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Sample records for metabolite para hydroxy

  1. Extractive biotransformation for production of metabolites of poorly soluble compounds: synthesis of 32-hydroxy-rifalazil.

    Mozhaev, Vadim V; Mozhaeva, Lyudmila V; Michels, Peter C; Khmelnitsky, Yuri L

    2008-10-01

    A novel reaction system was developed for the production of metabolites of poorly water-soluble parent compounds using mammalian liver microsomes. The system includes the selection and use of an appropriate hydrophobic polymeric resin as a reservoir for the hydrophobic parent compounds and its metabolites. The utility of the extractive biotransformation approach was shown for the production of a low-yielding, synthetically challenging 32-hydroxylated metabolite of the antibiotic rifalazil using mouse liver microsomes. To address the low solubility and reactivity of rifalazil in the predominantly aqueous microsomal catalytic system, a variety of strategies were tested for the enhanced delivery of hydrophobic substrates, including the addition of mild detergents, polyvinylpyrrolidone, glycerol, bovine serum albumin, and hydrophobic polymeric resins. The latter strategy was identified as the most suitable for the production of 32-hydroxy-rifalazil, resulting in up to 13-fold enhancement of the volumetric productivity compared with the standard aqueous system operating at the solubility limit of rifalazil. The production process was optimized for a wide range of reaction parameters; the most important for improving volumetric productivity included the type and amount of the polymeric resin, cofactor recycling system, concentrations of the biocatalyst and rifalazil, reaction temperature, and agitation rate. The optimized extractive biotransformation system was used to synthesize 32-hydroxy-rifalazil on a multimilligram scale.

  2. Microbial transformation of hydroxy metabolites of 1-oxohexyl derivatives of theobromine by Cunninghamella echinulata NRRL 1384.

    Pekala, E; Kochan, M; Carnell, A J

    2009-01-01

    The biotransformation of pentoxifylline (PTX), propentofylline (PPT) and their racemic hydroxy metabolites ((+/-)-OHPTX and (+/-)-OHPPT) by using the fungus Cunninghamella echinulata NRRL 1384. A fungus Cunninghamella echinulata NRRL 1384 was used to catalyse the (S)-selective oxidation of the racemic hydroxy metabolites: (+/-)-OHPTX and (+/-)-OHPPT and for reduction of PTX and PPT. The first oxidation step appears to be selective and relatively fast while the second reduction step is slower and more selective with PTX. Modifications involving supplementing the bioconversion with glucose give yields and enantiomeric excess (ee) values similar to those obtained without glucose. The bioconversion of (+/-)-OHPTX gave an (R)-enantiomer (LSF-lisofylline) with a higher enantiopurity (maximum approximately 93% ee) compared to the bioconversion of (+/-)-OHPPT, when the maximum ee value for (R)-OHPPT was recorded at 83%. The conversion of (+/-)-OHPTX and (+/-)-OHPPT using Cunninghamella echinulata can be recognized as a process, which may be recommended as an alternative to the methods used to obtain (R)-OHPTX and (R)-OHPPT.

  3. Identification of glucuronides as in vivo liver conjugates of seven cannabinoids and some of their hydroxy and acid metabolites.

    Harvey, D J; Martin, B R; Paton, W D

    1977-02-01

    Glucuronide conjugates of cannabidiol (CBD), 7-hydroxy-CBD, propyl-CBD, cannabinol (CBN), 7-hydroxy-CBN, CBN-7-oic acid, propyl CBN and cannabichromene have been identified as major metabolites of CBD, CBN and their propyl homologues and of cannabichromene in mouse liver. Trace amounts of the glucuronide conjugates of delta1- and delta1(6)-tetrahydrocannabinol (THC) were also detected. Identification was made by combined gas-liquid chromatographic and mass spectrometric studies of the trimethylsilyl (TMS), d9-TMS and methyl ester-TMS derivatives of the glucuronides and the TMS derivatives of the product of the reduction of the metabolites with lithium aluminium deuteride.

  4. Hydroxy and methylsulfone metabolites of polychlorinated biphenyls in the human blood and tissues

    Masuda, Yoshito; Haraguchi, Koichi [Daiichi College of Pharmaceutical Sciences, Fukuoka (Japan)

    2004-09-15

    Polychlorinated biphenyls (PCBs) are a group of chlorinated compounds which have polluted the global environment, persistently retained in wildlife and humans, and eventually affected the human health. PCBs are biotransformed to mainly hydroxy (HO-) and methylsulfone (MeSO{sub 2}-) metabolites in the animal and human tissues. About ten thousands of chemical and biological researches on PCBs, HOPCBs and MeSO{sub 2}-PCBs have been reported and reviewed so far. Letcher et al. cleverly reviewed the HO-PCBs and MeSO2-PCBs in 2000. We review the contamination of HO-PCBs and MeSO{sub 2}-PCBs in human tissues and their possible effects to human health. Different positional numberings of Cl-, HO- and MeSO{sub 2}- on biphenyl rings were used by different authors. Then, nomenclature of PCB metabolite was assessed by Maervoet et al. and they suggested to use the IUPAC chemical name and number of parent PCB congener with the subsequent assignment of the phenyl ring position number of the HO- or MeSO{sub 2}- substituent number afterward.

  5. Identification of di- and tri-substituted hydroxy and ketone metabolites of delta1-tetrahydrocannabinol in mouse liver.

    Harvey, D J; Martin, B R; Paton, W D

    1977-08-01

    In vivo liver metabolites of delta1-tetrahydrocannabinol (delta1-THC) were examined with a gas chromatograph--mass spectrometer--computer system as trimethylsilyl (TMS), [2H9]TMS and methyloxime-TMS derivatives. In addition to the reported monohydroxy, acid, and hydroxyacid metabolites, the following multiply substituted metabolites were identified: 2'',7-, 3'', 7-, and 6beta,7-dihydroxy-delta1-THC; 2'',6alpha,7-, and 3'',6alpha,7-trihydroxy-delta1-THC; 2''-, 3''-, and 7-hydroxy-6-oxo-delta1-THC, and 2'',7- and 3'',7-dihydroxy-6-oxo-delta1-THC. The ketones and hydroxyacids were reduced to common alcohols with lithium aluminium deuteride and the number of deuterium atoms in the product was used to distinguish the metabolic alcohols from those produced by reduction.

  6. [Monograph for N-Methyl-pyrrolidone (NMP) and human biomonitoring values for the metabolites 5-Hydroxy-NMP and 2-Hydroxy-N-methylsuccinimide].

    2015-10-01

    1-Methyl-pyrrolidone (NMP) is used as a solvent in many technical applications. The general population may be exposed to NMP from the use as ingredient in paint and graffiti remover, indoors also from use in paints and carpeting. Because of developmental toxic effects, the use of NMP in consumer products in the EU is regulated. The developmental effects accompanied by weak maternally toxic effects in animal experiments are considered as the critical effects by the German HBM Commission. Based on these effects, HBM-I values of 10 mg/l urine for children and of 15 mg/l for adults, respectively, were derived for the metabolites 5-Hydroxy-NMP and 2-Hydroxy-N-methylsuccinimide. HBM-II-values were set to 30 mg/l urine for children and 50 mg/l for adults, respectively. Because of similar effects of the structural analogue 1-ethyl-2-pyrrolidone (NEP), the possible mixed exposure to both compounds has to be taken into account when evaluating the total burden.

  7. Estimation of vitamin D2 vitamin D3, and their 25-hydroxy metabolites in animal tissues and foods

    Travis, B.D.

    1987-01-01

    A method was developed for the determination of vitamins D 2 and D 3 and their 25-hydroxy metabolites that could be applicable to a variety of tissues and foods. Tritiated vitamin D 3 and 25-hydroxyvitamin D 3 were used to monitor vitamin losses through the assay procedure. The first step used a saponification and extraction to free the vitamins D from their matrix and reduce the lipids. Most samples were saponified using the AOAC method, while a new procedure was developed for high fat samples. This utilized greater extraction volumes, a more polar extraction solvent, and three salt washes. Three different types of chromatography were then used to enable quantitation. The method was reproducible and accurate for the estimation of vitamin D 3 and 25-hydroxyvitamin D 3 , but not as accurate for determining vitamin D 2 and 25-hydroxyvitamin D 2 due to a lack of radioisotope standards of these compounds

  8. Detection of metabolites of lysergic acid diethylamide (LSD) in human urine specimens: 2-oxo-3-hydroxy-LSD, a prevalent metabolite of LSD.

    Poch, G K; Klette, K L; Hallare, D A; Manglicmot, M G; Czarny, R J; McWhorter, L K; Anderson, C J

    1999-03-05

    Seventy-four urine specimens previously found to contain lysergic acid diethylamide (LSD) by gas chromatography-mass spectrometry (GC-MS) were analyzed by a new procedure for the LSD metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) using a Finnigan LC-MS-MS system. This procedure proved to be less complex, shorter to perform and provides cleaner chromatographic characteristics than the method currently utilized by the Navy Drug Screening Laboratories for the extraction of LSD from urine by GC-MS. All of the specimens used in the study screened positive for LSD by radioimmunoassay (Roche Abuscreen). Analysis by GC-MS revealed detectable amounts of LSD in all of the specimens. In addition, isolysergic diethylamide (iso-LSD), a byproduct of LSD synthesis, was quantitated in 64 of the specimens. Utilizing the new LC-MS-MS method, low levels of N-desmethyl-LSD (nor-LSD), another identified LSD metabolite, were detected in some of the specimens. However, all 74 specimens contained O-H-LSD at significantly higher concentrations than LSD, iso-LSD, or nor-LSD alone. The O-H-LSD concentration ranged from 732 to 112 831 pg/ml (mean, 16340 pg/ml) by quantification with an internal standard. The ratio of O-H-LSD to LSD ranged from 1.1 to 778.1 (mean, 42.9). The presence of O-H-LSD at substantially higher concentrations than LSD suggests that the analysis for O-H-LSD as the target analyte by employing LC-MS-MS will provide a much longer window of detection for the use of LSD than the analysis of the parent compound, LSD.

  9. A urinary metabolite of {Delta}{sup 1}-tetrahydrocannabinol. The first synthesis of 4``-hydroxy-{Delta}{sup 1}-tetrahydrocannabinol-7-oic acid labelled with deuterium

    Szirmai, Maria; Odqvist, Helena [Uppsala Univ. (Sweden). Dept. of Pharmacognosy; Halldin, M.M. [Karolinska Inst., Stockholm (Sweden). Dept. of Pharmacology

    1996-04-01

    The first synthesis of 4``-hydroxy-{Delta}-{sup 1}-THC-7-oic acid, one of the three major metabolites of {Delta}{sup 1}-THC identified in human urine is discussed. Methyl 4-(3,5-dihydroxyphenyl)butanoate was prepared from 3,5-diydroxybenzoic acid in an overall yield of 15% was condensed with a terpene synthon under acidic conditions followed by hydrolysis and conversion of the 4``-carboxylic acid function to the corresponding methyl ketone using methyllithium. Reduction with NaBH{sub 4} afforded the secondary alcohol in the side-chain. Acetylation and removal of the 1,3-dithiane masking group gave the aldehyde in C-7-position which was further oxidized using NaClO{sub 2} followed by deacetylation to give the desired metabolite. The same procedure may be used for the synthesis of unlabelled 4``-hydroxy-{Delta}{sup 1}-THC-7-oic acid. (author).

  10. Metabolic engineering of Pseudomonas putida KT2440 for the production of para-hydroxy benzoic acid

    Shiqin Yu

    2016-11-01

    Full Text Available para-hydroxy benzoic acid (PHBA is the key component for preparing parabens, a common preservatives in food, drugs and personal care products, as well as high performance bioplastics such as liquid crystal polymers (LCP. Pseudomonas putida KT2440 was engineered to produce PHBA from glucose via the shikimate pathway intermediate chorismate. To obtain the PHBA production strain, chorismate lyase UbiC from Escherichia coli and a feedback resistant 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase encoded by gene aroGD146N were overexpressed individually and simultaneously. In addition, genes related to product degradation (pobA or competing for the precursor chorismate (pheA and trpE were deleted from the genome. To further improve PHBA production, the glucose metabolism repressor hexR was knocked out in order to increase erythrose-4- phosphate and NAPH supply. The best strain achieved a maximum titre of 1.73 g L-1 and a carbon yield of 18.1 % (C-mol C-mol-1 in a non-optimized fed-batch fermentation. This is to date the highest PHBA concentration produced by P. putida using a chorismate lyase.

  11. Determination of vitamin D3, vitamin D2 and their 25-hydroxy metabolites in porcine liver using high performance liquid chromatography

    Travis, B.D.; Holmes, R.P.

    1986-01-01

    A method has been developed for the determination of vitamin D 3 , vitamin D 2 and their corresponding 25-hydroxy metabolites in porcine liver. The vitamins and metabolites were estimated by extracting the non-saponifiable lipids from the saponifiable lipids from the samples. This was followed by purification and separation of the vitamin D 2 and vitamin D 3 from their 25-hydroxy metabolites using a 3 ml Bond Elut SCX column that was impregnated with silver nitrate. The two fractions were further purified on a Resolve cyanopropyl HPLC column. This column does not separate vitamin D 2 and vitamin D 3 but will separate 25-hydroxyvitamin D 2 from 25-hydroxyvitamin D 2 . Quantitation used Nova Pak C-18 and Resolve C-18 HPLC columns in series, measuring the absorbance at 254 nm. This gave baseline separation of vitamin D 2 and vitamin D 3 . Recoveries were determined by adding 3 H-vitamin D 3 and 3 H-25-hydroxyvitamin D 3 before saponification and assuming similar recoveries for the vitamin D 2 and 25-hydroxyvitamin D 2 . The method was found to be reproducible when a sample was minced and subdivided. The range of vitamin D 3 in liver was 5.2 to 14.0 ng/g. Vitamin D 2 , 25-hydroxyvitamin D 2 were not detectable. Preliminary results indicate the method may also be used with muscle, kidney and adipose, with adipose having a much higher level of vitamin D 3 than liver

  12. The pharmacokinetics of oxcarbazepine and its active metabolite 10-hydroxy-carbazepine in healthy subjects and in epileptic patients treated with phenobarbitone or valproic acid.

    Tartara, A; Galimberti, C A; Manni, R; Morini, R; Limido, G; Gatti, G; Bartoli, A; Strada, G; Perucca, E

    1993-01-01

    The kinetics of oxcarbazepine (OXC) and its active metabolite 10-hydroxy-carbazepine (10-OH-CZ) after a single oral OXC dose (600 mg) were compared in healthy control subjects and in epileptic patients treated with phenobarbitone or sodium valproate (n = 8 in each group). In all groups, serum 10-OH-CZ concentrations were much higher than those of the parent drug. In patients on valproate, the kinetics of OXC and 10-OH-CZ did not differ significantly from those observed in controls. In patients on phenobarbitone, AUC values of both OXC and 10-OH-CZ were lower than in controls (2.9 +/- 0.4 vs 5.1 +/- 0.7 microg ml(-1) h and 89 +/- 7 vs 119 +/- 10 microg ml(-1) h respectively, means +/- s.e. mean, P effect is unlikely to be of great clinical significance. PMID:12959317

  13. Cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene and 1-chloro-3-buten-2-one, two alternative metabolites of 1,3-butadiene

    Liu, Xin-Jie; Zeng, Fang-Mao; An, Jing; Yu, Ying-Xin [Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444 (China); Zhang, Xin-Yu, E-mail: xyzhang999@shu.edu.cn [Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444 (China); Elfarra, Adnan A., E-mail: elfarra@svm.vetmed.wisc.edu [Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706 (United States); Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI 53706 (United States)

    2013-08-15

    The cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene (CHB), a known in vitro metabolite of the human carcinogen 1,3-butadiene, have not previously been investigated. Because CHB can be bioactivated by alcohol dehydrogenases to yield 1-chloro-3-buten-2-one (CBO), a bifunctional alkylating agent that caused globin-chain cross-links in erythrocytes, in the present study we investigated the cytotoxic and genotoxic potential of CHB and CBO in human normal hepatocyte L02 cells using the MTT assay, the relative cloning efficiency assay and the comet assay. We also investigated the mutagenic potential of these compounds with the Ames test using Salmonella strains TA1535 and TA1537. The results provide clear evidence for CHB and CBO being both cytotoxic and genotoxic with CBO being approximately 100-fold more potent than CHB. Interestingly, CHB generated both single-strand breaks and alkali-labile sites on DNA, whereas CBO produced only alkali-labile sites. CHB did not directly result in DNA breaks, whereas CBO was capable of directly generating breaks on DNA. Interestingly, both compounds did not induce DNA cross-links as examined by the comet assay. The Ames test results showed that CHB induced point mutation but not frameshift mutation, whereas the toxic effects of CBO made it difficult to reliably assess the mutagenic potential of CBO in the two strains. Collectively, the results suggest that CHB and CBO may play a role in the mutagenicity and carcinogenicity of 1,3-butadiene. - Highlights: • 1-Chloro-2-hydroxy-3-butene (CHB) is cytotoxic and genotoxic in human liver cells. • The CHB metabolite, 1-chloro-3-buten-2-one (CBO) is ∼ 100-fold more toxic than CHB. • CHB and CBO cause DNA alkali-labile sites, but only CBO directly causes DNA breaks. • CHB is mutagenic in the Ames test, but CBO is too toxic in the assay. • The results suggest a role for CHB in 1,3-butadiene genotoxicity and mutagenicity.

  14. 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.

  15. Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism

    Wilkinson, D J; Hossain, T; Hill, D S; Phillips, B E; Crossland, H; Williams, J; Loughna, P; Churchward-Venne, T A; Breen, L; Phillips, S M; Etheridge, T; Rathmacher, J A; Smith, K; Szewczyk, N J; Atherton, P J

    2013-01-01

    Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium (fasted losses–fed gains) in protein turnover. Of all nutrients, the single amino acid leucine (Leu) possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis. While the mechanisms by which Leu is ‘sensed’ have been the subject of great scrutiny, as a branched-chain amino acid, Leu can be catabolized within muscle, thus posing the possibility that metabolites of Leu could be involved in mediating the anabolic effect(s) of Leu. Our objective was to measure muscle protein anabolism in response to Leu and its metabolite HMB. Using [1,2-13C2]Leu and [2H5]phenylalanine tracers, and GC-MS/GC-C-IRMS we studied the effect of HMB or Leu alone on MPS (by tracer incorporation into myofibrils), and for HMB we also measured muscle proteolysis (by arteriovenous (A–V) dilution). Orally consumed 3.42 g free-acid (FA-HMB) HMB (providing 2.42 g of pure HMB) exhibited rapid bioavailability in plasma and muscle and, similarly to 3.42 g Leu, stimulated muscle protein synthesis (MPS; HMB +70%vs. Leu +110%). While HMB and Leu both increased anabolic signalling (mechanistic target of rapamycin; mTOR), this was more pronounced with Leu (i.e. p70S6K1 signalling ≤90 min vs. ≤30 min for HMB). HMB consumption also attenuated muscle protein breakdown (MPB; −57%) in an insulin-independent manner. We conclude that exogenous HMB induces acute muscle anabolism (increased MPS and reduced MPB) albeit perhaps via distinct, and/or additional mechanism(s) to Leu. PMID:23551944

  16. Determination of vitamins D2, D3, K1 and K3 and some hydroxy metabolites of vitamin D3 in plasma using a continuous clean-up-preconcentration procedure coupled on-line with liquid chromatography-UV detection.

    Ortiz Boyer, F; Fernández Romero, J M; Luque de Castro, M D; Quesada, J M

    1999-03-01

    A semi-automatic procedure for the continuous clean-up and concentration of several fat-soluble vitamins prior to their separation by HPLC and UV detection is reported. The procedure is based on the use of a minicolumn packed with aminopropylsilica as sorbent located prior to the chromatographic detection system. The overall process was developed and applied to the main liposoluble vitamins (A, D2, D3, E, K1, K3) and several hydroxy metabolites of vitamin D3 [25-(OH)-D3,24,25-(OH)2-D3 and 1,25-(OH)2-D3]. All the analytes were monitored at a compromise wavelength of 270 nm. Calibration graphs were constructed between 0.01 and 100 ng ml-1 for vitamin D2 and D3 and their hydroxy metabolites, between 0.1 and 100 ng ml-1 for vitamin A, K1 and K3 and between 1 and 100 ng ml-1 for vitamin E, with excellent regression coefficients (> or = 0.9901) in all cases. The precision was established at two concentration levels with acceptable RSDs in all instances (between 3.6 and 8.7%). The method was appropriate for the determination of vitamin D2, D3, K1 and K3 and the 24,25-dihydroxy and 25-hydroxy metabolites of vitamin D3 in human plasma. The method was applied to plasma samples spiked with the target analytes and the recoveries ranged between 78 and 109%.

  17. Effect of tibolone and its principal metabolites (3α- and 3β-hydroxy, 3α-sulfate, and 4-ene derivatives) on estrone sulfatase activity in normal and cancerous human breast tissue.

    Chetrite, Gérard S; Cortes-Prieto, Joaquin; Pasqualini, Jorge R

    2011-12-01

    Tibolone (Org-OD14) is the active substance of Livial®, a synthetic steroid with the structure 7α,17α-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, possessing weak tissue-specific estrogenic, progestogenic, and androgenic properties, used to treat menopausal complaints. After oral administration, tibolone is extensively metabolized into the 3α-(Org-4904) and 3β-(Org-30126) hydroxy derivatives with estrogenic properties, its 4-ene (Org-OM38) isomer with progestogenic/androgenic activities, and the 3α-sulfate (Org-34322) derivative, a major biologically inactive circulating form. We compared the dose response of tibolone and its metabolites on estrone sulfatase activity [conversion of estrone sulfate (E1S) to estrone (E1)] in normal and cancerous human breast tissues. Tissue minces were incubated with physiological concentrations of [3H]-E1S (5×10-9M) alone or in the presence of tibolone and its metabolites (concentration range: 5×10-7to 5×10-5M) for 4 h. Tritiated E1, estradiol (E2), and E1S were separated and evaluated quantitatively by thin-layer chromatography. The sulfatase activity was significantly higher in cancerous breast but strongly inhibited by tibolone and the different metabolites, whereas 3α- and 3β-hydroxy derivatives were the most potent inhibitors. This very significant inhibitory effect of tibolone and its principal metabolites on the enzyme involved in E2biosynthesis in the human breast provides interesting perspectives to study the biological responses of these compounds in trials with breast cancer patients.

  18. A metabolite of leucine (β-hydroxy-β-methylbutyrate given to sows during pregnancy alters bone development of their newborn offspring by hormonal modulation.

    Tomasz Blicharski

    Full Text Available The effects of dietary β-hydroxy-β-methylbutyrate (HMB supplementation during gestation on bone, growth plate, and articular cartilage in newborns were determined. Thermal analysis of articular cartilage was performed to examine the structural changes in collagen. At day 70 of gestation, a total of 12 sows (Large White Polish breed, at the second parity were randomly assigned to two groups, with each group receiving either a basal diet or the same diet supplemented with 0.2 g/day HMB until the 90th day. Maternal HMB supplementation enhanced body weight, bone length, and diameter in males. It also improved geometric and mechanical properties contributing to increased bone morphology and endurance. In turn, alteration of the length was only observed in females. The positive effects were mediated by increased serum concentrations of insulin-like growth factor-1 and leptin. HMB-treatment enhanced the concentration of FSH, LH, estradiol, and testosterone. Serum TAP was enhanced by the HMB-treatment by 34% in females and 138% in males. Beneficial effects of the HMB-treatment on trabecular bone and content of proteoglycans in articular cartilage were shown. The HMB-treatment significantly changed the collagen structure in cartilages, especially in the females, which was demonstrated by the PSR analysis. Differences between the HMB-supplemented and the control females in the calorimetric peak temperatures were presumably related to different collagen fibril density in the articular cartilage structure. In summary, maternal HMB supplementation in the mid-gestation period significantly improved general growth and mechanical endurance of long bones by the influence on the somatotropic and pituitary-gonadal axes in the offspring.

  19. Simultaneous determination of flurbiprofen and its hydroxy metabolite in human plasma by liquid chromatography-tandem mass spectrometry for clinical application.

    Lee, Hye-In; Choi, Chang-Ik; Byeon, Ji-Yeong; Lee, Jung-Eun; Park, So-Young; Kim, Young-Hoon; Kim, Se-Hyung; Lee, Yun-Jeong; Jang, Choon-Gon; Lee, Seok-Yong

    2014-11-15

    Flurbiprofen (FLB) is one of the phenylalkanoic acid derivatives of non-steroidal anti-inflammatory drugs used for the management of pain and inflammation in patients with arthritis. We developed and validated a rapid and sensitive high-performance liquid chromatography analytical method utilizing tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of FLB and its major metabolite, 4'-hydroxyflurbiprofen (4'-OH-FLB), in human plasma. Probenecid was used as an internal standard (IS). After liquid-liquid extraction with methyl t-butyl ether, chromatographic separation of the two analytes was achieved using a reversed-phase Luna C18 column (2.0mm×50mm, 5μm particles) with a mobile phase of 10mM ammonium formate buffer (pH 3.5)-methanol (15:85, v/v) and quantified by MS/MS detection in ESI negative ion mode. The flow rate of the mobile phase was 250μl/min and the retention times of FLB, 4'-OH-FLB, and IS were 1.1, 0.8, and 0.9min, respectively. The calibration curves were linear over a range of 0.01-10μg/ml for FLB and 0.01-1μg/ml for 4'-OH-FLB. The lower limit of quantifications using 100μl of human plasma was 0.01μg/ml for both analytes. The mean accuracy and precision for intra- and inter-run validation of FLB and 4'-OH-FLB were all within acceptable limits. The present HPLC-MS/MS method showed improved sensitivity for quantification of the FLB and its major metabolite in human plasma compared with previously described analytical methods. The validated method was successfully applied to a pharmacokinetic study in humans. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. 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...

  1. 17,20β-P and cortisol are the main in vitro metabolites of 17-hydroxy-progesterone produced by spermiating testes of Micropogonias furnieri (Desmarest, 1823 (Perciformes: Sciaenidae

    Denise Vizziano Cantonnet

    Full Text Available The aim was to investigate the major C21 steroids produced by spermiating white croaker Micropogonias furnieri (Sciaenidae in order to establish the potential mediator of gamete maturation in males of this species. The testes steroid production at the spawning season was identified incubating the 3H-17-hydroxy-4-pregnene-3,20-dione precursor through thin layer chromatography, high pressure liquid chromatography, enzymatic oxydation, acetylation and immunochemistry analyses. 17,20β-Dihydroxy-4-pregnen-3-one (17,20β-P and 11β,17,21-Trihydroxy-4-pregnene-3,20-dione (cortisol were the main metabolites produced. Contrary to what we expected, 17,20β,21-Trihydroxy-4-pregnen-3-one was not detected. Circulating levels of 17,20β-P were undetectable in immature testes and in those at the first spermatogenesis stages, while a clear increase was observed during the whole spermatogenesis and spermiation phases (from undetectable to 1047 pg mL-1. In vitro studies together with plasma detection suggest that 17,20β-P is a good steroid candidate involved in M. furnieri testes maturation. The role of cortisol during late phases of testes development needs further studies.

  2. Plasma and urine profiles of Delta9-tetrahydrocannabinol and its metabolites 11-hydroxy-Delta9-tetrahydrocannabinol and 11-nor-9-carboxy-Delta9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes.

    Brenneisen, Rudolf; Meyer, Pascale; Chtioui, Haithem; Saugy, Martial; Kamber, Matthias

    2010-04-01

    Since 2004, cannabis has been prohibited by the World Anti-Doping Agency for all sports competitions. In the years since then, about half of all positive doping cases in Switzerland have been related to cannabis consumption. In doping urine analysis, the target analyte is 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH), the cutoff being 15 ng/mL. However, the wide urinary detection window of the long-term metabolite of Delta(9)-tetrahydrocannabinol (THC) does not allow a conclusion to be drawn regarding the time of consumption or the impact on the physical performance. The purpose of the present study on light cannabis smokers was to evaluate target analytes with shorter urinary excretion times. Twelve male volunteers smoked a cannabis cigarette standardized to 70 mg THC per cigarette. Plasma and urine were collected up to 8 h and 11 days, respectively. Total THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (THC-OH), and THC-COOH were determined after hydrolysis followed by solid-phase extraction and gas chromatography/mass spectrometry. The limits of quantitation were 0.1-1.0 ng/mL. Eight puffs delivered a mean THC dose of 45 mg. Plasma levels of total THC, THC-OH, and THC-COOH were measured in the ranges 0.2-59.1, 0.1-3.9, and 0.4-16.4 ng/mL, respectively. Peak concentrations were observed at 5, 5-20, and 20-180 min. Urine levels were measured in the ranges 0.1-1.3, 0.1-14.4, and 0.5-38.2 ng/mL, peaking at 2, 2, and 6-24 h, respectively. The times of the last detectable levels were 2-8, 6-96, and 48-120 h. Besides high to very high THC-COOH levels (245 +/- 1,111 ng/mL), THC (3 +/- 8 ng/mL) and THC-OH (51 +/- 246 ng/mL) were found in 65 and 98% of cannabis-positive athletes' urine samples, respectively. In conclusion, in addition to THC-COOH, the pharmacologically active THC and THC-OH should be used as target analytes for doping urine analysis. In the case of light cannabis use, this may allow the estimation of more recent consumption, probably influencing

  3. Effects of atorvastatin metabolites on induction of drug-metabolizing enzymes and membrane transporters through human pregnane X receptor

    Hoffart, E; Ghebreghiorghis, L; Nussler, AK; Thasler, WE; Weiss, TS; Schwab, M; Burk, O

    2012-01-01

    BACKGROUND AND PURPOSE Atorvastatin metabolites differ in their potential for drug interaction because of differential inhibition of drug-metabolizing enzymes and transporters. We here investigate whether they exert differential effects on the induction of these genes via activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR). EXPERIMENTAL APPROACH Ligand binding to PXR or CAR was analysed by mammalian two-hybrid assembly and promoter/reporter gene assays. Additionally, surface plasmon resonance was used to analyse ligand binding to CAR. Primary human hepatocytes were treated with atorvastatin metabolites, and mRNA and protein expression of PXR-regulated genes was measured. Two-hybrid co-activator interaction and co-repressor release assays were utilized to elucidate the molecular mechanism of PXR activation. KEY RESULTS All atorvastatin metabolites induced the assembly of PXR and activated CYP3A4 promoter activity. Ligand binding to CAR could not be proven. In primary human hepatocytes, the para-hydroxy metabolite markedly reduced or abolished induction of cytochrome P450 and transporter genes. While significant differences in co-activator recruitment were not observed, para-hydroxy atorvastatin demonstrated only 50% release of co-repressors. CONCLUSIONS AND IMPLICATIONS Atorvastatin metabolites are ligands of PXR but not of CAR. Atorvastatin metabolites demonstrate differential induction of PXR target genes, which results from impaired release of co-repressors. Consequently, the properties of drug metabolites have to be taken into account when analysing PXR-dependent induction of drug metabolism and transport. The drug interaction potential of the active metabolite, para-hydroxy atorvastatin, might be lower than that of the parent compound. PMID:21913896

  4. Development and validation of an LC-MS/MS method to quantify lysergic acid diethylamide (LSD), iso-LSD, 2-oxo-3-hydroxy-LSD, and nor-LSD and identify novel metabolites in plasma samples in a controlled clinical trial

    Dolder, Patrick C.; Liechti, Matthias E.; Rentsch, Katharina M.

    2018-01-01

    Lysergic acid diethylamide (LSD) is a widely used recreational drug. The aim of this study was to develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the quantification of LSD, iso-LSD, 2-oxo-3-hydroxy LSD (O-H-LSD), and nor-LSD in plasma samples from 24 healthy subjects after controlled administration of 100 μg LSD in a clinical trial. In addition, metabolites that have been recently described in in vitro studies, including lysergic acid monoethylamide...

  5. Alpha Hydroxy Acids

    ... or tenderness (8), chemical burns (6), and increased sunburn (3). The frequency of such reports for skin ... bear a statement that conveys the following information: Sunburn Alert: This product contains an alpha hydroxy acid ( ...

  6. Development and validation of an LC-MS/MS method to quantify lysergic acid diethylamide (LSD), iso-LSD, 2-oxo-3-hydroxy-LSD, and nor-LSD and identify novel metabolites in plasma samples in a controlled clinical trial.

    Dolder, Patrick C; Liechti, Matthias E; Rentsch, Katharina M

    2018-02-01

    Lysergic acid diethylamide (LSD) is a widely used recreational drug. The aim of this study was to develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the quantification of LSD, iso-LSD, 2-oxo-3-hydroxy LSD (O-H-LSD), and nor-LSD in plasma samples from 24 healthy subjects after controlled administration of 100 μg LSD in a clinical trial. In addition, metabolites that have been recently described in in vitro studies, including lysergic acid monoethylamide (LAE), lysergic acid ethyl-2-hydroxyethylamide (LEO), 2-oxo-LSD, trioxylated-LSD, and 13/14-hydroxy-LSD, should be identified. Separation of LSD and its metabolites was achieved on a reversed phase chromatography column after turbulent-flow online extraction. For the identification and quantification, a triple-stage quadrupole LC-MS/MS instrument was used. The validation data showed slight matrix effects for LSD, iso-LSD, O-H-LSD, or nor-LSD. Mean intraday and interday accuracy and precision were 105%/4.81% and 105%/4.35% for LSD, 98.7%/5.75% and 99.4%/7.21% for iso-LSD, 106%/4.54% and 99.4%/7.21% for O-H-LSD, and 107%/5.82% and 102%/5.88% for nor-LSD, respectively. The limit of quantification was 0.05 ng/mL for LSD, iso-LSD, and nor-LSD and 0.1 ng/mL for O-H-LSD. The limit of detection was 0.01 ng/mL for all compounds. The method described herein was accurate, precise, and the calibration range within the range of expected plasma concentrations. LSD was quantified in the plasma samples of the 24 subjects of the clinical trial, whereas iso-LSD, O-H-LSD, nor-LSD, LAE, LEO, 13/14-hydroxy-LSD, and 2-oxo-LSD could only sporadically be detected but were too low for quantification. © 2017 Wiley Periodicals, Inc.

  7. Measurement of 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid and its metabolite 12-oxo-5Z,8E,10E-heptadecatrienoic acid in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry

    Hofmann, U.; Seefried, S.; Meese, C.O.; Mettang, T.; Huebel, E.K.; Kuhlmann, U.

    1990-01-01

    Thromboxane A2, the predominant product of arachidonic acid metabolism in the blood platelet, is a potent vasoconstrictor and platelet agonist. During its biosynthesis from cyclic endoperoxide, 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) is formed in equal amounts. The further metabolism of HHT, catalyzed by 15-hydroxyprostaglandin dehydrogenase, leads to 12-oxo-5Z,8E,10E-heptadecatrienoic acid (Oxo-HT). Sample workup procedures are described which allow for the sensitive and reproducible determination of these two arachidonic acid metabolites in human plasma by gas chromatography-mass spectrometry in the presence of deuterated analogues as internal standards. HHT is derivatized to the pentafluorobenzyl ester tert-butyldimethylsilyl ether. In order to enable quantification of low concentrations of about 10 pg/ml in nonstimulated human plasma, the samples have to be purified by HPLC. Oxo-HT is derivatized to the pentafluorobenzyl ester, which is purified by HPLC, and then derivatized to the trimethylsilyloxime. The method allows quantification of Oxo-HT in concentrations down to 10 pg/ml plasma. The reported methods have been used to measure HHT and Oxo-HT in stimulated platelet rich plasma and to quantify HHT in nonstimulated plasma. Determination of endogenous levels of these two arachidonic acid metabolites may give new insights into the overall biosynthesis of thromboxane A2 in man

  8. The quantitation of 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) in human urine specimens, a metabolite of LSD: comparative analysis using liquid chromatography-selected ion monitoring mass spectrometry and liquid chromatography-ion trap mass spectrometry.

    Poch, G K; Klette, K L; Anderson, C

    2000-04-01

    This paper compares the potential forensic application of two sensitive and rapid procedures (liquid chromatography-mass spectrometry and liquid chromatography-ion trap mass spectrometry) for the detection and quantitation of 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) a major LSD metabolite. O-H-LSD calibration curves for both procedures were linear over the concentration range 0-8,000 pg/mL with correlation coefficients (r2) greater than 0.99. The observed limit of detection (LOD) and limit of quantitation (LOQ) for O-H-LSD in both procedures was 400 pg/mL. Sixty-eight human urine specimens that had previously been found to contain LSD by gas chromatography-mass spectrometry were reanalyzed by both procedures for LSD and O-H-LSD. These specimens contained a mean concentration of O-H-LSD approximately 16 times higher than the LSD concentration. Because both LC methods produce similar results, either procedure can be readily adapted to O-H-LSD analysis for use in high-volume drug-testing laboratories. In addition, the possibility of significantly increasing the LSD detection time window by targeting this major LSD metabolite for analysis may influence other drug-free workplace programs to test for LSD.

  9. Identification of 2,5-dimethyl-4-hydroxy-3[2H]-furanone beta-D-glucuronide as the major metabolite of a strawberry flavour constituent in humans.

    Roscher, R; Koch, H; Herderich, M; Schreier, P; Schwab, W

    1997-08-01

    2,5-Dimethyl-4-hydroxy-3[2H]furanone (Furaneol, DMHF) [3658-77-3], an important flavour constituent of strawberry fruit, was administered to four male and two female volunteers using fresh strawberries as a natural DMHF source. The amount excreted was determined by measuring urinary levels of DMHF and DMHF glucuronide. DMHF glucuronide was synthesized and the structure elucidated by mens of 1H, 13C and two dimensional nuclear magnetic resonance, as well as mass spectral data. Identification and quantification of DMHF glucuronide in human urine were achieved after solid phase extraction on XAD-2 using reverse-phase reverse-phase HPLC with either on-line UV/VIS or electrospray tandem mass spectrometry detection. Male and female volunteers excreted 59-69% and 81-94%, respectively, of the DMHF dose (total of free and glycosidically bound DMHF in strawberries) as DMHF glucuronide in urine within 24 hr. The amount of DMHF excretion was independent of the dose size and the ratio of free to glycosidically bound forms of DMHF in strawberry fruit. DMHF, DMHF glucoside and its 6'-O-malonyl derivative, naturally occurring in strawberries, were not detected in human urine.

  10. The study of DNA adduct 8-hydroxy-2‧deoxyguanosine (8-OHdG) formation of butylated hydroxyanisole (BHA) and its metabolite ter-butyl hydroquinone (TBHQ) through in vitro reaction with Calf Thymus DNA and 2‧deoxyguanosine

    Budiawan; Purwaningsih, S. S.; Cahaya, D. I.

    2017-04-01

    Butylated Hydroxyanisole (BHA) and its metabolite Tert-Butyl Hydroquinone (TBHQ) are synthetic antioxidants, commonly used as food and beverage preservatives. Although WHO declared their safety, the use of these preservatives are still controversial because some studies showed that BHA induced proliferative effects in animal testing and TBHQ is considered as carcinogenic and causes DNA cleavage. This study is aimed to analyze the interaction between Calf Thymus DNA with BHA and TBHQ which are mediated with Copper (II) Chloride. The result of the study in spectrophotometric showed there was bathochromic shift as much as 2-3 nm in DNA treated with TBHQ. The next analysis used HPLC method in stationary phase of ODS, mobile phase of 10mM Natrium Hydrogen Phosphate Buffer and Methanol (85 : 15) for DNA adduct formation, 8-Hydroxy-2-Deoxyguanosine (8-OHDG) as biomarker of risk cancer. The resultof the study showed the formation of DNA adduct 8-OHDG in the interaction between DNA and 20-500 ppm of TBHQ. The 8-OHdG formation was greatly increased by the higher concentration of TBHQ. The relative amount of 8 OHDG which formed was reached 946/105 deoxyguanosine in DNA bases. Confirmation test by LCMS/MS was characterized with the detection of mother ion peak (m/z 284); fragment ion peaks at m/z 167.9, and 139.9; at retention time 3.52 min. Meanwhile the interaction between DNA and 50-250 ppm BHA did not induce 8-OHDG.

  11. Antagonism of presynaptic dopamine receptors by phenothiazine drug metabolites

    Nowak, J.Z.; Arbilla, S.; Langer, S.Z.; Dahl, S.G.

