites on CYP, as well as the necessity to develop the advanced in vitro models that would allow a better quantitative predictive value of in vivo studies.

  12. Comparative Pharmacokinetics of Chlorpyrifos versus its Major Metabolites Following Oral Administration in the Rat

    Busby-Hjerpe, Andrea L.; Campbell, James A.; Smith, Jordan N.; Lee, Sookwang; Poet, Torka S.; Barr, Dana; Timchalk, Charles

    2010-01-31

    Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of in vivo metabolism and environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. Hence, urinary biomonitoring of TCPy, DEP and DETP may be reflective of an individual’s contact with both the parent pesticide and exposure to these metabolites. In the current study, simultaneous dosing of 13C- or 2H- isotopically labeled CPF (13Clabeled CPF, 5 13C on the TCPy ring; or 2H-labeled CPF, diethyl-D10 (deuterium labeled) on the side chain) were exploited to directly compare the pharmacokinetics and metabolism of CPF with TCPy, and DETP. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 μmol/kg; ~5mg/kg CPF). The key objective in the current study was to quantitatively evaluate the pharmacokinetics of the individual metabolites relative to their formation following a dose of CPF. Major differences in the pharmacokinetics between CPF and metabolites doses were observed within the first 3 h of exposure, due to the required metabolism of CPF to initially form TCPy and DETP. Nonetheless, once a substantial amount of CPF has been metabolized (≥ 3 h post-dosing) pharmacokinetics for both treatment groups and metabolites were very comparable. Urinary excretion rates for orally administered TCPy and DETP relative to 13C-CPF or 2H-CPF derived 13C-TCPy and 2H-DETP were consistent with blood pharmacokinetics, and the urinary clearance of metabolite dosed groups were comparable with the results for the 13C- and 2H-CPF groups. Since the pharmacokinetics of the individual metabolites were not modified by co-exposure to 3 CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact the pharmacokinetics of either.

  13. LC-MS metabolomic analysis of environmental stressor impacts on the metabolite diversity in Nephthea spp.

    Hedi Indra Januar

    2012-01-01

    Full Text Available Context: The soft coral Nephthea spp. is a source of terpenoid class that potentially has pharmaceutical properties. However, metabolite diversity and cytotoxic activity of this species are varied among coral reefs from various sites. Aim: To analyze the water quality in Nephthea spp. environment as a possible factor causing a difference in its metabolite diversity. Settings and Design: Nephthea spp. from seven sites were taken in October 2010 at the Alor District of Marine Protected Area, Indonesia. Materials and Methods: Water quality assessment was analyzed in situ and indexed by Canadian Council of Ministry Environment-Water Quality Index (CCME-WQI method. Meanwhile, metabolite diversity was analyzed by a LC-MS metabolomic method, using C18 reversed phase and gradient water-acetonitrile system. Statistical Analysis Used: Spearman′s rho and regression analysis were applied to correlate the water quality index to ecological index (richness, diversity, and evenness from LC-MS results. Results: The water quality index had a significant positive correlation and strong linear regression determinant to the total metabolite (R 2 = 0.704, particularly to semipolar metabolite richness (R 2 = 0.809, the area of terpenoid class in the organism. Conclusion: It can be concluded that water quality may serve as a major factor that affects the amount of richness in Nephthea spp. metabolites. When the water quality is lower, as environment stresses increases, it may affect the metabolite richness within direct disrupt of metabolite biosynthesis or indirect ecological means. Terpenoids are known as a soft coral antipredator (coral fishes, the amount of which depends on the water quality.

  14. Integrating Multiple Analytical Datasets to Compare Metabolite Profiles of Mouse Colonic-Cecal Contents and Feces.

    Zeng, Huawei; Grapov, Dmitry; Jackson, Matthew I; Fahrmann, Johannes; Fiehn, Oliver; Combs, Gerald F

    2015-09-11

    The pattern of metabolites produced by the gut microbiome comprises a phenotype indicative of the means by which that microbiome affects the gut. We characterized that phenotype in mice by conducting metabolomic analyses of the colonic-cecal contents, comparing that to the metabolite patterns of feces in order to determine the suitability of fecal specimens as proxies for assessing the metabolic impact of the gut microbiome. We detected a total of 270 low molecular weight metabolites in colonic-cecal contents and feces by gas chromatograph, time-of-flight mass spectrometry (GC-TOF) and ultra-high performance liquid chromatography, quadrapole time-of-flight mass spectrometry (UPLC-Q-TOF). Of that number, 251 (93%) were present in both types of specimen, representing almost all known biochemical pathways related to the amino acid, carbohydrate, energy, lipid, membrane transport, nucleotide, genetic information processing, and cancer-related metabolism. A total of 115 metabolites differed significantly in relative abundance between both colonic-cecal contents and feces. These data comprise the first characterization of relationships among metabolites present in the colonic-cecal contents and feces in a healthy mouse model, and shows that feces can be a useful proxy for assessing the pattern of metabolites to which the colonic mucosum is exposed.