    1990-01-01

    Electrically evoked release of dopamine from the caudate nucleus is reduced by the dopamine receptor agonists, apomorphine and bromocriptine, and facilitated by neuroleptic drugs, which act as dopamine autoreceptor antagonists. The potencies of chlorpromazine, fluphenazine, levomepromazine and their hydroxy-metabolites in modulating electrically evoked release of dopamine were examined by superfusion of rabbit caudate nucleus slices pre-incubated with 3 H-dopamine. O-Desmethyl levomepromazine, 3-hydroxy- and 7-hydroxy metabolites of chlorpromazine and levomepromazine facilitated electrically evoked release of 3 H-dopamine, having potencies similar to that of the parent compounds. 7-Hydroxy fluphenazine was less active than fluphenazine in this system. These results indicate that phenolic metabolites of chlorpromazine and levomepromazine, but not of fluphenazine, may contribute to effects of the drugs mediated by presynaptic dopamine receptors

  12. 2-Hydroxy-5-nitrobenzaldehyde

    Şamil Işık

    2009-12-01

    Full Text Available The title compound, C7H5NO4, is essentially planar, with a maximum deviation from the mean plane of 0.0116 (11 Å for the hydroxy O atom. The molecular and crystal structure are stabilized by intra- and intermolecular interactions. An intramolecular O—H...O hydrogen bond generates a six-membered ring, producing an S(6 ring motif. The C—H...O interactions result in the formation of C(5 chains and R22(8 rings forming an approximately planar network parallel to (10overline{1}. These planes are interconnected through π–π interactions [centroid–centroid distance 3.582 (2 Å].

  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. Relationships between acute toxicities of para nitrophenol (p-NP) and nitrobenzene (NB) to Daphnia magna and Photobacterium phosphoreum: Physicochemical properties and metabolites under anaerobic/aerobic sequentials

    Sponza, Delia Teresa, E-mail: delya.sponza@deu.edu.tr [Dokuz Eyluel University, Engineering Faculty, Environmental Engineering Department, Buca Kaynaklar Campus, Buca, Izmir (Turkey); Kuscu, Ozlem Selcuk [Department of Environmental Engineering, Engineering and Architecture Faculty, Sueleyman Demirel University, Cuenuer Campus, 32260 Isparta (Turkey)

    2011-01-30

    In this study, the acute toxicities of nitrobenzene (NB) and para nitrophenol (p-NP) were investigated in a high rate sequential anaerobic migrating blanket (AMBR)/aerobic completely stirred tank reactor (CSTR) using Microtox and Daphnia magna tests. After sequential anaerobic and aerobic treatments, the inhibitions in the Microtox bacteria decreased from an initial 78.10-48.20% and 4.00%, respectively, in wastewater containing 40.00 mg/L p-NP. The inhibitions of the influent wastewater containing 60.00 mg/L NB decreased from 72.10% to 45.30% and to 4.00% after anaerobic and aerobic treatment, respectively. The acute toxicity removals were 94% and 93% in the effluent of the whole sequential system, for p-NP and NB, respectively. The acute toxicity in the influent was dependent on the parent NB and p-NP concentrations and ons their physicochemical properties such as hydrophobicity, octanol/water partition coefficient and vapour density for both Microtox bacteria and Daphnia magna while the toxicity in the effluent of the anaerobic reactor was strongly dependent on the metabolites of p-NP (p-amino phenol, phenol, NH{sub 4}-N) and NB (aniline) for Microtox test. This effluent was not toxic to Daphnia magna.

  15. Relationships between acute toxicities of para nitrophenol (p-NP) and nitrobenzene (NB) to Daphnia magna and Photobacterium phosphoreum: Physicochemical properties and metabolites under anaerobic/aerobic sequentials

    Sponza, Delia Teresa; Kuscu, Ozlem Selcuk

    2011-01-01

    In this study, the acute toxicities of nitrobenzene (NB) and para nitrophenol (p-NP) were investigated in a high rate sequential anaerobic migrating blanket (AMBR)/aerobic completely stirred tank reactor (CSTR) using Microtox and Daphnia magna tests. After sequential anaerobic and aerobic treatments, the inhibitions in the Microtox bacteria decreased from an initial 78.10-48.20% and 4.00%, respectively, in wastewater containing 40.00 mg/L p-NP. The inhibitions of the influent wastewater containing 60.00 mg/L NB decreased from 72.10% to 45.30% and to 4.00% after anaerobic and aerobic treatment, respectively. The acute toxicity removals were 94% and 93% in the effluent of the whole sequential system, for p-NP and NB, respectively. The acute toxicity in the influent was dependent on the parent NB and p-NP concentrations and ons their physicochemical properties such as hydrophobicity, octanol/water partition coefficient and vapour density for both Microtox bacteria and Daphnia magna while the toxicity in the effluent of the anaerobic reactor was strongly dependent on the metabolites of p-NP (p-amino phenol, phenol, NH 4 -N) and NB (aniline) for Microtox test. This effluent was not toxic to Daphnia magna.

  16. Metabolite Profiles of Lactic Acid Bacteria in Grass Silage▿

    Broberg, Anders; Jacobsson, Karin; Ström, Katrin; Schnürer, Johan

    2007-01-01

    The metabolite production of lactic acid bacteria (LAB) on silage was investigated. The aim was to compare the production of antifungal metabolites in silage with the production in liquid cultures previously studied in our laboratory. The following metabolites were found to be present at elevated concentrations in silos inoculated with LAB strains: 3-hydroxydecanoic acid, 2-hydroxy-4-methylpentanoic acid, benzoic acid, catechol, hydrocinnamic acid, salicylic acid, 3-phenyllactic acid, 4-hydro...

  17. 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

  18. Clinical variability in 3-hydroxy-2-methylbutyryl-CoA dehydrogenase deficiency

    Ensenauer, Regina; Niederhoff, Helmut; Ruiter, Jos P. N.; Wanders, Ronald J. A.; Schwab, K. Otfried; Brandis, Matthias; Lehnert, Willy

    2002-01-01

    We report the identification of two new 7-year-old patients with 3-hydroxy-2-methylbutyryl-CoA dehydrogenase deficiency, a recently described inborn error of isoleucine metabolism. The defect is localized one step above 3-ketothiolase, resulting in a urinary metabolite pattern similar to that seen

  19. ESTRATEGIAS PARA INCREMENTAR LA PRODUCCIÓN DE METABOLITOS SECUNDARIOS EN CULTIVOS DE CÉLULAS VEGETALES STRATEGIES FOR THE IMPROVEMENT OF SECONDARY METABOLITES PRODUCTION IN PLAN CELL CULTURES

    Mario Arias Zabala

    2009-06-01

    Full Text Available El cultivo de células vegetales ha surgido como una alternativa para la obtención de metabolitos de alto valor agregado, producidos en las plantas en bajas concentraciones y para los cuales, no existen procesos de síntesis química conocidos; sin embargo, para la implementación de esta tecnología es necesario el desarrollo de estrategias que permitan incrementar la productividad de los cultivos in vitro. En este trabajo se discuten diferentes alternativas planteadas para lograr este objetivo: en la primera parte se presentan las formas para obtener líneas celulares sobreproductoras, abordando las estrategias clásicas de selección y la ingeniería genética; posteriormente se discuten los efectos que sobre el crecimiento y la producción de metabolitos secundarios pueden tener la composición química del medio de cultivo y las condiciones físicas en las que se conduce el proceso; finalmente, se presenta la elicitación como alternativa para inducir la síntesis de metabolitos secundarios en cultivos de células vegetales.The strategy of plant cell culture has become an alternative for the production of high value metabolites that are normally produced in low levels in plants and for which there is not chemical synthesis processes known. However, for the implementation of this technology it is necessary to develop strategies that let us improve the productivity of the in vitro cultures. In this work, different alternatives in order to fulfill that objective are presented: in the first part, the strategies to obtain overproducer cell lines are discussed, showing the clasic strategies for cell line selection and genetic engineering as alternatives; after that, the efect over the growth and secondary metabolite productition of the chemical medium composition and physical conditions of the process are reviewed; finally, the elicitation is presented as an alternative to induce the synthesis of secondary metabolites in plant cell cultures.

  20. Further studies on 4-hydroxy-3-methoxyphenylglycol oxidation in humans: effect of pool expansion and stereochemistry

    Mardh, G.

    1983-08-01

    The in vivo oxidation of the norepinephrine metabolite 4-hydroxy-3-methoxyphenylglycol (HMPG) to 4-hydroxy-3-methoxymandelic acid was studied in man with two different doses of deuterium-labeled HMPG and a tracer dose of (/sup 14/C)HMPG. HMPG oxidation appeared to be dose-dependent with an oxidation of 62-70% for doses below or equal to 2.2 mumol. With the use of a capillary column coated with an optically active phase (Chirasil-Val) and gas chromatography mass-spectrometry the human urinary excretions of the two stereoisomers of deuterium-labelled HMPG (free + conjugates) were found to be equal.

  1. Piperidinium 3-hydroxy-2-naphthoate

    Wen-Zhu Wan

    2008-09-01

    Full Text Available The crystals of the title salt, C5H12N+·C11H7O3−, were obtained from a methanol/water solution of 3-hydroxy-2-naphthoic acid and piperidine at room temperature. In the crystal structure, the piperidinium cations display a chair conformation and link with hydroxynaphthoate anions via N—H...O and C—H...O hydrogen bonds. An intramolecular O—H...O interaction is also present.

  2. Quantification of benzoxazinoids and their metabolites in Nordic breads

    Dihm, Katharina; Vendelbo Lind, Mads; Sundén, Henrik

    2017-01-01

    Benzoxazinoids (Bx) and their metabolites are molecules with suggested health effects in humans, found in cereal grains and consequently in cereal foods. However, to date little is known about the amount of Bx in our diet. In this study, deuterated standards 2-hydroxy-1,4-benzoxazin-3-one (HBOA-d4...

  3. Isolation and structural elucidation of tiamulin metabolites formed in liver microsomes of pigs.

    Lykkeberg, Anne Kruse; Cornett, Claus; Halling-Sørensen, Bent; Hansen, Steen Honoré

    2006-09-18

    Although the antimicrobial tiamulin is extensively metabolized in pigs, the metabolism is not well investigated. In this work the NADPH dependent metabolism of tiamulin in liver microsomes from pigs has been studied. The tiamulin metabolites formed in the incubations were analysed using LC-MS, and three major metabolites were isolated using solid phase extraction and preparative HPLC. The final structure elucidations were performed by tandem mass spectrometry and (1)H and (13)C NMR. The structures of the metabolites were found to be 2beta-hydroxy-tiamulin, 8alpha-hydroxy-tiamulin and N-deethyl-tiamulin. In addition, the LC-MS chromatograms revealed two other minor metabolites. From their chromatography and from MS(2) analysis the structures were estimated to be 2beta-hydroxy-N-deethyl-tiamulin and 8alpha-hydroxy-N-deethyl-tiamulin, but the structures were not confirmed by NMR. In these studies approximately 20% of tiamulin was deethylated, 10% was hydroxylated in the 2beta-position and 7% was hydroxylated in the 8alpha-position. About 40% of tiamulin was metabolized during the incubation conditions used. The protein precipitation in the incubations was performed using perchloric acid, and the preparative purification was performed under alkaline conditions. Therefore, the stability of the metabolites under these conditions was studied. The metabolites were found to be stable in the acid solution, but under alkaline conditions, particularly at room temperature, the stability of especially 8alpha-hydroxy-tiamulin was considerably reduced (40% loss after 1 week).

  4. 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...

  5. Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of Beta-hydroxy-Beta-methylbutyrate

    Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite Beta-hydroxy-Beta-methylbutyrate (HMB). To determine the effects of HMB on protein synthesi...

  6. Beta?hydroxy?beta?methylbutyrate supplementation and skeletal muscle in healthy and muscle?wasting conditions

    Hole?ek, Milan

    2017-01-01

    Abstract Beta?hydroxy?beta?methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that has been reported to have anabolic effects on protein metabolism. The aims of this article were to summarize the results of studies of the effects of HMB on skeletal muscle and to examine the evidence for the rationale to use HMB as a nutritional supplement to exert beneficial effects on muscle mass and function in various conditions of health and disease. The data presented here indicate ...

  7. 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.

  8. Production of hydroxy marilone C as a bioactive compound from

    Osama H. El Sayed

    2016-06-01

    Full Text Available Hydroxy marilone C is a bioactive metabolite produced from the culture broth of Streptomyces badius isolated from Egyptian soil. Hydroxy marilone C was purified and fractionated by a silica gel column with a gradient mobile phase dichloromethane (DCM:methanol then Sephadex LH-20 column using methanol as a mobile phase. It was subjected to many procedures such as infrared (IR, nuclear magnetic resonance (NMR, Mass spectroscopy (MS and UV spectroscopy for elucidation of its structure. It was evaluated for antioxidant, cytotoxicity against human alveolar basal epithelial cell line (A-549 and human breast adenocarcinoma cell line (MCF-7 and antiviral activities; showed that the maximum antioxidant activity was 78.8% at 3 mg/ml after 90 min. and the IC50 value against DPPH radical found about 1.5 mg/ml after 60 min. Using MTT assay the effect of the pure compound on the proliferation of A-549 cells and MCF-7 cells was 443 μg/ml and 147.9 μg/ml, respectively, while for detection of antiviral activity using Madin–Darby canine kidney (MDCK cells the maximum cytotoxicity was at 27.9% and IC50 was 128.1 μg/ml. The maximum concentration required for protecting 50% of the virus-infected cells against H1N1 viral cytopathogenicity (EC50 was 33.25% for 80 μg/ml. These results indicated that the hydroxy marilone C has potential antitumor and antiviral activities.

  9. Association of atmospheric concentrations of polycyclic aromatic hydrocarbons with their urinary metabolites in children and adolescents.

    Poursafa, Parinaz; Amin, Mohammad Mehdi; Hajizadeh, Yaghoub; Mansourian, Marjan; Pourzamani, Hamidreza; Ebrahim, Karim; Sadeghian, Babak; Kelishadi, Roya

    2017-07-01

    This study aims to determine the atmospheric concentrations of particulate matter 2.5 (PM 2.5 )-bounded polycyclic aromatic hydrocarbons (PAHs) and their association with their urinary metabolites in children and adolescents. This study was conducted from October 2014 to March 2016 in Isfahan, Iran. We measured 16 species of PAHs bounded to PM 2.5 by gas chromatography mass spectrometry (GC/MS) from 7 parts of the city. Moreover, PAH urinary metabolites were measured in 186 children and adolescents, randomly selected from households. Urinary metabolites consisted of 1-hydroxy naphthalene (1-naphthol), 2-hydroxy naphthalene (2-naphthol), 9-hydroxy phenanthrene (9-phenanthrol), and 1-hydroxy pyrene using GC/MS. Considering the short half-lives of PAHs, we measured the metabolites twice with 4 to 6 months of time interval. We found that the ambient concentrations of PAHs were significantly associated with their urinary metabolites. 1-hydroxy naphthalene and 2-hydroxy naphthalene concentrations showed an increase of 1.049 (95% CI: 1.030, 1.069) and 1.047 (95% CI: 1.025, 1.066) for each unit increase (1 ng/m 3 ) in ambient naphthalene. Similarly, 1-hydroxy pyrene showed an increase of 1.009 (95% CI: 1.006-1.011) for each unit increase (1 ng/m 3 ) in ambient pyrene concentration after adjustment for body mass index, physical activity level, urinary creatinine, age, and sex. The association of urinary 9-hydroxyphenanthrene and ambient phenantherene was significant in the crude model; however after adjustment for the abovementioned covariates, it was no more significant. We found significant correlations between exposure to ambient PM 2.5 -bounded PAHs and their urinary excretion. Considering the adverse health effects of PAHs in the pediatric age group, biomonitoring of PAHs should be underscored; preventive measures need to be intensified.

  10. An Assessment of those Metabolites Considered to be of Value in the Diagnosis of Exposure to Radiation; Evaluation des Metabolites Consideres Comme Utiles dans le Diagnostic des Expositions aux Rayonnements; 041e 0426 0414 ; Evaluacion de los Metabolitos Considerados Utiles para Diagnosticar la Exposicion a las Radiaciones

    Smith, H.; Bates, T. H. [United Kingdom Atomic Energy Authority, Chapelcross, Annan, Scotland (United Kingdom)

    1965-06-15

    a suivi de pres - du point de vue quantitatif - l'excretion urinaire des substances suivantes: creatinine, creatine, {beta}-nitramine (total), acide {beta}-amino isobutyrique, acide pyrrole-2-carboxylique, acide hydroxy-5-indolylacetique et indoxyle-sulfate. Bien qu'aucun des sujets n'ait subi une irradiation de l'organisme entier, on constate que des modifications de la fonction metabolique resultant de radiolesions peuvent influer sur l'excretion urinaire. Les auteurs examinent les raisons biochimiques et l'interpretation de ces formes d'excretion pour la partie de l'organisme qui a ete irradiee; cependant, au stade actuel de l'enquete, ils arrivent a la conclusion qu'une evaluation quantitative des lesions biologiques n'est pas possible. Neanmoins, ces essais peuvent faciliter au clinicien le choix de la therapie a appliquer. Des essais preliminaires sur les changements observes dans certains metabolites du plasma, chez des rats exposes a une seule dose sous-letale de rayons X, meritent d'etre extrapoles en vue de leur application a des etudes sur l'homme. On a mesure les concentrations dans le plasma des matieres ci-apres: hydroxy- 5-tryptamine, acide urique, transaminases glutamo-oxalacetique et glutamo-pyruvique du serum, 'fractions globuliniques de la proteine, phosphokinase de creatine, aminopeptidase de leucine, aminopeptidase de lysyle, callicreine, callidine, zinc et manganese. Des changements qualitatifs pourtant assez importants ont ete observes, apres irradiation, dans les teneurs du plasma en acide urique, en aminopeptidase de leucine, en aminopeptidase de lysyle, en zinc et en manganese. Les auteurs examinent la portee de ces donnees. Dans ces etudes, ils ont surtout utilize des methodes simples et rapides. (author) [Spanish] Se han examinado algunos metabolitos excretados por via urinaria por seres humanos expuestos a radiaciones X y {gamma} con fines terapeuticos. Dichos pacientes habian recibido dosis de hasta 5000 r durante un periodo comprendido

  11. Yttria hydroxy-salt binders

    Holcombe, C.E. Jr.

    1978-01-01

    Binder phase (primarily chloride or nitrate) formation was examined in YX 3 --NaOH--H 2 O, Y 2 O 3 --acid--H 2 O, and Y 2 O 3 --salt--H 2 O systems. The cementitious phase consisted mostly of plate- (or needle-) shaped hydroxy salts of the general formula Y 2 (OH)/sub 6-m/X/sub m/ nH 2 O, where m and n normally equal one. These binders were examined by x-ray diffraction and thermal analysis techniques. Nitrate binders decompose to Y 2 O 3 by 600 0 C, whereas chloride binders form oxychlorides that sublime or convert to Y 2 O 3 after oxygen replacement of chlorine (in air) at > 1000 0 C. Although nitric and hydrochloric acid solutions form porous ( 2 O 3 powder, salt solutions (i.e., NH 4 NO 3 , Mg(NO 3 ) 2 , NH 4 Cl, and YCl 3 approx. = 6H 2 O) slow the reaction considerably (48 h to 4 weeks), allowing 70- to 80%-dense cements to form. The effects of formation conditions on physical properties of binders were studied. Examination of scandium and lanthanide oxides showed that several behave in the same way as yttria

  12. Efeitos da suplementação de b-hidroxi-b-metilbutirato sobre a força e a hipertrofia Effects of b-hydroxy-b-methylbutyrate supplementation on strength and hypertrophy

    Thiago da Silveira Alvares

    2008-02-01

    Full Text Available O b-hidroxi-b-metilbutirato é um metabólito da leucina estudado devido aos seus efeitos anticatabólicos e possíveis implicações sobre os ganhos de força e massa muscular associados ao treinamento contra-resistência (conhecido como musculação. O objetivo deste trabalho foi revisar a literatura referente à suplementação de b-hidroxi-b-metilbutirato e os seus efeitos sobre força e hipertrofia em adultos jovens e idosos iniciantes ou treinados em treinamento contra-resistência. Estudos em indivíduos iniciando um programa de treinamento contra-resistência sugerem que a suplementação diária de 1,5 a 3,0g de b-hidroxi-b-metilbutirato pode trazer benefício ergogênico durante as primeiras quatro ou cinco semanas. Entretanto, à medida que o programa de treinamento evolui, tais efeitos não permanecem e os ganhos de força e massa muscular são proporcionados apenas pelo treinamento contra-resistência. Em indivíduos treinados, os resultados parecem não ser os mesmos, uma vez que, desde o início da suplementação, o b-hidroxi-b-metilbutirato não demonstra qualquer benefício adicional aos induzidos pelo treinamento contra-resistência. Alguns efeitos do b-hidroxi-b-metilbutirato na redução do colesterol total e lipoproteína de baixa densidade também foram observados, porém, devido às poucas evidências, não há recomendações para tal finalidade. Nenhum efeito adverso da suplementação foi observado, sendo, aparentemente, segura, contudo a maioria dos estudos foi realizada em curto prazo (menos de 4 semanas e em indivíduos destreinados. Assim, mais estudos são necessários para esclarecer o mecanismo fisiológico por meio do qual o b-hidroxi-b-metilbutirato exerce seus efeitos anticatabólicos em destreinados e para observar possíveis efeitos adversos.b-hydroxy-b-methylbutyrate is a leucine metabolite studied for its anticatabolic effects and potential benefits on strength and muscle mass gains associated with

  13. Mathematical modelling for fumonisin production in corn and chromatographic profile of metabolites of Fusarium verticillioides/ Modelagem matemática para fumonisinas em milho e perfil cromatográfico de metabólitos produzidos por Fusarium verticillioides

    Antônio Carlos Gerage

    2008-08-01

    Full Text Available Mycotoxin requires special attention in public health due to pathological hazard in human and animals. Among these toxins, emphasized are the fumonisin produced mainly by Fusarium verticillioides, which is primary pathogen in corn. This study aimed the development of mathematical models in fumonisin production, as well as to evaluate the chromatography profile of secondary metabolites of Fusarium verticillioides. Corn (heat-treated or not was adjusted to 15, 20 and 25% moisture content, and it was inoculated or not with F. verticillioides. These flasks were incubated at 20, 25 and 30º C for 20 days, and the fumonisins were quantified by high performance liquid chromatography (HPLC. The temperature affected the fumonisin production in higher extension than moisture content, and the highest fumonisin level was reached at 20º C with 25% moisture content. The chromatogram profiles showed many peaks with retention time which differed of fumonisin, suggesting diversity in compounds arisen from metabolic pathway, which were also from F. verticillioides. These metabolites were not observed in optimized condition for fumonisin production, showing decreased trend when other fungal growth was increased. The mathematical models predicted the fumonisin level trend at the 20th day’s performance in a real data contamination evaluated in corn, which were submitted to graphical and mathematical/ statistical validations. The mathematical modelling can be an important tool in understanding the dynamic of fumonisin production and further decision of adequate raw material destination.As micotoxinas merecem atenção especial no contexto de saúde pública por desencadearem alterações patológicas em humanos e animais. Dentre estas toxinas, destacam-se as fumonisinas, produzidas principalmente por Fusarium verticillioides, um patógeno primário de milho. O trabalho objetivou desenvolver modelos matemáticos para produção de fumonisinas, bem como avaliar o

  14. Analysis of Cannabinoids and Their Metabolites in Human Urine

    Wei, Binnian; Wang, Lanqing; Blount, Benjamin C.

    2015-01-01

    Biologically monitoring marijuana exposure from active and passive use requires both a wide linear range and sensitive detection. We have developed and validated a multifunctional method using ultrahigh performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS) for analysis of urinary Δ9-tetrahydrocannabinol (THC), cannabidiol and cannabinol, and two major metabolites of THC, 11-nor-9-carboxy-THC and 11-hydroxy-THC, in active users and particularly in people exposed...

  15. Differentiation of clobenzorex use from amphetamine abuse using the metabolite 4-hydroxyclobenzorex.

    Valtier, S; Cody, J T

    2000-10-01

    Clobenzorex (Asenlix) is an anorectic drug metabolized by the body to amphetamine, thus causing difficulty in the interpretation of amphetamine-positive drug tests. Previous studies have shown the parent drug and several metabolites are excreted in urine. Clobenzorex itself has been detected for as long as 29 h postdose using a detection limit of 1 ng/mL. Despite this fact, several amphetamine-positive samples (> or = 500 ng/mL) contained no detectable clobenzorex. Thus, the absence of clobenzorex in the urine does not exclude the possibility of its use. To more definitively assess the possibility of clobenzorex use, evaluation of another metabolite was considered. One study reported the presence of unidentified hydroxy metabolites of clobenzorex for as long as amphetamine was detected in some subjects. To assess the viability of using a hydroxy metabolite to confirm the use of clobenzorex in samples containing amphetamine, 4-hydroxyclobenzorex was synthesized for this study. This metabolite proved to be easily detected and was typically found at levels higher than amphetamine in amphetamine-positive urines, long after clobenzorex itself was no longer detected. Samples obtained from a controlled single-dose study involving the administration of clobenzorex (30 mg) were analyzed for the presence of the 4-hydroxy metabolite. The analytical procedure used acid hydrolysis followed by liquid-liquid extraction and analysis with gas chromatography-mass spectrometry by monitoring ions at m/z 125, 330, and 364. 4-Hydroxyclobenzorex and its 3-Cl regioisomer were used in the identification and quantitation of the metabolite. Peak concentrations of 4-hydroxyclobenzorex were found at approximately 1:30-5:00 h postdose and ranged from approximately 5705 to 88,410 ng/mL. Most importantly, however, all samples that contained amphetamine at > or = 500 ng/mL also contained detectable amounts of this hydroxy metabolite (LOD 10 ng/mL), making it a valuable tool in differentiating use

  16. Metabolism of carbon-14 labelled l-tryptophan, l-kynerenine and hydroxy-l-kynerenine in miners with scleroderma

    Hankes, L.V.; De Bruin, E.; Jansen, C.R.; Voster, L.; Schmaeler, M.

    1977-01-01

    Six South African white miners were studied with the 2-g l-tryptophan load test and tracer doses of L-tryptophan-7a-carbon-14, L-kynurenine-keto-carbon-14 and hydroxy-L-kynerenine-keto-carbon-14. The breath 14 CO 2 and 14 urinary metabolites were measured. When they were compared with a previous study of American women with scleroderma, similar 14 CO 2 and tryptophan metabolite excretion patterns were observed in the data from the miners. The labelled quinolinic acid excretion was more significantly elevated in the South African miners' urine than in the urine of the American women. The data from both studies suggest that some patients with scleroderma have an altered step in the tryptophan metabolic pathway after hydroxy-anthranilic acid. What relationship exists between the induction of pulmonary silicosis and the subsequent development of scleroderma, requires additional human studies

  17. Synthesis of deuterium-labelled methylphenidate, p-hydroxy-methylphenidate, ritalinic acid and p-hydroxyritalinic acid

    Patrick, K.; Kilts, C.; Breese, G.

    1982-01-01

    The synthesis of threo-dl-methylphenidate (Ritalin 1), threo-dl-p-hydroxy-methylphenidate (3), threo-dl-ritalinic acid (2), and threo-dl-p-hydroxyritalinic acid (4) with deuterium incorporated in the piperidine ring is described. These compounds were synthesized for use as internal standards for mass fragmentographic assays of methylphenidate and its metabolites. The synthetic scheme described resulted in less than 0.05% 2 H 0 in the piperidine ring in any of the preparations. (author)

  18. Preparation of ω-hydroxy pelargonic acid

    Hadi, Siti Faieza Abd; Salimon, Jumat

    2018-04-01

    Utilization of plant oil as renewable raw material for monomers and polymers in bioplastic industry has a great potential to replace conventional petroleum-based plastic usage especially in packaging and adhesive applications. One of useful monomer is ω-hydroxy pelargonic acid that can be polymerizing as biodegradable polyester. In this study, the aim is to synthesis ω-hydroxy pelargonic acid from oleic acid based on oxidation/ esterification/ saponification and reduction methodology. The yield obtained after aqueous workup is 53% and the compound structure is determined by FT-IR and 1H and 13C NMR.

  19. Biological roles and therapeutic potential of hydroxy-carboxylic acid receptors

    Kashan eAhmed

    2011-10-01

    Full Text Available In the recent past, deorphanization studies have described intermediates of energy metabolism to activate G protein-coupled receptors (GPCRs and to thereby regulate metabolic functions. GPR81, GPR109A and GPR109B, formerly known as the nicotinic acid receptor family, are encoded by clustered genes and share a high degree of sequence homology. Recently, hydroxy-carboxylic acids were identified as endogenous ligands of GPR81, GPR109A and GPR109B, and therefore these receptors have been placed into a novel receptor family of hydroxy-carboxylic acid (HCA receptors. The HCA1 receptor (GPR81 is activated by the glycolytic metabolite 2-hydroxy-propionic acid (lactate, the HCA2 receptor is activated by the ketone body 3-hydroxy-butyric acid and the HCA3 receptor (GPR109B is a receptor for the β-oxidation intermediate 3-hydroxy-octanoic acid. While HCA1 and HCA2 receptors are present in most mammalian species, the HCA3 receptor is exclusively found in humans and higher primates. HCA receptors are expressed in adipose tissue and mediate anti-lipolytic effects in adipocytes through Gi-type G-protein-dependent inhibition of adenylyl cyclase. HCA2 and HCA3 inhibit lipolysis during conditions of increased β-oxidation such as prolonged fasting, whereas HCA1 mediates the anti-lipolytic effects of insulin in the fed state. As HCA2 is a receptor for the established anti-dyslipidemic drug nicotinic acid, HCA1 and HCA3 also represent promising drug targets and several synthetic ligands for HCA receptors have been developed. In this article, we will summarize the deorphanization and pharmacological characterization of HCA receptors. Moreover, we will discuss recent progress in elucidating the physiological and pathophysiological role to further evaluate the therapeutic potential of the HCA receptor family for the treatment of metabolic disease.

  20. Radiation curable coatings containing hydroxy functional polyethers and polyesters of monoethylenic acids or hydroxy esters thereof

    Kaufman, M.L.

    1978-01-01

    Relatively water insoluble hydroxy functional monoethylenic polyethers or polyesters of monoethylenic carboxylic acids or hydroxy alkyl esters thereof are formed by adducting the monoethylenic acid or its hydroxy ester with an anhydride selected from monoepoxides, lactones, or mixtures thereof in the presence of a Lewis acid catalyst, such as BF 3 etherate, at a temperature below that at which the unsaturation is consumed, typically about 30 to 70 0 C. These adducts are of low volatility and of low toxicity and can be radiation cured in admixture with polyacrylates to form coatings having improved resistance to elevated temperature exposure

  1. [Monograph on di-2-propylheptyl phthalate (DPHP) - human biomonitoring (HBM) values for the sum of metabolites oxo-mono-propylheptyl phthalate (oxo-MPHP) and hydroxy-mono-propylheptyl phthalate (OH MPHP) in adult and child urine. Opinion of the Commission "Human Biomonitoring" of the Federal Environment Agency, Germany].

    2015-07-01

    1,2-benzenedicarboxylic acid, bis(2-propylheptyl)ester (bis(2-propylheptyl)phthalate, DPHP) is used as plasticizer for the manufacture of plastics, i.e. mainly polyvinylchloride (PVC). A subchronic feeding study with rats revealed a NOAEL (no observed adverse effect level) of 40 mg/(kg bw · d), which can be used as a point of departure (POD) for the derivation of an HBM-I value. Application of a total assessment factor of 200 leads to an estimation of 200 µg/kg bw as a tolerable daily intake of DPHP. On the basis of the results of metabolism studies with humans it is possible to calculate from the tolerable daily intake of DPHP to the tolerable concentration of specific metabolites in urine. Thus an HBM-I value of 1 mg/L morning urine for children and 1.5 mg/L morning urine for adults was derived for the sum of the oxidized monoesters oxo-MPHP and OH-MPHP, which were identified as robust and conclusive biomarkers for DPHP.

  2. Direct Amination of alpha-Hydroxy Amides

    Chandgude, Ajay L.; Dömling, Alexander

    A TiCl4-mediated reaction for the direct amination of alpha-hydroxy amides has been developed. This simple, general, additive/base/ligand-free reaction is mediated by economical TiCl4. The reaction runs under mild conditions. This highly efficient C-N bond formation protocol is valid for diverse

  3. Biotransformation of cannabidiol in mice. Identification of new acid metabolites.

    Martin, B R; Harvey, D J; Paton, W D

    1977-01-01

    The in vivo metabolism of cannabidiol (CBD) was investigated in mice. Following the ip administration of CBD to mice, livers were removed and metabolites were extracted with ethyl acetate prior to partial purification on Sephadex LH-20 columns. Fractions from the columns were converted into trimethylsilyl, d9-trimethylsilyl, and methylester-trimethylsilyl derivatives for analysis by gas-liquid chromatography-mass spectrometry. In addition, metabolites containing carboxylic acid and ketone functional groups were reduced to alcohols with lithium aluminum deuteride before trimethylsilation. A total of 22 metabolites were characterized, 14 of which had not been reported previously. The metabolites could be categorized as follows: monohydroxylated (N=2), dihydroxylated (N=3), CBD-7-oic acid, side chain hydroxy-GBD-7-oic acids (N=3), side-chain acids (N=3), 7-hydroxy-side-chain acids (N=4), 6-oxo-side-chain acids (N=3) and glucuronide conjugates (N=3). The most significant biotransformations were glucuronide conjugation and, to a lesser extent, formation of CBD-7-oic acid.

  4. Susceptibility of bacteria isolated from pigs to tiamulin and enrofloxacin metabolites

    Lykkeberg, Anne Kruse; Halling-Sørensen, Bent; Jensen, Lars Bogø

    2007-01-01

    :Susceptibilities to metabolites of tiamulin (TIA) and enrofloxacin (ENR) were tested using selected bacteria with previously defined minimal inhibitory concentrations,(,MIC). The TIA metabolites tested were: N-deethyl-tiamulin (I)TIA), 2 beta-hydroxy-tiamulin (2 beta-HTIA),and Sammhydroxy......-tiamulin (8 alpha-HTIA), and the ENR metabolites were: ciprofloxacin (CIP) and enrofloxacin N-oxide (ENR-N). Bacteria, all of porcine origin, we're selected as representatives of bacterial infections (Stap4ylococcus hyicus and Actinobacillus pleuropneumoniae), zoonotic bacteria (Campylobacter coli...

  5. Comprehensive Analysis of Tiamulin Metabolites in Various Species of Farm Animals Using Ultra-High-Performance Liquid Chromatography Coupled to Quadrupole/Time-of-Flight.

    Sun, Feifei; Yang, Shupeng; Zhang, Huiyan; Zhou, Jinhui; Li, Yi; Zhang, Jinzhen; Jin, Yue; Wang, Zhanhui; Li, Yanshen; Shen, Jianzhong; Zhang, Suxia; Cao, Xingyuan

    2017-01-11

    Tiamulin is an antimicrobial widely used in veterinary practice to treat dysentery and pneumonia in pigs and poultry. However, knowledge about the metabolism of tiamulin is very limited in farm animals. To better understand the biotransformation of tiamulin, in the present study, in vitro and in vivo metabolites of tiamulin in rats, chickens, swine, goats, and cows were identified and elucidated using ultra-high performance liquid chromatography coupled to quadrupole/time-of-flight. As a result, a total of 26 metabolites of tiamulin, identified in vitro and in vivo, and majority of metabolites were revealed for the first time. In all farm animals, tiamulin undergoes phase I metabolic routes of hydroxylation in the mutilin part (the ring system), S-oxidation and N-deethylation on side chain, and no phase II metabolite was detected. Among these, 2β- and 8α-hydroxylation and N-deethylation were the main metabolic pathways of tiamulin in farm animals. In addition, we have put forward that 8a-hydroxy-tiamulin and 8a-hydroxy-N-deethyl-tiamulin could be hydroxylated into 8a-hydroxy-mutilin, the marker residue of tiamulin in swine. Furthermore, a significant interspecies difference was observed on the metabolism of tiamulin among various farm animals. The possible marker residues for tiamulin in swine were 8α-hydroxy-tiamulin, N-deethyl-tiamulin, and 8α-hydroxy-N-deethyl-tiamulin, which were consistent with the hypothesis proposed by the European Agency for the Evaluation of Medicinal Products. However, results in present study indicated that three metabolites (2β-hydroxy-tiamulin, N-deethyl-tiamulin, and 2β-hydroxy-N-deethyl-tiamulin) of tiamulin in chickens had larger yields, which implied that 2β-hydroxy-mutilin or N-deethyl-tiamulin was more likely to be regarded as the potential marker residue of tiamulin in chickens.

  6. Analytical study of zirconium and hafnium α-hydroxy carboxylates

    Terra, V.R.

    1991-01-01

    The analytical study of zirconium and hafnium α-hydroxy carboxylates was described. For this purpose dl-mandelic, dl-p-bromo mandelic, dl-2-naphthyl glycolic, and benzilic acids were prepared. These were used in conjunction with glycolic, dl-lactic, dl-2-hydroxy isovaleric, dl-2-hydroxy hexanoic, and dl-2-hydroxy dodecanoic acids in order to synthesize the zirconium(IV) and hafnium(IV) tetrakis(α-hydroxy carboxylates). The compounds were characterized by melting point determination, infrared spectroscopy, thermogravimetric analysis, calcination to oxides and X-ray diffractometry by the powder method. (C.G.C)

  7. Oxidative metabolites of diethylstilbestrol in the fetal Syrian golden hamster

    Maydl, R.; Metzler, M.

    1984-01-01

    14 C-Diethylstilbestrol was administered orally, intraperitoneally, and intrafetally to 15-day pregnant hamsters at a dose of 20 mg/kg body weight, and the radioactivity was determined in the fetus, placenta, and maternal liver after 6 hours. Significant amounts of radioactivity were found in these tissues in every case, indicating maternal-fetal and fetal-maternal transfer of diethylstilbestrol. Part of the radioactivity found in the tissues could not be extracted even after excessive washing. This implied the presence of reactive metabolites. In the fetal and placental extracts, eight oxidative metabolites of diethylstilbestrol were identified by mass fragmentography as hydroxy- and methoxy-derivatives of diethylstilbestrol, pseudodiethylstilbestrol, and dienestrol. The presence of oxidative metabolites in the hamster fetus and the covalent binding to tissue macromolecules are possibly associated with the fetotoxic effects of diethylstilbestrol

  8. Aquatic toxicity of the macrolide antibiotic clarithromycin and its metabolites.

    Baumann, Michaela; Weiss, Klaus; Maletzki, Dirk; Schüssler, Walter; Schudoma, Dieter; Kopf, Willi; Kühnen, Ute

    2015-02-01

    The human macrolide antibiotic clarithromycin is widespread in surface waters. Our study shows that its major metabolite 14-hydroxy(R)-clarithromycin is found in surface waters in comparable amounts. This metabolite is known to be pharmacologically active. Additionally, clarithromycin is partly metabolised to N-desmethyl-clarithromycin, which has no antimicrobial activity. For clarithromycin, some ecotoxicological studies on aquatic organisms have been published. However, many of them are not conform with the scientific principles as given in the "Technical guidance for deriving environmental quality standards" (TGD-EQS), because numerous studies were poorly documented and the methods did not contain analytical measurements confirming that the exposure concentrations were in the range of ± 20% of the nominal concentrations. Ecotoxicological effects of clarithromycin and its two metabolites on the zebrafish Danio rerio (embryo test), the microcrustacean Daphnia magna, the aquatic monocotyledonous macrophyte Lemna minor, the freshwater green alga Desmodesmus subspicatus (Chlorophyta) and the cyanobacterium Anabaena flosaquae were investigated in compliance with the TGD-EQS. Environmental risk assessment was performed using ErC10 values of Anabaena, the species most sensitive to clarithromycin and 14-hydroxy(R)-clarithromycin in our testing. Based oncomparable toxicity and similar concentrations of clarithromycin and its active metabolite 14-hydroxy(R)-clarithromycin in surface waters, an additional multiplication factor of 2 to the assessment factor of 10 on the ErC10 of clarithromycin should be used. Consequently, a freshwater quality standard of 0.130 μg L(-1) is proposed for clarithromycin as the "lead substance". Taking this additional multiplication factor of 2 into account, single monitoring of clarithromycin may be sufficient, in order to reduce the number of substances listed for routine monitoring programs. Copyright © 2014 Elsevier Ltd. All rights

  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. Determination of 5-hydroxy-N-methyl-2-pyrrolidone and 2-hydroxy-N-methylsuccinimide in human plasma and urine using liquid chromatography-electrospray tandem mass spectrometry.

    Carnerup, M A; Akesson, B; Jönsson, B A

    2001-09-15

    A method for simultaneous determination of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) was developed. These compounds are metabolites from N-methyl-2-pyrrolidone (NMP), a powerful and widely used organic solvent. 5-HNMP and 2-HMSI were purified from plasma and urine by solid-phase extraction using Isolute ENV+ columns, and analysed by liquid chromatography coupled to a mass spectrometer fitted with an atmospheric pressure turbo ion spray ionisation interface in the positive ion mode. The method was validated for plasma and urine concentrations from 0.12 to 25 microg/ml. The recoveries for 5-HNMP and 2-HMSI in plasma were 99 and 98%, respectively, and in urine 111 and 106%, respectively. For 5-HNMP and 2-HMSI, the within-day precision in plasma was 1-4 and 3-6%, respectively, and in urine 2-12 and 3-10%, respectively. The corresponding data for the between-day precision was 5 and 3-6%, respectively, and 4-6 and 7-8%, respectively. The detection limit for 5-HNMP was 4 ng/ml in plasma and 120 ng/ml in urine. For 2-HMSI, it was 5 ng/ml in plasma and 85 ng/ml in urine. The method is applicable for analysis of plasma and urine samples from workers exposed to NMP.

  11. Succinct synthesis of saturated hydroxy fatty acids and

    Kaspersen, Mads Holmgaard; Jenkins, Laura; Dunlop, Julia

    2017-01-01

    Saturated hydroxy fatty acids make up a class of underexplored lipids with potentially interesting biological activities. We report a succinct and general synthetic route to saturated hydroxy fatty acids hydroxylated at position 6 or higher, and exemplify this with the synthesis of hydroxylauric ...... acids. All regioisomers of hydroxylauric acids were tested on free fatty acid receptors FFA1, FFA4 and GPR84. The results show that the introduction of a hydroxy group and its position have a high impact on receptor activity....

  12. Synthesis of tritium or deuterium labelled 19-nor-3. cap alpha. -hydroxy-5. cap alpha. -androstan-17-one from nortestosterone

    Protiva, J; Klinotova, E [Karlova Univ., Prague (Czechoslovakia). Prirodovedecka Fakulta; Filip, J [Ustav pro Vyzkum, Vyrobu a Vyuziti Radioisotopu, Prague (Czechoslovakia); Hampl, R [Research Inst. of Endocrinology, Praha (Czechoslovakia)

    1982-10-20

    Tritium and/or deuterium (5-H) labelled 19-nor-3..cap alpha..-hydroxy-5..cap alpha..-androstan-17-one (norandrosterone) was prepared from nortestosterone in view to use it as a radioligand for radioimmunoassay of the main nortestosterone metabolites. Based upon model experiments using testosterone and deuterium labelling, the following four step procedure was established: nortestosterone was oxidized with pyridine chlorochromate and the resulting 19-nor-4-androsten-3,17-dione was tritiated with tritium gas under catalysis with tris(triphenylphosphine)rhodium chloride to give (4,5..cap alpha..-/sup 3/H)19-nor-5..cap alpha..-androstan-3,17-dione. A selective reduction of the latter compound yielded (5-/sup 3/H)19-nor-3..cap alpha..-hydroxy-5..cap alpha..-androstan-17-one of the molar radioactivity 0.3 TBq (8.15 Ci)/mmol.

  13. Metabolism of /sup 14/C-labelled L-tryptophan, L-kynurenine, and hydroxy-L-kynurenine in miners with scleroderma

    Hankes, L.V.; De Bruin, E.; Jansen, C.R.; Vorster, L.; Schmaeler, M.

    1977-03-19

    Six South African white miners were studied with the 2-g L-tryptophan load test and tracer doses of L-tryptophan-7a-/sup 14/C, L-kynurenine-keto-/sup 14/C and hydroxy-L-kynurenine-keto-/sup 14/C. The breath /sup 14/CO/sub 2/ and 14 urinary metabolites were measured. When they were compared with a previous study of American women with scleroderma, similar /sup 14/CO/sub 2/ and tryptophan metabolite excretion patterns were observed in the data from the miners. The labelled quinolinic acid excretion was more significantly elevated in the South African miners' urine than in the urine of the American women. The data from both studies suggest that some patients with scleroderma have an altered step in the tryptophan metabolic pathway after hydroxy-anthranilic acid. What relationship exists between the induction of pulmonary silicosis and the subsequent development of scleroderma, requires additional human studies.

  14. Localization of a defensive volatile 4-hydroxy-4-methylpentan-2-one in the capitate glandular trichomes of Oenothera glazioviana

    Yanyun Tan; Desen Li; Juan Hua; Shihong Luo; Yan Liu; Shenghong Li

    2017-01-01

    Glandular trichomes of plants produce a wide variety of secondary metabolites which are considered as major defensive chemicals. The capitate glandular trichomes of Oenothera glazioviana (Onagraceae) were collected with laser microdissection and analyzed by gas chromatography-mass spectrometry. The volatile compound 4-hydroxy-4-methylpentan-2-one (1) was identified. We found that compound 1 displays antimicrobial, insecticidal, and phytotoxic activities. These results suggest that compound 1 might function as a defensive compound in the capitate glandular trichomes of O. glazioviana against pathogens, insect herbivores, and presumably competitive plants as well.

  15. Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of β-hydroxy-β-methylbutyrate

    Wheatley, Scott M.; El-Kadi, Samer W.; Suryawan, Agus; Boutry, Claire; Orellana, Renán A.; Nguyen, Hanh V.; Davis, Steven R.; Davis, Teresa A.

    2013-01-01

    Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB). To determine the effects of HMB on protein synthesis and the regulation of translation initiation and degradation pathways, overnight-fasted neonatal pigs were infused with HMB at 0, 20, 100, or 400 μmol·kg body wt−1·h−1 for 1 h (HMB 0, HMB 20, HMB 100, ...

  16. Localization of a defensive volatile 4-hydroxy-4-methylpentan-2-one in the capitate glandular trichomes of Oenothera glazioviana

    Yanyun Tan

    2017-06-01

    Full Text Available Glandular trichomes of plants produce a wide variety of secondary metabolites which are considered as major defensive chemicals. The capitate glandular trichomes of Oenothera glazioviana (Onagraceae were collected with laser microdissection and analyzed by gas chromatography–mass spectrometry. The volatile compound 4-hydroxy-4-methylpentan-2-one (1 was identified. We found that compound 1 displays antimicrobial, insecticidal, and phytotoxic activities. These results suggest that compound 1 might function as a defensive compound in the capitate glandular trichomes of O. glazioviana against pathogens, insect herbivores, and presumably competitive plants as well.

  17. Mitochondrial toxicity of diclofenac and its metabolites via inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2016-01-01

    Diclofenac is a widely prescribed NSAID, which by itself and its reactive metabolites (Phase-I and Phase-II) may be involved in serious idiosyncratic hepatotoxicity. Mitochondrial injury is one of the mechanisms of drug induced liver injury (DILI). In the present work, an investigation of the inh......Diclofenac is a widely prescribed NSAID, which by itself and its reactive metabolites (Phase-I and Phase-II) may be involved in serious idiosyncratic hepatotoxicity. Mitochondrial injury is one of the mechanisms of drug induced liver injury (DILI). In the present work, an investigation...... of the inhibitory effects of diclofenac (Dic) and its phase I [4-hydroxy diclofenac (4'-OH-Dic) and 5-hydroxy diclofenac (5-OH-dic)] and Phase-II [diclofenac acyl glucuronide (DicGluA) and diclofenac glutathione thioester (DicSG)] metabolites, on ATP synthesis in rat liver mitochondria was carried out. A mechanism...

  18. Plasma hydroxy-metronidazole/ metronidazole ratio in hepatitis C virus-induced liver disease

    M.A.M. Marchioretto

    2005-03-01

    Full Text Available It has been suggested that the measurement of metronidazole clearance is a sensitive method for evaluating liver function. The aim of this study was to evaluate the usefulness of plasma hydroxy-metronidazole/metronidazole ratios as indicators of dynamic liver function to detect changes resulting from the various forms of chronic hepatitis C virus (HCV infection. A total of 139 individuals were studied: 14 healthy volunteers, 22 healthy, asymptomatic, consecutive anti-HCV-positive HCV-RNA negative subjects, 81 patients with chronic hepatitis C (49 with moderate/severe chronic hepatitis and 34 with mild hepatitis, and 20 patients with cirrhosis of the liver. HCV status was determined by the polymerase chain reaction. Plasma concentrations of metronidazole and its hydroxy-metabolite were measured by reverse-phase high-performance liquid chromatography with ultraviolet detection in a blood sample collected 10 min after the end of a metronidazole infusion. Anti-HCV-positive HCV-RNA-negative individuals demonstrated a significantly reduced capacity to metabolize intravenously infused metronidazole compared to healthy individuals (0.0478 ± 0.0044 vs 0.0742 ± 0.0232. Liver cirrhosis patients also had a reduced plasma hydroxy-metronidazole/metronidazole ratio when compared to the other groups of anti-HCV-positive individuals (0.0300 ± 0.0032 vs 0.0438 ± 0.0027 (moderate/severe chronic hepatitis vs 0.0455 ± 0.0026 (mild chronic hepatitis and vs 0.0478 ± 0.0044 (anti-HCV-positive, HCV-RNA-negative individuals. These results suggest an impairment of the metronidazole metabolizing system induced by HCV infection that lasts after viral clearance. In those patients with chronic hepatitis C, this impairment is paralleled by progression of the disease to liver cirrhosis.

  19. Norepinephrine metabolism in man using deuterium labeling: turnover 4-hydroxy-3-methoxymandelic acid

    Mardh, G.; Sjoequist, B.; Anggard, E.

    1982-06-01

    4-Hydroxy-3-methoxymandelic acid (HMMA; VMA) labeled with three deuterium atoms was used to study the turnover and fate of HMMA following intravenous injection. Five healthy men were given a pulse dose of 5.0 mumol of labeled HMMA. Plasma and urinary levels of both endogenous and labeled HMMA were subsequently followed by gas chromatography-mass spectrometry using selected ion detection. The kinetic parameters were determined both with and without compensation for the pool expansion caused by the injection of labeled HMMA. The urinary recovery of labeled HMMA was 85 +/- 10% (mean +/- SD). No conversion of HMMA to 4-hydroxy-3-methoxyphenyl glycol (HMPG) occurred. The biological half-life of HMMA was 0.54 +/- 0.22 h. The apparent volume of distribution was 0.36 +/- 0.11 L/kg. The production rate or body turnover was 1.27 +/- 0.51 mumol HMMA/h and urinary excretion rate was 0.82 +/- 0.22 mumol/h. These results show that HMMA is turnover over rapidly in a relatively small volume of distribution and that, unlike HMPG, it is an end metabolite of norepinephrine in man.

  20. The absolute configurations of hydroxy fatty acids from the royal jelly of honeybees (Apis mellifera).

    Kodai, Tetsuya; Nakatani, Takafumi; Noda, Naoki

    2011-03-01

    9-Hydroxy-2E-decenoic acid (9-HDA) is a precursor of the queen-produced substance, 9-oxo-2E-decenoic acid (9-ODA), which has various important functions and roles for caste maintenance in honeybee colonies (Apis mellifera). 9-HDA in royal jelly is considered to be a metabolite of 9-ODA produced by worker bees, and it is fed back to the queen who then transforms it into 9-ODA. Recently we found that 9-HDA is present in royal jelly as a mixture of optical isomers (R:S, 2:1). The finding leads us to suspect that chiral fatty acids in royal jelly are precursors of semiochemicals. Rather than looking for semiochemicals in the mandibular glands of the queen bee, this study involves the search for precursors of pheromones from large quantities of royal jelly. Seven chiral hydroxy fatty acids, 9,10-dihydroxy-2E-decenoic, 4,10-dihydroxy-2E-decenoic, 4,9-dihydroxy-2E-decenoic, 3-hydroxydecanoic, 3,9-dihydroxydecanoic, 3,11-dihydroxydodecanoic, and 3,10-dihydroxydecanoic acids were isolated. The absolute configurations of these acids were determined using the modified Mosher's method, and it was revealed that, similar to 9-HDA, five acids are present in royal jelly as mixtures of optical isomers.

  1. Mass fragmentography of 25-hydroxy vitamin D3

    Bjoerkhem, I.; Holmberg, I.

    1978-01-01

    A mass fragmentographic assay of 25-hydroxy vitamin D 3 has been developed. [26- 2 H 3 ]-labelled vitamin D 3 is used as internal standard. A fixed amount of the standard is added to a fixed amount of serum or incubation mixture. 25-Hydroxy vitamin D 3 is extracted and the 3-t -butyldimethylsilyl derivation of 25-hydroxy vitamin D 3 is prepared. The latter is purified by means of thin layer chromatography. A trimethylsilyl group is introduced in position 25 prior to analysis by gas chromatography/mass spectrometry. The molecular ion at m/e 586 for unlabelled and m/e 589 for deuterium labelled 3-t-butyldimethylsilyl/25-trimethylsilyl derivative of 25-hydroxy vitamin D 3 are used in the analysis. The assay is designed to determine a few nanograms of 25-hydroxy vitamin D 3 . It has been used for the determination of 25-hydroxy vitamin D 3 in blood serum. The mean value for 25-hydroxy vitamin D 3 obtained from 12 healthy men and women was 21 ng/ml. The relative standard deviation of the method was about 3 %. The assay has also been used to determine the rate of 25-hydroxylation of vitamin D 3 in mitrochondrial fractions of rat liver. (Auth.)

  2. 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

  3. Metabolites of the 1',2'-dimethylheptyl analogue of delta-8-tetrahydrocannabinol in the mouse and their identification by gas chromatography/mass spectrometry.

    Harvey, D J; Brown, N K

    1990-10-01

    Metabolism of the 1,2-dimethylheptyl analogue of delta-8-tetrahydrocannabinol (delta-8-DMHP) was studied in vitro using mouse hepatic microsomes and in vivo in mouse liver. Metabolites were extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20 and examined by low-resolution mass spectrometry as trimethylsilyl (TMS), (2H9)TMS and methyl ester/TMS derivatives. Reduction of metabolites with lithium aluminium deuteride also provided structural information. The electron-impact-induced mass spectrum of the TMS derivative of DMHP differed from that of its unbranched side-chain analogues in that prominent ions were produced by fragmentation of the side-chain at the expense of the retro-Diels-Alder fragmentation that was prominent in the spectra of the latter compounds. This, however, was found to reduce the relative abundance of ions diagnostic of side-chain hydroxy substitution in the spectra of the metabolites. In vitro, the only significant metabolite was 11-hydroxy-delta-8-DMHP. This is in contrast with metabolism of the corresponding delta-8-tetrahydrocannabinol (delta-8-THC, n-C5-side-chain) where a number of other monohydroxy metabolites are produced. Fifteen metabolites were found in vivo, of which nine were identified. Mass spectral information was not sufficient to determine the position of one of the hydroxy groups in the other six metabolites. The major site of hydroxylation was at C-11 and the resulting hydroxy metabolite was oxidized to delta-8-DMHP-11-oic acid. In this respect metabolism paralleled that of delta-8-THC. Dihydroxylation of the double bond also occurred, presumably via the epoxide.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. LC-mS analysis of human urine specimens for 2-oxo-3-hydroxy LSD: method validation for potential interferants and stability study of 2-oxo-3-hydroxy LSD under various storage conditions.

    Klette, Kevin L; Horn, Carl K; Stout, Peter R; Anderson, Cynthia J

    2002-01-01

    2-Oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD), a major LSD metabolite, has previously been demonstrated to be a superior marker for identifying LSD use compared with the parent drug, LSD. Specifically, O-H-LSD analyzed using liquid chromatography-mass spectrometry has been reported to be present in urine at concentrations 16 to 43 times greater than LSD. To further support forensic application of this procedure, the specificity of the assay was assessed using compounds that have structural and chemical properties similar to O-H-LSD, common over-the-counter products, prescription drugs and some of their metabolites, and other drugs of abuse. Of the wide range of compounds studied, none were found to interfere with the detection of O-H-LSD or the internal standard 2-oxo-3-hydroxy lysergic acid methyl propylamide. The stability of O-H-LSD was investigated from 0 to 9 days at various temperatures, pH conditions, and exposures to fluorescent light. Additionally, the effect of long-term frozen storage and pH was investigated from 0 to 60 days. There was no significant loss of O-H-LSD under both refrigerated and frozen conditions within the normal human physiological pH range of urine (4.6-8.4). However, significant loss of O-H-LSD was observed in samples prepared at pH 4.6-8.4 and stored at room temperature or higher (24-50 degrees C).

  5. 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.

  6. O-hydroxy-functionalized diamines, polymides, methods of making each, and methods of use

    Ma, Xiaohua; Ghanem, Bader S.; Pinnau, Ingo

    2016-01-01

    Embodiments of the present disclosure provide for an ortho (o)-hydroxy-functionalized diamine, a method of making an o-hydroxy-functionalized diamine, an o-hydroxy-functionalized diamine-based polyimide, a method of making an o-hydroxy-functionalized diamine imide, methods of gas separation, and the like.

  7. O-hydroxy-functionalized diamines, polymides, methods of making each, and methods of use

    Ma, Xiaohua

    2016-01-21

    Embodiments of the present disclosure provide for an ortho (o)-hydroxy-functionalized diamine, a method of making an o-hydroxy-functionalized diamine, an o-hydroxy-functionalized diamine-based polyimide, a method of making an o-hydroxy-functionalized diamine imide, methods of gas separation, and the like.

  8. synthesis of schiff bases derived from 2-hydroxy-1-naphth

    of 2-hydroxy-1-naphthaldehyde (HN) with L-histidine and sulfamethazine have .... Relevant IR spectral bands of the ligands and their tin complexes along with ..... species Bacillus subtilis (22 mm) for HNSM have almost near to the standard.

  9. Synthesis of Hydroxy-Terminated Dinitropropyl Acrylate Polymers and Improved Characterization of Hydroxy-Terminated Prepolymers

    1983-03-01

    CH CH OH P."" 2 2 2 " 2" 2 I2",’C-H CN CN B-2000 Poly-(1,2-butylene)- glycol from DOW Chemical Carbowax Polyethylene glycol from Union Carbide CH...Carbonate GPC Gel Permeation Chromatography HEDS Hydroxyethyl Disulfide HPLC High Pressure Liquid Chromatography NMIM N-methyl imidazole NPGA Neopentyl ...PEG Polyethylene glycol PPG Polypropylene glycol from Wyandotte PY Pyridine R-45M Hydroxy-terminated polybutadeine from ARCO Teracol Poly

  10. Widespread occurrence of neuro-active pharmaceuticals and metabolites in 24 Minnesota rivers and wastewaters

    Writer, Jeffrey; Ferrer, Imma; Barber, Larry B.; Thurman, E. Michael

    2013-01-01

    Concentrations of 17 neuro-active pharmaceuticals and their major metabolites (bupropion, hydroxy-bupropion, erythro-hydrobupropion, threo-hydrobupropion, carbamazepine, 10,11,-dihydro-10,11,-dihydroxycarbamazepine, 10-hydroxy-carbamazepine, citalopram, N-desmethyl-citalopram, fluoxetine, norfluoxetine, gabapentin, lamotrigine, 2-N-glucuronide-lamotrigine, oxcarbazepine, venlafaxine and O-desmethyl-venlafaxine), were measured in treated wastewater and receiving surface waters from 24 locations across Minnesota, USA. The analysis of upstream and downstream sampling sites indicated that the wastewater treatment plants were the major source of the neuro-active pharmaceuticals and associated metabolites in surface waters of Minnesota. Concentrations of parent compound and the associated metabolite varied substantially between treatment plants (concentrations ± standard deviation of the parent compound relative to its major metabolite) as illustrated by the following examples; bupropion and hydrobupropion 700 ± 1000 ng L−1, 2100 ± 1700 ng L−1, carbamazepine and 10-hydroxy-carbamazepine 480 ± 380 ng L−1, 360 ± 400 ng L−1, venlafaxine and O-desmethyl-venlafaxine 1400 ± 1300 ng L−1, 1800 ± 2300 ng L−1. Metabolites of the neuro-active compounds were commonly found at higher or comparable concentrations to the parent compounds in wastewater effluent and the receiving surface water. Neuro-active pharmaceuticals and associated metabolites were detected only sporadically in samples upstream from the effluent outfall. Metabolite to parent ratios were used to evaluate transformation, and we determined that ratios in wastewater were much lower than those reported in urine, indicating that the metabolites are relatively more labile than the parent compounds in the treatment plants and in receiving waters. The widespread occurrence of neuro-active pharmaceuticals and metabolites in Minnesota effluents and surface waters indicate that

  11. A 3-hydroxy β-end group in xanthophylls is preferentially oxidized to a 3-oxo ε-end group in mammals.

    Nagao, Akihiko; Maoka, Takashi; Ono, Hiroshi; Kotake-Nara, Eiichi; Kobayashi, Miyuki; Tomita, Mie

    2015-02-01

    We previously found that mice fed lutein accumulated its oxidative metabolites (3'-hydroxy-ε,ε-caroten-3-one and ε,ε-carotene-3,3'-dione) as major carotenoids, suggesting that mammals can convert xanthophylls to keto-carotenoids by the oxidation of hydroxyl groups. Here we elucidated the metabolic activities of mouse liver for several xanthophylls. When lutein was incubated with liver postmitochondrial fraction in the presence of NAD(+), (3'R,6'R)-3'-hydroxy-β,ε-caroten-3-one and (6RS,3'R,6'R)-3'-hydroxy-ε,ε-caroten-3-one were produced as major oxidation products. The former accumulated only at the early stage and was assumed to be an intermediate, followed by isomerization to the latter. The configuration at the C3' and C6' of the ε-end group in lutein was retained in the two oxidation products. These results indicate that the 3-hydroxy β-end group in lutein was preferentially oxidized to a 3-oxo ε-end group via a 3-oxo β-end group. Other xanthophylls such as β-cryptoxanthin and zeaxanthin, which have a 3-hydroxy β-end group, were also oxidized in the same manner as lutein. These keto-carotenoids, derived from dietary xanthophylls, were confirmed to be present in plasma of normal human subjects, and β,ε-caroten-3'-one was significantly increased by the ingestion of β-cryptoxanthin. Thus, humans as well as mice have oxidative activity to convert the 3-hydroxy β-end group of xanthophylls to a 3-oxo ε-end group. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  12. A 3-hydroxy β-end group in xanthophylls is preferentially oxidized to a 3-oxo ε-end group in mammals[S

    Nagao, Akihiko; Maoka, Takashi; Ono, Hiroshi; Kotake-Nara, Eiichi; Kobayashi, Miyuki; Tomita, Mie

    2015-01-01

    We previously found that mice fed lutein accumulated its oxidative metabolites (3′-hydroxy-ε,ε-caroten-3-one and ε,ε-carotene-3,3′-dione) as major carotenoids, suggesting that mammals can convert xanthophylls to keto-carotenoids by the oxidation of hydroxyl groups. Here we elucidated the metabolic activities of mouse liver for several xanthophylls. When lutein was incubated with liver postmitochondrial fraction in the presence of NAD+, (3′R,6′R)-3′-hydroxy-β,ε-caroten-3-one and (6RS,3′R,6′R)-3′-hydroxy-ε,ε-caroten-3-one were produced as major oxidation products. The former accumulated only at the early stage and was assumed to be an intermediate, followed by isomerization to the latter. The configuration at the C3′ and C6′ of the ε-end group in lutein was retained in the two oxidation products. These results indicate that the 3-hydroxy β-end group in lutein was preferentially oxidized to a 3-oxo ε-end group via a 3-oxo β-end group. Other xanthophylls such as β-cryptoxanthin and zeaxanthin, which have a 3-hydroxy β-end group, were also oxidized in the same manner as lutein. These keto-carotenoids, derived from dietary xanthophylls, were confirmed to be present in plasma of normal human subjects, and β,ε-caroten-3′-one was significantly increased by the ingestion of β-cryptoxanthin. Thus, humans as well as mice have oxidative activity to convert the 3-hydroxy β-end group of xanthophylls to a 3-oxo ε-end group. PMID:25502844

  13. Enantioselective conjugate radical addition to alpha'-hydroxy enones.

    Lee, Sunggi; Lim, Chae Jo; Kim, Sunggak; Subramaniam, Rajesh; Zimmerman, Jake; Sibi, Mukund P

    2006-09-14

    Enantioselective conjugate radical addition to alpha'-hydroxy alpha,beta-unsaturated ketones, compounds containing bidentate donors, has been investigated. It has been found that radical additions to alpha'-hydroxy alpha,beta-unsaturated ketones in the presence of Mg(NTf2)2 and bisoxazoline ligand 5a proceeded cleanly, yielding the addition products in high chemical yields and good enantiomeric excesses.

  14. Identification of three new phase II metabolites of a designer drug methylone formed in rats by N-demethylation followed by conjugation with dicarboxylic acids.

    Židková, Monika; Linhart, Igor; Balíková, Marie; Himl, Michal; Dvořáčková, Veronika; Lhotková, Eva; Páleníček, Tomáš

    2018-06-01

    1. Methylone (3,4-methylenedioxy-N-methylcathinone, MDMC), which appeared on the illicit drug market in 2004, is a frequently abused synthetic cathinone derivative. Known metabolic pathways of MDMC include N-demethylation to normethylone (3,4-methylenedioxycathinone, MDC), aliphatic chain hydroxylation and oxidative demethylenation followed by monomethylation and conjugation with glucuronic acid and/or sulphate. 2. Three new phase II metabolites, amidic conjugates of MDC with succinic, glutaric and adipic acid, were identified in the urine of rats dosed subcutaneously with MDMC.HCl (20 mg/kg body weight) by LC-ESI-HRMS using synthetic reference standards to support identification. 3. The main portion of administered MDMC was excreted unchanged. Normethylone, was a major urinary metabolite, of which a minor part was conjugated with dicarboxylic acids. 4. Previously identified ring-opened metabolites 4-hydroxy-3-methoxymethcathinone (4-OH-3-MeO-MC), 3-hydroxy-4-methoxymeth-cathinone (3-OH-4-MeO-MC) and 3,4-dihydroxymethcathinone (3,4-di-OH-MC) mostly in conjugated form with glucuronic and/or sulphuric acids were also detected. 5. Also, ring-opened metabolites derived from MDC, namely, 4-hydroxy-3-methoxycathinone (4-OH-3-MeO-C), 3-hydroxy-4-methoxycathinone (3-OH-4-MeO-C) and 3,4-dihydroxycathinone (3,4-di-OH-C) were identified for the first time in vivo.

  15. Simultaneous quantification of major cannabinoids and metabolites in human urine and plasma by HPLC-MS/MS and enzyme-alkaline hydrolysis

    Aizpurua-Olaizola, Oier; Zarandona, Iratxe; Ortiz, Laura; Navarro, Patricia; Etxebarria, Nestor; Usobiaga, Aresatz

    A high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) method for simultaneous quantification of Δ9-tetrahydrocannabinol (THC), its two metabolites 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), and four

  16. Synthesis of 5'-bromo-2'-hydroxy-4,4',6'-trimethoxychalcone from Garcinia nervosa and of its isomer 3'-bromo-2'-hydroxy-4,4',6'- trimethoxychalcone

    Parab, S.J.; Kapdi, S.G.; Naik, C.G.; Kamat, S.P.

    The unambiguous syntheses of the naturally occurring 5'-bromo-2'-hydroxy-4,4',6'-trimethoxychalcone 1, a constituent of Garcinia nervosa, and its positional isomer 3'-bromo-2'-hydroxy-4,4',6'-trimethoxychalcone 6 are described...

  17. 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.

  18. 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

  19. 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...

  20. Enantioselective semi-preparative HPLC separation of PCB metabolites and their absolute structures determined by electronic and vibrational circular dichroism

    Tuan, H.P.; Larsson, C.; Huehnerfuss, H. [Hamburg Univ. (Germany). Inst. fuer Organische Chemie; Hoffmann, F.; Froeba, M. [Giessen Univ. (Germany). Inst. fuer Anorganische und Analytische Chemie; Bergmann, Aa. [Stockholm Univ. (Sweden). Dept. of Environmental Chemistry

    2004-09-15

    The present paper represents a first result of an ongoing systematic study of atropisomeric methylsulfonyl, methylthionyl, hydroxy, and methoxy metabolites of environmentally most relevant PCBs. This involves semi-preparative enantioselective HPLC separation to obtain pure atropisomers from synthesized PCB metabolite standards, their configuration estimation using the electronic circular dichroism (UV-CD) method and the determination / confirmation of these absolute configurations applying the combined vibrational circular dichroism (VCD) / ab initio approach. The following substances have been investigated: 4-HO-, 4-MeO-, 4-MeS-, 4-MeSO2-, 3-MeS- and 3-MeSO{sub 2}-CB149.

  1. 4-Hydroxy-1-naphthaldehydes: proton transfer or deprotonation

    Manolova, Y; Kurteva, V; Antonov, L

    2015-01-01

    A series of naphthaldehydes, including a Mannich base, have been investigated by UV-Vis spectroscopy, NMR and theoretical methods to explore their potential tautomerism. In the case of 4-hydroxy-1-naphthaldehyde concentration dependent deprotonation has been detected in methanol and acetonitrile....... For 4-hydroxy-3-(piperidin-1-ylmethyl)-1-naphthaldehyde (a Mannich base) an intramolecular proton transfer involving the OH group and the piperidine nitrogen occurs. In acetonitrile the equilibrium is predominantly at the OH-form, whereas in methanol the proton transferred tautomer is the preferred form....... In chloroform and toluene, the OH form is completely dominant. Both 4-hydroxy-1-naphthaldehyde and 4-methoxy-1-naphthaldehyde (fixed enol form) show dimerization in the investigated solvents and the crystallographic data, obtained for the latter, confirm the existence of a cyclic dimer...

  2. Crystal structure of 5-hydroxy-5-propylbarbituric acid

    Thomas Gelbrich

    2015-11-01

    Full Text Available Molecules of the title compound, C7H10N2O4, systematic name 5-hydroxy-5-propylpyrimidine-2,4,6(1H,3H,5H-trione, form a hydrogen-bonded framework which is based on three independent hydrogen bonds, N—H...O(carbonyl, N—H...O(hydroxy and O—H...O(carbonyl. This framework has the topology of the 5-connected nov net. Each molecule is linked to five other molecules via six hydrogen bonds, and the descriptor of the hydrogen-bonded structure is F65[44.66-nov]. The crystal packing is isostructural with that of the previously reported 5-hydroxy-5-ethyl analogue.

  3. 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

  4. Characterisation of the Metabolites of 1,8-Cineole Transferred into Human Milk: Concentrations and Ratio of Enantiomers

    Kirsch, Frauke; Buettner, Andrea

    2013-01-01

    1,8-Cineole is a widely distributed odorant that also shows physiological effects, but whose human metabolism has hitherto not been extensively investigated. The aim of the present study was, thus, to characterise the metabolites of 1,8-cineole, identified previously in human milk, after the oral intake of 100 mg of this substance. Special emphasis was placed on the enantiomeric composition of the metabolites since these data may provide important insights into potential biotransformation pathways, as well as potential biological activities of these substances, for example on the breastfed child. The volatile fraction of the human milk samples was therefore isolated via Solvent Assisted Flavour Evaporation (SAFE) and subjected to gas chromatography-mass spectrometry (GC-MS). The absolute concentrations of each metabolite were determined by matrix calibration with an internal standard, and the ratios of enantiomers were analysed on chiral capillaries. The concentrations varied over a broad range, from traces in the upper ng/kg region up to 40 µg/kg milk, with the exception of the main metabolite α2-hydroxy-1,8-cineole that showed concentrations of 100–250 µg/kg. Also, large inter- and intra-individual variations were recorded for the enantiomers, with nearly enantiomerically pure α2-hydroxy- and 3-oxo-1,8-cineole, while all other metabolites showed ratios of ~30:70 to 80:20. PMID:24957890

  5. Investigation of the presence of β-hydroxy-β-methylbutyric acid and α-hydroxyisocaproic acid in bovine whole milk and fermented dairy products by a validated liquid chromatography-mass spectrometry method.

    Ehling, Stefan; Reddy, Todime M

    2014-02-19

    A simple, rugged, quantitative, and confirmatory method based on liquid chromatography-mass spectrometry was developed and comprehensively validated for the analysis of the leucine metabolites β-hydroxy-β-methylbutyric acid (HMB) and α-hydroxyisocaproic acid (HICA) in bovine whole milk and yogurt. Mean accuracy (90-110% for HMB and 85-115% for HICA) and total precision (dairy products with HMB and/or HICA appears to be justified.

  6. Effects of 3,4-methylenedioxymethamphetamine (MDMA) and its main metabolites on cardiovascular function in conscious rats.

    Schindler, Charles W; Thorndike, Eric B; Blough, Bruce E; Tella, Srihari R; Goldberg, Steven R; Baumann, Michael H

    2014-01-01

    The cardiovascular effects produced by 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') contribute to its acute toxicity, but the potential role of its metabolites in these cardiovascular effects is not known. Here we examined the effects of MDMA metabolites on cardiovascular function in rats. Radiotelemetry was employed to evaluate the effects of s.c. administration of racemic MDMA and its phase I metabolites on BP, heart rate (HR) and locomotor activity in conscious male rats. MDMA (1-20 mg·kg(-1)) produced dose-related increases in BP, HR and activity. The peak effects on HR occurred at a lower dose than peak effects on BP or activity. The N-demethylated metabolite, 3,4-methylenedioxyamphetamine (MDA), produced effects that mimicked those of MDMA. The metabolite 3,4-dihydroxymethamphetamine (HHMA; 1-10 mg·kg(-1)) increased HR more potently and to a greater extent than MDMA, whereas 3,4-dihydroxyamphetamine (HHA) increased HR, but to a lesser extent than HHMA. Neither dihydroxy metabolite altered motor activity. The metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA) and 4-hydroxy-3-methoxyamphetamine (HMA) did not affect any of the parameters measured. The tachycardia produced by MDMA and HHMA was blocked by the β-adrenoceptor antagonist propranolol. Our results demonstrate that HHMA may contribute significantly to the cardiovascular effects of MDMA in vivo. As such, determining the molecular mechanism of action of HHMA and the other hydroxyl metabolites of MDMA warrants further study. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  7. Synthesis of deuterium labelled metabolites of warfarin and phenprocoumon

    Heimark, L.D.; Toon, S.; Low, L.K.; Swinney, D.C.; Trager, W.F.

    1986-02-01

    The synthesis of deuterium labelled 4'-,6-,7- and 8-hydroxy metabolites of warfarin and phenprocoumon is described. The pentadeuterio labelled 6-,7- and 8-hydroxyphenprocoumons were prepared via alkylation of the respective 6-, 7- and 8-methoxy-4-hydroxycoumarins with 1-(phenyl-d/sub 5/)-1-bromopropane and subsequent cleavage of the methyl protecting group with boron tribromide. The synthesis of 1-(pentadeuteriophenyl)-1-bromopropane and the 6-, 7-and 8-methoxy-4-hydroxycoumarins are also presented. The pentadeuterio labelled 6-, 7- and 8-hydroxywarfarins were obtained by reaction of 4-(phenyl-d/sub 5/)-3-buten-2-one with the respective 6-, 7- and 8-hydroxy-4-hydroxycoumarins in methanol followed by hydrolysis of the intermediate cyclic methyl ketals in aqueous acid. 4-Hydroxycoumarin-5,6,7,8-d/sub 4/, prepared from phenyl-d/sub 6/ and tetradeuteriomalonic acid, was reacted with 1-(p-hydroxyphenyl)-1-propanol and 4-(p-hydroxyphenyl)-3-buten-2-one to yield labelled 4'-hydroxyphenprocoumon and 4'-hydroxywarfarin respectively.

  8. The synthesis of deuterium labelled metabolites of warfarin and phenprocoumon

    Heimark, L.D.; Toon, S.; Low, L.K.; Swinney, D.C.; Trager, W.F.

    1986-01-01

    The synthesis of deuterium labelled 4'-,6-,7- and 8-hydroxy metabolites of warfarin and phenprocoumon is described. The pentadeuterio labelled 6-,7- and 8-hydroxyphenprocoumons were prepared via alkylation of the respective 6-, 7- and 8-methoxy-4-hydroxycoumarins with 1-(phenyl-d 5 )-1-bromopropane and subsequent cleavage of the methyl protecting group with boron tribromide. The synthesis of 1-(pentadeuteriophenyl)-1-bromopropane and the 6-, 7- and 8-methoxy-4-hydroxycoumarins are also presented. The pentadeuterio labelled 6-, 7- and 8-hydroxywarfarins were obtained by reaction of 4-(phenyl-d 5 )-3-buten-2-one with the respective 6-, 7- and 8-hydroxy-4-hydroxycoumarins in methanol followed by hydrolysis of the intermediate cyclic methyl ketals in aqueous acid. 4-Hydroxycoumarin-5,6,7,8-d 4 , prepared from phenyl-d 6 and tetradeuteriomalonic acid, was reacted with 1-(p-hydroxyphenyl)-1-propanol and 4-(p-hydroxyphenyl)-3-buten-2-one to yield labelled 4'-hydroxyphenprocoumon and 4'-hydroxywarfarin respectively. (author)

  9. Development and validation of a sensitive liquid chromatographic-tandem mass spectrometric method for the simultaneous analysis of granisetron and 7-hydroxy granisetron in human plasma and urine samples: application in a clinical pharmacokinetic study in pregnant subject.

    Zhao, Yang; Chen, Hui-Jun; Caritis, Steve; Venkataramanan, Raman

    2016-02-01

    A liquid chromatography-tandem mass spectrometric method for the quantification of granisetron and its major metabolite, 7-hydroxy granisetron in human plasma and urine samples was developed and validated. Respective stable isotopically labeled granisetron and 7-hydroxy granisetron were used as internal standards (IS). Chromatography was performed using an Xselect HSS T3 analytical column with a mobile phase of 20% acetonitrile in water (containing 0.2 mM ammonium formate and 0.14% formic acid, pH 4) delivered in an isocratic mode. Tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring was used for quantification. The standard curves were linear in the concentration ranges of 0.5-100 ng/mL for granisetron and 0.1-100 ng/mL for 7-hydroxy granisetron in human plasma samples, and 2-2000 ng/mL for granisetron and 2-1000 ng/mL for 7-hydroxy granisetron in human urine samples, respectively. The accuracies were >85% and the precision as determined by the coefficient of variations was granisetron or 7-hydroxy granisetron in either plasma or urine samples. Granisetron was stable under various storage and experimental conditions. This validated method was successfully applied to a pharmacokinetic study after intravenous administration of 1 mg granisetron to a pregnant subject. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Suppression of SOS-inducing activity of chemical mutagens by metabolites from microbial transformation of (-)-isolongifolene.

    Sakata, Kazuki; Oda, Yoshimitsu; Miyazawa, Mitsuo

    2010-02-24

    In this study, biotransformation of (-)-isolongifolene (1) by Glomerella cingulata and suppressive effect on umuC gene expression by chemical mutagens 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide) and aflatoxin B(1) (AFB(1)) of the SOS response in Salmonella typhimurium TA1535/pSK1002 were investigated. Initially, 1 was carried out the microbial transformation by G. cingulata. The result found that 1 was converted into (-)-isolongifolen-9-one (2), (-)-(2S)-13-hydroxy-isolongifolen-9-one (3), and (-)-(4R)-4-hydroxy-isolongifolen-9-one (4) by G. cingulata, and their conversion rates were 60, 25, and 15%, respectively. The metabolites suppressed the SOS-inducing activity of furylfuramid and AFB(1) in the umu test. Comound 2 showed gene expression by chemical mutagens furylfuramide and AFB(1) was suppressed 54 and 50% at <0.5 mM, respectively. Compound 2 is the most effective compound in this experiment.