  15. Integrating Multiple Analytical Datasets to Compare Metabolite Profiles of Mouse Colonic-Cecal Contents and Feces

    Huawei Zeng

    2015-09-01

    Full Text Available The pattern of metabolites produced by the gut microbiome comprises a phenotype indicative of the means by which that microbiome affects the gut. We characterized that phenotype in mice by conducting metabolomic analyses of the colonic-cecal contents, comparing that to the metabolite patterns of feces in order to determine the suitability of fecal specimens as proxies for assessing the metabolic impact of the gut microbiome. We detected a total of 270 low molecular weight metabolites in colonic-cecal contents and feces by gas chromatograph, time-of-flight mass spectrometry (GC-TOF and ultra-high performance liquid chromatography, quadrapole time-of-flight mass spectrometry (UPLC-Q-TOF. Of that number, 251 (93% were present in both types of specimen, representing almost all known biochemical pathways related to the amino acid, carbohydrate, energy, lipid, membrane transport, nucleotide, genetic information processing, and cancer-related metabolism. A total of 115 metabolites differed significantly in relative abundance between both colonic-cecal contents and feces. These data comprise the first characterization of relationships among metabolites present in the colonic-cecal contents and feces in a healthy mouse model, and shows that feces can be a useful proxy for assessing the pattern of metabolites to which the colonic mucosum is exposed.

  16. Selected Plant Metabolites Involved in Oxidation-Reduction Processes during Bud Dormancy and Ontogenetic Development in Sweet Cherry Buds (Prunus avium L.

    Susanne Baldermann

    2018-05-01

    Full Text Available Many biochemical processes are involved in regulating the consecutive transition of different phases of dormancy in sweet cherry buds. An evaluation based on a metabolic approach has, as yet, only been partly addressed. The aim of this work, therefore, was to determine which plant metabolites could serve as biomarkers for the different transitions in sweet cherry buds. The focus here was on those metabolites involved in oxidation-reduction processes during bud dormancy, as determined by targeted and untargeted mass spectrometry-based methods. The metabolites addressed included phenolic compounds, ascorbate/dehydroascorbate, reducing sugars, carotenoids and chlorophylls. The results demonstrate that the content of phenolic compounds decrease until the end of endodormancy. After a long period of constancy until the end of ecodormancy, a final phase of further decrease followed up to the phenophase open cluster. The main phenolic compounds were caffeoylquinic acids, coumaroylquinic acids and catechins, as well as quercetin and kaempferol derivatives. The data also support the protective role of ascorbate and glutathione in the para- and endodormancy phases. Consistent trends in the content of reducing sugars can be elucidated for the different phenophases of dormancy, too. The untargeted approach with principle component analysis (PCA clearly differentiates the different timings of dormancy giving further valuable information.

  17. Phenylalanine and tyrosine levels are rate-limiting factors in production of health promoting metabolites in Vitis vinifera cv. Gamay Red cell suspension.

    Manela, Neta; Oliva, Moran; Ovadia, Rinat; Sikron-Persi, Noga; Ayenew, Biruk; Fait, Aaron; Galili, Gad; Perl, Avichai; Weiss, David; Oren-Shamir, Michal