  11. Anti-Helicobacter pylori metabolites from Rhizoctonia sp. Cy064, an endophytic fungus in Cynodon dactylon.

    Ma, Y M; Li, Y; Liu, J Y; Song, Y C; Tan, R X

    2004-07-01

    A new benzophenone, named rhizoctonic acid (1), together with three known compounds monomethylsulochrin (2), ergosterol (3) and 3beta,5alpha,6beta-trihydroxyergosta-7,22-diene (4) were isolated through bioassay-guided fractionations from the culture of Rhizoctonia sp. (Cy064), an endophytic fungus in the leaf of Cynodon dactylon. The structure of the new acid 1 was elucidated to be 5-hydroxy-2-(2-hydroxy-6-methoxy-4-methylbenzoyl)-3-methoxybenzoic acid by a combination of spectral analyses. Furthermore, the structure of monomethylsulochrin 2 was confirmed by 13C-NMR analysis. All four metabolites were subjected to a more detailed in vitro assessment of their antibacterial action against five clinically isolated and one reference (ATCC 43504) Helicobacter pylori strains.

  12. Engineering poly(hydroxy butyrate-co-hydroxy valerate) based vascular scaffolds to mimic native artery.

    Deepthi, S; Nivedhitha Sundaram, M; Vijayan, Ponni; Nair, Shantikumar V; Jayakumar, R

    2018-04-01

    Electrospun tri-layered fibrous scaffold incorporating VEGF and Platelet Factor Concentrate (PFC) in multiple layers having different layer architectures was designed to mimic native artery. The scaffold consisted of longitudinally aligned poly(hydroxy butyrate-co-hydroxy valerate) (PHBV) and poly(vinyl alcohol) (PVA) nanofibers (inner layer), radially aligned PHBV-elastin nanofibers (middle layer) to provide the bi-directional alignment and combination of longitudinally aligned PHBV-elastin and random PHBV/PVA multiscale fibers (peripheral layer). Tubular constructs of diameter <6 mm were developed. The developed electrospun fibers were characterised by Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy and Tensile tests. Further the burst strength, compliance and stiffness index of tri-layered tubular scaffold was evaluated. SEM images of fibrous layers showed the typical longitudinal and radial alignment of fibers in the tubular construct. SEM images showed that the prepared PHBV nanofibers were in the range of 500-800 nm and PHBV microfibers were of 1-2 μm in diameter in the tri-layered electrospun membrane. PVA nanofibers were of size 200-250 nm. The tensile strength, percentage compliance and stiffness index of tri-layered membrane was in accordance with that of native small blood vessels. The developed tri-layered membrane was blood compatible, with hemolysis degree 0.85 ± 0.21% and did not activate platelets. Controlled release of VEGF and PFC was observed from the scaffold. The biocompatibility of the tri-layered scaffold was evaluated using HUVECs, SMCs and MSCs and SMCs infiltration from the outer layer was also evaluated. Specific protein expression for the HUVECs and SMCs was evaluated by flow cytometry and immunocytochemistry. HUVECs and SMCs exhibited good elongation and alignment along the direction of fibers and was found to maintain its CD31, VE-Cadherin and αSMA expression respectively. The results

  13. Steroid receptor profiling of vinclozolin and its primary metabolites

    Molina-Molina, Jose-Manuel; Hillenweck, Anne; Jouanin, Isabelle; Zalko, Daniel; Cravedi, Jean-Pierre; Fernandez, Mariana-Fatima; Pillon, Arnaud; Nicolas, Jean-Claude; Olea, Nicolas; Balaguer, Patrick

    2006-01-01

    Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these chemicals can display estrogenic effects and/or anti-androgenic effects, but much less is known about the interaction of these compounds with other steroid receptors. Vinclozolin, a dicarboximide fungicide, like its primary metabolites 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), is known to bind androgen receptor (AR). Although vinclozolin and its metabolites were characterized as anti-androgens, relatively little is known about their effects on the function of the progesterone (PR), glucocorticoid (GR), mineralocorticoid (MR) or estrogen receptors (ERα and ERβ). Objectives of the study were to determine the ability of vinclozolin and its two primary metabolites to activate AR, PR, GR, MR and ER. For this purpose, we used reporter cell lines bearing luciferase gene under the control of wild type or chimeric Gal4 fusion AR, PR, GR, MR or ERs. We confirmed that all three were antagonists for AR, whereas only M2 was found a partial agonist. Interestingly, M2 was also a PR, GR and MR antagonist (MR >> PR > GR) while vinclozolin was an MR and PR antagonist. Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERβ. Although the potencies of the fungicide and its metabolites are low when compared to natural ligands, their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process

  14. Steroid receptor profiling of vinclozolin and its primary metabolites.

    Molina-Molina, José-Manuel; Hillenweck, Anne; Jouanin, Isabelle; Zalko, Daniel; Cravedi, Jean-Pierre; Fernández, Mariana-Fátima; Pillon, Arnaud; Nicolas, Jean-Claude; Olea, Nicolás; Balaguer, Patrick

    2006-10-01

    Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these chemicals can display estrogenic effects and/or anti-androgenic effects, but much less is known about the interaction of these compounds with other steroid receptors. Vinclozolin, a dicarboximide fungicide, like its primary metabolites 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), is known to bind androgen receptor (AR). Although vinclozolin and its metabolites were characterized as anti-androgens, relatively little is known about their effects on the function of the progesterone (PR), glucocorticoid (GR), mineralocorticoid (MR) or estrogen receptors (ERalpha and ERbeta). Objectives of the study were to determine the ability of vinclozolin and its two primary metabolites to activate AR, PR, GR, MR and ER. For this purpose, we used reporter cell lines bearing luciferase gene under the control of wild type or chimeric Gal4 fusion AR, PR, GR, MR or ERs. We confirmed that all three were antagonists for AR, whereas only M2 was found a partial agonist. Interestingly, M2 was also a PR, GR and MR antagonist (MR>PR>GR) while vinclozolin was an MR and PR antagonist. Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERbeta. Although the potencies of the fungicide and its metabolites are low when compared to natural ligands, their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process.

  15. Method for conversion of .beta.-hydroxy carbonyl compounds

    Lilga, Michael A.; White, James F.; Holladay, Johnathan E.; Zacher, Alan H.; Muzatko, Danielle S.; Orth, Rick J.

    2010-03-30

    A process is disclosed for conversion of salts of .beta.-hydroxy carbonyl compounds forming useful conversion products including, e.g., .alpha.,.beta.-unsaturated carbonyl compounds and/or salts of .alpha.,.beta.-unsaturated carbonyl compounds. Conversion products find use, e.g., as feedstock and/or end-use chemicals.

  16. The development of a radioimmunoassay for 18-hydroxy-corticosterone

    Martin, V.I.

    1980-03-01

    It has been suggested that 18-hydroxy-corticosterone (18-OH-B) is a precursor for aldosterone in the biosynthetic pathway. This steroid had not been measured in peripheral plasma and therefore to evaluate its clinical role a sensitive and specific radioimmunoassay was developed. The assay is described and was applied to measure the levels of 18-hydroxy-corticosterone in normal human subjects on (a) an ad libitum sodium intake whilst lying or standing, (b) on a high or low sodium intake whilst recumbent, (c) before and after treatment with either ACTH, metyrapone or dexamethasone on a high or low sodium intake whilst recumbent (d) after insulin induced hypoglycaemia and (e) after infusions of 18-hydroxy-corticosterone. The levels of 18-hydroxy-corticosterone were also measured in patients with (a) 17α-hydroxylase deficiency, (b) primary or secondary aldosteronism, (c) Bartter's syndrome, (d) Cushing's syndrome, (e) adrenalectomised patients or patient's with Addison's disease and (f) patients with essential hypertension. (author)

  17. Development of a radioimmunoassay for 18-hydroxy-corticosterone

    Martin, V I

    1980-03-01

    It has been suggested that 18-hydroxy-corticosterone (18-OH-B) is a precursor for aldosterone in the biosynthetic pathway. This steroid had not been measured in peripheral plasma and therefore to evaluate its clinical role a sensitive and specific radioimmunoassay was developed. The assay is described and was applied to measure the levels of 18-hydroxy-corticosterone in normal human subjects on (a) an ad libitum sodium intake whilst lying or standing, (b) on a high or low sodium intake whilst recumbent, (c) before and after treatment with either ACTH, metyrapone or dexamethasone on a high or low sodium intake whilst recumbent (d) after insulin induced hypoglycaemia and (e) after infusions of 18-hydroxy-corticosterone. The levels of 18-hydroxy-corticosterone were also measured in patients with (a) 17chemically bond-hydroxylase deficiency, (b) primary or secondary aldosteronism, (c) Bartter's syndrome, (d) Cushing's syndrome, (e) adrenalectomised patients or patient's with Addison's disease and (f) patients with essential hypertension. (author).

  18. Biotechnology for improving hydroxy fatty acid production in lesquerella

    P Lesquerella [Physaria fendleri (A. Gray)], formerly Lesquerella fendleri, (Brassicaceae), being developed as a new industrial oilseed crop in the southwestern region of the United States, is valued for its unusual hydroxy fatty acid (HFA) in seed. The majority of HFA in lesquerella is lesquerolic...

  19. Separation of Process Water using Hydroxy Sodalite Membranes

    Khajavi, S.

    2010-01-01

    This thesis describes the synthesis, characterization, and application of Hydroxy Sodalite (H-SOD) membranes in selective separation of water from aqueous solutions and reaction media. The emphasis has been put on the development of a tight membrane film that could be primarily used for water

  20. Transition metal chemistry of hydroxy(–OH)-rich molecules ...

    Administrator

    Appropriately designed hydroxy(–OH) containing Schiff's base and Mannich base molecules have been recently found to be important for development of the coordination chemistry of a number of metal ions in the biomimetic chemistry of metalloenzymes. In this context, our group has studied the coordination role of these ...

  1. Novel alpha-hydroxy phosphonic acids via castor oil

    Hydroxy fatty acids (HFAs) have found a number of uses in today’s market, with uses ranging from materials to pharmaceuticals. Castor oil has served as a versatile HFA; its principle component, ricinoleic acid, can be isolated from castor oil and has been modified extensively for a number of applica...

  2. Substituted 4-hydroxy-1,2,3-triazoles

    Pippione, Agnese C.; Dosio, Franco; Ducime, Alex

    2015-01-01

    the distal (S)-glutamic acid carboxyl group using the 4-hydroxy-1,2,3-triazole moiety is applied, to obtain two promising glutamate analogs. In the second example, a scaffold hopping approach is applied, replacing the phenolic moiety present in MDG-1-33A, a potent inhibitor of Onchocerca volvulus chitinase...

  3. 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.

  4. 21 CFR 582.5477 - Methionine hydroxy analog and its calcium salts.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methionine hydroxy analog and its calcium salts... Nutrients and/or Dietary Supplements 1 § 582.5477 Methionine hydroxy analog and its calcium salts. (a) Product. Methionine hydroxy analog and its calcium salts. (b) [Reserved] (c) Limitations, restrictions, or...

  5. Beta-hydroxy-beta-methyl butyrate (HMB): From experimental data to clinical evidence in sarcopenia.

    Cruz-Jentoft, Alfonso J

    2017-05-28

    β-hydroxy-β-methylbutyrate (HMB) is a metabolite derived from leucine and its ketoacid alpha-ketoisocaproate. Leucine has a role in regulating protein synthesis in muscle cells, and HMB seems to be a key active metabolite in such regulation. HMB has been shown to modulate muscle protein degradation by inhibiting the ubiquitin-proteasome proteolytic pathway, to up-regulate protein synthesis via the mTOR pathway, and to stabilize cell membranes via the rate limiting enzyme to cholesterol synthesis HMG- coenzyme A reductase. It can also decrease cell apoptosis, therefore improving cell survival; and increase proliferation and differentiation of muscle stem cell, via the MAPK/ERK and PI3K/Akt pathways. HMB is widely used as an ergogenic supplement by athletes and bodybuilders, usually combined with exercise training, to increase muscle mass and strength. Some studies have explored the role of HMB in chronic diseases associated with muscle wasting (cancer, acquired immunodeficiency syndrome, chronic obstructive pulmonary disease) This review focuses on the role of HMB in the management of sarcopenia (age or disease-related loss of muscle mass and function) in older persons. A small number of studies have shown increases in lean (muscle) mass and some muscle function and physical performance parameters in older people with or without resistance exercise, and preservation of muscle mass during bed rest. However, heterogeneous methodological approaches preclude solid conclusions, and more studies are needed to confirm the role of HMB as a promising agent to treat sarcopenia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Formation of the accumulative human metabolite and human-specific glutathione conjugate of diclofenac in TK-NOG chimeric mice with humanized livers.

    Kamimura, Hidetaka; Ito, Satoshi; Nozawa, Kohei; Nakamura, Shota; Chijiwa, Hiroyuki; Nagatsuka, Shin-ichiro; Kuronuma, Miyuki; Ohnishi, Yasuyuki; Suemizu, Hiroshi; Ninomiya, Shin-ichi

    2015-03-01

    3'-Hydroxy-4'-methoxydiclofenac (VI) is a human-specific metabolite known to accumulate in the plasma of patients after repeated administration of diclofenac sodium. Diclofenac also produces glutathione-conjugated metabolites, some of which are human-specific. In the present study, we investigated whether these metabolites could be generated in humanized chimeric mice produced from TK-NOG mice. After a single oral administration of diclofenac to humanized mice, the unchanged drug in plasma peaked at 0.25 hour and then declined with a half-life (t1/2) of 2.4 hours. 4'-Hydroxydiclofenac (II) and 3'-hydroxydiclofenac also peaked at 0.25 hour and were undetectable within 24 hours. However, VI peaked at 8 hours and declined with a t1/2 of 13 hours. When diclofenac was given once per day, peak and trough levels of VI reached plateau within 3 days. Studies with administration of II suggested VI was generated via II as an intermediate. Among six reported glutathione-conjugated metabolites of diclofenac, M1 (5-hydroxy-4-(glutathion-S-yl)diclofenac) to M6 (2'-(glutathion-S-yl)monoclofenac), we found three dichlorinated conjugates [M1, M2 (4'-hydroxy-3'-(glutathion-S-yl)diclofenac), and M3 (5-hydroxy-6-(glutathion-S-yl)diclofenac)], and a single monochlorinated conjugate [M4 (2'-hydroxy-3'-(glutathion-S-yl)monoclofenac) or M5 (4'-hydroxy-2'-(glutathion-S-yl)monoclofenac)], in the bile of humanized chimeric mice. M4 and M5 are positional isomers and have been previously reported as human-specific in vitro metabolites likely generated via arene oxide and quinone imine-type intermediates, respectively. The biliary monochlorinated metabolite exhibited the same mass spectrum as those of M4 and M5, and we discuss whether this conjugate corresponded to M4 or M5. Overall, humanized TK-NOG chimeric mice were considered to be a functional tool for the study of drug metabolism of diclofenac in humans. Copyright © 2015 by The American Society for Pharmacology and Experimental

  7. Metabolic and functional effects of beta-hydroxy-beta-methylbutyrate (HMB) supplementation in skeletal muscle.

    Pinheiro, Carlos Hermano da Justa; Gerlinger-Romero, Frederico; Guimarães-Ferreira, Lucas; de Souza, Alcione Lescano; Vitzel, Kaio Fernando; Nachbar, Renato Tadeu; Nunes, Maria Tereza; Curi, Rui

    2012-07-01

    Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite derived from leucine. The anti-catabolic effect of HMB is well documented but its effect upon skeletal muscle strength and fatigue is still uncertain. In the present study, male Wistar rats were supplemented with HMB (320 mg/kg per day) for 4 weeks. Placebo group received saline solution only. Muscle strength (twitch and tetanic force) and resistance to acute muscle fatigue of the gastrocnemius muscle were evaluated by direct electrical stimulation of the sciatic nerve. The content of ATP and glycogen in red and white portions of gastrocnemius muscle were also evaluated. The effect of HMB on citrate synthase (CS) activity was also investigated. Muscle tetanic force was increased by HMB supplementation. No change was observed in time to peak of contraction and relaxation time. Resistance to acute muscle fatigue during intense contractile activity was also improved after HMB supplementation. Glycogen content was increased in both white (by fivefold) and red (by fourfold) portions of gastrocnemius muscle. HMB supplementation also increased the ATP content in red (by twofold) and white (1.2-fold) portions of gastrocnemius muscle. CS activity was increased by twofold in red portion of gastrocnemius muscle. These results support the proposition that HMB supplementation have marked change in oxidative metabolism improving muscle strength generation and performance during intense contractions.

  8. 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.

  9. Effects of CYP2C19 polymorphism on the pharmacokinetics of lansoprazole and its main metabolites in healthy Chinese subjects.

    Zhang, Dan; Wang, Xiaolin; Yang, Man; Wang, Guocai; Liu, Huichen

    2011-06-01

    The aim of the study was to determine the pharmacokinetics of lansoprazole and its main metabolites (5'-hydroxy lansoprazole and lansoprazole sulphone) after administration of enteric-coated tablet in healthy Chinese subjects classified by CYP2C19 genotypes, and evaluate the effects of CYP2C19 genotypes on the pharmacokinetics of the three compounds. A single oral dose of 30 mg lansoprazole was administrated to 24 healthy Chinese male volunteers in different CYP2C19 genotype groups. Blood samples were collected from pre-dose up to 14-h post-dose. Plasma concentration of lansoprazole and its main metabolites were quantified by liquid chromatography-tandem mass spectrometry. CYP2C19 polymorphism had significant effects on the pharmacokinetics of lansoprazole and its main metabolites. The differences in the pharmacokinetics between CYP2C19 extensive metabolizers (Ems) (homo-EMs and hete-EMs) and PMs were more significant for lansoprazole sulphone than for 5'-hydroxy lansoprazole. The results indicate that the monitoring of lansoprazole and its main metabolites in plasma at the time-points in the elimination phase for lansoprazole could reflect the activity of CYP2C19. Simultaneously monitored with lansoprazole sulphone, lansoprazole might be a useful probe drug for CYP2C19.

  10. The use of hydroxy-DL-proline-2-14C in the investigation of hydroxyproline metabolism in normal subjects and in patients with renal insufficiency

    Hart, W.; Sluys Veer, J. van der

    1976-01-01

    The metabolism of hydroxproline was investigated in six healthy subjects and four patients with chronic renal insufficiency (creatinine clearances respectively 40, 10, 7, 2.5 ml/min). For this purpose, hydroxy-DL-proline-2- 14 C was administered intravenously and the excretion patterns of radio-activity in plasma, urine and expired air ( 14 CO 2 ) were determined. A separation procedure (using thin layer chromatography followed by oxidation with D-animo acid oxidase) made it possible to determine the concentration of hydroxy-L-proline-2- 14 C in the presence of the D-isomer and the degradation products of both. Although the use of a racemic mixture as tracer made conclusions more difficult, it could be shown that in uremic patients the concentration of hydroxy-DL-proline-2 14 C remained high in the blood for a longer period, the metabolites appeared in the urine later, and the peak respiratory 14 CO 2 excretion was reached later and was lower than in the healthy subjects. On this basis it was concluded that the metabolism of hydroxyproline is diminished in patients with renal insufficiency

  11. Qualitative profiling and quantification of neonicotinoid metabolites in human urine by liquid chromatography coupled with mass spectrometry.

    Kumiko Taira

    Full Text Available Neonicotinoid pesticides have been widely applied for the production of fruits and vegetables, and occasionally detected in conventionally grown produce. Thus oral exposure to neonicotinoid pesticides may exist in the general population; however, neonicotinoid metabolites in human body fluids have not been investigated comprehensively. The purpose of this study is the qualitative profiling and quantitative analysis of neonicotinoid metabolites in the human spot urine by liquid chromatography coupled with mass spectrometry (LC/MS. Human urine samples were collected from three patients suspected of subacute exposure to neonicotinoid pesticides. A qualitative profiling of urinary metabolites was performed using liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS with a database of nominal molecular weights of 57 known metabolites of three neonicotinoid pesticides (acetamiprid, Imidacloprid, and clothianidin, as well as the parent compounds. Then a quantitative analysis of selected urinary metabolites was performed using liquid chromatography/tandem mass spectrometry (LC/MS/MS with a standard pesticide and metabolite, which were detected by the qualitative profiling. The result of qualitative profiling showed that seven metabolites, i.e. an acetamiprid metabolite, N-desmethyl-acetamiprid; three Imidacloprid metabolites, 5-hydroxy-Imidacloprid, 4,5-dihydroxy-imidacloprid, 4,5-dehydro-Imidacloprid; a common metabolite of acetamiprid and Imidacloprid, N-(6-chloronicotinoyl-glycine; and two clothianidin metabolites, N-desmethyl-clothianidin, N-(2-(methylsulfanylthiazole-5-carboxyl-glycine, as well as acetamiprid, were detected in the urine of three cases. The result of the quantitative analysis showed N-desmethyl-acetamiprid was determined in the urine of one case, which had been collected on the first visit, at a concentration of 3.2 ng/mL. This is the first report on the qualitative and quantitative detection of N-desmethyl-acetamiprid in

  12. 3-hydroxy-2(1H)-pyridinone chelating agents

    Raymond, K.; Xu, J.

    1999-04-06

    Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. 2 figs.

  13. Antifouling activity of green-synthesized 7-hydroxy-4-methylcoumarin.

    Pérez, Miriam; García, Mónica; Ruiz, Diego; Autino, Juan Carlos; Romanelli, Gustavo; Blustein, Guillermo

    2016-02-01

    In the search for new environmental-friendly antifoulants for replace metallic biocides, 7-hydroxy-4-methylcoumarin was synthesized according to green chemistry procedures. This compound was characterized by current organic analysis and its antifouling properties were firstly evaluated on the bivalve Mytilus edulis platensis in the laboratory. In the second stage, a soluble matrix antifouling coating formulated with this compound was assayed in marine environment. Laboratory experiments showed that 7-hydroxy-4-methylcoumarin was effective in inhibiting both the settlement as well as the byssogenesis of mussels. In addition, after exposure time in the sea, painted panels containing this compound showed strong antifouling effect on conspicuous species of the fouling community of Mar el Plata harbor. In conclusion, green-synthesized coumarin could be a suitable antifoulant candidate for marine protective coatings. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Spectrophotometric determination of La (III) with sulphamethoxazole based hydroxy triazene

    Manwani, Sapana; Chauhan, R.S.; Goswami, A.K.

    2015-01-01

    In the present study, 3-hydroxy-3-p-chlorophenyll-1-(4-amino-N-(5-methyl-1,2-oxazole-3- yl) benzenesulphonamide-methane) triazene has been synthesized by coupling of hydroxylamine obtained by reduction of nitro compound with diazonium salt obtained from sulphamethoxazole taking hydroxylamine in excess at temperature between 0-5°C. Chemical structure of the synthesized compound was confirmed by IR, 1 H NMR, MASS and by elemental analysis. The complex of the reagent with La (III) has been studied. 3-hydroxy-3-p-chlorophenyll-1-(4-amino-N-(5-methyl-1,2-oxazole-3-yl) benzenesulphonamide-methane) triazene has been used for spectrophotometric determination of lanthanum (III) at 392 nm, keeping the pH between 8.5 to 8.9

  15. Baker's yeast: production of D- and L-3-hydroxy esters

    Dahl, Allan Carsten; Madsen, Jørgen Øgaard

    1998-01-01

    harvested while growing. In contrast, the stereoselectivity was shifted towards L-hydroxy esters when the oxo esters were added slowly to ordinary baker's yeast supplied with gluconolactone as co-substrate. The reduction rate with gluconolactone was increased by active aeration. Ethyl L-(S)-3......Baker's yeast grown under oxygen limited conditions and used in the reduction of 3-oxo esters results in a shift of the stereoselectivity of the yeast towards D-hydroxy esters as compared with ordinary baker's yeast. The highest degree of stereoselectivity was obtained with growing yeast or yeast......-hydroxybutanoate was afforded in >99% ee. Both enantiomers of ethyl 3-hydroxypentanoate, D-(R) in 96% ee and L-(S) in 93% ee, and of ethyl 4-chloro-3-hydroxybutanoate, D-(S) in 98% ee and L-(R) in 94% ee, were obtained. The results demonstrate that the stereoselectivity of baker's yeast can be controlled...

  16. Preventive Effects of Beta-Hydroxy-Beta-Methyl Butyrate

    N. Ravanbakhsh; N. Torabi; M. Foadoddini

    2016-01-01

    Aims: One of the major factors in sudden cardiac arrest is the initiation and continuation of deadly arrhythmias during ischemia. It is known that beta-hydroxy-beta-methylbutyrate (HMB) has useful effects such as anti-inflammatory and anti-apoptosis effects in the skeletal muscles. The aim of this study was to investigate the preventive effects of HMB on the ventricular arrhythmias due to the ischemia. Materials & Methods: In the experimental study, 30 Wistar male rats were randomly div...

  17. Technetium (tin) ethane-1-hydroxy-1, 1-diphosphonate complexes

    Brand, J.A.G.M.

    1981-10-01

    The aim of this thesis is to establish the experimental conditions for the optimal preparation of the sup(99m)Tc(Sn)EHDP bone scanning agent. The pH and the concentrations of EHDP (ethane-1-hydroxy-1,1-disodium diphosphonate) and of Sn(II) may affect the yield and the biodistribution of the radiopharmacon. The investigation of the influence of these parameters is the subject of this investigation. (Auth.)

  18. Applications of hydroxy acids: classification, mechanisms, and photoactivity

    Andrija Kornhauser

    2010-11-01

    Full Text Available Andrija Kornhauser1, Sergio G Coelho2, Vincent J Hearing21US Food and Drug Administration [retired], Annandale, VA, USA; 2Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USAAbstract: Hydroxy acids (HAs represent a class of compounds which have been widely used in a number of cosmetic and therapeutic formulations in order to achieve a variety of beneficial effects for the skin. We review and discuss the most frequently used classes of these compounds, such as a-hydroxy acids, β-hydroxy acids, polyhydroxy acids, and bionic acids, and describe their applications as cosmetic and therapeutic agents. Special emphasis is devoted to the safety evaluation of these formulations, in particular on the effects of their prolonged use on sun-exposed skin. Furthermore, we summarize the very limited number of studies dealing with the modifications evoked by topical application of products containing HAs on photocarcinogenesis. In spite of the large number of reports on the cosmetic and clinical effects of HAs, their biological mechanism(s of action still require more clarification. Some of these mechanisms are discussed in this article along with important findings on the effect of HAs on melanogenesis and on tanning. We also emphasize the important contribution of cosmetic vehicles in these types of studies. Thus, HAs play an important role in cosmetic formulations, as well as in many dermatologic applications, such as in treating photoaging, acne, ichthyosis, rosacea, pigmentation disorders, and psoriasis.Keywords: hydroxy acids, glycolic acid, salicylic acid, UV, erythema, cosmetics

  19. Polyketide family of novel antibacterial 7-O-methyl-5'-hydroxy-3'-heptenoate-macrolactin from seaweed-associated Bacillus subtilis MTCC 10403.

    Chakraborty, Kajal; Thilakan, Bini; Raola, Vamshi Krishna

    2014-12-17

    Seaweed-associated heterotrophic bacterial communities were screened to isolate potentially useful antimicrobial strains, which were characterized by phylogenetic analysis. The bacteria were screened for the presence of metabolite genes involved in natural product biosynthetic pathway, and the structural properties of secondary metabolites were correlated with the genes. Bioactivity-guided isolation of polyene antibiotic 7-O-methyl-5'-hydroxy-3'-heptenoate-macrolactin from Bacillus subtilis MTCC10403 associated with seaweed Anthophycus longifolius using mass spectrometry and extensive 2D-NMR studies was carried out. The newly isolated macrolactin compound is a bactericidal antibiotic with broad spectrum activity against human opportunistic clinical pathogens. The biosynthetic pathway of 7-O-methyl-5'-hydroxy-3'-heptenoate-macrolactin by means of a stepwise, decarboxylative condensation pathway established the PKS-assisted biosynthesis of the parent macrolactin and the side-chain 5-hydroxyhept-3-enoate moiety attached to the macrolactin ring system at C-7. Antimicrobial activity analysis combined with the results of amplifying genes encoding for polyketide synthetase and nonribosomal peptide synthetase showed that seaweed-associated bacteria had broad-spectrum antimicrobial activity. The present work may have an impact on the exploitation of macrolactins for pharmaceutical and biotechnological applications.

  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. Ligand Binding Affinities of Arctigenin and Its Demethylated Metabolites to Estrogen Receptor Alpha

    Masao Hattori

    2013-01-01

    Full Text Available Phytoestrogens are defined as plant-derived compounds with estrogen-like activities according to their chemical structures and activities. Plant lignans are generally categorized as phytoestrogens. It was reported that (−-arctigenin, the aglycone of arctiin, was demethylated to (−-dihydroxyenterolactone (DHENL by Eubacterium (E. sp. ARC-2. Through stepwise demethylation, E. sp. ARC-2 produced six intermediates, three mono-desmethylarctigenins and three di-desmethylarctigenins. In the present study, ligand binding affinities of (−-arctigenin and its seven metabolites, including DHENL, were investigated for an estrogen receptor alpha, and found that demethylated metabolites had stronger binding affinities than (−-arctigenin using a ligand binding screen assay method. The IC50 value of (2R,3R-2-(4-hydroxy-3-methoxybenzyl-3-(3,4-dihydroxybenzyl-butyrolactone was 7.9 × 10−4 M.

  3. Pharmacology, pharmacokinetics and metabolism of the dopamine receptor agonist 5-hydroxy-6-methyl-2-di-n-propylaminotetralin (DK-118) in the cat

    Koons, J.C.

    1985-01-01

    The dopamine receptor agonist 5-hydroxy-6-methyl-2-di-n-propylaminotetralin (DK-118) lowers blood pressure, heart rat and inhibits tachycardia induced in cats by electrical stimulation of sympathetic nerves innervating the heart. DK-118, unlike most of its chemically related dopaminergic analogs, exhibits a slow onset of activity suggesting that one or more metabolites of the drug may be responsible for its pharmacologic effects. The purpose of the work described in this thesis was to gain information regarding the possible bioactivation of DK-118 in cats. In one series of experiments, cats were pretreated with inhibitors of drug metabolism, metyrapone or SKF 525-A, and alterations of the pharmacologic effects of DK-118 determined. A high-performance liquid chromatography assay-using electrochemical detection was developed to quantify urine and plasma concentrations of DK-118 in control, metyrapone pretreated and SKF 525-A pretreated cats. Urinary metabolites of [ 14 C]DK-118 were identified employing HPLC, GC/MS and FAB/MS. Pharmacologic activity and receptor binding of selected metabolites were determined. Data presented in this thesis are consistent with the hypothesis that metabolites contribute to some of the pharmacologic effects of DK-118

  4. DNA adduct formation by the ubiquitous environmental pollutant 3-nitrobenzanthrone and its metabolites in rats

    Arlt, Volker M.; Sorg, Bernd L.; Osborne, Martin; Hewer, Alan; Seidel, Albrecht; Schmeiser, Heinz H.; Phillips, David H.

    2003-01-01

    Diesel exhaust is known to induce tumours in animals and is suspected of being carcinogenic in humans. Of the compounds found in diesel exhaust, 3-nitrobenzanthrone (3-NBA) is an extremely potent mutagen and suspected human carcinogen forming multiple DNA adducts in vitro. 3-Aminobenzanthrone (3-ABA), 3-acetylaminobenzanthrone (3-Ac-ABA), and N-acetyl-N-hydroxy-3-aminobenzanthrone (N-Ac-N-OH-ABA) were identified as 3-NBA metabolites. In order to gain insight into the pathways of metabolic activation leading to 3-NBA-derived DNA adducts we treated Wistar rats intraperitoneally with 2 mg/kg body weight of 3-NBA, 3-ABA, 3-Ac-ABA, or N-Ac-N-OH-ABA and compared DNA adducts present in different organs. With each compound either four or five DNA adduct spots were detected by TLC in all tissues examined (lung, liver, kidney, heart, pancreas, and colon) using the nuclease P1 or butanol enrichment version of the 32 P-postlabelling method, respectively. Using HPLC co-chromatographic analysis we showed that all major 3-NBA-DNA adducts produced in vivo in rats are derived from reductive metabolites bound to purine bases and lack an N-acetyl group. Our results indicate that 3-NBA metabolites (3-ABA, 3-Ac-ABA and N-Ac-N-OH-ABA) undergo several biotransformations and that N-hydroxy-3-aminobenzanthrone (N-OH-ABA) appears to be the common intermediate in 3-NBA-derived DNA adduct formation. Therefore, 3-NBA-DNA adducts are useful biomarkers for exposure to 3-NBA and its metabolites and may help to identify enzymes involved in their metabolic activation

  5. 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.

  6. Susceptibility of bacteria isolated from pigs to tiamulin and enrofloxacin metabolites.

    Lykkeberg, Anne Kruse; Halling-Sørensen, Bent; Jensen, Lars Bogø

    2007-03-31

    Susceptibilities to metabolites of tiamulin (TIA) and enrofloxacin (ENR) were tested using selected bacteria with previously defined minimal inhibitory concentrations (MIC). The TIA metabolites tested were: N-deethyl-tiamulin (DTIA), 2beta-hydroxy-tiamulin (2beta-HTIA) and 8alpha-hydroxy-tiamulin (8alpha-HTIA), and the ENR metabolites were: ciprofloxacin (CIP) and enrofloxacin N-oxide (ENR-N). Bacteria, all of porcine origin, were selected as representatives of bacterial infections (Staphylococcus hyicus and Actinobacillus pleuropneumoniae), zoonotic bacteria (Campylobacter coli) and indicator bacteria (Escherichia coli and enterococci). Furthermore the effects of these compounds were tested on the microbial community of active sludge to test any negative effect on colony forming units (CFU). DTIA had a potency of 12.5-50% of the potency of TIA. 2beta-HTIA and 8alpha-HTIA had potencies less than 1% of the potency of TIA. ENR-N had a potency of 0.75-1.5% of the potency of ENR, while CIP and ENR had similar potencies. Results obtained here indicate that CIP and DTIA could contribute to the selective pressure for upholding antimicrobial resistant bacteria in animals under ENR or TIA treatment. The most potent metabolites CIP and DTIA showed considerable potencies against activated sludge bacteria compared to the parent compounds. EC(50) (microg/ml) for ENR, CIP, TIA and DTIA were 0.018 [95% CI: 0.028-0.149], 0.064 [95% CI: 0.007-0.046], 6.0 [95% CI: 3.6-9.8], and 9.7 [95% CI: 5.8-16.3], respectively. This indicates that the compounds can change the bacterial population in the sludge, and hereby alter the properties of the sludge.

  7. Derivatives of 16alpha-hydroxy-dehydroepiandrosterone with an additional 7-oxo or 7-hydroxy substituent: synthesis and gas chromatography/mass spectrometry analysis.

    Pouzar, Vladimír; Cerný, Ivan; Hill, Martin; Bicíková, Marie; Hampl, Richard

    2005-10-01

    Derivatives of 16alpha-hydroxy-dehydroepiandrosterone, which have an additional oxygen substituent at position 7 (oxo or hydroxy group), were synthesized. Firstly, 17,17-dimethoxyandrost-5-ene-3beta,16alpha-diyl diacetate was prepared and then oxidized with a complex of chromium(VI) oxide and 2,5-dimethylpyrazole to the respective 7-oxo derivative. This key intermediate was both deprotected or reduced by l-Selectride or sodium borohydride in the presence of cerium(III) chloride and then deprotected to give 7-oxo, 7alpha-hydroxy and 7beta-hydroxy derivatives of 16alpha-hydroxy-dehydroepiandrosterone. The target compounds were characterized by (1)H and (13)C NMR spectra and in the form of O-methyloxime-trimethylsilyl derivatives, by gas chromatography/mass spectrometry methods.

  8. Determination of Urinary PAH Metabolites Using DLLME Hyphenated to Injector Port Silylation and GC-MS-MS.

    Gupta, Manoj Kumar; Jain, Rajeev; Singh, Pratibha; Ch, Ratnasekhar; Mudiam, Mohana Krishna Reddy

    2015-06-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants and well-known carcinogens. Hydroxy derivatives of PAH are considered as biomarkers of PAH exposure, and there is a need to measure these metabolites at low concentrations. So, a precise and eco-friendly analytical method has been developed for rapid determination of PAH metabolites. For the first time, a new analytical method based on coupling of dispersive liquid-liquid microextraction (DLLME) with auto-injector port silylation (auto-IPS) followed by gas chromatography-tandem mass spectrometry (GC-MS-MS) analysis is reported for the analysis of seven urinary PAH metabolites. Factors affecting DLLME and IPS, such as type and volume of extraction and disperser solvent, pH, ionic strength, injector port temperature, volume of N,O-bis(trimethylsilyl)trifluoroacetamide and type of solvent were investigated. Under optimized conditions, the limit of detection and limit of quantification were found to be in the range of 1-9 and 3-29 ng/mL, respectively. Satisfactory recoveries of metabolites in urine samples in the range of 87-95% were found. The developed method has been successfully applied for the determination of PAH metabolites in urine samples of exposed workers. DLLME-auto-IPS-GC-MS-MS method is time, labor, solvent and reagent saving, which can be routinely used for the analysis of urinary PAH metabolites. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Assessment of Imidacloprid and Its Metabolites in Foliage of Eastern Hemlock Multiple Years Following Treatment for Hemlock Woolly Adelgid, Adelges tsugae (Hemiptera: Adelgidae), in Forested Conditions.

    Benton, E P; Grant, J F; Webster, R J; Nichols, R J; Cowles, R S; Lagalante, A F; Coots, C I

    2015-12-01

    Widespread decline and mortality of eastern hemlock, Tsuga canadensis (L.) Carrière, have been caused by hemlock woolly adelgid, Adelges tsugae (Annand) (HWA) (Hemiptera: Adelgidae). The current study is a retrospective analysis conducted in collaboration with Great Smoky Mountains National Park (GRSM) to determine longevity of imidacloprid and its insecticidal metabolites (imidacloprid olefin, 5-hydroxy, and dihydroxy) in GRSM's HWA integrated pest management (IPM) program. Foliage samples were collected from three canopy strata of hemlocks that were given imidacloprid basal drench treatments 4-7 yr prior to sampling. Foliage was analyzed to assess concentrations in parts per billion (ppb) of imidacloprid and its metabolites. Imidacloprid and its olefin metabolite were present in most, 95 and 65%, respectively, branchlets 4-7 yr post-treatment, but the 5-hydroxy and dihydroxy metabolites were present in only 1.3 and 11.7%, respectively, of the branchlets. Imidacloprid and olefin concentrations significantly decreased between 4 and 7 yr post-treatment. Concentrations of both imidacloprid and olefin were below the LC50 for HWA 5-7 yr post-treatment. Knowledge of the longevity of imidacloprid treatments and its metabolite olefin can help maximize the use of imidacloprid in HWA IPM programs. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Identification and quantification of predominant metabolites of synthetic cannabinoid MAB-CHMINACA in an authentic human urine specimen.

    Hasegawa, Koutaro; Minakata, Kayoko; Gonmori, Kunio; Nozawa, Hideki; Yamagishi, Itaru; Watanabe, Kanako; Suzuki, Osamu

    2018-02-01

    An autopsy case in which the cause of death was judged as drug poisoning by two synthetic cannabinoids, including MAB-CHMINACA, was investigated. Although unchanged MAB-CHMINACA could be detected from solid tissues, blood and stomach contents in the case, the compound could not be detected from a urine specimen. We obtained six kinds of reference standards of MAB-CHMINACA metabolites from a commercial source. The MAB-CHMINACA metabolites from the urine specimen of the abuser were extracted using a QuEChERS method including dispersive solid-phase extraction, and analyzed by liquid chromatography-tandem mass spectrometry with or without hydrolysis with β-glucuronidase. Among the six MAB-CHMINACA metabolites tested, two predominant metabolites could be identified and quantified in the urine specimen of the deceased. After hydrolysis with β-glucuronidase, an increase of the two metabolites was not observed. The metabolites detected were a 4-monohydroxycyclohexylmethyl metabolite M1 (N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-((4-hydroxycyclohexyl)methyl)-1H-indazole-3-carboxamide) and a dihydroxyl (4-hydroxycyclohexylmethyl and tert-butylhydroxyl) metabolite M11 (N-(1-amino-4-hydroxy-3,3-dimethyl-1-oxobutan-2-yl)-1-((4-hydroxycyclohexyl)methyl)-1H-indazole-3-carboxamide). Their concentrations were 2.17 ± 0.15 and 10.2 ± 0.3 ng/mL (n = 3, each) for M1 and M11, respectively. Although there is one previous in vitro study showing the estimation of metabolism of MAB-CHMINACA using human hepatocytes, this is the first report dealing with in vivo identification and quantification of MAB-CHMINACA metabolites in an authentic human urine specimen. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Metabolites of hirsuteine and hirsutine, the major indole alkaloids of Uncaria rhynchophylla, in rats.