    2015-01-01

    Environmental stresses such as high light intensity and temperature cause induction of the shikimate pathway, aromatic amino acids (AAA) pathways, and of pathways downstream from AAAs. The induction leads to production of specialized metabolites that protect the cells from oxidative damage. The regulation of the diverse AAA derived pathways is still not well understood. To gain insight on that regulation, we increased AAA production in red grape Vitis vinifera cv. Gamay Red cell suspension, without inducing external stress on the cells, and characterized the metabolic effect of this induction. Increased AAA production was achieved by expressing a feedback-insensitive bacterial form of 3-deoxy- D-arabino-heptulosonate 7-phosphate synthase enzyme (AroG (*)) of the shikimate pathway under a constitutive promoter. The presence of AroG(*) protein led to elevated levels of primary metabolites in the shikimate and AAA pathways including phenylalanine and tyrosine, and to a dramatic increase in phenylpropanoids. The AroG (*) transformed lines accumulated up to 20 and 150 fold higher levels of resveratrol and dihydroquercetin, respectively. Quercetin, formed from dihydroquercetin, and resveratrol, are health promoting metabolites that are induced due to environmental stresses. Testing the expression level of key genes along the stilbenoids, benzenoids, and phenylpropanoid pathways showed that transcription was not affected by AroG (*). This suggests that concentrations of AAAs, and of phenylalanine in particular, are rate-limiting in production of these metabolites. In contrast, increased phenylalanine production did not lead to elevated concentrations of anthocyanins, even though they are also phenylpropanoid metabolites. This suggests a control mechanism of this pathway that is independent of AAA concentration. Interestingly, total anthocyanin concentrations were slightly lower in AroG(*) cells, and the relative frequencies of the different anthocyanins changed as well.

  18. Phenylalanine and tyrosine levels are rate-limiting factors in production of health promoting metabolites in Vitis vinifera cv. Gamay Red cell suspension

    Neta eManela

    2015-07-01

    Full Text Available Environmental stresses such as high light intensity and temperature cause induction of the shikimate pathway, aromatic amino acids (AAA pathways, and of pathways downstream from AAAs. The induction leads to production of specialized metabolites that protect the cells from oxidative damage. The regulation of the diverse AAA derived pathways is still not well understood. To gain insight on that regulation, we increased AAA production in red grape Vitis vinifera cv. Gamay Red cell suspension, without inducing external stress on the cells, and characterized the metabolic effect of this induction. Increased AAA production was achieved by expressing a feedback-insensitive bacterial form of 3-deoxy- D-arabino-heptulosonate 7-phosphate synthase enzyme (AroG* of the shikimate pathway under a constitutive promoter. The presence of AroG* protein led to elevated levels of primary metabolites in the shikimate and AAA pathways including phenylalanine and tyrosine, and to a dramatic increase in phenylpropanoids. The AroG* transformed lines accumulated up to 20 and 150 fold higher levels of resveratrol and dihydroquercetin, respectively. Quercetin, formed from dihydroquercetin, and resveratrol, are health promoting metabolites that are induced due to environmental stresses. Testing the expression level of key genes along the stilbenoids, benzenoids and phenylpropanoid pathways showed that transcription was not affected by AroG*. This suggests that concentrations of AAAs, and of phenylalanine in particular, are rate-limiting in production of these metabolites. In contrast, increased phenylalanine production did not lead to elevated concentrations of anthocyanins, even though they are also phenylpropanoid metabolites. This suggests a control mechanism of this pathway that is independent of AAA concentration. Interestingly, total anthocyanin concentrations were slightly lower in AroG* cells, and the relative frequencies of the different anthocyanins changed as

  19. Analysis of metabolic networks of Streptomyces leeuwenhoekii C34 by means of a genome scale model: Prediction of modifications that enhance the production of specialized metabolites.

    Razmilic, Valeria; Castro, Jean F; Andrews, Barbara; Asenjo, Juan A

    2018-07-01

    The first genome scale model (GSM) for Streptomyces leeuwenhoekii C34 was developed to study the biosynthesis pathways of specialized metabolites and to find metabolic engineering targets for enhancing their production. The model, iVR1007, consists of 1,722 reactions, 1,463 metabolites, and 1,007 genes, it includes the biosynthesis pathways of chaxamycins, chaxalactins, desferrioxamines, ectoine, and other specialized metabolites. iVR1007 was validated using experimental information of growth on 166 different sources of carbon, nitrogen and phosphorous, showing an 83.7% accuracy. The model was used to predict metabolic engineering targets for enhancing the biosynthesis of chaxamycins and chaxalactins. Gene knockouts, such as sle03600 (L-homoserine O-acetyltransferase), and sle39090 (trehalose-phosphate synthase), that enhance the production of the specialized metabolites by increasing the pool of precursors were identified. Using the algorithm of flux scanning based on enforced objective flux (FSEOF) implemented in python, 35 and 25 over-expression targets for increasing the production of chaxamycin A and chaxalactin A, respectively, that were not directly associated with their biosynthesis routes were identified. Nineteen over-expression targets that were common to the two specialized metabolites studied, like the over-expression of the acetyl carboxylase complex (sle47660 (accA) and any of the following genes: sle44630 (accA_1) or sle39830 (accA_2) or sle27560 (bccA) or sle59710) were identified. The predicted knockouts and over-expression targets will be used to perform metabolic engineering of S. leeuwenhoekii C34 and obtain overproducer strains. © 2018 Wiley Periodicals, Inc.