    Nakazawa, Takahiro; Banba, Koh-ichi; Hata, Kazumasa; Nihei, Yutaka; Hoshikawa, Ayumi; Ohsawa, Keisuke

    2006-08-01

    The metabolic fate of hirsuteine (HT) and hirsutine (HS), the major indole alkaloids of Uncaria rhynchophylla, was investigated using rats. On HPLC analysis, urine from rats orally administered HT were found to contain two metabolites (HT1 and HT2) together with unchanged HT. Similarly HS also was metabolized to two compounds (HS1 and HS2). Metabolite structures were determined to be 11-hydroxyhirsuteine-11-O-beta-D-glucuronide (HT1), 11-hydroxyhirsuteine (HT2), 11-hydroxyhirsutine-11-O-beta-D-glucuronide (HS1) and 11-hydroxyhirsutine (HS2), based on spectroscopic and chemical data. HT1 and HS1 were also detected in bile from rats administered HT and HS, respectively. Total cumulative urinary excretion within 72 h of oral administration was approximately 14% and 26% of the HT and HS doses, respectively, while total cumulative biliary excretion was 35% and 46%, respectively. HT and HS 11-hydroxylation were catalyzed by rat liver microsomes. This 11-hydroxylation activity was inhibited by addition of SKF-525A (a nonselective CYP inhibitor) or cimetidine (a CYP2C inhibitor). These results indicate that orally administered HT and HS are converted to 11-hydroxy metabolites in rats, and that the metabolites are predominantly excreted in bile rather than urine following glucuronidation. Furthermore, the results suggest that CYP2C enzymes are involved, at least in part, in the specific 11-hydroxylation of HT and HS.

  12. Body composition of piglets from sows fed the leucine metabolite β-hydroxy β-methyl butyrate in late gestation

    Flummer, Christine; Kristensen, Niels Bastian; Theil, Peter Kappel

    2012-01-01

    piglets were weighed at day 28 and water content was assessed by deuterium oxide dilution. Piglets were euthanized, organ weights and lengths were recorded, the empty carcass was analyzed for dry matter, ash, and crude protein content, and body fat content was calculated. Two litters were treated......% heavier in HMB piglets (P carcasses of HMB piglets had a lower DM and fat content (P

  13. 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....

  14. Mass-fragmentographic determination of 25-hydroxy-vitamin D3 using deuterium labeled internal standard

    Bjorkhem, I.; Holmberg, I.

    1975-01-01

    25-[26- 2 H 3 ] Hydroxy-vitamin D 3 has been synthesized according to the following route: 3β-acetoxy-27-nor-cholest-5-en-25-one → 3β-acetoxy-27-nor-cholesta-5,7-dien-25-one → [26- 2 H 3 ] cholesta-5,7-diene-3β,25-diol → 25-[26- 2 H 3 ] hydroxy-vitamin D 3 . A fixed amount of 25-[26- 2 H 3 ] hydroxy-vitamin D 3 , usually 250 ng, is added to a fixed amount of serum, usually 2.5 ml, and the mixture is extracted with a chloroform-methanol mixture. The extract is chromatographed on a Sephadex LH-20 column together with a trace amount of 25-[26- 3 H] hydroxy-vitamin D 3 . The chromatographic fraction corresponding to 25-hydroxy-vitamin D 3 is collected and the amount of unlabeled 25-hydroxy-vitamin D 3 is determined from the ratio between the mass fragmentographic recording of m/e 131 (base peak of unlabeled 25-hydroxy-vitamin D 3 ) and m/e 134 (base peak of 25-[26- 2 H 3 ] hydroxy-vitamin D 3 ). The relative standard deviation of the method was about 5%. The mean value for 25-hydroxy-vitamin D 3 obtained from 23 different serum samples from healthy Swedish men and women was 27 ng/ml with a standard deviation of 10 ng/ml

  15. Occurrence and metabolism of 7-hydroxy-2-indolinone-3-acetic acid in Zea mays

    Lewer, P.; Bandurski, R. S.

    1987-01-01

    7-Hydroxy-2-indolinone-3-acetic acid was identified as a catabolite of indole-3-acetic acid in germinating kernels of Zea mays and found to be present in amounts of ca 3.1 nmol/kernel. 7-Hydroxy-2-indolinone-3-acetic acid was shown to be a biosynthetic intermediate between 2-indolinone-3-acetic acid and 7-hydroxy-2-indolinone-3-acetic acid-7'-O-glucoside in both kernels and roots of Zea mays. Further metabolism of 7-hydroxy-2-[5-3H]-indolinone-3-acetic acid-7'-O-glucoside occurred to yield tritiated water plus, as yet, uncharacterized products.

  16. Primary Screening of 10 - Hydroxy - 2 - Decenoic Acid Productive Strains

    2002-01-01

    In this paper, eleven strains, which vere screened strictly from raw royal.jelly, soil and honeycomb etc. by means of dilution plate and spread plate methods, were cultured at 28°C for60 h with shaking. To determine whether they could yield 10-Hydroxy-2-decenoic acid during fermentation, gas chromatography and gas chromatography-mass spectrometry methods were used. The results showed that the strains BH002 and BH004. were both identified as Crvtococcaceae. where BH002 was primarily classified into Candida for possessing the abilities. The 10-HDA productivity of Candida BH002 and that of BH004 were 0.327% and 0.2648% respectively.

  17. 1-[(E-(3-Hydroxy-4-methoxybenzylideneamino]-3-methylthiourea

    Md. Azharul Arafath

    2016-10-01

    Full Text Available In the title thiosemicarbazone Schiff base compound, C10H13N3O2S, the dihedral angle between the benzene ring and methyl carbothioamide side arm was found to be 17.4 (4°. The presence of two intramolecular hydrogen bonds is noted, namely hydroxy-O—H...O(methoxy and amine-N—H...N(imine. In the crystal, pairwise amine-N—H...S hydrogen bonds give rise to centrosymmetric {...HNCS}2 synthons, which lead to dimeric aggregates.

  18. Radiation effects in x-irradiated hydroxy compounds

    Budzinski, E.E.; Potter, W.R.; Box, H.C.

    1980-01-01

    Radiation effects are compared in single crystals of xylitol, sorbitol, and dulcitol x-irradiated at 4.2 0 K. In xylitol and dulcitol, but not in sorbitol, a primary oxidation product is identified as an alkoxy radical. ENDOR measurements detected three proton hyperfine couplings associated with the alkoxy ESR absorption, one of which is attributed to a proton three bond lengths removed from the seat of unpaired spin density. Intermolecular trapping of electrons is observed in all three crystals. ENDOR measurements were made of the hyperfine couplings between the trapped electron and the hydroxy protons forming the trap

  19. 6-Chloro-N′-(2-hydroxy-1-naphthylmethylenenicotinohydrazide

    Feng Zhi

    2008-01-01

    Full Text Available The title compound, C17H12ClN3O2, was synthesized by the Schiff base condensation reaction of 2-hydroxy-1-naphthaldehyde with 6-chloronicotinic acid hydrazide in a methanol solution. The molecule displays a trans configuration with respect to the C=N and C—N bonds. The dihedral angle between the naphthyl ring system and the pyridine ring is 7.6 (4°. There is an intramolecular O—H...N hydrogen bond. The crystal structure is stabilized by intermolecular N—H...O and C—H...O hydrogen bonds, forming chains running along the b axis.

  20. One pot synthesis of 2-hydroxy pyrrolidine derivatives

    Putta. P. Varma

    2011-01-01

    Full Text Available One pot reaction of various 2-amino-thiadiazoles or thiazoles and 2,3- dihydrofuran under mild condition in presence of CeCl 3.7H 2O as catalyst transformed the amino group of 2-amino-thiadiazoles or thiazoles into a medicinally important 2-hydroxy pyrrolidine ring system in good to excellent yields. The generality of the reaction was sufficiently investigated and demonstrated. The new reaction path way for this conversion was established by spectroscopic and analytical methods.

  1. Parabens and Their Metabolites in Pet Food and Urine from New York State, United States.

    Karthikraj, Rajendiran; Borkar, Sonali; Lee, Sunmi; Kannan, Kurunthachalam

    2018-03-20

    The exposure of pets, such as dogs and cats, to a wide range of chemicals present in the indoor environment and the concomitant increase in noninfectious diseases in these companion animals are a concern. Nevertheless, little is known about the sources and pathways of exposure to chemicals in pets. In this study, we determined the concentrations of parabens in commercially available cat and dog foods as well as in urine samples from these pets collected from the Albany area of the state of New York in the United States. Parabens, especially methyl paraben (MeP), and their metabolites were found in all pet food and urine samples. The mean concentrations of total parabens (i.e., sum of parabens and their metabolites) in dog ( n = 23) and cat ( n = 35) food were 1350 and 1550 ng/g fresh wt, respectively. Dry food contained higher concentrations of parabens and their metabolites than did wet food, and cat food contained higher concentrations of target chemicals than did dog food. The mean concentrations of total parabens found in dog ( n = 30) and cat ( n = 30) urine were 7230 and 1040 ng/mL, respectively. In both pet food and urine, MeP (among parabens) and 4-hydroxy benzoic acid (4-HB) (among metabolites) were the dominant compounds. The metabolites of parabens accounted for ∼99% (∼99.1% in food and ∼98.9% in urine) of the total concentrations in both food and urine. The profiles of parabens and their metabolites in the urine of dogs and cats varied. In addition to diet, other sources of paraben exposures were found for dogs, whereas, for cats, the majority of exposures was identified as related to diet.

  2. Seasonal Variations in Surface Metabolite Composition of Fucus vesiculosus and Fucus serratus from the Baltic Sea.

    Esther Rickert

    Full Text Available Perennial macroalgae within the genus Fucus are known to exude metabolites through their outer thallus surface. Some of these metabolites have pro- and/or antifouling properties. Seasonal fluctuations of natural fouling pressure and chemical fouling control strength against micro- and macrofoulers have previously been observed in Fucus, suggesting that control strength varies with threat. To date, a study on the seasonal composition of surface associated metabolites, responsible for much of the fouling control, has not been done. We sampled individuals of the two co-occurring species F. vesiculosus and F. serratus at monthly intervals (six per species and month during a one-year field study. We analysed the chemical composition of surface associated metabolites of both Fucus species by means of gas chromatography-mass spectrometry (GC-MS to describe temporal patterns in chemical surface composition. Additionally, we correlated abiotic and biotic parameters recorded monthly within the sampled habitat with the variation in the chemical surface landscape of Fucus. Our study revealed that the chemical surface composition of both Fucus species exhibits substantial seasonal differences between spring/summer and autumn/winter months. Light and temperature explained most of the seasonal variability in surface metabolite composition of both Fucus species. A strong summerly up-regulation of eighteen saccharides and two hydroxy acids in F. vesiculosus as well as of four fatty acids and two saccharides in F. serratus was observed. We discuss how these up-regulated molecules may have a complex effect on associated microfoulers, both promoting or decreasing fouling depending on metabolite and bacterial identity. These seasonal shifts in the surface metabolome seem to exert a compound control of density and composition of the Fucus associated biofilm.

  3. The application of HPLC-F and GC-MS to the analysis of selected hydroxy polycylic hydrocarbons in two certified fish bile reference materials

    Jonsson, G.; Beyer, J.; Wells, D.; Ariese, F.

    2003-01-01

    Four selected hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), 2-hydroxy-naphthalene (2-OH-NPH), 1-hydroxy-phenanthrene (1-OH-PHE), 1-hydroxy-pyrene (1-OH-PYR) and 3-hydroxy-benzo[a]pyrene (3-OH-BaP) have been analysed in two certified fish bile reference materials (CRMs) for exposure monitoring

  4. The application of HPLC-F and GC-MS to the analysis of selected hydroxy polycyclic hydrocarbons in two certified fish bile reference materials

    Jonsson, G.; Beyer, J.; Wells, D.E.; Ariese, F.

    2003-01-01

    Four selected hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), 2-hydroxy-naphthalene (2-OH-NPH), 1-hydroxy-phenanthrene (1-OH-PHE), 1-hydroxy-pyrene (1-OH-PYR) and 3-hydroxy-benzo[a]pyrene (3-OH-BaP) have been analysed in two certified fish bile reference materials (CRMs) for exposure monitoring

  5. Plasma and milk concentrations of vitamin D3 and 25-hydroxy vitamin D3 following intravenous injection of vitamin D3 or 25-hydroxy vitamin D3.

    Hidiroglou, M; Knipfel, J E

    1984-01-01

    Plasma levels of vitamin D3 or 25-hydroxyvitamin D3 in ewes after administration of a single massive intravenous dose of vitamin D3 (2 X 10(6) IU) or 25-hydroxy vitamin D3 (5 mg) were determined at zero, one, two, three, five, ten and 20 days postinjection. In six ewes injected with vitamin D3 conversion of vitamin D3 to 25-hydroxy vitamin D3 resulted in a six-fold increase in the plasma 25-hydroxy vitamin D3 level within one day. Elevated levels were maintained until day 10 but by day 20 a s...

  6. Relationship between mono-hydroxy-carbazepine serum concentrations and adverse effects in patients on oxcarbazepine monotherapy.

    Sattler, Annika; Schaefer, Marion; May, Theodor W

    2015-09-01

    To evaluate the relationship between serum concentrations of mono-hydroxy-carbazepine (MHD), the main metabolite of oxcarbazepine (OXC), and the occurrence of adverse effects (AE) in a large group of patients on OXC monotherapy. An antiepileptic drug (AED) therapeutic drug monitoring (TDM) database was analyzed especially with regard to OXC dosage, MHD serum concentration, and the occurrence of AE. In total, 893 blood samples of 442 patients were included in this retrospective study. The statistical evaluation was performed by means of Kaplan-Meier estimates, log-rank tests and generalized estimating equations (GEE). At least one AE was reported in 78 (17.6%) of the 442 patients. At MHD serum concentrations of 30.0 μg/ml and 43.7 μg/ml and OXC dosages of 33.1 mg/kg and 62.3 mg/kg, 25% and 75% of patients, respectively, experienced at least one AE. Log-rank tests indicated that younger patients (<18 years) may be able to tolerate higher MHD serum levels (p = 0.006) and higher OXC dosages per body weight (p < 0.001) compared to adult patients (≥ 18 years). Furthermore, AEs occurred at higher body-weight adjusted OXC dosages of extended release formulations compared to immediate-release formulations (p = 0.010), whereas MHD serum levels at which AEs occurred did not differ significantly between formulations (p = 0.125). Multivariate GEE confirmed the results. The occurrence of AEs is significantly (and non-linearly) dependent on MHD serum level, whereas the dependence of OXC dosage is less distinctive. But, tolerability of OXC seems to depend on age of the patients as well as on pharmaceutical formulation of OXC. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  7. Determination of N-methylsuccinimide and 2-hydroxy-N-methylsuccinimide in human urine and plasma.

    Jönsson, B A; Akesson, B

    1997-12-19

    A method for determination of N-methylsuccinimide (MSI) and 2-hydroxy-N-methylsuccinimide (2-HMSI) in human urine and of MSI in human plasma was developed. MSI and 2-HMSI are metabolites of the widely used organic solvent N-methyl-2-pyrrolidone (NMP). MSI and 2-HMSI were purified from urine and plasma by C8 solid-phase extraction and analysed by gas chromatography-mass spectrometry in the negative-ion chemical ionisation mode. The intra-day precisions in urine were 2-6% for MSI (50 and 400 ng/ml) and 3-5% for 2-HMSI (1000 and 8000 ng/ml). For MSI in plasma it was 2% (60 and 1200 ng/ml). The between-day precisions in urine were 3-4% for MSI (100 and 1000 ng/ml) and 2-4% for 2-HMSI (10,000 and 18,000 ng/ml) and 3-4% for MSI in plasma (100 and 900 ng/ml). The recoveries from urine were 109-117% for MSI (50 and 400 ng/ml) and 81-89% for 2-HMSI (1000 and 8000 ng/ml). The recovery of MSI from plasma was 91-101% (50 and 500 ng/ml). The detection limits for MSI were 3 ng/ml in urine and 1 ng/ml in plasma and that of 2-HMSI in urine was 200 ng/ml. The method is applicable for analysis of urine and plasma samples from workers exposed to NMP.

  8. Efficacy of beta-hydroxy-beta-methylbutyrate supplementation in maintenance hemodialysis patients.

    Fitschen, Peter J; Biruete, Annabel; Jeong, Jinny; Wilund, Kenneth R

    2017-01-01

    Maintenance hemodialysis (MHD) patients suffer from a number of co-morbidities including declines in muscle mass and physical function. Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the amino acid leucine that has been shown to improve lean mass and physical function in elderly and clinical populations, but had not been studied in MHD patients. The purpose of this study was to investigate the efficacy of HMB in this population. We performed a double-blind, placebo-controlled, randomized trial to assess the effects of daily HMB supplementation on co-morbidities in MHD patients. MHD patients were recruited and assigned to either daily supplementation with HMB (n = 16) or placebo (n = 17) for 6 months. Measurements of body composition, bone density, strength, physical function, fall risk, quality of life, and blood parameters were measured at baseline and 6 months. Blood was drawn at baseline, 3, and 6 months to measure compliance. No significant effects of HMB on body composition, bone density, strength, physical function, fall risk, quality of life, or blood parameters were observed. On analysis of plasma HMB concentrations, 5 of 16 patients (31%) in the HMB group were found to be noncompliant at 3 or 6 months. Therefore, we performed a per-protocol analysis with compliant participants only and observed no significant differences in our outcomes of interest. These results do not support the efficacy of HMB to attenuate co-morbid conditions in MHD patients. Moreover, this highlights the need for future interventions targeted at reducing pill burden and improving pill compliance in this population. © 2016 International Society for Hemodialysis.

  9. β-hydroxy-β-methylbutyrate (HMB) attenuates muscle and body weight loss in experimental cancer cachexia.

    Aversa, Zaira; Bonetto, Andrea; Costelli, Paola; Minero, Valerio Giacomo; Penna, Fabio; Baccino, Francesco Maria; Lucia, Simone; Rossi Fanelli, Filippo; Muscaritoli, Maurizio

    2011-03-01

    β-hydroxy-β-methylbutyrate (HMB), a leucine metabolite, improves muscle mass and function. This study aimed at evaluating the effects of HMB administration in an experimental in vivo model of cancer cachexia (CC). Wistar rats were randomized to receive standard or 4% HMB-enriched chow. Rats from both groups were randomized to receive an i.p. inoculum of AH-130 cells (TB). All rats were weighed and sacrificed at day 24. Liver, heart and muscles were dissected and weighed. The protein levels of p-p70S6k, p-eIf2α, p-mTOR and p-4-EB-P1 were evaluated by Western blotting on gastrocnemius muscle (GSN). As expected, the growth of the AH-130 ascites hepatoma induced significant carcass weight and GSN muscle loss. HMB treatment significantly increased GSN and heart weight in controls (p=0.002 and pHMB-treated TB, body weight was not lost but significantly (p=0.003) increased, and GSN loss was significantly (p=0.04) attenuated with respect to TB. Phosphorylated eIF2α markedly decreased in TB-rats vs. C. Feeding the HMB-enriched diet resulted in decreased p-eIF2α levels in control animals, while no changes could be observed in the TB group. Phosphorylated p70S6K and phosphorylated mTOR were markedly increased by HMB treatment in controls and further increased in TB. Phosphorylated 4-EB-P1 was markedly increased in TB but substantially unaffected by HMB treatment. Administration of HMB attenuates body weight and muscle loss in experimental CC. Increased phosphorylation of key anabolic molecules suggests that these actions are mediated by improved protein anabolism in muscle.

  10. Enteral β-hydroxy-β-methylbutyrate supplementation increases protein synthesis in skeletal muscle of neonatal pigs

    Kao, Michelle; Columbus, Daniel A.; Suryawan, Agus; Steinhoff-Wagner, Julia; Hernandez-Garcia, Adriana; Nguyen, Hanh V.; Fiorotto, Marta L.

    2016-01-01

    Many low-birth weight infants are at risk for poor growth due to an inability to achieve adequate protein intake. Administration of the amino acid leucine stimulates protein synthesis in skeletal muscle of neonates. To determine the effects of enteral supplementation of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) on protein synthesis and the regulation of translation initiation and degradation pathways, overnight-fasted neonatal pigs were studied immediately (F) or fed one of five diets for 24 h: low-protein (LP), high-protein (HP), or LP diet supplemented with 4 (HMB4), 40 (HMB40), or 80 (HMB80) μmol HMB·kg body wt−1·day−1. Cell replication was assessed from nuclear incorporation of BrdU in the longissimus dorsi (LD) muscle and jejunum crypt cells. Protein synthesis rates in LD, gastrocnemius, rhomboideus, and diaphragm muscles, lung, and brain were greater in HMB80 and HP and in brain were greater in HMB40 compared with LP and F groups. Formation of the eIF4E·eIF4G complex and S6K1 and 4E-BP1 phosphorylation in LD, gastrocnemius, and rhomboideus muscles were greater in HMB80 and HP than in LP and F groups. Phosphorylation of eIF2α and eEF2 and expression of SNAT2, LAT1, MuRF1, atrogin-1, and LC3-II were unchanged. Numbers of BrdU-positive myonuclei in the LD were greater in HMB80 and HP than in the LP and F groups; there were no differences in jejunum. The results suggest that enteral supplementation with HMB increases skeletal muscle protein anabolism in neonates by stimulation of protein synthesis and satellite cell proliferation. PMID:27143558

  11. 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...

  12. A validated LC–MS/MS method for the determination of tolterodine and its metabolite in rat plasma and application to pharmacokinetic study

    Rihana Parveen Shaik

    2013-12-01

    Full Text Available Liquid chromatography–tandem mass spectrometry (LC–MS/MS method was used for simultaneous quantification of tolterodine and its metabolite 5-hydroxy methyl tolterodine in rat plasma. Tolterodine-d6 and 5-hydroxy methyl tolterodine-d14 were used as internal standards (IS. Chromatographic separation was performed on Ascentis Express RP amide (50 mm×4.6 mm, 2.7 μm column with an isocratic mobile phase composed of 10 mM ammonium acetate and acetonitrile in the ratio of 20:80 (v/v, at a flow-rate of 0.5 mL/min. Tolterodine, tolterodine-d6, 5-hydroxy methyl tolterodine and 5-hydroxy methyl tolterodine-d14 were detected with proton adducts at m/z 326.1→147.1, 332.3→153.1, 342.2→223.1 and 356.2→223.1 in multiple reaction monitoring (MRM positive mode respectively. The drug, metabolite and internal standards were extracted by liquid–liquid extraction method. The method was validated over a linear concentration range of 20.00–5000.00 pg/mL for tolterodine and 20.00–5000.00 pg/mL for 5-hydroxy methyl tolterodine. This method demonstrated intra- and inter-day precision of 0.62–6.36% and 1.73–4.84% for tolterodine, 1.38–4.22% and 1.62–4.25% for 5-hydroxy methyl tolterodine respectively. This method also demonstrated intra- and inter-day accuracy of 98.75–103.56% and 99.20–104.40% for tolterodine, 98.08–104.67% and 98.73–103.06% for 5-hydroxy methyl tolterodine respectively. Both analytes were found to be stable throughout freeze–thaw cycles, bench top and postoperative stability studies. This method was successfully applied for the pharmacokinetic analysis of rat plasma samples following i.v. administration. Keywords: LC–MS/MS, Tolterodine, 5-Hydroxy methyl tolterodine, Pharmacokinetics

  13. rac-N-[Hydroxy(4-pyridylmethyl]picolinamide: a hemiamidal

    Muhammad Altaf

    2010-07-01

    Full Text Available The title compound, C12H11N3O2, a hemiamidal, was synthesized by solvent-free aldol condensation at room temperature by grinding picolinamide with isonicotinaldehyde in a 1:1 molar ratio. In the molecule, the two pyridine rings are inclined to one another by 58.75 (6°. They are linked, at positions 2 and 4, by the hemiamidal bridge (–CO—NH—CHOH–. The NH-group H atom forms an intramolecular hydrogen bond with the N atom of the picolinamide pyridine ring. In the crystal, symmetry-related molecules are linked via N—H...O hydrogen bonds, involving the NH group H atom of the hemiamidal bridge and the hydroxy O atom, forming inversion-related dimers, with graph-set R22(8. Adjacent molecules are also linked via O—H...N hydrogen bonds, involving the hydroxy substituent and the 4-pyridine N atom. Together these interactions lead to the formation of double-stranded ribbon-like hydrogen-bonded polymers propagating in [010]. The latter are further connected via C—H...O hydrogen bonds involving the carbonyl O atom, so forming a two-dimensional network in (011.

  14. 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

  15. Use of liquid chromatography/electrospray ionization tandem mass spectrometry to study the degradation pathways of terbuthylazine (TER) by Typha latifolia in constructed wetlands: identification of a new TER metabolite.

    Gikas, Evagelos; Papadopoulos, Nikolaos G; Bazoti, Fotini N; Zalidis, Georgios; Tsarbopoulos, Anthony

    2012-01-30

    S-Triazines are used worldwide as herbicides for agricultural and non-agricultural purposes. Although terbuthylazine (TER) is the second most frequently used S-triazine, there is limited information on its metabolism. For this reason, an analytical method based on liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI MS/MS) has been developed aiming at the identification of TER and its five major metabolites (desisopropyl-hydroxy-atrazine, desethyl-hydroxy-terbuthylazine, desisopropyl-atrazine, hydroxy-terbuthylazine and desethyl-terbuthylazine) in constructed wetland water samples. The separation of TER and its major metabolites was performed by reversed-phase high-performance liquid chromatography (HPLC) on a C(8) column using a gradient elution of aqueous acetic acid 1% (solvent A) and acetonitrile (solvent B), followed by MS/MS analysis on a triple quadrupole mass spectrometer. The data-depended analysis (DDA) scan approach has been employed and the main degradation pathways of both hydroxyl and chloro (dealkylated and alkylated) metabolites are elucidated through the tandem mass spectral (MS/MS) interpretation of triazine fragments under CID conditions. In addition, another major metabolite of TER, namely N2-tert-butyl-N4-ethyl-6-methoxy-1,3,5-triazine-2,4-diamine, has been identified. This methodology can be further employed in biodegradation studies of TER, thus assisting the assessment of its environmental impact. Copyright © 2011 John Wiley & Sons, Ltd.

  16. Theoretical study on the molecular tautomerism of the 3-hydroxy-pyridin-4-one system

    Zborowski, Krzysztof K.; Mohammadpour, Mehrdad; Sadeghi, Amir; Proniewicz, Leonard M.

    2013-04-01

    3-hydroxy-pyridin-4-one is a parent molecule for the family of hydroxypyridinones that are known in coordination chemistry as efficient metal ions chelators. In this work, relative stabilities of some possible tautomers were investigated using several quantum chemical methods: CBS (complete basis set methods), Gn, DFT (density functional theory), Hartree-Fock and MP2. Performed calculations show that the system under consideration exists as a mixture of two tautomers with comparable energies. Among them, the hydroxypyridinone structure of the studied molecular system seems to be a bit more stable than the o-dihydroxypyridine one, by a few kJ/mol only. Aromaticity and intra-molecular hydrogen bonding are the main effects influencing the stability of the studied tautomeric structures. Consequently, aromatic effects were calculated using several indices of aromaticity: HOMA (harmonic oscillator model of aromaticity), NICS (nucleus independent chemical shift), H, PDI (para delocalisation index), MCI (multi-centre index) and ASE (aromatic stabilisation energy). The strength of possible intra-molecular hydrogen bonds (H-bonds) was determined by means of the AIM (atoms-in-molecules) method and by calculating enthalpies for theoretical reactions that do or do not involve H-bonds. The AIM method was employed to understand how variations in atomic energies influence the stability of different tautomeric structures.

  17. Mitochondrial toxicity of diclofenac and its metabolites via inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria: Possible role in drug induced liver injury (DILI).

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2016-03-01

    Diclofenac is a widely prescribed NSAID, which by itself and its reactive metabolites (Phase-I and Phase-II) may be involved in serious idiosyncratic hepatotoxicity. Mitochondrial injury is one of the mechanisms of drug induced liver injury (DILI). In the present work, an investigation of the inhibitory effects of diclofenac (Dic) and its phase I [4-hydroxy diclofenac (4'-OH-Dic) and 5-hydroxy diclofenac (5-OH-dic)] and Phase-II [diclofenac acyl glucuronide (DicGluA) and diclofenac glutathione thioester (DicSG)] metabolites, on ATP synthesis in rat liver mitochondria was carried out. A mechanism based inhibition of ATP synthesis is exerted by diclofenac and its metabolites. Phase-I metabolite (4'-OH-Dic) and Phase-II metabolites (DicGluA and DicSG) showed potent inhibition (2-5 fold) of ATP synthesis, where as 5-OH-Dic, one of the Phase-I metabolite, was a less potent inhibitor as compared to Dic. The calculated kinetic constants of mechanism based inhibition of ATP synthesis by Dic showed maximal rate of inactivation (Kinact) of 2.64 ± 0.15 min(-1) and half maximal rate of inactivation (KI) of 7.69 ± 2.48 μM with Kinact/KI ratio of 0.343 min(-1) μM(-1). Co-incubation of mitochondria with Dic and reduced GSH exhibited a protective effect on Dic mediated inhibition of ATP synthesis. Our data from this study strongly indicate that Dic as well as its metabolites could be involved in the hepato-toxic action through inhibition of ATP synthesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Dissipation kinetics and effect of processing on imidacloprid and its metabolites in cardamom (Elettaria cardamomum Maton).

    Pratheeshkumar, N; Chandran, M; Beevi, S Naseema; Mathew, Thomas Biju; George, Thomas; Paul, Ambily; Xavier, George; Ravi, K Prathibha; Kumar, S Visal; Rajith, R

    2016-01-01

    Dissipation behaviour of the chloronicotinyl insecticide, imidacloprid (Tatamida 17.8 % SL), in fresh and cured cardamom capsules was studied following application at doses 20 and 40 g a.i. ha(-1) in a cardamom plantation of Indian Cardamom Hills (ICH), Idukki, Kerala, India. A single-laboratory ultra performance liquid chromatography mass spectrometry (UPLC-MS/MS) method was developed and validated for the estimation of imidacloprid and its six metabolites (5-hydroxy, olefin, guanidine, urea, 6-chloronicotinic acid and nitrosimine) in fresh and cured cardamom. At the lower dose, the initial deposits of total imidacloprid residues were 1.91 and 7.23 μg g(-1), respectively, in fresh and cured cardamom. At the higher dose, the initial residues were 3.94 and 14.72 μg g(-1), respectively, in fresh and cured capsules. The residues dissipated below the quantitation level of 0.01 μg g(-1) after 21 and 28 days at lower dose and after 28 days for both at higher dose. The half-lives of imidacloprid in fresh and cured cardamom were 4.02 and 3.63 days, respectively, at lower dose and 3.61 days for both at higher dose. The waiting periods of imidacloprid on fresh and cured cardamom at lower and higher doses were 21.40, 27.10, 23.85 and 30.70 days, respectively. The mean processing factor of imidacloprid was 3.96 at 20 g a.i. ha(-1). Amongst metabolites of imidacloprid, urea had maximum residues in fresh and cured cardamom followed by 5-hydroxy and guanidine. Other metabolites such as 6-chloronicotinic acid, olefin and nitrosimine were not detected either in fresh or cured cardamom.

  19. Liquid-chromatography mass spectrometry (LC-MS) of steroid hormone metabolites and its applications

    Penning, Trevor M.; Lee, Seon-Hwa; Jin, Yi; Gutierrez, Alejandro; Blair, Ian A.

    2010-01-01

    Advances in liquid chromatography-mass spectrometry (LC-MS) can be used to measure steroid hormone metabolites in vitro and in vivo. We find that LC-Electrospray Ionization (ESI)-MS using a LCQ ion trap mass spectrometer in the negative ion mode can be used to monitor the product profile that results from 5α–dihydrotestosterone(DHT)-17β-glucuronide, DHT-17β-sulfate, and tibolone-17β-sulfate reduction catalyzed by human members of the aldo-keto reductase (AKR) 1C subfamily and assign kinetic constants to these reactions. We also developed a stable-isotope dilution LC-electron capture atmospheric pressure chemical ionization (ECAPCI)-MS method for the quantitative analysis of estrone (E1) and its metabolites as pentafluorobenzyl (PFB) derivatives in human plasma in the attomole range. The limit of detection for E1-PFB was 740 attomole on column. Separations can be performed using normal-phase LC because ionization takes place in the gas phase rather than in solution. This permits efficient separation of the regioisomeric 2- and 4-methoxy-E1. The method was validated for the simultaneous analysis of plasma E2 and its metabolites: 2-methoxy-E2, 4-methoxy-E2, 16α-hydroxy-E2, estrone (E1), 2-methoxy-E1, 4-methoxy-EI, and 16α-hydroxy-E1 from 5 pg/mL to 2,000 pg/mL. Our LC-MS methods have sufficient sensitivity to detect steroid hormone levels in prostate and breast tumors and should aid their molecular diagnosis and treatment. PMID:20083198

  20. Ketamine and the metabolite norketamine: persistence and phototransformation toxicity in hospital wastewater and surface water.

    Lin, Angela Yu-Chen; Lee, Wan-Ning; Wang, Xiao-Huan

    2014-04-15

    Ketamine has been increasingly used both recreationally and medicinally around the world. Although the metabolic pathways to form its metabolite norketamine have been carefully investigated in humans and animals, knowledge of their environmental occurrence and fate is limited. In this study, we investigated the occurrence of ketamine and norketamine in 20 natural bodies of water, effluents from 13 hospitals, two wastewater treatment plants and one water supply plant. Ketamine was found at concentrations as high as 10 μg/L. Ketamine and norketamine were consistently found in similar concentrations (ketamine/norketamine ratio: 0.3-4.6) in the collected water samples, and this ratio similar to that found in urine samples. Dark incubation experiments have shown that ketamine is not susceptible to microbial degradation or hydrolysis. Phototransformation was demonstrated to significantly reduce the concentration of ketamine and norketamine in river waters (t(1/2) = 12.6 ± 0.4 and 10.1 ± 0.4 h, respectively) and resulted in byproducts that are similar to human metabolites. Both direct and indirect photolysis led to the N-demethylation of ketamine to form norketamine and other byproducts, including hydroxy-norketamine (HNK), dehydronorketamine (DNK), hydroxy-ketamine (HK) and isomer forms of ketamine and norketamine. Irradiated solutions exhibited higher toxicity (via the Microtox test). Although a final risk assessment could not be made due to a lack of studies on the chronic effects on aquatic organisms, the high and persistent environmental occurrences of ketamine and norketamine as well as the increasingly acute toxicity of the photo byproducts demonstrate the importance of including metabolites in evaluation of the overall risk of ketamine. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. PROCESS FOR HYDROGENOLYSIS OF ALPHA-HYDROXY ESTERS OR ACIDS USING A HETEROGENEOUS CATALYST

    2017-01-01

    The present invention relates to a method for hydrogenolysis of alpha-hydroxy esters or acids, comprising reacting the alpha-hydroxy ester or acid in the presence of a heterogeneous catalyst. The present invention also relates to a method for producing propionic acid ester, and the use of any...

  2. Comparison of hydroxy naphthoquinone from North Qinglongyi with different storage times

    Xin, G. S.; Ji, Y. B.; Wei, C.

    2017-12-01

    Objective: To determine the appropriate solvent for the extraction of hydroxy naphthoquinone, and to establish a method for the determination of the content of hydroxy naphthoquinone in the North Qinglongyi, and compare the changes of the content of hydroxy naphthoquinone in North Qinglongyi with different storage times. Methods: According to the nature of hydroxy naphthoquinone in alkaline solution will be discolored, so this experiment for Juglone as the standard reagent, 5% KOH solution as a developer, and the absorbance was measured by UV-spectrophotometry at the wavelength of 515 nm. The content of hydroxy naphthoquinone in North Qinglongyi was determined by colorimetric method, and the contents of hydroxy naphthoquinone in North Qinglongyi of different storage times were compared. Results: The optimum extraction solvent was ethyl acetate. The recoveries were 97.73%±1.11% and the RSD was 1.14% (n = 6). The contents of hydroxy naphthoquinone in the North Qinglunyi were 0.0141%, 0.0104% and 0.0073%, respectively, for one year, two years and three years. The content of hydroxy naphthoquinone decreased with the storage time prolonged. Conclusion This experimental method was stability, high recovery rate, simple and reliable. According to the results of this experiment, we can see that the storage time of North Qinglunyi should not be too long. Should try to choose this year’s North Qinglunyi for experimental research.

  3. Direct fluorination of melatonin and 5-hydroxy-L-tryptophan with [18F]F2

    Chirakal, R.; Firnau, G.; Garnett, E.S.

    1986-01-01

    In order that melatonin receptors may be studied in man with positron emission tomography, melatonin labelled with a positron emitting isotope is needed. The preparation of 6-fluoro-melatonin labelled with F-18 is described. Using the same fluorination method, 5-hydroxy-6-(F-18)fluorotryptophan and 4-(F-18)fluoro-5-hydroxy-tryptophan were also prepared. (UK)

  4. 40 CFR 721.10063 - Halo substituted hydroxy nitrophenyl amide (generic).

    2010-07-01

    ... amide (generic). 721.10063 Section 721.10063 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10063 Halo substituted hydroxy nitrophenyl amide (generic). (a) Chemical... as halo substituted hydroxy nitrophenyl amide (PMN P-04-792) is subject to reporting under this...

  5. A single-run liquid chromatography mass spectrometry method to quantify neuroactive kynurenine pathway metabolites in rat plasma.

    Orsatti, Laura; Speziale, Roberto; Orsale, Maria Vittoria; Caretti, Fulvia; Veneziano, Maria; Zini, Matteo; Monteagudo, Edith; Lyons, Kathryn; Beconi, Maria; Chan, Kelvin; Herbst, Todd; Toledo-Sherman, Leticia; Munoz-Sanjuan, Ignacio; Bonelli, Fabio; Dominguez, Celia

    2015-03-25

    Neuroactive metabolites in the kynurenine pathway of tryptophan catabolism are associated with neurodegenerative disorders. Tryptophan is transported across the blood-brain barrier and converted via the kynurenine pathway to N-formyl-L-kynurenine, which is further degraded to L-kynurenine. This metabolite can then generate a group of metabolites called kynurenines, most of which have neuroactive properties. The association of tryptophan catabolic pathway alterations with various central nervous system (CNS) pathologies has raised interest in analytical methods to accurately quantify kynurenines in body fluids. We here describe a rapid and sensitive reverse-phase HPLC-MS/MS method to quantify L-kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxy-L-kynurenine (3HK) and anthranilic acid (AA) in rat plasma. Our goal was to quantify these metabolites in a single run; given their different physico-chemical properties, major efforts were devoted to develop a chromatography suitable for all metabolites that involves plasma protein precipitation with acetonitrile followed by chromatographic separation by C18 RP chromatography, detected by electrospray mass spectrometry. Quantitation range was 0.098-100 ng/ml for 3HK, 9.8-20,000 ng/ml for KYN, 0.49-1000 ng/ml for KYNA and AA. The method was linear (r>0.9963) and validation parameters were within acceptance range (calibration standards and QC accuracy within ±30%). Copyright © 2015 Elsevier B.V. All rights reserved.

  6. NMDAR inhibition-independent antidepressant actions of ketamine metabolites

    Zanos, Panos; Moaddel, Ruin; Morris, Patrick J.; Georgiou, Polymnia; Fischell, Jonathan; Elmer, Greg I.; Alkondon, Manickavasagom; Yuan, Peixiong; Pribut, Heather J.; Singh, Nagendra S.; Dossou, Katina S.S.; Fang, Yuhong; Huang, Xi-Ping; Mayo, Cheryl L.; Wainer, Irving W.; Albuquerque, Edson X.; Thompson, Scott M.; Thomas, Craig J.; Zarate, Carlos A.; Gould, Todd D.