  20. Enzymatic production by tissue extracts of a metabolite of nicotinamide adenine dinucleotide with calcium-releasing ability

    Tich, N.R.

    1989-01-01

    This research investigated the occurrence and characterization of the metabolite in mammalian tissues. In all mammalian tissues tested, including rabbit liver, heart, spleen, kidney, and brain, the factor to convert NAD into its active metabolite was present. The conversion exhibited many characteristics of an enzymatic process such as temperature sensitivity, concentration dependence and protease sensitivity. Production of the NAD metabolite occurred within a time frame of 15-45 minutes at 37 degree C, depending upon the particular preparation. The metabolite was isolated using high performance liquid chromatography from all mammalian tissues. This purified metabolite was then tested for its effectiveness in releasing intracellular calcium in an intact cell by microinjecting it into unfertilized sea urchin eggs. These eggs undergo a massive morphological change upon fertilization which is dependent upon the release of calcium from inside the cell. Upon injection of the NAD metabolite into unfertilized eggs, this same morphological change was observed showing indirectly that the metabolite released intracellular calcium from an intact, viable cell. In addition, radioactive studies using 45 Ca 2+ loaded into permeabilized hepatocytes, indicated in preliminary studies that the NAD metabolite could also release calcium from intracellular stores of mammalian cells

  1. Alterations of urinary metabolite profile in model diabetic nephropathy

    Stec, Donald F. [Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Wang, Suwan; Stothers, Cody [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Avance, Josh [Berea College, 1916 CPO, Berea, KY 40404 (United States); Denson, Deon [Choctaw Central High School, Philadelphia, MS 39350 (United States); Harris, Raymond [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Voziyan, Paul, E-mail: paul.voziyan@vanderbilt.edu [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

    2015-01-09

    Highlights: • {sup 1}H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be

  2. Alterations of urinary metabolite profile in model diabetic nephropathy

    Stec, Donald F.; Wang, Suwan; Stothers, Cody; Avance, Josh; Denson, Deon; Harris, Raymond; Voziyan, Paul

    2015-01-01

    Highlights: • 1 H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS −/− C57BLKS and eNOS −/− C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS −/− C57BLKS and eNOS −/− C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be useful new tools in

  3. Physiological and biochemical effect of neem and other Meliaceae plants secondary metabolites against Lepidopteran insects

    Senthil-Nathan eSengottayan

    2013-12-01

    Full Text Available This review described the physiological and biochemical effects of various secondary metabolites from Meliaceae against major Lepidopteran insect pest including, Noctuidae and Pyralidae. The biochemical effect of major Meliaceae secondary metabolites were discussed more in this review. Several enzymes based on food materials have critical roles in nutritional indices (food utilization of the insect pest population. Several research work has been referred and the effect of Meliaceae secondary metabolites on feeding parameters of insects by demonstrating food consumption, approximate digestibility of consumed food, efficiency of converting the ingested food to body substance, efficiency of converting digested food to body substance and consumption index was reviewed in detail. Further how the digestive enzymes including a-Amylases, α and β- glucosidases (EC 3.2.1.1, lipases (EC 3.1.1 Proteases, serine, cysteine, and aspartic proteinases affected by the Meliaceae secondary metabolites was reviewed. Further effect of Meliaceae secondary metabolites on detoxifying enzymes have been found to react against botanical insecticides including general esterases (EST, glutathione S-transferase (GST and phosphatases was reviewed. Alkaline phosphatase (ALP, E.C.3.1.3.1 and acid phosphatase (ACP, E.C.3.1.3.2 are hydrolytic enzymes, which hydrolyze phosphomonoesters under alkaline or acid conditions, respectively. These enzymes were affected by the secondary metabolites treatment. The detailed mechanism of action was further explained in this review. Acethylcholine esterase (AChE is a key enzyme that terminates nerve impulses by catalyzing the hydrolysis of neurotransmitter, acetylcholine, in the nervous system of various organisms. How the AChE activity was altered by the Meliaceae secondary metabolites reviewed in detail.

  4. Sulindac metabolites inhibit epidermal growth factor receptor activation and expression

    Ahnen Dennis

    2005-01-01

    Full Text Available Abstract Background Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs is associated with a decreased mortality from colorectal cancer (CRC. NSAIDs induce apoptotic cell death in colon cancer cells in vitro and inhibit growth of neoplastic colonic mucosa in vivo however, the biochemical mechanisms required for these growth inhibitory effects are not well defined. We previously reported that metabolites of the NSAID sulindac downregulate extracellular-signal regulated kinase 1/2 (ERK1/2 signaling and that this effect is both necessary and sufficient for the apoptotic effects of these drugs. The goal of this project was to specifically test the hypothesis that sulindac metabolites block activation and/or expression of the epidermal growth factor (EGF receptor (EGFR. Methods HT29 human colon cancer cells were treated with EGF, alone, or in the presence of sulindac sulfide or sulindac sulfone. Cells lysates were assayed by immunoblotting for phosphorylated EGFR (pEGFR, pY1068, total EGFR, phosphorylated ERK1/2 (pERK1/2, total ERK1/2, activated caspase-3, and α-tubulin. Results EGF treatment rapidly induced phosphorylation of both EGFR and ERK1/2 in HT29 colon cancer cells. Pretreatment with sulindac metabolites for 24 h blocked EGF-induced phosphorylation of both EGFR and ERK1/2 and decreased total EGFR protein expression. Under basal conditions, downregulation of pEGFR and total EGFR was detected as early as 12 h following sulindac sulfide treatment and persisted through at least 48 h. Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1 h and 24 h, respectively, following drug treatment, and persisted through at least 72 h. EGFR downregulation by sulindac metabolites was observed in three different CRC cell lines, occurred prior to the observed downregulation of pERK1/2 and induction of apoptosis by these drugs, and was not dependent of caspase activation. Conclusion These results suggest that

  5. Optimization of metabolite basis sets prior to quantitation in magnetic resonance spectroscopy: an approach based on quantum mechanics

    Lazariev, A; Graveron-Demilly, D; Allouche, A-R; Aubert-Frécon, M; Fauvelle, F; Piotto, M; Elbayed, K; Namer, I-J; Van Ormondt, D

    2011-01-01

    High-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) is playing an increasingly important role for diagnosis. This technique enables setting up metabolite profiles of ex vivo pathological and healthy tissue. The need to monitor diseases and pharmaceutical follow-up requires an automatic quantitation of HRMAS 1 H signals. However, for several metabolites, the values of chemical shifts of proton groups may slightly differ according to the micro-environment in the tissue or cells, in particular to its pH. This hampers the accurate estimation of the metabolite concentrations mainly when using quantitation algorithms based on a metabolite basis set: the metabolite fingerprints are not correct anymore. In this work, we propose an accurate method coupling quantum mechanical simulations and quantitation algorithms to handle basis-set changes. The proposed algorithm automatically corrects mismatches between the signals of the simulated basis set and the signal under analysis by maximizing the normalized cross-correlation between the mentioned signals. Optimized chemical shift values of the metabolites are obtained. This method, QM-QUEST, provides more robust fitting while limiting user involvement and respects the correct fingerprints of metabolites. Its efficiency is demonstrated by accurately quantitating 33 signals from tissue samples of human brains with oligodendroglioma, obtained at 11.7 tesla. The corresponding chemical shift changes of several metabolites within the series are also analyzed

  6. Optimization of metabolite basis sets prior to quantitation in magnetic resonance spectroscopy: an approach based on quantum mechanics

    Lazariev, A.; Allouche, A.-R.; Aubert-Frécon, M.; Fauvelle, F.; Piotto, M.; Elbayed, K.; Namer, I.-J.; van Ormondt, D.; Graveron-Demilly, D.

    2011-11-01

    High-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) is playing an increasingly important role for diagnosis. This technique enables setting up metabolite profiles of ex vivo pathological and healthy tissue. The need to monitor diseases and pharmaceutical follow-up requires an automatic quantitation of HRMAS 1H signals. However, for several metabolites, the values of chemical shifts of proton groups may slightly differ according to the micro-environment in the tissue or cells, in particular to its pH. This hampers the accurate estimation of the metabolite concentrations mainly when using quantitation algorithms based on a metabolite basis set: the metabolite fingerprints are not correct anymore. In this work, we propose an accurate method coupling quantum mechanical simulations and quantitation algorithms to handle basis-set changes. The proposed algorithm automatically corrects mismatches between the signals of the simulated basis set and the signal under analysis by maximizing the normalized cross-correlation between the mentioned signals. Optimized chemical shift values of the metabolites are obtained. This method, QM-QUEST, provides more robust fitting while limiting user involvement and respect