    2016-01-01

    Major depressive disorder afflicts ~16 percent of the world population at some point in their lives. Despite a number of available monoaminergic-based antidepressants, most patients require many weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), exerts rapid and sustained antidepressant effects following a single dose in depressed patients. Here we show that the metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant actions in vivo. Notably, we demonstrate that these antidepressant actions are NMDAR inhibition-independent but they involve early and sustained α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activation. We also establish that (2R,6R)-HNK lacks ketamine-related side-effects. Our results indicate a novel mechanism underlying ketamine’s unique antidepressant properties, which involves the required activity of a distinct metabolite and is independent of NMDAR inhibition. These findings have relevance for the development of next generation, rapid-acting antidepressants. PMID:27144355

  7. Persistence behavior of metamifop and its metabolite in rice ecosystem.

    Barik, Suhrid Ranjan; Ganguly, Pritam; Patra, Sandip; Dutta, Swaraj Kumar; Goon, Arnab; Bhattacharyya, Anjan

    2018-02-01

    A field experiment was conducted to determine the persistence of metamifop in transplanted rice crop for two seasons. Metamifop 10% EC was applied at two doses: 100 g a.i. ha -1 and 200 g a.i. ha -1 at 2-3 leaf stage of Echinochloa crusgalli. The residues of metamifop along with its major metabolite, N-(2-fluorophenyl)-2-hydroxy-N-methylpropionamide (HFMPA), were estimated in rice plant, field water and soil using Liquid Chromatography Mass Spectrometry. Limit of detection and limit of quantification of the method for both the compounds were set at 0.003 μg g -1 and 0.010 μg g -1 respectively. Metamifop showed less persistence in field water and rice plant as compared to soil samples. Presence of HFMPA was recorded in rice plant and soil. Both the compounds were found below level of quantification in harvest samples of straw, grains, husk and soil. A safe waiting period of 52 d was suggested for harvesting of rice when metamifop was applied at 100 g a.i. ha -1 (recommended dose). Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Anti-urease Secondary Metabolites from Seriphidium quettense

    Muhammad Imran Tousif

    2017-03-01

    Full Text Available Ethyl acetate layer of the methanolic extract of Seriphidium quettense was subjected to silica gel column chromatography to isolate one new; seriphiloid (1, and four known compounds; ilicic acid (2, 6 a -hydroxy-8(10-oplopen-14-one (3, 2-(4-hydroxyphenyl-5,6,7-trimethoxy-4H-chromen-4-one (4 and 2-(3,4-dihydroxyphenyl-5,6,7-trimethoxy-4H-chromen-4-one (5. The chemical structure of the new isolate was established with the help of 1D, 2D NMR techniques and high resolution mass spectrometry. Known compounds were identified because of 1D NMR and mass spectrometric analysis and in comparison with the literature values. Compounds 1-5 were evaluated for their acetylcholinesterase, butyrylcholinesterase, a -glucosidase and urease inhibitory activities. Most of the metabolites were found inactive; however, compounds 2 and 3 showed good antiurease activity with IC 50 value 21.5±0.1 and 20.8±0.1 µg/mL, respectively.

  9. 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 ...

  10. 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.

  11. Identification and characterization of novel long-term metabolites of oxymesterone and mesterolone in human urine by application of selected reaction monitoring GC-CI-MS/MS.

    Polet, Michael; Van Gansbeke, Wim; Geldof, Lore; Deventer, Koen; Van Eenoo, Peter

    2017-11-01

    The search for metabolites with longer detection times remains an important task in, for example, toxicology and doping control. The impact of these long-term metabolites is highlighted by the high number of positive cases after reanalysis of samples that were stored for several years, e.g. samples of previous Olympic Games. A substantial number of previously alleged negative samples have now been declared positive due to the detection of various long-term steroid metabolites the existence of which was unknown during the Olympic Games of 2008 and 2012. In this work, the metabolism of oxymesterone and mesterolone, two anabolic androgenic steroids (AAS), was investigated by application of a selected reaction monitoring gas chromatography-chemical ionization-triple quadrupole mass spectrometry (GC-CI-MS/MS) protocol for metabolite detection and identification. Correlations between AAS structure and GC-CI-MS/MS fragmentation behaviour enabled the search for previously unknown but expected AAS metabolites by selection of theoretical transitions for expected metabolites. Use of different hydrolysis protocols allowed for evaluation of the detection window of both phase I and phase II metabolites. For oxymesterone, a new metabolite, 18-nor-17β-hydroxymethyl-17α-methyl-4-hydroxy-androst-4,13-diene-3-one, was identified. It was detectable up to 46 days by using GC-CI-MS/MS, whereas with a traditional screening (detection of metabolite 17-epioxymesterone with electron ionization GC-MS/MS) oxymesterone administration was only detectable for 3.5 days. A new metabolite was also found for mesterolone. It was identified as 1α-methyl-5α-androstan-3,6,16-triol-17-one and its sulfate form after hydrolysis with Helix pomatia resulted in a prolonged detection time (up to 15 days) for mesterolone abuse. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  12. The microstructure of irradiated hydroxy-terminated polybutadiene

    Wu Yiming; Zhou Dezhen; Zhang Zhiping; Jing Yudong; Ying Shengkang

    1989-01-01

    Hydroxy-terminated polybutadiene (HTPB) is one kind of plybutadiene chief chain structure polymer terminated with hydroxyl groups. Because there are double-bonds in the chief chain, the α-hydrogen atom is very active, and crosslink reaction is easy to take place under γ-ray irradiation. The property of HTPB is affected by γ-ray directly. So it is significant practically and theoreticaly to study the change in structure and property under radiation. The microstructure of HTPB solute molecules and the change of molecular weight with radiation dose were studied by infrared spectra, NMR and GPC in the work. The effects of radiation on HTPB were discussed from the viewpoint of the change of solute molecular structure and gel kinetics. The measured gel dose of HPTB is 0.605 MGY, G = 1.802, thus the authors came to the conclusion that reaction is the chief process in the irradiation of HPTB

  13. Structure of dichloro(4-hydroxy-L-proline)cadmium(II)

    Yukawa, Yasuhiko; Inomata, Yoshie; Takeuchi, Toshio [Jochi Univ., Tokyo (Japan). Faculty of Science and Technology; Shimoi, Mamoru; Ouchi, Akira

    1982-10-01

    An X-ray diffraction study of the title complex has been carried out. The crystal is monoclinic, with the space group P2/sub 1/; Z = 2; a = 8.196(4), b = 7.275(3), c = 7.740(4) A, beta = 103.73(4)/sup 0/. Full-matrix least-squares refinements have led to the final R value of 0.030. The structure consists of one-demensional polymers bridged by chlorine atoms and a carboxyl group. Four chlorine atoms coordinate to a cadmium atom and form a square plane. The planes extend in the direction of the b axis like an infinite folding screen, sharing opposite edges. From the trough positions in the zigzag structure, the carboxyl oxygen atoms of 4-hydroxy-L-proline coordinate forkedly to two cadmium atoms. The ligand is a switter ion in the complex.

  14. Formation of glutathione conjugates by reactive metabolites of vinylidene chloride in microsomes and isolated hepatocytes

    Liebler, D.C.; Meredith, M.J.; Guengerich, F.P.

    1985-01-01

    Oxidation of the vinyl halide carcinogen and hepatotoxin vinylidene chloride (VDC) by microsomal cytochrome P-450 yields 2,2-dichloroacetaldehyde, 2-chloroacetyl chloride, 2-chloroacetic acid, and 1,1-dichloroethylene oxide. The roles of these metabolites in covalent modification of proteins and reduced glutathione (GSH) were examined. 2-Chloroacetyl chloride reacted with model thiols at least 10(3)-fold faster than did 1,1-dichloroethylene oxide and at least 10(5)-fold faster than did 2,2-dichloroacetaldehyde or 2-chloroacetic acid. Microsomal covalent binding of [ 14 C]VDC was inhibited by GSH but not by lysine, suggesting that protein thiols, rather than amino groups, are major targets. Liver microsomes catalyzed the formation of three GSH:VDC metabolite conjugates, identified as S-(2,2-dichloro-1-hydroxy)ethylglutathione, 2-(S-glutathionyl)acetate, and S-(2-glutathionyl)acetylglutathione, a novel conjugate containing both stable (thioether) and labile (thioester) linkages. The latter two conjugates also were formed in isolated rat hepatocytes and measurable amounts of 2-(S-glutathionyl)acetate were released into the incubation medium. Both 2-(S-glutathionyl)acetate and S-(2-glutathionyl)acetylglutathione were formed with [ 35 S]GSH added to the hepatic medium, indicating that reactive VDC metabolites are capable of crossing the plasma membrane to react with extracellular targets. Unlabeled S-(2-glutathionyl)-acetylglutathione underwent carbonyl substitution with added [ 35 S]GSH, suggesting that this conjugate may participate in modification of protein thiols. This conjugate also underwent hydrolysis with a half-life of approximately 3 hr. GSH:VDC metabolite conjugates may serve as accessible models for labile covalent adducts formed between VDC metabolites and protein thiols

  15. Pharmacokinetics of dextromethorphan and its metabolites in horses following a single oral administration.

    Corado, Carley R; McKemie, Daniel S; Knych, Heather K

    2017-06-01

    Dextromethorphan is an N-methyl-D-aspartate (NMDA) non-competitive antagonist commonly used in human medicine as an antitussive. Dextromethorphan is metabolized in humans by cytochrome P450 2D6 into dextrorphan, which is reported to be more potent than the parent compound. The goal of this study is to describe the metabolism of and determine the pharmacokinetics of dextromethorphan and its major metabolites following oral administration to horses. A total of 23 horses received a single oral dose of 2 mg/kg. Blood samples were collected at time 0 and at various times up to 96 h post drug administration. Urine samples were collected from 12 horses up to 120 h post administration. Plasma and urine samples were analyzed using liquid chromatography-mass spectrometry, and the resulting data analyzed using non-compartmental analysis. The C max , T max , and the t 1/2 of dextromethorphan were 519.4 ng/mL, 0.55 h, and 12.4 h respectively. The area under the curve of dextromethorphan, free dextrorphan, and conjugated dextrorphan were 563.8, 2.19, and 6,691 h*ng/mL respectively. In addition to free and glucuronidated dextrorphan, several additional glucuronide metabolites were identified in plasma, including hydroxyl-desmethyl dextrorphan, desmethyl dextrorphan, and three forms of hydroxylated dextrorphan. Dextromethorphan was found to be eliminated from the urine predominately as the O-demethylated metabolite, dextrorphan. Several additional metabolites including several novel hydroxy-dextrorphan metabolites were also detected in the urine in both free and glucuronidated forms. No significant undesirable behavioural effects were noted throughout the duration of the study. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Quantification of 8-α-hydroxy-mutilin as marker residue for tiamulin in rabbit tissues by high-performance liquid chromatography-mass spectrometry.

    De Baere, Siegrid; Devreese, Mathias; Maes, An; De Backer, Patrick; Croubels, Siska

    2015-06-01

    For the first time, a sensitive and specific method was developed and fully validated for the quantification of the EU marker residue of tiamulin, 8-α-hydroxy-mutilin, in rabbit muscle and liver tissues using liquid chromatography combined with positive heated electrospray ionization triple quadrupole mass spectrometry. The mass spectrometer was operated in the selected reaction monitoring (SRM) mode with selection of the [M + H](+) ion in both quadrupoles 1 and 3, resulting in the SRM transition m/z 337.25 > 337.25 for quantification. Chromatography was performed using a Hypersil Gold C18 column using a gradient elution program with water and methanol as mobile phases. The sample preparation procedure for the analysis of 8-α-hydroxy-mutilin in liver and muscle samples consisted of three main steps: (1) extraction of the tissue matrix using 0.1 N hydrochloric acid/acetone (50/50, v/v), (2) hydrolysis of tiamulin and metabolites to 8-α-hydroxy-mutilin in alkaline medium at 45 °C, and (3) liquid-liquid extraction in acidic medium using ethyl acetate. This is the first method presenting fully validated results, encompassing a linearity of 50 to 2,000 μg/kg, within-run and between-run accuracy and precision, limit of quantification (50 μg/kg for both muscle and liver tissues), limit of detection (muscle, 11.9 μg/kg; liver, 20.6 μg/kg), extraction recovery (muscle, 66.2%; liver, 75.5%), signal suppression and enhancement (muscle, 51.7%; liver, 43.3%), carryover, applicability and practicability, and stability during storage and analysis. This novel method is therefore sensitive enough to be used for residue depletion studies of tiamulin in rabbits and for food safety monitoring with respect to MRL compliance of residues.

  17. Hydrophilic interaction liquid chromatography/positive ion electrospray ionization mass spectrometry method for the quantification of alprazolam and α-hydroxy-alprazolam in human plasma.

    Kalogria, Eleni; Pistos, Constantinos; Panderi, Irene

    2013-12-30

    A hydrophilic interaction liquid chromatography/positive ion electrospray-mass spectrometry (HILIC-ESI/MS) has been developed and fully validated for the quantification of alprazolam and its main metabolite, α-hydroxy-alprazolam, in human plasma. The assay is based on 50μL plasma samples, following liquid-liquid extraction. All analytes and the internal standard (tiamulin) were separated by hydrophilic interaction liquid chromatography using an X-Bridge-HILIC analytical column (150.0mm×2.1mm i.d., particle size 3.5μm) under isoscratic elution. The mobile phase was composed of a 7% 10mM ammonium formate water solution in acetonitrile and pumped at a flow rate of 0.20mLmin(-1). Running in positive electrospray ionization and selected ion monitoring (SIM) the mass spectrometer was set to analyze the protonated molecules [M+H](+) at m/z 309, 325 and 494 for alprazolam, α-hydroxy-alprazolam and tiamulin (ISTD) respectively. The assay was linear over the concentration range of 2.5-250ngmL(-1) for alprazolam and 2.5-50ngmL(-1) for α-hydroxy alprazolam. Intermediate precision was less than 4.1% over the tested concentration ranges. The method is the first reported application of HILIC in the analysis benzodiazepines in human plasma. With a small sample size (50μL human plasma) and a run time less than 10.0min for each sample the method can be used to support a wide range of clinical studies concerning alprazolam quantification. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. 40 CFR 721.5252 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, zinc salt.

    2010-07-01

    ...-methylenebis [3-hydroxy-, zinc salt. 721.5252 Section 721.5252 Protection of Environment ENVIRONMENTAL...′-methylenebis [3-hydroxy-, zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, zinc...

  19. Synthesis of a new allelopathic agent from the biotransformation of ent-15α-hydroxy-16-kauren-19-oic acid with Fusarium proliferatum.

    Rocha, A D; Vieira, H da S; Takahashi, J A; Boaventura, M A D

    2017-11-01

    The use of kaurane diterpenes as substrates in fungal biotransformation to achieve bioactive compounds has been widely reported. In this work, the natural product kaurenoic acid, a diterpene widely distributed in the plant Kingdom, was chemically converted into ent-15α-hydroxy-kaur-16-en-19-oic acid (1). Substrate 1 was subjected to biotransformation by the fungus Fusarium proliferatum, furnishing a new derivative, ent-2α,15α-dihydroxy-kaur-16-en-19-oic acid (2). The structure of metabolite 2 was deduced on the basis of spectroscopy and MS data. Derivative 2 showed allelopathic activity on germination and growth of root and stem of lettuce (Lactuca sativa), inhibiting 100% of germination and growth of roots and stem, at higher concentration assayed (10 -4  mol/L).

  20. Effects of gamma radiation on the concentration of 5-hydroxy-L-tryptophan and 5-hydroxytryptamine in presence of radioprotector in Sprague Dawley rats

    Upadhyay, S.N.; Sharma, Ashok; Nagpal, K.K.; Saini, S.K.

    1997-01-01

    The result of variation of 5-hydroxy-L-tryptophan (HT) and 5-hydroxytryptamine (5-HT) in different tissues of control and gamma-irradiated Sprague Dawley rats with and without a radioprotector β-amino-ethylisothiuronium bromide hydrobromide (AET) combination e.g. (HT+AET) have been studied. The retention of HT, in the tissues studied, decreased after lethal dose (10.5 Gy) but for 5-HT, no such trend was observed after incorporation of HT+AET. A slight tendency of both metabolites to come back to control level was also observed for Sprague Dawley rats. In urine concentration of HT was less compared to 5-HT with a lethal dose (10.5 Gy). After incorporation of HT+AET the turnover rate of HT and 5-HT were found to be maximum when it was injected through intraperitoneal route. (author)

  1. Stereoselective synthesis of an active metabolite of the potent PI3 kinase inhibitor PKI-179.

    Chen, Zecheng; Venkatesan, Aranapakam M; Dos Santos, Osvaldo; Delos Santos, Efren; Dehnhardt, Christoph M; Ayral-Kaloustian, Semiramis; Ashcroft, Joseph; McDonald, Leonard A; Mansour, Tarek S

    2010-03-05

    The synthesis and stereochemical determination of 1-(4-(4-((1R,5R,6R)-6-hydroxy-3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-morpholino-1,3,5-triazin-2-yl)phenyl)-3-(pyridin-4-yl)urea (2), an active metabolite of the potent PI3 kinase inhibitor PKI-179 (1), is described. Stereospecific hydroboration of the double bond of 2,5-dihydro-1H-pyrrole 8 gave the 2,3-trans alcohol 9 exclusively. The configuration of the 3-hydroxyl group in 9 was inverted by an oxidation and stereoselective reduction sequence to give the corresponding 2,3-cis isomer 23. Both exo (21) and endo (27) isomers of the metabolite 2 were prepared via a practical synthetic route from 9 and 23, respectively, and the stereochemistry of 2 was determined to be endo. The endo isomer (27) was separated into two enantiomers 28 and 29 by chiral HPLC. Compound 2 was found to be enantiomerically pure and identical to the enantiomer 28. The absolute stereochemistry of the enantiomer 28 was determined by Mosher's method, thus establishing the stereochemistry of the active metabolite 2.

  2. “Twin peaks”: Searching for 4-hydroxynonenal urinary metabolites after oral administration in rats

    Julia Keller

    2015-04-01

    Radioactivity distribution revealed that 48% of the administered radioactivity was excreted into urine and 15% into feces after 24 h, while 3% were measured in intestinal contents and 2% in major organs, mostly in the liver. Urinary radio-HPLC profiles revealed 22 major peaks accounting for 88% of the urinary radioactivity. For identification purpose, HNE and its stable isotope [1,2-13C]-HNE were given at equimolar dose to be able to univocally identify HNE metabolites by tracking twin peaks on HPLC–HRMS spectra. The major peak was identified as 9-hydroxy-nonenoic acid (27% of the urinary radioactivity followed by classical HNE mercapturic acid derivatives (the mercapturic acid conjugate of di-hydroxynonane (DHN-MA, the mercapturic acid conjugate of 4-hydroxynonenoic acid (HNA-MA in its opened and lactone form and by metabolites that are oxidized in the terminal position. New urinary metabolites as thiomethyl and glucuronide conjugates were also evidenced. Some analyses were also performed on feces and gastro-intestinal contents, revealing the presence of tritiated water that could originate from beta-oxidation reactions.

  3. Occurrence of organic UV filters and metabolites in lebranche mullet (Mugil liza) from Brazil.

    Molins-Delgado, Daniel; Muñoz, Ramón; Nogueira, Sylvia; Alonso, Mariana B; Torres, João Paulo; Malm, Olaf; Ziolli, Roberta Lourenço; Hauser-Davis, Rachel Ann; Eljarrat, Ethel; Barceló, Damià; Díaz-Cruz, M Silvia

    2018-03-15

    UV filters (UV-Fs) constitute a heterogeneous group of chemicals used as protection against the effects of UV radiation, widely used in all sort of goods and ubiquitous in the environment. The presence of these chemicals in fish is a matter of concern, because many UV-Fs display hormonal activity. In this study, muscle, gills, and liver from 11 Mugil liza individuals from the highly urbanized Guanabara Bay (Rio de Janeiro, Brazil) were analysed in order to detect eight UV-Fs and metabolites (4-dihydroxybenzophenone [BP1] (2-hydroxy-4-methoxybenzophenone [BP3], 4-methylbenzylidiene camphor [4MBC], ethylhexyl methoxycinnamate [EHMC], ethylhexyl dimethyl p-aminobenzoic acid [ODPABA], octocrylene [OC], 4-hydroxybenzophenone [4HB], and 4,4'-dihydroxybenzophenone [4DHB]) using liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results showed that both target UV-Fs and metabolites were ubiquitous in the analysed tissues. Lower concentrations were observed in muscle and gills (3.07-31.6ngg -1 dry weight (dw)), whereas in liver significant amounts of metabolites (5.47-451ngg -1 dw) were present. With the concentrations determined in the fish, an estimation of the daily intake revealed that consumption of muscle in the diet represent from 0.3 to 15.2ng UV-Fs (kg body weight -1 ) d -1 , higher than those reported in fish for selected persistent organic pollutants (POPs). Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Aflatoxin metabolism in humans: detection of metabolites and nucleic acid adducts in urine by affinity chromatography

    Groopman, J.D.; Donahue, P.R.; Zhu, J.Q.; Chen, J.S.; Wogan, G.N.

    1985-01-01

    A high-affinity IgM monoclonal antibody specific for aflatoxins was covalently bound to Sepharose 4B and used as a preparative column to isolate aflatoxin derivatives from the urine of people and experimental animals who had been exposed to the carcinogen environmentally or under laboratory conditions. Aflatoxin levels were quantified by radioimmunoassay and high-performance liquid chromatography after elution from the affinity column. In studies on rats injected with [ 14 C]aflatoxin B1, the authors identified the major aflatoxin-DNA adduct, 2,3-dihydro-2-(N7-guanyl)-3-hydroxy-aflatoxin B1 (AFB1-N7-Gua), and the oxidative metabolites M1 and P1 as the major aflatoxin species present in the urine. When this methodology was applied to human urine samples obtained from people from the Guangxi Province of China exposed to aflatoxin B1 through dietary contamination, the aflatoxin metabolites detected were also AFB1-N7-Gua and aflatoxins M1 and P1. Therefore, affinity chromatography using a monoclonal antibody represents a useful and rapid technique with which to isolate this carcinogen and its metabolites in biochemical epidemiology and for subsequent quantitative measurements, providing exposure information that can be used for risk assessment

  5. Accumulation of metabolites during bacterial degradation of PAH-mixtures

    Vila, J.; Lopez, Z.; Bauza, J.I. [Universitat de Barcelona (Spain). Department de Microbiologia; Minguillon, C. [Parc Cientific de Barcelona (ES). Institut de Recerca de Barcelona (IRB-PCB); Grifoll, M.

    2003-07-01

    acidic metabolites diphenic acid and 1-hydroxy-2-naphthoic acid, respectively. (orig.)

  6. Role of 3-Hydroxy Fatty Acid-Induced Hepatic Lipotoxicity in Acute Fatty Liver of Pregnancy

    Sathish Kumar Natarajan

    2018-01-01

    Full Text Available Acute fatty liver of pregnancy (AFLP, a catastrophic illness for both the mother and the unborn offspring, develops in the last trimester of pregnancy with significant maternal and perinatal mortality. AFLP is also recognized as an obstetric and medical emergency. Maternal AFLP is highly associated with a fetal homozygous mutation (1528G>C in the gene that encodes for mitochondrial long-chain hydroxy acyl-CoA dehydrogenase (LCHAD. The mutation in LCHAD results in the accumulation of 3-hydroxy fatty acids, such as 3-hydroxy myristic acid, 3-hydroxy palmitic acid and 3-hydroxy dicarboxylic acid in the placenta, which are then shunted to the maternal circulation leading to the development of acute liver injury observed in patients with AFLP. In this review, we will discuss the mechanistic role of increased 3-hydroxy fatty acid in causing lipotoxicity to the liver and in inducing oxidative stress, mitochondrial dysfunction and hepatocyte lipoapoptosis. Further, we also review the role of 3-hydroxy fatty acids in causing placental damage, pancreatic islet β-cell glucolipotoxicity, brain damage, and retinal epithelial cells lipoapoptosis in patients with LCHAD deficiency.

  7. Role of 3-Hydroxy Fatty Acid-Induced Hepatic Lipotoxicity in Acute Fatty Liver of Pregnancy

    Ibdah, Jamal A.

    2018-01-01

    Acute fatty liver of pregnancy (AFLP), a catastrophic illness for both the mother and the unborn offspring, develops in the last trimester of pregnancy with significant maternal and perinatal mortality. AFLP is also recognized as an obstetric and medical emergency. Maternal AFLP is highly associated with a fetal homozygous mutation (1528G>C) in the gene that encodes for mitochondrial long-chain hydroxy acyl-CoA dehydrogenase (LCHAD). The mutation in LCHAD results in the accumulation of 3-hydroxy fatty acids, such as 3-hydroxy myristic acid, 3-hydroxy palmitic acid and 3-hydroxy dicarboxylic acid in the placenta, which are then shunted to the maternal circulation leading to the development of acute liver injury observed in patients with AFLP. In this review, we will discuss the mechanistic role of increased 3-hydroxy fatty acid in causing lipotoxicity to the liver and in inducing oxidative stress, mitochondrial dysfunction and hepatocyte lipoapoptosis. Further, we also review the role of 3-hydroxy fatty acids in causing placental damage, pancreatic islet β-cell glucolipotoxicity, brain damage, and retinal epithelial cells lipoapoptosis in patients with LCHAD deficiency. PMID:29361796

  8. 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.

  9. Quantitative determination of 21-hydroxy-deflazacort in human plasma using gradient semi-microbore liquid chromatography.

    Reynolds, D L; Burmaster, S D; Eichmeier, L S

    1994-01-01

    A sensitive and selective liquid chromatographic procedure to quantitate the deflazacort metabolite 21-hydroxy-deflazacort (DF-21OH) in human plasma was developed and validated. DF-21OH and fludrocortisone acetate (internal standard, IS) were isolated from human plasma (2 mL) by solid-phase extraction onto C-18 cartridges. Potential interferences were selectively removed and analytes were eluted with ethyl acetate. Following evaporation, the residue was reconstituted for HPLC analysis. Separation was achieved by gradient elution using a 5 microns YMC Basic column (2.0 x 100 mm) with mobile phases consisting of 20% methanol and 50% acetonitrile in 50 mM phosphate buffer (pH 3) at a temperature of 50 degrees C. Flow rate was maintained at 0.3 mL/min., and analytes were quantified spectrophotometrically at 246 nm. The assay was validated over the range 1.0 to 500 ng/mL DF-21OH. Calibration curves were prepared using a weighted (1/concentration) nonlinear quadratic regression algorithm. Peak-height ratios were proportional to the amount of DF-21OH added to plasma. Assay precision (%RSD) ranged from 4.2 to 11%, with a corresponding assay accuracy (% relative error) of +/- 2.8%. Absolute recovery of DF-21OH from plasma was 78-86% over the concentration range. The minimum quantitation limit was 1.0 ng/mL.

  10. Effect of beta-hydroxy-beta-methylbutyrate (HMB) on protein metabolism in whole body and in selected tissues.

    Holecek, M; Muthny, T; Kovarik, M; Sispera, L

    2009-01-01

    Beta-hydroxy-beta-methylbutyrate (HMB) is a leucine metabolite with protein anabolic effect. The aim of the study was to examine the role of exogenous HMB on leucine and protein metabolism in whole body and selected tissues. Rats were administered by HMB (0.1 g/kg b.w.) or by saline. The parameters of whole-body protein metabolism were evaluated 24 h later using L-[1-14C]leucine and L-[3,4,5-3H]phenylalanine. Changes in proteasome dependent proteolysis and protein synthesis were determined according the "chymotrypsin-like" enzyme activity and labeled leucine and phenylalanine incorporation into the protein. A decrease in leucine clearance and whole-body protein turnover (i.e., a decrease in whole-body proteolysis and protein synthesis) was observed in HMB treated rats. Proteasome-dependent proteolysis decreased significantly in skeletal muscle, changes in heart, liver, jejunum, colon, kidney, and spleen were insignificant. Decrease in protein synthesis was observed in the heart, colon, kidney, and spleen, while an increase was observed in the liver. There were no significant changes in leucine oxidation. We conclude that protein anabolic effect of HMB in skeletal muscle is related to inhibition of proteolysis in proteasome. Alterations in protein synthesis in visceral tissues may affect several important functions and the metabolic status of the whole body.

  11. Overexpressing 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR in the lactococcal mevalonate pathway for heterologous plant sesquiterpene production.

    Adelene Ai-Lian Song

    Full Text Available Isoprenoids are a large and diverse group of metabolites with interesting properties such as flavour, fragrance and therapeutic properties. They are produced via two pathways, the mevalonate pathway or the 2-C-methyl-D-erythritol-4-phosphate (MEP pathway. While plants are the richest source of isoprenoids, they are not the most efficient producers. Escherichia coli and yeasts have been extensively studied as heterologous hosts for plant isoprenoids production. In the current study, we describe the usage of the food grade Lactococcus lactis as a potential heterologous host for the production of sesquiterpenes from a local herbaceous Malaysian plant, Persicaria minor (synonym Polygonum minus. A sesquiterpene synthase gene from P. minor was successfully cloned and expressed in L. lactis. The expressed protein was identified to be a β-sesquiphellandrene synthase as it was demonstrated to be functional in producing β-sesquiphellandrene at 85.4% of the total sesquiterpenes produced based on in vitro enzymatic assays. The recombinant L. lactis strain developed in this study was also capable of producing β-sesquiphellandrene in vivo without exogenous substrates supplementation. In addition, overexpression of the strain's endogenous 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR, an established rate-limiting enzyme in the eukaryotic mevalonate pathway, increased the production level of β-sesquiphellandrene by 1.25-1.60 fold. The highest amount achieved was 33 nM at 2 h post-induction.

  12. 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

  13. A Derivatization and Validation Strategy for Determining the Spatial Localization of Endogenous Amine Metabolites in Tissues using MALDI Imaging Mass Spectrometry

    Manier, M. Lisa; Spraggins, Jeffrey M.; Reyzer, Michelle L.; Norris, Jeremy L.; Caprioli, Richard M.

    2014-01-01

    Imaging mass spectrometry (IMS) studies increasingly focus on endogenous small molecular weight metabolites and consequently bring special analytical challenges. Since analytical tissue blanks do not exist for endogenous metabolites, careful consideration must be given to confirm molecular identity. Here we present approaches for the improvement in detection of endogenous amine metabolites such as amino acids and neurotransmitters in tissues through chemical derivatization and matrix-assisted laser desorption/ionization (MALDI) IMS. Chemical derivatization with 4-hydroxy-3-methoxycinnamaldehyde (CA) was used to improve sensitivity and specificity. CA was applied to the tissue via MALDI sample targets precoated with a mixture of derivatization reagent and ferulic acid (FA) as a MALDI matrix. Spatial distributions of chemically derivatized endogenous metabolites in tissue were determined by high-mass resolution and MSn imaging mass spectrometry. We highlight an analytical strategy for metabolite validation whereby tissue extracts are analyzed by high-performance liquid chromatography (HPLC)-MS/MS to unambiguously identify metabolites and distinguish them from isobaric compounds. PMID:25044893

  14. 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

  15. Identification of phase I and II metabolites of the new designer drug α-pyrrolidinohexiophenone (α-PHP) in human urine by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS).

    Paul, Michael; Bleicher, Sergej; Guber, Susanne; Ippisch, Josef; Polettini, Aldo; Schultis, Wolfgang

    2015-11-01

    Pyrrolidinophenones represent one emerging class of newly encountered drugs of abuse, also known as 'new psychoactive substances', with stimulating psychoactive effects. In this work, we report on the detection of the new designer drug α-pyrrolidinohexiophenone (α-PHP) and its phase I and II metabolites in a human urine sample of a drug abuser. Determination and structural elucidation of these metabolites have been achieved by liquid chromatography electrospray ionisation quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS). By tentative identification, the exact and approximate structures of 19 phase I metabolites and nine phase II glucuronides were elucidated. Major metabolic pathways revealed the reduction of the ß-keto moieties to their corresponding alcohols, didesalkylation of the pyrrolidine ring, hydroxylation and oxidation of the aliphatic side chain leading to n-hydroxy, aldehyde and carboxylate metabolites, and oxidation of the pyrrolidine ring to its lactam followed by ring cleavage and additional hydroxylation, reduction and oxidation steps and combinations thereof. The most abundant phase II metabolites were glucuronidated ß-keto-reduced alcohols. Besides the great number of metabolites detected in this sample, α-PHP is still one of the most abundant ions together with its ß-keto-reduced alcoholic dihydro metabolite. Monitoring of these metabolites in clinical and forensic toxicology may unambiguously prove the abuse of the new designer drug α-PHP. Copyright © 2015 John Wiley & Sons, Ltd.

  16. 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.

  17. [Secondary metabolites from a deep-sea-derived actinomycete Micrococcus sp. R21].

    Peng, Kun; Su, Rui-qiang; Zhang, Gai-yun; Cheng, Xuan-xuan; Yang, Quan; Liu, Yong-hong; Yang, Xian-wen

    2015-06-01

    To investigate cytotoxic secondary metabolites of Micrococcus sp. R21, an actinomycete isolated from a deep-sea sediment (-6 310 m; 142 degrees 19. 9' E, 10 degrees 54. 6' N) of the Western Pacific Ocean, column chromatography was introduced over silica gel, ODS, and Sephadex LH-20. As a result, eight compounds were obtained. By mainly detailed analysis of the NMR data, their structures were elucidated as cyclo(4-hydroxy-L-Pro-L-leu) (1), cyclo(L-Pro-L-Gly) (2), cyclo( L-Pro-L-Ala) (3), cyclo( D-Pro-L-Leu) (4), N-β-acetyltryptamine (5), 2-hydroxybenzoic acid (6), and phenylacetic acid (7). Compound 1 exhibited weak cytotoxic activity against RAW264. 7 cells with IC50 value of 9.1 μmol x L(-1).

  18. Secondary metabolites from Sida rhombifolia L. (Malvaceae) and the vasorelaxant activity of cryptolepinone.

    Chaves, Otemberg Souza; Gomes, Roosevelt Albuquerque; Tomaz, Anna Cláudia de Andrade; Fernandes, Marianne Guedes; das Graças Mendes, Leônidas; de Fátima Agra, Maria; Braga, Valdir Andrade; de Fátima Vanderlei de Souza, Maria

    2013-03-01

    The phytochemical study of Sida rhombifolia L. (Malvaceae) led to the isolation through chromatographic techniques of eleven secondary metabolites: sitosterol (1a) and stigmasterol (1b), sitosterol-3-O-b-D-glucopyranoside (2a) and stigmasterol-3-O-b-D-glucopyranoside (2b), phaeophytin A (3), 17³-ethoxypheophorbide A (4), 13²-hydroxy phaeophytin B (5), 17³-ethoxypheophorbide B (6), 5,7-dihydroxy-4'-methoxyflavone (7), cryptolepinone (8) and a salt of cryptolepine (9). Their structures were identified by ¹H- and ¹³C-NMR using one- and two-dimensional techniques. In addition, the vasorelaxant activity of cryptolepinone in rat mesenteric artery rings is reported herein for the first time.

  19. Secondary Metabolites from Sida rhombifolia L. (Malvaceae and the Vasorelaxant Activity of Cryptolepinone

    Maria de Fátima Vanderlei de Souza

    2013-03-01

    Full Text Available The phytochemical study of Sida rhombifolia L. (Malvaceae led to the isolation through chromatographic techniques of eleven secondary metabolites: sitosterol (1a and stigmasterol (1b, sitosterol-3-O-b-D-glucopyranoside (2a and stigmasterol-3-O-b-D-glucopyranoside (2b, phaeophytin A (3, 173-ethoxypheophorbide A (4, 132-hydroxy phaeophytin B (5, 173-ethoxypheophorbide B (6, 5,7-dihydroxy-4'-methoxyflavone (7, cryptolepinone (8 and a salt of cryptolepine (9. Their structures were identified by 1H- and 13C-NMR using one- and two-dimensional techniques. In addition, the vasorelaxant activity of cryptolepinone in rat mesenteric artery rings is reported herein for the first time.

  20. A new aurone and two rare metabolites from the leaves of Diospyros melanoxylon.

    Mallavadhani, Uppuluri V; Mahapatra, Anita

    2005-01-01

    A new aurone, 4,6-dihydroxy-2-[alpha,alpha-(4-hydroxyphenyl)hydroxy]methylene-3(2H)-benzofuranone (2) and two rare metabolites viz. selin-4(15)-en-1beta,11-diol (5) and 5,7-dihydroxy-3-O-beta-D-glucopyranosyl-l''' --> 6''glucopyranoside-2-{4-hydroxyphenyl}-4H-benzopyran-4-one (6) in addition to the known protocatechuic acid methyl ester (1), quercitin (3) and gallic acid (4) were isolated from the methanol extract of Diospyros melanoxylon leaves. The structures were elucidated by a combination of chemical and spectroscopic analysis. Interestingly, compound 2 was found to exist in both E- and Z-isomeric forms in a 15:85 ratio. The present isolation of compounds 2 and 5 assumes taxonomic significance as aurones and sesquiterpenes have not yet been reported from the Diospyros genus, consisting of more than 350 identified species.

  1. 7-cysteine-pyrrole conjugate: A new potential DNA reactive metabolite of pyrrolizidine alkaloids.

    He, Xiaobo; Xia, Qingsu; Ma, Liang; Fu, Peter P

    2016-01-01

    Pyrrolizidine alkaloids (PAs) require metabolic activation to exert cytotoxicity, genotoxicity, and tumorigenicity. We previously reported that (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts are responsible for PA-induced liver tumor formation in rats. In this study, we determined that metabolism of riddelliine and monocrotaline by human or rat liver microsomes produced 7-cysteine-DHP and DHP. The metabolism of 7-glutathionyl-DHP by human and rat liver microsomes also generated 7-cysteine-DHP. Further, reaction of 7-cysteine-DHP with calf thymus DNA in aqueous solution yielded the described DHP-derived DNA adducts. This study represents the first report that 7-cysteine-DHP is a new PA metabolite that can lead to DNA adduct formation.

  2. 7-Glutathione-pyrrole and 7-cysteine-pyrrole are potential carcinogenic metabolites of pyrrolizidine alkaloids.

    He, Xiaobo; Xia, Qingsu; Fu, Peter P

    2017-04-03

    Many pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic phytochemicals. Metabolism of PAs in vivo generates four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA adducts that have been proposed to be responsible for PA-induced liver tumor formation in rats. In this present study, we determined that the same set of DHP-DNA adducts was formed upon the incubation of 7-glutathione-DHP and 7-cysteine-DHP with cultured human hepatocarcinoma HepG2 cells. These results suggest that 7-glutathione-DHP and 7-cysteine-DHP are reactive metabolites of PAs that can bind to cellular DNA to form DHP-DNA adducts in HepG2 cells, and can potentially initiate liver tumor formation.

  3. Cytotoxic and Antifungal Constituents Isolated from the Metabolites of Endophytic Fungus DO14 from Dendrobium officinale

    Ling-Shang Wu

    2015-12-01

    Full Text Available Two novel cytotoxic and antifungal constituents, (4S,6S-6-[(1S,2R-1, 2-dihydroxybutyl]-4-hydroxy-4-methoxytetrahydro-2H-pyran-2-one (1, (6S,2E-6-hydroxy-3-methoxy-5-oxodec-2-enoic acid (2, together with three known compounds, LL-P880γ (3, LL-P880α (4, and Ergosta-5,7,22-trien-3b-ol (5 were isolated from the metabolites of endophytic fungi from Dendrobium officinale. The chemical structures were determined based on spectroscopic methods. All the isolated compounds 1–5 were evaluated by cytotoxicity and antifungal effects. Our present results indicated that compounds 1–4 showed notable anti-fungal activities (minimal inhibitory concentration (MIC ≤ 50 μg/mL for all the tested pathogens including Candida albicans, Cryptococcus neoformans, Trichophyton rubrum, Aspergillus fumigatus. In addition, compounds 1–4 possessed notable cytotoxcities against human cancer cell lines of HL-60 cells with the IC50 values of below 100 μM. Besides, compounds 1, 2, 4 and 5 showed strong cytotoxities on the LOVO cell line with the IC50 values were lower than 100 μM. In conclusion, our study suggested that endophytic fungi of D. officinale are great potential resources to discover novel agents for preventing or treating pathogens and tumors.

  4. Cytotoxic and Antifungal Constituents Isolated from the Metabolites of Endophytic Fungus DO14 from Dendrobium officinale.

    Wu, Ling-Shang; Jia, Min; Chen, Ling; Zhu, Bo; Dong, Hong-Xiu; Si, Jin-Ping; Peng, Wei; Han, Ting

    2015-12-22

    Two novel cytotoxic and antifungal constituents, (4S,6S)-6-[(1S,2R)-1, 2-dihydroxybutyl]-4-hydroxy-4-methoxytetrahydro-2H-pyran-2-one (1), (6S,2E)-6-hydroxy-3-methoxy-5-oxodec-2-enoic acid (2), together with three known compounds, LL-P880γ (3), LL-P880α (4), and Ergosta-5,7,22-trien-3b-ol (5) were isolated from the metabolites of endophytic fungi from Dendrobium officinale. The chemical structures were determined based on spectroscopic methods. All the isolated compounds 1-5 were evaluated by cytotoxicity and antifungal effects. Our present results indicated that compounds 1-4 showed notable anti-fungal activities (minimal inhibitory concentration (MIC) ≤ 50 μg/mL) for all the tested pathogens including Candida albicans, Cryptococcus neoformans, Trichophyton rubrum, Aspergillus fumigatus. In addition, compounds 1-4 possessed notable cytotoxcities against human cancer cell lines of HL-60 cells with the IC50 values of below 100 μM. Besides, compounds 1, 2, 4 and 5 showed strong cytotoxities on the LOVO cell line with the IC50 values were lower than 100 μM. In conclusion, our study suggested that endophytic fungi of D. officinale are great potential resources to discover novel agents for preventing or treating pathogens and tumors.

  5. Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions.

    Holeček, Milan

    2017-08-01

    Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that has been reported to have anabolic effects on protein metabolism. The aims of this article were to summarize the results of studies of the effects of HMB on skeletal muscle and to examine the evidence for the rationale to use HMB as a nutritional supplement to exert beneficial effects on muscle mass and function in various conditions of health and disease. The data presented here indicate that the beneficial effects of HMB have been well characterized in strength-power and endurance exercise. HMB attenuates exercise-induced muscle damage and enhances muscle hypertrophy and strength, aerobic performance, resistance to fatigue, and regenerative capacity. HMB is particularly effective in untrained individuals who are exposed to strenuous exercise and in trained individuals who are exposed to periods of high physical stress. The low effectiveness of HMB in strength-trained athletes could be due to the suppression of the proteolysis that is induced by the adaptation to training, which may blunt the effects of HMB. Studies performed with older people have demonstrated that HMB can attenuate the development of sarcopenia in elderly subjects and that the optimal effects of HMB on muscle growth and strength occur when it is combined with exercise. Studies performed under in vitro conditions and in various animal models suggest that HMB may be effective in treatment of muscle wasting in various forms of cachexia. However, there are few clinical reports of the effects of HMB on muscle wasting in cachexia; in addition, most of these studies evaluated the therapeutic potential of combinations of various agents. Therefore, it has not been possible to determine whether HMB was effective or if there was a synergistic effect. Although most of the endogenous HMB is produced in the liver, there are no reports regarding the levels and the effects of HMB supplementation in subjects with

  6. Protein precipitation: an expedient procedure for the routine analysis of the plasma metabolites of [123I]IBZM

    Zea-Ponce, Yolanda; Laruelle, Marc

    1999-01-01

    Plasma metabolite analysis of the single photon emission computed tomography (SPECT) D 2 /D 3 receptor radiotracer (S)(-)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-hydroxy-3-[ 123 I] iodo-6-methoxyb enzamide ([ 123 I]IBZM) is needed for the equilibrium analysis of the SPECT data, in brain imaging studies involving bolus plus constant infusion paradigm. The purpose of these experiments was to find an appropriate procedure to expedite this analysis during routine determinations. The procedure was applied to the plasma analysis of 22 human subjects. Each plasma sample was subjected to acetonitrile protein precipitation. After separation of the pellet, the acetonitrile fraction contained 91%±2% (n=88) of the mixture of labeled metabolites and parent compound. The recovery coefficient of unmetabolized [ 123 I]IBZM determined with an standard plasma sample was 95%±2% (n=22). The percent parent compound present in the extracted fraction, measured by high performance liquid chromatography, was 16%±9% (n=85) and the percent metabolites was 84%±9% (n=85). Free fraction determination (f 1 , fraction of radiotracer unbound to protein), was 4%±0.8% (n=22). Free fraction of parent was 15%±8% (n=85). The results indicate that acetonitrile protein precipitation is an adequate method for the analysis of the [ 123 I]IBZM plasma metabolites

  7. Sensitivity and proportionality assessment of metabolites from microdose to high dose in rats using LC-MS/MS.

    Ni, Jinsong; Ouyang, Hui; Seto, Carmai; Sakuma, Takeo; Ellis, Robert; Rowe, Josh; Acheampong, Andrew; Welty, Devin; Szekely-Klepser, Gabriella

    2010-03-01

    The objective of this study was to evaluate the sensitivity requirement for LC-MS/MS as an analytical tool to characterize metabolites in plasma and urine at microdoses in rats and to investigate proportionality of metabolite exposure from a microdose of 1.67 µg/kg to a high dose of 5000 µg/kg for atorvastatin, ofloxacin, omeprazole and tamoxifen. Only the glucuronide metabolite of ofloxacin, the hydroxylation metabolite of omeprazole and the hydration metabolite of tamoxifen were characterized in rat plasma at microdose by LC-MS/MS. The exposure of detected metabolites of omeprazole and tamoxifen appeared to increase in a nonproportional manner with increasing doses. Exposure of ortho- and para-hydroxyatorvastatin, but not atorvastatin and lactone, increased proportionally with increasing doses. LC-MS/MS has demonstrated its usefulness for detecting and characterizing the major metabolites in plasma and urine at microdosing levels in rats. The exposure of metabolites at microdose could not simply be used to predict their exposure at higher doses.

  8. Improvement of RVNRL film properties by adding fumed silica and hydroxy apatite

    Adul Thiangchanya

    2003-01-01

    Full Text Available The effect of adding fumed silica and hydroxy apatite to Radiation Vulcanized Natural Rubber Latex (RVNRL for improving tear strength, aging properties, degradability and water-soluble protein content of rubber films has been investigated. The addition of fumed silica and hydroxy apatite in RVNRL improves tear strength and aging properties of rubber films, whereas tensile strength and degradability of rubber films were unchanged during storage at room temperature. The water-soluble protein content in rubber films was reduced by immobilization of the fumed silica and hydroxy apatite and enhanced by addition of ZnO. This may reduce allergy problems of natural rubber latex products caused by water-soluble protein. The MST of the RVNRL with fumed silica and hydroxy apatite indicated that the latex must be used within two months after mixing because of its stability.

  9. Genetics Home Reference: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency

    ... disorder have been from Saudi Arabia, Portugal, or Spain. Related Information What information about a genetic condition ... Targets Orphanet: 3-hydroxy-3-methylglutaric aciduria Screening, Technology, and Research in Genetics Virginia Department of Health ( ...

  10. The 1-hydroxy-2-methyl-butenyl 4-diphosphate reductase gene from ...

    The 1-hydroxy-2-methyl-butenyl 4-diphosphate reductase gene from Taxus media: Cloning, characterization and functional identification. Y Sun, M Chen, J Tang, W Liu, C Yang, Y Yang, X Lan, M Hsieh, Z Liao ...

  11. Bioactive secondary metabolites from chrozophora plicata

    Riaz, N.; Tabussum, A.; Saleem, M.; Parveen, S.

    2014-01-01

    Fourteen compounds (1-14) namely 3-carbomethoxyindole (1), 6-hydroxy-7-methoxycoumarin (2), methyl-4-hydroxybenzoate (3), 4-hydroxybenzoic acid (4), p-coumaric acid (5), oleanolic acid (6), 4-ketopinoresinol (7), apigenin (8), apigenin-7-p-coumerate (9) apigenin-7-O-beta-D-glucopyranoside (10), acacetin-7-O-(4-hydroxy-E-cinnamoyl-(6)-beta-D-glucopyranoside (11), apigenin-7-O-(4-hydroxy-E-cinnamoyl-(6)-beta-D-glucopyranoside (12), -bis(4-hydroxy-E-cinnamoyl))glucopyranoside 6 apigenin 7-O-beta-D-(2 (13) and apigenin 7-O-rutinoside (14) were isolated from the methanolic extract of the whole plant of Chrozophora plicata. The structures of these compounds were confirmed by UV, IR, NMR (1H and 13C) spectroscopy and mass spectrometry (EIMS, HREIMS, FABMS, HRFABMS) and in comparison with reported data in literature. These isolates (1-14) showed DPPH radical scavenging and enzyme inhibitory activities against enzyme acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and lipoxygenase (LOX). (author)

  12. Highly Luminescent Lanthanide Complexes of 1 Hydroxy-2-pyridinones

    University of California, Berkeley; Lawrence National Laboratory; Raymond, Kenneth; Moore, Evan G.; Xu, Jide; Jocher, Christoph J.; Castro-Rodriguez, Ingrid; Raymond, Kenneth N.

    2007-11-01

    The synthesis, X-ray structure, stability, and photophysical properties of several trivalent lanthanide complexes formed from two differing bis-bidentate ligands incorporating either alkyl or alkyl ether linkages and featuring the 1-hydroxy-2-pyridinone (1,2-HOPO) chelate group in complex with Eu(III), Sm(III) and Gd(III) are reported. The Eu(III) complexes are among some of the best examples, pairing highly efficient emission ({Phi}{sub tot}{sup Eu} {approx} 21.5%) with high stability (pEu {approx} 18.6) in aqueous solution, and are excellent candidates for use in biological assays. A comparison of the observed behavior of the complexes with differing backbone linkages shows remarkable similarities, both in stability and photophysical properties. Low temperature photophysical measurements for a Gd(III) complex were also used to gain insight into the electronic structure, and were found to agree with corresponding TD-DFT calculations for a model complex. A comparison of the high resolution Eu(III) emission spectra in solution and from single crystals also revealed a more symmetric coordination geometry about the metal ion in solution due to dynamic rotation of the observed solid state structure.

  13. Evaluation of Plasma Spray hydroxy Apatite Coatings on Metallic Materials

    Take, S.; Mitsul, K.; Kasahara, M.; Sawal, R.; Izawa, S.; Nakayama, M.; Itoi, Y.

    2007-01-01

    Biocompatible Hydroxy apatite (HAp) coatings on metallic substrate by plasma spray techniques have been developed. Long-term credibility of plasma spray HAp coatings has been evaluated in physiological saline by electrochemical measurements. It was found that the corrosion resistance of SUS316L based HAp/Ti combined coatings was excellent even after more than 10 weeks long-term immersion. It was shown that postal heat treatment improved both the crystallinity and corrosion resistance of HAp. By lowering cooling rate during heat treatment process, less cracks produced in HAp coating layer, which lead to higher credibility of HAp during immersion in physiological saline. The ICP results showed that the dissolution level of substrate metallic ions was low and HAp coatings produced in this research can be acceptable as biocompatible materials. Also, the concentration of dissolved ions from HAp coatings with postal heat treatment was lower compared to those from samples without postal heat treatment. The adherence of HAp coatings with Ti substrate and other mechanical properties were also assessed by three-point bending test. The poor adhesion of HAp coating to titanium substrate can be improved by introducing a plasma spray titanium intermediate layer

  14. Rheokinetic Analysis of Hydroxy Terminated Polybutadiene Based Solid Propellant Slurry

    Abhay K Mahanta

    2010-01-01

    Full Text Available The cure kinetics of propellant slurry based on hydroxy-terminated polybutadiene (HTPB and toluene diisocyanate (TDI polyurethane reaction has been studied by viscosity build up method. The viscosity (ɳ–time (t plots conform to the exponential function ɳ = aebt, where a & b are empirical constants. The rate constants (k for viscosity build up at various shear rate (rpm, evaluated from the slope of dɳ/dt versus ɳ plots at different temperatures, were found to vary from 0.0032 to 0.0052 min-1. It was observed that the increasing shear rate did not have significant effect on the reaction rate constants for viscosity build up of the propellant slurry. The activation energy (Eɳ, calculated from the Arrhenius plots, was found to be 13.17±1.78 kJ mole-1, whereas the activation enthalpy (∆Hɳ* and entropy (∆Sɳ* of the propellant slurry, calculated from Eyring relationship, were found to be 10.48±1.78 kJ mole-1 and –258.51± 5.38 J mole-1K-1, respectively. The reaction quenching temperature of the propellant slurry was found to be -9 ° C, based upon the experimental data. This opens up an avenue for a “freeze-and-store”, then “warm-up and cast”, mode of manufacturing of very large solid rocket propellant grains.

  15. Resistance training & beta-hydroxy-beta-methylbutyrate supplementation on hormones

    Hamid Arazi

    2015-10-01

    Full Text Available RESUMOIntroduction:In recent years, there was an increased interest on the effects of beta-hydroxy-beta-methylbutyrate (HMB supplementation on skeletal muscle due to its anti-catabolic effects.Objectives:To investigate the effect of HMB supplementation on body composition, muscular strength and anabolic-catabolic hormones after resistance training.Methods:Twenty amateur male athletes were randomly assigned to supplement and control groups in a double-blind crossover design and participated in four weeks resistance training. Before and after the test period fasting blood samples were obtained to determine anabolic (the growth hormone and testosterone and catabolic (cortisol hormones, and fat mass, lean body mass (LBM and muscular strength were measured. Dependent and independent t-tests were used to analyze data.Results:After the training period, there were no significant differen-ces between the groups with respect to fat mass, LBM and anabolic-catabolic hormones. HMB supplementation resulted in a significantly greater strength gain (p≤0.05.Conclusion:Greater increase in strength for HMB group was not accompanied by body composition and basal circulating anabolic-catabolic hormonal changes. It seems that HMB supplementation may have beneficial effects on neurological adaptations of strength gain.

  16. Synthesis of 20-14C 3β-hydroxy-5β-pregnan-20-one

    Garraffo, H.M.; Gros, E.G.

    1982-01-01

    20 - 14 C 3β-hydroxy-5β-pregnan-20-one was synthesised by condensing 3β-acetoxy-5β-androstan-17-one with potassium 14 C cyanide to produce cyanohydrin. This was dehydrated and the resulting unsaturated nitrile treated with methylmagnesiumiodide to produce hydroxypregnenone. Hydrogenation of this gave 14 C 3β-hydroxy-5β-pregnan-20-one. (U.K.)

  17. Kinetic tritium isotopic effects in the position 2 for 5'-hydroxy-L-tryptophane

    Boroda, E.; Kanska, M.

    2006-01-01

    Tryptophanase converts 5'-hydroxy-L-tryptophane to pyrogronic acid and ammonia, however there are known conditions for the reversed reaction. Mechanism of the processes are not known till now. Kinetic isotopic effect (KIE) permits finding the rate determining stage in the multistage process. In presented communication, 5'-hydroxy-[2- 3 H]-L-tryptophane was synthesized and the KIE in the room temperature determined for different reaction stages

  18. Zeolite-catalysed preparation of alpha-hydroxy carboxylic acids and esters thereof

    2010-01-01

    A process for the production of lactic acid and 2-hydroxy-3-butenoic acid or esters thereof by conversion of glucose, fructose, sucrose, xylose and glycolaldehyde dissolved in a solvent in presence of a solid Lewis acidic catalyst.......A process for the production of lactic acid and 2-hydroxy-3-butenoic acid or esters thereof by conversion of glucose, fructose, sucrose, xylose and glycolaldehyde dissolved in a solvent in presence of a solid Lewis acidic catalyst....

  19. 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

  20. Biological responses of progestogen metabolites in normal and cancerous human breast.

    Pasqualini, Jorge R; Chetrite, Gérard S

    2010-12-01

    At present, more than 200 progestogen molecules are available, but their biological response is a function of various factors: affinity to progesterone or other receptors, their structure, the target tissues considered, biological response, experimental conditions, dose, method of administration and metabolic transformations. Metabolic transformation is of huge importance because in various biological processes the metabolic product(s) not only control the activity of the maternal hormone but also have an important activity of its own. In this regard, it was observed that the 20-dihydro derivative of the progestogen dydrogesterone (Duphaston®) is significantly more active than the parent compound in inhibiting sulfatase and 17β-hydroxysteroid dehydrogenase in human breast cancer cells. Estrone sulfatase activity is also inhibited by norelgestromin, a norgestimate metabolite. Interesting information was obtained with a similar progestogen, tibolone, which is rapidly metabolized into the active 3α/3β-hydroxy and 4-ene metabolites. All these metabolites can inhibit sulfatase and 17β-hydroxysteroid dehydrogenase and stimulate sulfotransferase in human breast cancer cells. Another attractive aspect is the metabolic transformation of progesterone itself in human breast tissues. In the normal breast progesterone is mainly converted to 4-ene derivatives, whereas in the tumor tissue it is converted mostly to 5α-pregnane derivatives. 20α-Dihydroprogesterone is found mainly in normal breast tissue and possesses antiproliferative properties as well as the ability to act as an anti-aromatase agent. Consequently, this progesterone metabolite could be involved in the control of estradiol production in the normal breast and therefore implicated in one of the multifactorial mechanisms of the breast carcinogenesis process. In conclusion, a better understanding of both natural and synthetic hormone metabolic transformations and their control could potentially provide

  1. 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.

  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. In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone.

    Attardi, Barbara J; Burgenson, Janet; Hild, Sheri A; Reel, Jerry R

    2004-03-01

    In determining the biological profiles of various antiprogestins, it is important to assess the hormonal and antihormonal activity, selectivity, and potency of their proximal metabolites. The early metabolism of mifepristone is characterized by rapid demethylation and hydroxylation. Similar initial metabolic pathways have been proposed for CDB-2914 (CDB: Contraceptive Development Branch of NICHD) and CDB-4124, and their putative metabolites have been synthesized. We have examined the functional activities and potencies, in various cell-based assays, and relative binding affinities (RBAs) for progesterone receptors (PR) and glucocorticoid receptors (GR) of the putative mono- and didemethylated metabolites of CDB-2914, CDB-4124, and mifepristone and of the 17alpha-hydroxy and aromatic A-ring derivatives of CDB-2914 and CDB-4124. The binding affinities of the monodemethylated metabolites for rabbit uterine PR and human PR-A and PR-B were similar to those of the parent compounds. Monodemethylated mifepristone bound to rabbit thymic GR with higher affinity than monodemethylated CDB-2914 or CDB-4124. T47D-CO cells were used to assess inhibition of R5020-stimulated endogenous alkaline phosphatase activity and transactivation of the PRE(2)-thymidine kinase (tk)-luciferase (LUC) reporter plasmid in transient transfections. The antiprogestational potency was as follows: mifepristone/CDB-2914/CDB-4124/monodemethylated metabolites (IC(50)'s approximately 10(-9)M) > aromatic A-ring derivatives (IC(50)'s approximately 10(-8)M) > didemethylated/17alpha-hydroxy derivatives (IC(50)'s approximately 10(-7)M). Antiglucocorticoid activity was determined by inhibition of dexamethasone-stimulated transcriptional activity in HepG2 cells. The mono- and didemethylated metabolites of CDB-2914 and CDB-4124 had less antiglucocorticoid activity (IC(50)'s approximately 10(-6)M) than monodemethylated mifepristone (IC(50) approximately 10(-8)M) or the other test compounds. At 10(-6)M in

  4. 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

  5. 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.

  6. 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 ...

  7. 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...

  8. Measuring urinary N-acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (IPMA3) as a potential biomarker of isoprene exposure.

    Alwis, K Udeni; Bailey, T Liz; Patel, Dhrusti; Wang, Liqun; Blount, Benjamin C

    2016-10-19

    Isoprene, the 2-methyl analog of 1,3-butadiene, is identified as a possible human carcinogen by the International Agency for Research on Cancer (IARC). Isoprene is ubiquitous in the environment with numerous natural and anthropogenic sources. Tobacco smoke is the main exogenous source of isoprene exposure in indoor environments. Among smoke constituents, isoprene is thought to contribute significantly to cancer risk; however, no selective urinary biomarkers of isoprene exposure have been identified for humans. In this manuscript, we measured the minor isoprene metabolite IPMA1 (mixture of N-acetyl-S-(1-[hydroxymethyl]-2-methyl-2-propen-1-yl)-L-cysteine and N-acetyl-S-(2-hydroxy-3-methyl-3-buten-1-yl)-L-cysteine), and we identified IPMA3 (N-acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine) as a major isoprene metabolite and novel isoprene exposure biomarker for humans. Urinary isoprene metabolites were measured using ultra high performance liquid chromatography coupled with electrospray ionization triple quad tandem mass spectrometry (UPLC/ESI-MSMS). The detection rates of IPMA1 and IPMA3 are <20% and 82%, respectively. The selectivity and abundance of IPMA3 make it a useful urinary biomarker of isoprene exposure. The limit of detection of IPMA3 in urine was 0.5 ng mL -1 . IPMA3 was stable under different storage temperatures and following ten freeze-thaw cycles. The average recovery of urine spiked with IPMA3 at three different levels was 99%. IPMA3 was measured in urine samples received from 75 anonymous subjects; the median (25th percentile, 75th percentile) IPMA3 level in smokers was 36.2 (18.2, 56.8) ng mL -1 and non-smokers 2.31 (2.31, 4.38) ng mL -1 . Application of this method to large population studies will help to characterize isoprene exposure and assess potential health impact. Published by Elsevier B.V.

  9. Preventive Effects of Beta-Hydroxy-Beta-Methyl Butyrate

    N. Ravanbakhsh

    2016-09-01

    Full Text Available Aims: One of the major factors in sudden cardiac arrest is the initiation and continuation of deadly arrhythmias during ischemia. It is known that beta-hydroxy-beta-methylbutyrate (HMB has useful effects such as anti-inflammatory and anti-apoptosis effects in the skeletal muscles. The aim of this study was to investigate the preventive effects of HMB on the ventricular arrhythmias due to the ischemia. Materials & Methods: In the experimental study, 30 Wistar male rats were randomly divided into three groups including control, HMB320, and HMB700. As control group received normal saline, HMB320 and HMB700 groups orally received 320 and 700 mg/Kg HMB as gavage for 2 weeks, respectively. The rats, having been anesthetized, underwent 30-minute ischemia. Then, the numbers of premature ventricular contractions (PVC, the appearance duration of ventricular tachycardia (VT, and the ventricular fibrillation (VF were assessed. Data was analyzed by SPSS 16 software using Kruskal-Walis, one-way ANOVA, Tukey’s post-hoc, and Chi-square tests. Findings: There was a significant reduction in the mean PVC number in HMB320 and HMB700 groups than control group (p=0.001. In addition, there was such a significant difference between the groups received the doses (p=0.008. There was a reduction in the mean appearance duration of VT in HMB320 and HMB700 groups than control group (p=0.001. There was a significant reduction in the mean appearance duration of VF in HMB700 group compared to control group, only (p=0.003. Conclusion: Through arrhythmias reduction, 2-week preventive consumption of HMB might considerably reduce the severe side effects of ischemia.

  10. 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

  11. 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.

  12. 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.

  13. Role of oxidative metabolites of cocaine in toxicity and addiction: oxidative stress and electron transfer.

    Kovacic, Peter

    2005-01-01

    Cocaine is one of the principal drugs of abuse. Although impressive advances have been made, unanswered questions remain concerning mechanism of toxicity and addiction. Discussion of action mode usually centers on receptor binding and enzyme inhibition, with limited attention to events at the molecular level. This review provides extensive evidence in support of the hypothesis that oxidative metabolites play important roles comprising oxidative stress (OS), reactive oxygen species (ROS), and electron transfer (ET). The metabolites include norcocaine and norcocaine derivatives: nitroxide radical, N-hydroxy, nitrosonium, plus cocaine iminium and formaldehyde. Observed formation of ROS is rationalized by redox cycling involving several possible ET agents. Three potential ones are present in the form of oxidative metabolites, namely, nitroxide, nitrosonium, and iminium. Most attention has been devoted to the nitroxide-hydroxylamine couple which has been designated by various investigators as the principal source of ROS. The proximate ester substituent is deemed important for intramolecular stabilization of reactive intermediates. Reduction potential of nitroxide is in accord with plausibility of ET in the biological milieu. Toxicity by cocaine, with evidence for participation of OS, is demonstrated for many body components, including liver, central nervous system, cardiovascular system, reproductive system, kidney, mitochondria, urine, and immune system. Other adverse effects associated with ROS comprise teratogenesis and apoptosis. Examples of ROS generated are lipid peroxides and hydroxyl radical. Often observed were depletion of antioxidant defenses, and protection by added antioxidants, such as, thiol, salicylate, and deferoxamine. Considerable evidence supports the contention that oxidative ET metabolites of cocaine are responsible for much of the observed OS. Quite significantly, the pro-oxidant, toxic effects, including generation of superoxide and lipid peroxyl

  14. [Study on the phase I metabolites of phenoprolamine hydrochloride in rat bile by LC/DAD/MSD].

    Ding, L; Zhang, Z X; Ni, P Z; Wang, G J; An, D K

    2001-03-01

    To study the phase I metabolites of phenoprolamine hydrochloride (DDPH) in rat bile. DDPH was administered i.p. to bile duct-cannulated rats. Bile samples were collected before administration and up to 12 h after administration. After being treated with beta-glucuronidase, the bile samples were purified and enriched with C-18 SPE columns, and then were analyzed by LC/DAD/MSD. The samples containing synthesized reference standards of DDPH metabolite 1-(2, 6-dimethylphenoxy)-2-(3-methoxy-4-hydroxyphenylethylamino)-propane (M1), 1-(2, 6-dimethyl-3-hydroxyphenoxy)-2-(3, 4-methoxy-phenylethylamino)-propane (M2), 1-(2,6-dimethyl-4-hydroxyphenoxy)-2-(3,4- methoxyphenylethylamino)-propane (M3), 1-(2, 6-dimethyl-3-hydroxyphenoxy)-2-(3-hydroxy-4- methoxyphenylethylamino)-propane (M4), 1-(2, 6-dimethyl-3-hydroxyphenoxy)-2- (3-hydroxy-4-methoxyphenylethylamino)-propane (M5) and 1-(2,6-dimethyl-4-hydroxyphenoxy)-2-(3-methoxy-4- hydroxyphenylethylamino)-propane (M6) were analyzed by LC/DAD/MSD under identical conditions. The retention times, UV spectra, molecular weights and production spectra (obtained by collision-induced dissociation) of the apparent ions of peak A, B, C, D, E and F in the total ion chromatogram of DDPH treated rat bile sample were consistent with those of M1, M2, M3, M5, M4 and M6, respectively. M1, M2, M3, M4, M5 and M6 were identified as the phase I metabolites of DDPH in the rat.

  15. Metabolism of ecdysteroids during the vitellogenesis of the tick Ornithodoros moubata (Ixodoidea, Argasidae): Accumulation of apolar metabolites in the eggs

    Connat, Jean-Louis; Diehl, Peter A.; Morici, M

    2008-01-01

    The fate of injected [3H]ecdysone ([3H]E) and 20-hydroxy-[3H]ecdysone ([3H]20E) has been investigated in the female tick Ornithodoros moubata (Murray, 1877; sensu Walton, 1962). When injected into fed mated vitellogenic females, [3H]E is converted into [3H]20E and two apolar classes of metabolites, AP1 and AP2. Injected [3H]20E is directly converted into AP1 and AP2. AP2 is incorporated into the ovaries in a high proportion and at the end of the vitellogenic cycle represents about 25% of the ...

  16. Crystal and molecular structures of 3-amino-4-hydroxy benzenesulfonamide and its hydrochloride: Quantum-chemical study of their tautomerism

    Kovalchukova, O. V., E-mail: okovalchukova@mail.ru; Strashnova, S. B.; Romashkina, E. P.; Strashnov, P. V.; Zaitsev, B. E. [Peoples' Friendship University of Russia (Russian Federation); Sergienko, V. S. [Russian Academy of Sciences, Kurnakov Institute of General and Inorganic Chemistry (Russian Federation)

    2013-03-15

    3-amino-4-hydroxy benzenesulfonamide and its hydrochloride have been isolated in the crystalline state. Their crystal and molecular structures are determined by X-ray diffraction. The equilibrium between neutral tautomeric forms of the 3-amino-4-hydroxy benzenesulfonamide molecule is studied within the approximation of density functional theory (B3LYP/aug-cc-pVDZ). The constants of acid-base equilibrium of 3-amino-4-hydroxy benzenesulfonamide are deter-mined using spectrophotometry.

  17. Secondary Metabolites Isolated from Iris germanica

    Muhammad I. Choudhary

    2009-06-01

    Full Text Available Phytochemical investigations of methanol extract of rhizome of Iris germanica L. resulted in the isolation of one new compound, 6,6-ditetradecyl-6,7-dihydrooxepin-2(3H-one (1 and five known compounds, 1-(2-(6′-hydroxy-2′-methylcyclohex-1′-enyloxy-5-methoxyphenylethanone (2 4-hydroxy-3-methoxyacetophenone (3, irisolone (4 irisolidone (5 and 2-acetoxy-3,6-dimethoxy-1,4-benzoquinone (6 .The structures of the compounds were determined on the basis of spectroscopic techniques. The antifungal activity of different soluble portions was measured. The hexane soluble portion of the methanol extract showed significant antifungal activity where as the ethyl acetate and chloroform soluble portions showed moderate activity. The methanol extract showed no antifungal activity.

  18. Comparative evaluation of two Trichoderma harzianum strains for major secondary metabolite production and antifungal activity.

    Ahluwalia, Vivek; Kumar, Jitendra; Rana, Virendra S; Sati, Om P; Walia, S

    2015-01-01

    This investigation was undertaken to identify the major secondary metabolite, produced by two Trichoderma harzianum strains (T-4 and T-5) with their antifungal activity against phytopathogenic fungi using poison food technique. The ethyl acetate extract was subjected to column chromatography using n-hexane, ethyl acetate and methanol gradually. Chromatographic separation of ethyl acetate extract of T. harzianum (T-4) resulted in the isolation and identification of palmitic acid (1), 1,8-dihydroxy-3-methylanthraquinone (2), 6-pentyl-2H-pyran-2-one (3), 2(5H)-furanone (4), stigmasterol (5) and β-sitosterol (6), while T. harzianum (T-5) gave palmitic acid (1), 1-hydroxy-3-methylanthraquinone (7), δ-decanolactone (8), 6-pentyl-2H-pyran-2-one (3), ergosterol (9), harzianopyridone (10) and 6-methyl-1,3,8-trihydroxyanthraquinone (11) as major metabolites. Among compounds screened for antifungal activity, compound 10 was found to be most active (EC50 35.9-50.2 μg mL(-1)). In conclusion, the present investigation provided significant information about antifungal activity and compounds isolated from two different strains of T. harzianum obtained from two different Himalayan locations.

  19. Optimized Jasmonic Acid Production by Lasiodiplodia theobromae Reveals Formation of Valuable Plant Secondary Metabolites.

    Felipe Eng

    Full Text Available Jasmonic acid is a plant hormone that can be produced by the fungus Lasiodiplodia theobromae via submerged fermentation. From a biotechnological perspective jasmonic acid is a valuable feedstock as its derivatives serve as important ingredients in different cosmetic products and in the future it may be used for pharmaceutical applications. The objective of this work was to improve the production of jasmonic acid by L. theobromae strain 2334. We observed that jasmonic acid formation is dependent on the culture volume. Moreover, cultures grown in medium containing potassium nitrate as nitrogen source produced higher amounts of jasmonic acid than analogous cultures supplemented with ammonium nitrate. When cultivated under optimal conditions for jasmonic acid production, L. theobromae secreted several secondary metabolites known from plants into the medium. Among those we found 3-oxo-2-(pent-2-enyl-cyclopentane-1-butanoic acid (OPC-4 and hydroxy-jasmonic acid derivatives, respectively, suggesting that fungal jasmonate metabolism may involve similar reaction steps as that of plants. To characterize fungal growth and jasmonic acid-formation, we established a mathematical model describing both processes. This model may form the basis of industrial upscaling attempts. Importantly, it showed that jasmonic acid-formation is not associated to fungal growth. Therefore, this finding suggests that jasmonic acid, despite its enormous amount being produced upon fungal development, serves merely as secondary metabolite.

  20. Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A.

    Miyata, Rie; Tanuma, Naoyuki; Sakuma, Hiroshi; Hayashi, Masaharu

    2016-01-01

    Xeroderma pigmentosum group A (XPA) is a genetic disorder in DNA nucleotide excision repair (NER) with severe neurological disorders, in which oxidative stress and disturbed melatonin metabolism may be involved. Herein we confirmed the diurnal variation of melatonin metabolites, oxidative stress markers, and antioxidant power in urine of patients with XPA and age-matched controls, using enzyme-linked immunosorbent assay (ELISA). The peak of 6-sulfatoxymelatonin, a metabolite of melatonin, was seen at 6:00 in both the XPA patients and controls, though the peak value is lower, specifically in the younger age group of XPA patients. The older XPA patients demonstrated an increase in the urinary levels of 8-hydroxy-2'-deoxyguanosine and hexanoyl-lysine, a marker of oxidative DNA damage and lipid peroxidation, having a robust peak at 6:00 and 18:00, respectively. In addition, the urinary level of total antioxidant power was decreased in the older XPA patients. Recently, it is speculated that oxidative stress and antioxidant properties may have a diurnal variation, and the circadian rhythm is likely to influence the NER itself. We believe that the administration of melatonin has the possibility of ameliorating the augmented oxidative stress in neurodegeneration, especially in the older XPA patients, modulating the melatonin metabolism and the circadian rhythm.

  1. Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A

    Rie Miyata

    2016-01-01

    Full Text Available Xeroderma pigmentosum group A (XPA is a genetic disorder in DNA nucleotide excision repair (NER with severe neurological disorders, in which oxidative stress and disturbed melatonin metabolism may be involved. Herein we confirmed the diurnal variation of melatonin metabolites, oxidative stress markers, and antioxidant power in urine of patients with XPA and age-matched controls, using enzyme-linked immunosorbent assay (ELISA. The peak of 6-sulfatoxymelatonin, a metabolite of melatonin, was seen at 6:00 in both the XPA patients and controls, though the peak value is lower, specifically in the younger age group of XPA patients. The older XPA patients demonstrated an increase in the urinary levels of 8-hydroxy-2′-deoxyguanosine and hexanoyl-lysine, a marker of oxidative DNA damage and lipid peroxidation, having a robust peak at 6:00 and 18:00, respectively. In addition, the urinary level of total antioxidant power was decreased in the older XPA patients. Recently, it is speculated that oxidative stress and antioxidant properties may have a diurnal variation, and the circadian rhythm is likely to influence the NER itself. We believe that the administration of melatonin has the possibility of ameliorating the augmented oxidative stress in neurodegeneration, especially in the older XPA patients, modulating the melatonin metabolism and the circadian rhythm.

  2. Quantification of four major metabolites of embryotoxic N-methyl- and N-ethyl-2-pyrrolidone in human urine by cooled-injection gas chromatography and isotope dilution mass spectrometry.

    Schindler, Birgit K; Koslitz, Stephan; Meier, Swetlana; Belov, Vladimir N; Koch, Holger M; Weiss, Tobias; Brüning, Thomas; Käfferlein, Heiko U

    2012-04-17

    N-Methyl- and N-ethyl-2-pyrollidone (NMP and NEP) are frequently used industrial solvents and were shown to be embryotoxic in animal experiments. We developed a sensitive, specific, and robust analytical method based on cooled-injection (CIS) gas chromatography and isotope dilution mass spectrometry to analyze 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI), two newly identified presumed metabolites of NEP, and their corresponding methyl counterparts (5-HNMP, 2-HMSI) in human urine. The urine was spiked with deuterium-labeled analogues of these metabolites. The analytes were separated from urinary matrix by solid-phase extraction and silylated prior to quantification. Validation of this method was carried out by using both, spiked pooled urine samples and urine samples from 56 individuals of the general population with no known occupational exposure to NMP and NEP. Interday and intraday imprecision was better than 8% for all metabolites, while the limits of detection were between 5 and 20 μg/L depending on the analyte. The high sensitivity of the method enables us to quantify NMP and NEP metabolites at current environmental exposures by human biomonitoring.

  3. 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...

  4. 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...

  5. 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).

  6. 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.

  7. 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.

  8. Effects of β-hydroxy-β-methyl butyrate on working memory and cognitive flexibility in an animal model of aging.

    Hankosky, Emily R; Sherrill, Luke K; Ruvola, Lauren A; Haake, Rachel M; Kim, Taehyeon; Hammerslag, Lindsey R; Kougias, Daniel G; Juraska, Janice M; Gulley, Joshua M

    2017-09-01

    Normal aging results in cognitive decline and nutritional interventions have been suggested as potential approaches for mitigating these deficits. Here, we used rats to investigate the effects of short- and long-term dietary supplementation with the leucine metabolite β-hydroxy-β-methyl butyrate (HMB) on working memory and cognitive flexibility. Beginning ∼12 months of age, male and female Long-Evans rats were given twice daily access to sipper tubes containing calcium HMB (450 mg/kg) or vehicle (285 mg/kg calcium lactate) in a sucrose solution (20% w/v). Supplementation continued for 1 or 7 months (middle- and old-age (OA) groups, respectively) before testing began. Working memory was assessed by requiring rats to respond on a previously sampled lever following various delays. Cognitive flexibility was assessed by training rats to earn food according to a visual strategy and then, once acquired, shifting to an egocentric response strategy. Treatment with HMB improved working memory performance in middle-age (MA) males and OA rats of both sexes. In the cognitive flexibility task, there was a significant age-dependent deficit in acquisition of the visual strategy that was not apparent in OA males treated with HMB. Furthermore, HMB ameliorated an apparent deficit in visual strategy acquisition in MA females. Together, these findings suggest that daily nutritional supplementation with HMB facilitates learning and improves working memory performance. As such, HMB supplementation may mitigate age-related cognitive deficits and may therefore be an effective tool to combat this undesirable feature of the aging process.

  9. Increased levels of 8-hydroxy-2′-deoxyguanosine are attributable to organophosphate pesticide exposure among young children

    Ding Guodong; Han Song; Wang, Pei; Gao Yu; Shi Rong; Wang, Guoquan; Tian Ying

    2012-01-01

    Oxidative damage has been proposed as an important mechanism linking pesticide exposure to health effects. A study of 268 young Shanghai children was conducted to examine the relationship between organophosphate pesticide (OP) exposure and a biomarker of oxidative DNA damage. Urine samples were analyzed for five nonspecific dialkyl phosphate (DAP) metabolites [dimethyl phosphates (DMs) and diethyl phosphates (DEs)] and 8-hydroxy-2′-deoxyguanosine (8-OHdG). The creatinine-adjusted median of 8-OHdG in urine samples was 3.99 ng/mg. Increased exposure to OPs was associated with greater levels of urinary 8-OHdG [total DAPs: ß (adjusted) = 0.46 per log 10 unit increase, 95% confidence interval (CI) = 0.40–0.53, p = 0.000; DMs: ß (adjusted) = 0.34, 95% CI = 0.28–0.41, p = 0.000; DEs: ß (adjusted) = 0.48, 95% CI = 0.42–0.54, p = 0.000]. Thus, the 8-OHdG biomarker is useful for increasing our understanding of the link between childhood exposure to OPs and health outcomes. - Highlights: ► OP exposures are thought to affect health by mechanisms related to oxidative stress. ► We assessed the correlation between OP exposure and a biomarker of oxidative stress. ► Increased exposure to OPs was associated with greater levels of urinary 8-OHdG. - Environmental exposure to OPs may play an important role in oxidative DNA damage in children.

  10. Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of β-hydroxy-β-methylbutyrate

    Wheatley, Scott M.; El-Kadi, Samer W.; Suryawan, Agus; Boutry, Claire; Orellana, Renán A.; Nguyen, Hanh V.; Davis, Steven R.

    2013-01-01

    Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB). To determine the effects of HMB on protein synthesis and the regulation of translation initiation and degradation pathways, overnight-fasted neonatal pigs were infused with HMB at 0, 20, 100, or 400 μmol·kg body wt−1·h−1 for 1 h (HMB 0, HMB 20, HMB 100, or HMB 400). Plasma HMB concentrations increased with infusion and were 10, 98, 316, and 1,400 nmol/ml in the HMB 0, HMB 20, HMB 100, and HMB 400 pigs. Protein synthesis rates in the longissimus dorsi (LD), gastrocnemius, soleus, and diaphragm muscles, lung, and spleen were greater in HMB 20 than in HMB 0, and in the LD were greater in HMB 100 than in HMB 0. HMB 400 had no effect on protein synthesis. Eukaryotic initiation factor (eIF)4E·eIF4G complex formation and ribosomal protein S6 kinase-1 and 4E-binding protein-1 phosphorylation increased in LD, gastrocnemius, and soleus muscles with HMB 20 and HMB 100 and in diaphragm with HMB 20. Phosphorylation of eIF2α and elongation factor 2 and expression of system A transporter (SNAT2), system L transporter (LAT1), muscle RING finger 1 protein (MuRF1), muscle atrophy F-box (atrogin-1), and microtubule-associated protein light chain 3 (LC3-II) were unchanged. Results suggest that supplemental HMB enhances protein synthesis in skeletal muscle of neonates by stimulating translation initiation. PMID:24192287

  11. Impact of β-hydroxy β-methylbutyrate (HMB) on age-related functional deficits in mice.

    Munroe, Michael; Pincu, Yair; Merritt, Jennifer; Cobert, Adam; Brander, Ryan; Jensen, Tor; Rhodes, Justin; Boppart, Marni D

    2017-01-01

    β-Hydroxy β-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine. Recent studies demonstrate a decline in plasma HMB concentrations in humans across the lifespan, and HMB supplementation may be able to preserve muscle mass and strength in older adults. However, the impact of HMB supplementation on hippocampal neurogenesis and cognition remains largely unexplored. The purpose of this study was to simultaneously evaluate the impact of HMB on muscle strength, neurogenesis and cognition in young and aged mice. In addition, we evaluated the influence of HMB on muscle-resident mesenchymal stem/stromal cell (Sca-1 + CD45 - ; mMSC) function to address these cells potential to regulate physiological outcomes. Three month-old (n=20) and 24 month-old (n=18) female C57BL/6 mice were provided with either Ca-HMB or Ca-Lactate in a sucrose solution twice per day for 5.5weeks at a dose of 450mg/kg body weight. Significant decreases in relative peak and mean force, balance, and neurogenesis were observed in aged mice compared to young (age main effects, p≤0.05). Short-term HMB supplementation did not alter activity, balance, neurogenesis, or cognitive function in young or aged mice, yet HMB preserved relative peak force in aged mice. mMSC gene expression was significantly reduced with age, but HMB supplementation was able to recover expression of select growth factors known to stimulate muscle repair (HGF, LIF). Overall, our findings demonstrate that while short-term HMB supplementation does not appear to affect neurogenesis or cognitive function in young or aged mice, HMB may maintain muscle strength in aged mice in a manner dependent on mMSC function. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Nocturnal activity of 11β-hydroxy steroid dehydrogenase type 1 is increased in type 1 diabetic children.

    Barat, P; Brossaud, J; Lacoste, A; Vautier, V; Nacka, F; Moisan, M-P; Corcuff, J-B

    2013-04-01

    The objective of this study was to investigate low-grade inflammation in children with type 1 diabetes (T1D) and its association with cortisol levels as well as its bioavailability through 11β-hydroxy steroid dehydrogenase type 1 (11β-HSD1) activity. Children with T1D (n=45) and their non-diabetic siblings (n=28) participated in the study. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein (CRPhs) were measured between 1400 and 1800h. Glucocorticoid metabolites were measured in the first morning urine on clinic day and 11β-HSD1 activity was estimated by tetrahydrocortisol/tetrahydrocortisone (THF/THE) ratio. Diabetic patients presented with an increased THF/THE ratio compared with controls (median: 0.68 [range: 0.45-1.18] vs 0.45 [0.27-0.98], respectively; Pvs 0.6 [0.6-2.2], respectively; P=0.43) and CRPhs (0.4mg/L [0-7.4] vs 0.3 [0-8.2]; P=0.26, respectively). When adjusted for age, gender and BMI, the THF/THE ratio was significantly associated with CRPhs (β=0.32, P=0.02) in diabetic patients, but not in controls. Low-grade inflammation assessed by plasma CRPhs and IL-6 concentrations was not detectable in our cohort of T1D children. Nocturnal 11β-HSD1 activity was increased and associated with plasma CRPhs concentration in diabetic patients. These results may be explained by either a direct or inflammation-mediated effect of the relative hepatic lack of insulin due to subcutaneous insulin therapy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  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. 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.

  15. 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

  16. 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....

  17. Experimental Study of Hydroxy Gas (HHO) Production with Variation in Current, Voltage and Electrolyte Concentration

    Alam, Noor; Pandey, K. M.

    2017-08-01

    In this paper, work has been carried out experimentally for the investigation of the effects of variation incurrent, voltage, temperature, chemical concentration and reaction time on the amount of hydroxy gas produced. Further effects on the overall electrolysis efficiency of advance alkaline water is also studied. The hydroxy gas (HHO) has been produced experimentally by the electrolysis of alkaline water with parallel plate electrode of 316L-grade stainless steel. The electrode has been selected on the basis of corrosion resistance and inertness with respect to electrolyte (KOH). The process used for the production of HHO is conventional as compared to the other production processes because of reduced energy consumption, less maintenance and low setup cost. From the experimental results, it has been observed that with increase in voltage, temperature and electrolyte concentration of alkaline solution, the production of hydroxy gas has increased about 30 to 40% with reduction in electrical energy consumption.

  18. Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone

    Khan Naik Tameen

    2012-12-01

    Full Text Available Abstract Background Biotransformation of organic compounds by using microbial whole cells provides an efficient approach to obtain novel analogues which are often difficult to synthesize chemically. In this manuscript, we report for the first time the microbial transformation of a synthetic anabolic steroidal drug, oxymetholone, by fungal cell cultures. Results Incubation of oxymetholone (1 with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17β-hydroxy-2-(hydroxy-methyl-17α-methyl-5α-androstan-1-en-3-one (2, 2α,17α-di(hydroxyl-methyl-5α-androstan-3β,17β-diol (3, 17α-methyl-5α-androstan-2α,3β,17β-triol (4, 17β-hydroxy-2-(hydroxymethyl-17α-methyl-androst-1,4-dien-3-one (5, 17β-hydroxy-2α-(hydroxy-methyl-17α-methyl-5α-androstan-3-one (6, and 2α-(hydroxymethyl-17α-methyl-5α-androstan-3β-17β-diol (7. Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2–5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1–7 were evaluated by observing their effects on T-cell proliferation, reactive oxygen species (ROS production, and normal cell growth in MTT assays, respectively. These compounds showed immunosuppressant effect in the T-cell proliferation assay with IC50 values between 31.2 to 2.7 μg/mL, while the IC50 values for ROS inhibition, representing anti-inflammatory effect, were in the range of 25.6 to 2.0 μg/mL. All the compounds were found to be non-toxic in a cell-based cytotoxicity assay. Conclusion Microbial transformation of oxymetholone (1 provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo stereoselective reduction of the enone system, isomerization of double bond, insertion of double bond and hydroxylation. The transformed products, which showed significant

  19. 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.

  20. Metabolism and excretion of 1-hydroxymethylpyrene, the proximate metabolite of the carcinogen 1-methylpyrene, in rats

    Bendadani, Carolin; Steinhauser, Lisa; Albert, Klaus; Glatt, Hansruedi; Monien, Bernhard H.

    2016-01-01

    1-Methylpyrene, an alkylated polycyclic aromatic hydrocarbon and environmental carcinogen, is activated by side-chain hydroxylation to 1-hydroxymethylpyrene (1-HMP) and subsequent sulfo conjugation to the DNA-reactive 1-sulfooxymethylpyrene. In addition to the bioactivation, processes of metabolic detoxification and transport greatly influence the genotoxicity of 1-methylpyrene. For a better understanding of 1-HMP detoxification in vivo we studied urinary and fecal metabolites in rats following intraperitoneal doses of 19.3 mg 1-HMP/kg body weight (5 rats) or the same dose containing 200 μCi [ 14 C]1-HMP/kg body weight (2 rats). After 48 h, 48.0% (rat 1) and 29.1% (rat 2) of the radioactivity was recovered as 1-HMP in the feces. Six major metabolites were observed by UV and on-line radioactivity detection in urine samples and feces after HPLC separation. The compounds were characterized by mass spectrometry, 1 H NMR and 1 H- 1 H COSY NMR spectroscopy, which allowed assigning tentative molecular structures. Two prominent metabolites, 1-pyrene carboxylic acid (M-6) and the acyl glucuronide of 1-pyrene carboxylic acid (M-5) accounted for 17.7% (rat 1) and 25.2% (rat 2) of the overall radioactive dose. Further, we detected the acyl glucuronide of 6-hydroxy-1-pyrene carboxylic acid (M-1) and 8-sulfooxy-1-pyrene carboxylic acid (M-3) together with two regioisomers of M-3 (M-2 and M-4) differing in position of the sulfate group at the pyrene ring. In urine samples, the radioactivity of 1-pyrene carboxylic acid and its five derivatives amounted to 32.4% (rat 1) or 45.5% (rat 2) of the total [ 14 C]1-HMP dose.

  1. 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.

  2. Transformation products and human metabolites of triclocarban and tricllosan in sewage sludge across the United States

    Pycke, Benny F.G.; Roll, Isaac B.; Brownawell, Bruce J.; Kinney, Chad A.; Furlong, Edward T.; Kolpin, Dana W.; Halden, Rolf U.

    2014-01-01

    Removal of triclocarban (TCC) and triclosan (TCS) from wastewater is a function of adsorption, abiotic degradation, and microbial mineralization or transformation, reactions that are not currently controlled or optimized in the pollution control infrastructure of standard wastewater treatment. Here, we report on the levels of eight transformation products, human metabolites, and manufacturing byproducts of TCC and TCS in raw and treated sewage sludge. Two sample sets were studied: samples collected once from 14 wastewater treatment plants (WWTPs) representing nine states, and multiple samples collected from one WWTP monitored for 12 months. Time-course analysis of significant mass fluxes (α = 0.01) indicate that transformation of TCC (dechlorination) and TCS (methylation) occurred during sewage conveyance and treatment. Strong linear correlations were found between TCC and the human metabolite 2′-hydroxy-TCC (r = 0.84), and between the TCC-dechlorination products dichlorocarbanilide (DCC) and monochlorocarbanilide (r = 0.99). Mass ratios of DCC-to-TCC and of methyl-triclosan (MeTCS)-to-TCS, serving as indicators of transformation activity, revealed that transformation was widespread under different treatment regimes across the WWTPs sampled, though the degree of transformation varied significantly among study sites (α = 0.01). The analysis of sludge sampled before and after different unit operation steps (i.e., anaerobic digestion, sludge heat treatment, and sludge drying) yielded insights into the extent and location of TCC and TCS transformation. Results showed anaerobic digestion to be important for MeTCS transformation (37–74%), whereas its contribution to partial TCC dechlorination was limited (0.4–2.1%). This longitudinal and nationwide survey is the first to report the occurrence of transformation products, human metabolites, and manufacturing byproducts of TCC and TCS in sewage sludge.

  3. Antimicrobial activity of α-(2-hydroxy-2-methylpropyl)-ω-(2-hydroxy-3-methylbut-2-en-1-yl) polymethylene from caesalpinia bonducella (L.) Flem

    Sagar, Kavitha; Vidyasagar, G. M.

    2010-01-01

    The compound, α-(2-hydroxy-2-methylpropyl)-ω-(2-hydroxy-3-methylbut-2-en-1-yl)polymethylene, isolated from ethyl acetate leaf extract of Caesalpinia bonducella (L.) Flem. was evaluated for antimicrobial activity against clinical isolates, Proteus vulgaris, Pseudomonas aeruginosa, Klebsiella sp., Staphylococcus citrus, Staphylococcus aureus, Escherichia coli, Candida albicans and Rhodotorula sp. using agar diffusion method. The compound exerted inhibitory zone at all concentrations and revealed the concentration-dependent activity against all tested bacterial and yeast strains comparable to standards streptomycin sulphate and gentamycin for bacteria and fluconazole and griseofulvin for Candida albicans and Rhodotorula sp. The inhibition zones were wider and clear for C. albicans and Rhodotorula sp. (IZ >20 mm) and for Pseudomonas aeruginosa, P. vulgaris and E. coli zones were greater than standards tested, whereas, zones for Klebsiella sp. and S. aureus were similar to standards. PMID:21218063

  4. 5-[(3-Fluorophenyl(2-hydroxy-6-oxocyclohex-1-en-1-ylmethyl]-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H-dione

    Assem Barakat

    2016-09-01

    Full Text Available 5-[(3-Fluorophenyl(2-hydroxy-6-oxocyclohex-1-en-1-yl-methyl]-6-hydroxy-1,3-di-methylpyrimidine-2,4(1H,3H-dione 3 was synthesized via a multicomponent reaction. The Aldol–Michael addition reactions of N,N-dimethylbarbituric acid, cyclohexane-1,3-dione, and 3-fluorobenzaldehyde in aqueous solution gave the product in high yield. The molecular structure of the compound was confirmed by spectroscopic methods and X-ray crystallography. The title compound (C19H19FN2O5·H2O crystallizes in the Monoclinic form, P21/c, a = 7.8630 (5 Å, b = 20.0308 (13 Å, c = 11.3987 (8 Å, β = 104.274 (3°, V = 1739.9 (2° Å3, Z = 4, Rint = 0.117, wR(F2 = 0.124, T = 100 K.

  5. Docking Studies, Synthesis and Biological Evaluation of β-aryl-β-hydroxy Propanoic Acids for Anti-inflammatory Activity.

    Savic, Jelena; Dilber, Sanda; Milenkovic, Marina; Kotur-Stevuljevic, Jelena; Markovic, Bojan; Vladimirov, Sote; Brboric, Jasmina

    2017-01-01

    Nonsteriodal anti-inflammatory drugs (NSAIDs) are numerous and widely used for more than 60 years, but there is still a strong need for developing novel selective NSAIDs. The need is justified by the fact that nonselective NSAIDs can produce serious gastric side effects and that some of the selective NSAID are withdrawn due to their cardiotoxic side effects. Eight β-hydroxy-β-arylpropanoic acids, which belong to the arylpropanoic acid class of compounds, structurally similar to some nonsteroidal anti-inflammatory drugs (NSAIDs), were docked into 3D catalytic site of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Seven out of those eight acids were synthesized using already published modification of Reformatsky reaction additionally optimized by increasing temperature. Synthesized compounds were tested in vivo in order to elucidate anti-inflammatory activity, gastric tolerability and impact on liver function of rats. Results of docking studies have indicated that all compounds have potential to selectively inhibit COX-2 isoform, but that the compounds containing polar substituents on phenyl ring are better inhibitors. Results of carrageenan-induced rat paw oedema test have shown that all compounds exhibit dose dependence and good gastric tolerability and none of the tested compounds have shown negative effect on liver function compared to ibuprofen. The compound containing polar nitro group in para position has shown the best docking results, anti-inflammatory activity, low hepatotoxicity and good gastric tolerability. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. [Sudden death of a patient with 3-hydroxy-3-methylglutaryl coenzyme A lyase deficiency].

    Vilaseca Busca, M A; Ribes Rubio, A; Briones Godino, P; Cusi Sánchez, V; Baraíbar Castelló, R; Gairi Taull, J M

    1990-02-01

    A new case of neonatal 3-hydroxy-3-methylglutaric aciduria is described. 3-hydroxy-3-methylglutaryl CoA lyase activities in leukocytes demonstrated the patient's homozygosity and the heterozygous character of the parents and two other members of the family. Dietetic management with low fat high carbohydrate diet together with protein restriction and carnitine resulted in a good control of the metabolic acidosis, the hypoglycemia, and the physical and neurological development. Nevertheless, sudden death occurred at the age thirteen months without any previous apparent trouble and the necropsia showed neither signs of infection nor hepatic or cardiac derangement.

  7. Electron impact ionization mass spectra of 3-substituted-2-hydroxy-4(3H)-quinazolinones

    El Deen, I. M.; Abd El Fattah, M. E.

    2003-01-01

    2-Amino-2-hydroxy-4(3H)-quinazolinone (3) was prepared via condensation of 1 with hydrazine hydrate. Treatment of 3 with appropriate acid in POCl 3 , ethyl chloroacetate and activated olefinic compounds in DMF yielded the corresponding 3-(substituted)amino-2-hydroxy-4(3H)-quinazolinones 4,5 and 6. The electron impact ionization mass spectra of compounds 3 and 4 show a weak molecular ion peak and a base peak of m/z 146 resulting from a cleavage fragmentation. The compounds 5 and 6 give a characteristics fragmentation pattern with a very stable fragment of benzopyrazolone (m/z 132)

  8. The occurrence of 2-hydroxy-6-methoxybenzoic acid methyl ester in Securidaca longepedunculata Fresen root bark

    Lognay G.

    2000-01-01

    Full Text Available As part of our ongoing search for natural fumigants from Senegalese plants, we have investigated Securicicidaca longepedunculata root barks and demonstrated that 2-hydroxy-benzoic acid methyl ester (methyl salicylate, I is responsible of their biocide effect against stored grain insects. A second unknown apparented product, II has been systematically observed in all analyzed samples. The present paper describes the identification of this molecule. The analytical investigations including GCMS, GLC and 1H-NMR. spectrometry led to the conclusion that II corresponds to the 2-hydroxy-6-methoxybenzoic acid methyl ester.

  9. Spectroscopic study, antimicrobial activity and crystal structures of N-(2-hydroxy-5-nitrobenzalidene)4-aminomorpholine and N-(2-hydroxy-1-naphthylidene)4-aminomorpholine

    Yıldız, Mustafa; Ünver, Hüseyin; Dülger, Başaran; Erdener, Diğdem; Ocak, Nazan; Erdönmez, Ahmet; Durlu, Tahsin Nuri

    2005-03-01

    Schiff bases N-(2-hydroxy-3-nitrobenzalidene)4-aminomorpholine ( 1) and N-(2-hydroxy-1-naphthylidene)4-aminomorpholine ( 2) were synthesized from the reaction of 4-aminomorpholine with 2-hydroxy-5-nitrobenzaldehyde and 2-hydroxy-1-naphthaldehyde. Compounds 1 and 2 were characterized by elemental analysis, IR, 1H NMR, 13C NMR and UV-Visible techniques. The UV-Visible spectra of the Schiff bases with OH group in ortho position to the imino group were studied in polar and nonpolar solvents in acidic and basic media. The structures of compounds 1 and 2 have been examined cyrstallographically, for two compounds exist as dominant form of enol-imines in both the solutions and solid state. The title compounds 1 and 2 crystallize in the monoclinic space group P2 1/ c and P2 1/ n with unit cell parameters: a=8.410(1) and 11.911(3), b=6.350(9) and 4.860(9), c=21.728(3) and 22.381(6) Å, β=90.190(1) and 95.6(2)°, V=1160.6(3) and 1289.5(5) Å 3, Dx=1.438 and 1.320 g cm -3, respectively. The crystal structures were solved by direct methods and refined by full-matrix least squares. The antimicrobial activities of compounds 1 and 2 have also been studied. The antimicrobial activities of the ligands have been screened in vitro against the organisms Escherichia coli ATCC 11230, Staphylococcus aureus ATCC 6538, Klebsiella pneumoniae UC57, Micrococcus luteus La 2971, Proteus vulgaris ATCC 8427, Pseudomonas aeruginosa ATCC 27853, Mycobacterium smegmatis CCM 2067, Bacillus cereus ATCC 7064, Listeria monocytogenes ATCC 15313, Candida albicans ATCC 10231, Kluyveromyces fragilis NRRL 2415, Rhodotorula rubra DSM 70403, Debaryomyces hansenii DSM 70238 and Hanseniaspora guilliermondii DSM 3432.

  10. Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.

    Varsha Agarwal

    2008-06-01

    Full Text Available Cytochrome P450 (P450 is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.

  11. Mass spectrometry of the lithium adducts of diacylglycerols containing hydroxy FA in castor oil and two normal FA

    Castor oil can be used in industry. The molecular species of triacylglycerols containing hydroxy fatty acids (FA) in castor oil have been identified. We report here the identification of twelve diacylglycerols (DAG) containing hydroxy FA in castor oil using positive ion electrospray ionization mass ...

  12. Biosynthesis of secondary metabolites in sugarcane

    S.C. França

    2001-12-01

    Full Text Available A set of genes related to secondary metabolism was extracted from the sugarcane expressed sequence tag (SUCEST database and was used to investigate both the gene expression pattern of key enzymes regulating the main biosynthetic secondary metabolism pathways and the major classes of metabolites involved in the response of sugarcane to environmental and developmental cues. The SUCEST database was constructed with tissues in different physiological conditions which had been collected under varied situation of environmental stress. This database allows researchers to identify and characterize the expressed genes of a wide range of putative enzymes able to catalyze steps in the phenylpropanoid, isoprenoid and other pathways of the special metabolic mechanisms involved in the response of sugarcane to environmental changes. Our results show that sugarcane cDNAs encoded putative ultra-violet induced sesquiterpene cyclases (SC; chalcone synthase (CHS, the first enzyme in the pathway branch for flavonoid biosynthesis; isoflavone synthase (IFS, involved in plant defense and root nodulation; isoflavone reductase (IFR, a key enzyme in phenylpropanoid phytoalexin biosynthesis; and caffeic acid-O-methyltransferase, a key enzyme in the biosynthesis of lignin cell wall precursors. High levels of CHS transcripts from plantlets infected with Herbaspirillum rubri or Gluconacetobacter diazotroficans suggests that agents of biotic stress can elicit flavonoid biosynthesis in sugarcane. From this data we have predicted the profile of isoprenoid and phenylpropanoid metabolism in sugarcane and pointed the branches of secondary metabolism activated during tissue-specific stages of development and the adaptive response of sugarcane to agents of biotic and abiotic stress, although our assignment of enzyme function should be confirmed by careful biochemical and genetic supporting evidence.Este trabalho foi realizado com os objetivos de gerar uma coleção de genes

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Kinetic properties and inhibition of Trypanosoma cruzi 3-hydroxy-3-methylglutaryl CoA reductase

    Hurtado-Guerrrero, Ramón; Pena Diaz, Javier; Montalvetti, Andrea

    2002-01-01

    A detailed kinetic analysis of the recombinant soluble enzyme 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) from Trypanosoma cruzi has been performed. The enzyme catalyzes the normal anabolic reaction and the reductant is NADPH. It also catalyzes the oxidation of mevalonate but at a lower propo...

  19. Characterization and regulation of Leishmania major 3-hydroxy-3-methylglutaryl-CoA reductase

    Montalvetti, A; Pena Diaz, Javier; Hurtado, R

    2000-01-01

    In eukaryotes the enzyme 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase catalyses the synthesis of mevalonic acid, a common precursor to all isoprenoid compounds. Here we report the isolation and overexpression of the gene coding for HMG-CoA reductase from Leishmania major. The protein from L...

  20. Antioxidation behavior of milkweed oil 4-hydroxy-3-methyoxycinnamate esters in phospholipid bilayers

    Milkweed (Asclepia syriaca) has seed oil that is rich in polyunsaturated triacylglycerides that contain olefinic groups. The olefinic groups can be chemically oxidized to form either epoxy or polyhydroxy triacylglycerides that can be esterified with trans-4-hydroxy-3-methoxoycinnamic acid, commonly...

  1. Urinary 8-hydroxy-2-deoxyguanosine and cognitive function in Puerto Rican adults

    DNA oxidative stress has been suggested as an important pathogenic mechanism in cognitive impairment and dementia. We, therefore, examined whether urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of global DNA oxidation, was associated with cognitive function in a sample of Puerto Rican adul...

  2. Stereoselective synthesis of a-hydroxy-b-amino acids: the chiral pool approach

    RADOMIR N. SAICIC

    2004-11-01

    Full Text Available A method for the stereoselective homologation of a-amino acids into syn-a-hydroxy-b-amino acids is described, based on the conversion of stereoisomeric cyanohydrins into trans-oxazolines. The synthetic potential of the method is illustrated in the enantioselective formal synthesis of Bestatin.

  3. Influence of temperature and hydroxide concentration on the settling time of hydroxy-catalysis bonds

    Reid, S.; Cagnoli, G.; Elliffe, E.; Faller, J.; Hough, J.; Martin, I.; Rowan, S.

    2007-01-01

    Many applications using bonded optical components have stringent requirements on the strength, rigidity, stability and alignment of the bonds. Hydroxy-catalysis bonding fulfills these requirements. Here we investigate methods by which the bonding time may be extended to better aid the precise prealignment of optical components through controlling the temperature and concentration of the bonding solution

  4. Biotechnology for improved hHydroxy fatty acid production in oilseed lesquerella

    The conventional source of hydroxy fatty acid (HFA) is from castor (Ricinus communis), 90% of castor oil is ricinoleic acid (18:1OH). Ricinoleic acid and its derivatives are used as raw materials for numerous industrial products, such as lubricants, plasticizers and surfactants. The production of ca...

  5. 4-[(2-Hydroxy-4-pentadecyl-benzylidene-amino]-benzoic Acid Methyl Ester

    Gadada Naganagowda

    2013-11-01

    Full Text Available A new Schiff base, 4-[(2-hydroxy-4-pentadecyl-benzylidene-amino]-benzoic acid methyl ester was synthesized and its UV, IR, 1H-NMR, 13C-NMR and ESI-MS spectroscopic data are presented.

  6. Optimization of disintegration behavior of biodegradable poly (hydroxy butanoic acid) copolymer mulch films in soil environment

    Mahajan, Viabhav

    Biodegradation of polymeric films used for mulch film applications in agriculture not only eliminates problems of sorting out and disposal of plastics films, but also ensures increased yields in crop growth and cost reduction. One such polymer which is completely biodegradable in the soil is poly 3-hydroxy butanoic acid copolymer, which is a promising alternative to non-biodegradable incumbent polyethylene mulch films. The purpose of mulch film made of poly 3-hydroxy butanoic acid copolymers is to sustain itself during the crop growth and disintegrate and eventually biodegrade back to nature after the crop cycle is over. The disintegration phase of the biodegradation process was evaluated for poly 3-hydroxy butanoic acid copolymer incorporated with no additive, antimicrobial additives, varying amount of crystallinities, another biodegradable polymer, and in different soils, with or without varying soil moisture content. The tools used for quantification were weight loss and visual observation. The test method was standardized using repeatability tests. The onset of disintegration was optimized with addition of right anti-microbial additives, higher crystallinity of film, blending with other biodegradable polymers, compared to virgin poly 3-hydroxy butanoic acid copolymer film. The onset of disintegration time was reduced when soil moisture content was reduced. After the onset of disintegration, the polymer film was physically and mechanically deteriorated, withering away in soil, which is possible to tailor with the crop growth cycle.

  7. Facile synthesis of α-hydroxy carboxylic acids from the corresponding α-amino acids

    Stuhr-Hansen, Nicolai; Padrah, Shahrokh; Strømgaard, Kristian

    2014-01-01

    An effective and improved procedure is developed for the synthesis of α-hydroxy carboxylic acids by treatment of the corresponding protonated α-amino acid with tert-butyl nitrite in 1,4-dioxane-water. The amino moiety must be protonated and located α to a carboxylic acid function in order...

  8. Synthesis of new series of 3-hydroxy/acetoxy-2-phenyl-4H-chromen ...

    Abstract. 3-Hydroxy-2-aryl/heteroaryl-4H-chromones 4(a–n) were synthesized from appropriate chalcones. 3(a–n) and acetylated to afford the corresponding acetoxy derivatives 5(a–n). All compounds were evalu- ated for antimicrobial activity against Staphylococus aureus, Bacillus subtillis, Escherichia coli and Pseu-.

  9. Determination of Urinary 8-hydroxy-2''-deoxyguanosine in Obese Patiens by HPLC with Electrochemical Detection

    Samcová, E.; Marhol, P.; Opekar, F.; Langmaier, Jan

    2004-01-01

    Roč. 516, - (2004), s. 107-110 ISSN 0003-2670 R&D Projects: GA ČR GA203/01/0653 Institutional research plan: CEZ:AV0Z4040901 Keywords : 8-hydroxy-2''''-deoxyguanosine * DNA * obese patient Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.588, year: 2004

  10. 4-Hydroxy-oxyphenbutazone is a potent inhibitor of cytokine production

    ten Brinke, Anja; Dekkers, David W. C.; Notten, Silla M.; Karsten, Miriam L.; de Groot, Els R.; Aarden, Lucien A.

    2005-01-01

    4-Hydroxy-oxyphenbutazone (4OH-OPB), is currently in phase II trials for its immunosuppressive effect in patients with rheumatoid arthritis. 4OH-OPB and other compounds related to phenylbutazone were tested for their effect on in vitro cytokine production by monocytes and lymphocytes present in

  11. Microwave Synthesis of Zinc Hydroxy Sulfate Nanoplates and Zinc Oxide Nanorods in the Classroom

    Dziedzic, Rafal M.; Gillian-Daniel, Anne Lynn; Peterson, Greta M.; Martínez-Herna´ndez, Kermin J.

    2014-01-01

    In this hands-on, inquiry-based lab, high school and undergraduate students learn about nanotechnology by synthesizing their own nanoparticles in a single class period. This simple synthesis of zinc oxide nanorods and zinc hydroxy sulfate nanoplates can be done in 15 min using a household microwave oven. Reagent concentration, reaction…

  12. Adsorption of Pb(II) present in aqueous solution on calcium, strontium and barium hydroxy apatites

    Vilchis G, J.

    2013-01-01

    Calcium, strontium and barium hydroxy apatites were successfully synthesized by chemical precipitation method, the obtained powders were characterized by the techniques of X-ray diffraction (XRD), scanning electron microscopy (Sem), semi-quantitative elemental analysis (EDS), infrared spectroscopy (IR), and N 2 physisorption studies, complementary to these analytical techniques, was determined the surface fractal dimension (Df), and the amount of surface active sites of the materials, in order to know application as ceramic for water remediation. The ability of Pb(II) ion adsorption present in aqueous solution on the hydroxy apatites synthesized by batch type experiments was studied as a function of contact time, concentration of the adsorbate and temperature. The maximum lead adsorption efficiencies obtained were 0.31, 0.32 and 0.26 mg/g for calcium, strontium and barium hydroxy apatites respectively, achieved an equilibrium time of 20 minutes in the three solid-liquid systems studied. Experimental data were adequately adjusted at the adsorption kinetic model pseudo-second order, for the three cases. Moreover, experimental data of the strontium and calcium hydroxy apatites were adjusted to the Langmuir adsorption isotherm, indicating that the adsorption was through a monolayer, whereas barium hydroxyapatite was adjusted to the Freundlich adsorption isotherm, indicating a multilayer adsorption. The thermodynamic parameters obtained during adsorption studies as a function of temperature showed physisorption, exothermic and spontaneous processes respectively. The results showed that the calcium hydroxyapatite, strontium and barium are an alternative for the Pb(II) ion adsorption present in wastewaters. (Author)

  13. Pulse radiolytic reduction of amino and hydroxy disubstituted anthraquinones (Preprint no. RC-15)

    Pal, H.; Palit, D.K.; Mukherjee, T.; Mittal, J.P.

    1991-01-01

    One-electron reduction of 1-amino-4-hydroxy-9, 10-anthraquinone (AHAQ) and 1,4-diamino-9, 10-anthraquinone (DAAQ) in various matrices has been investigated by electron pulse radiolysis. Spectroscopic and kinetic parameters, acid dissociation constants (pK a ) of the reduced semiquinone radicals and one-electron reduction potential for AHAQ have been measured. (author). 2 tabs

  14. 3-Hydroxy-2-[(4-hydroxy-3,5-dimethoxyphenyl(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-ylmethyl]-5,5-dimethylcyclohex-2-en-1-one

    Xiao-Hui Yang

    2011-02-01

    Full Text Available In the title compound, C25H32O7, the 3-hydroxy-5,5-dimethylcyclohex-2-enone rings adopt slightly distorted envelope conformations with the two planes at the base of the envelope forming dihedral angles of 57.6 (4 and 53.9 (9° with the benzene ring. There is an intramolecular hydroxy–ketone O—H...O interaction between the two substituted cyclohexane rings as well as a short intramolecular phenol–methoxy O—H...O interaction.

  15. Whey protein delays gastric emptying and suppresses plasma fatty acids and their metabolites compared to casein, gluten, and fish protein

    Stanstrup, Jan; Schou, Simon S; Holmer-Jensen, Jens

    2014-01-01

    ), and cod (COD). Obese, nondiabetic subjects were included in the randomized, blinded, crossover meal study. Subjects ingested a high fat meal containing one of the four protein sources. Plasma samples were collected at five time points and metabolites analyzed using LC-Q-TOF-MS. In contrast to previous...... studies, the WI meal caused a decreased rate of gastric emptying compared to the other test meals. The WI meal also caused elevated levels of a number of amino acids, possibly stimulating insulin release leading to reduced plasma glucose. The WI meal also caused decreased levels of a number of fatty acids......, while the GLU meal caused elevated levels of a number of unidentified hydroxy fatty acids and dicarboxylic fatty acids. Also reported are a number of markers of fish intake unique to the COD meal....

  16. Quantitative analysis of hydroperoxy-, keto- and hydroxy-dienes in refined vegetable oils.

    Morales, Arturo; Marmesat, Susana; Dobarganes, M Carmen; Márquez-Ruiz, Gloria; Velasco, Joaquín

    2012-03-16

    Quantitative analysis of the main oxidation products of linoleic acid - hydroperoxy-, keto- and hydroxy-dienes - in refined oils is proposed in this study. The analytical approach consists of derivatization of TAGs into FAMEs and direct analysis by HPLC-UV. Two transmethylation methods run at room temperature were evaluated. The reactants were KOH in methanol in method 1 and sodium methoxide (NaOMe) in method 2. Method 1 was ruled out because resulted in losses of hydroperoxydienes as high as 90 wt%. Transmethylation with NaOMe resulted to be appropriate as derivatization procedure, although inevitably also gives rise to losses of hydroperoxydienes, which were lower than 10 wt%, and formation of keto- and hydroxy-dienes as a result. An amount of 0.6-2.1 wt% of hydroperoxydienes was transformed into keto- and hydroxy-dienes, being the formation of the former as much as three times higher. The method showed satisfactory sensitivity (quantification limits of 0.3 μg/mL for hydroperoxy- and keto-dienes and 0.6 μg/mL for hydroxydienes), precision (coefficients of variation ≤ 6% for hydroperoxydienes and ≤ 15% for keto- and hydroxy-dienes) and accuracy (recovery values of 85(± 4), 99(± 2) and 97.0(± 0.6) % for hydroperoxy-, keto- and hydroxy-dienes, respectively). The method was applied to samples of high-linoleic (HLSO), high-oleic (HOSO) and high-stearic high-oleic (HSHOSO) sunflower oils oxidized at 40 °C. Results showed that the higher the linoleic-to-oleic ratio, the higher were the levels of hydroperoxy-, keto- and hydroxy-dienes when tocopherols were completely depleted, i.e. at the end of the induction period (IP). Levels of 23.7, 2.7 and 1.1 mg/g oil were found for hydroperoxy-, keto- and hydroxy-dienes, respectively, in the HLSO when tocopherol was practically exhausted. It was estimated that hydroperoxydienes constituted approximately 100, 95 and 60% of total hydroperoxides in the HLSO, HOSO and HSHOSO, respectively, along the IP. Copyright © 2012

  17. 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...

  18. 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

  19. Specific rescue by ortho-hydroxy atorvastatin of cortical GABAergic neurons from previous oxygen/glucose deprivation: role of pCREB.

    Guirao, Verónica; Martí-Sistac, Octavi; DeGregorio-Rocasolano, Núria; Ponce, Jovita; Dávalos, Antoni; Gasull, Teresa

    2017-11-01

    The statin atorvastatin (ATV) given as a post-treatment has been reported beneficial in stroke, although the mechanisms involved are not well understood so far. Here, we investigated in vitro the effect of post-treatment with ATV and its main bioactive metabolite ortho-hydroxy ATV (o-ATV) on neuroprotection after oxygen and glucose deprivation (OGD), and the role of the pro-survival cAMP response element-binding protein (CREB). Post-OGD treatment of primary cultures of rat cortical neurons with o-ATV, but not ATV, provided neuroprotection to a specific subset of cortical neurons that were large and positive for glutamic acid decarboxylase (large-GAD (+) neurons, GABAergic). Significantly, only these GABAergic neurons showed an increase in phosphorylated CREB (pCREB) early after neuronal cultures were treated post-OGD with o-ATV. We found that o-ATV, but not ATV, increased the neuronal uptake of glutamate from the medium; this provides a rationale for the specific effect of o-ATV on pCREB in large-GABAergic neurons, which have a higher ratio of synaptic (pCREB-promoting) vs extrasynaptic (pCREB-reducing) N-methyl-D-aspartate (NMDA) receptors (NMDAR) than that of small-non-GABAergic neurons. When we pharmacologically increased pCREB levels post-OGD in non-GABAergic neurons, through the selective activation of synaptic NMDAR, we observed as well long-lasting neuronal survival. We propose that the statin metabolite o-ATV given post-OGD boosts the intrinsic pro-survival factor pCREB in large-GABAergic cortical neurons in vitro, this contributing to protect them from OGD. © 2017 International Society for Neurochemistry.

  20. Urinary Concentrations of Insecticide and Herbicide Metabolites among Pregnant Women in Rural Ghana: A Pilot Study

    Blair J. Wylie

    2017-03-01

    Full Text Available Use of pesticides by households in rural Ghana is common for residential pest control, agricultural use, and for the reduction of vectors carrying disease. However, few data are available about exposure to pesticides among this population. Our objective was to quantify urinary concentrations of metabolites of organophosphate (OP, pyrethroid, and select herbicides during pregnancy, and to explore exposure determinants. In 2014, 17 pregnant women from rural Ghana were surveyed about household pesticide use and provided weekly first morning urine voids during three visits (n = 51 samples. A total of 90.1% (46/51 of samples had detectable OP metabolites [geometric mean, GM (95% CI: 3,5,6-trichloro-2-pyridinol 0.54 µg/L (0.36–0.81, para-nitrophenol 0.71 µg/L (0.51–1.00], 75.5% (37/49 had detectable pyrethroid metabolites [GM: 3-phenoxybenzoic acid 0.23 µg/L (0.17, 0.32], and 70.5% (36/51 had detectable 2,4-dichlorophenoxyacetic acid levels, a herbicide [GM: 0.46 µg/L (0.29–0.73]. Concentrations of para-nitrophenol and 2,4-dichlorophenoxyacetic acid in Ghanaian pregnant women appear higher when compared to nonpregnant reproductive-aged women in a reference U.S. population. Larger studies are necessary to more fully explore predictors of exposure in this population.

  1. The use of stable isotopes and gas chromatography/mass spectrometry in the identification of steroid metabolites in the equine

    Houghton, E.; Dumasia, M.C.; Teale, P.; Smith, S.J.; Cox, J.; Marshall, D.; Gower, D.B.

    1990-01-01

    Stable isotope gas chromatography/mass spectrometry has been used successfully in the elucidation of structures of urinary steroid metabolites in the horse and in the identification of metabolites isolated from in vivo perfusion and in vitro incubation studies using equine tissue preparations. Deuterium-labeled steroids, testosterone, dehydroepiandrosterone, and 5-androstene-3 beta,17 beta-diol have been synthesized by base-catalyzed isotope exchange methods and the products characterized by gas chromatography/mass spectrometry. [16,16(-2)H2]Dehydroepiandrosterone (plus radiolabeled dehydroepiandrosterone) was perfused into a testicular artery of a pony stallion and was shown to be metabolized into 2H2-labeled testosterone, 4-androstenedione, isomers of 5-androstene-3,17-diol, 19-hydroxytestosterone, and 19-hydroxy-4-androstenedione. In further studies, equine testicular minces have been incubated with 2H2-labeled and radiolabeled dehydroepiandrosterone and 5-androstene-3 beta, 17 beta-diol. The metabolites, whose identity was confirmed by stable isotope gas chromatography/mass spectrometry, proved the interconversion of the two substrates, as well as formation of testosterone and 4-androstenedione. The aromatization of dehydroepiandrosterone was also confirmed, together with the formation of an isomer of 5(10)-estrene-3,17-diol from both substrates showing 19-demethylation without concomitant aromatization. In studies of the feto-placental unit, the allantochorion was shown to aromatize [2H5]testosterone to [2H4]estradiol, the loss of one 2H from the substrate being consistent with aromatization of the A ring. The formation of 6-hydroxyestradiol was also confirmed in this study. The same technique has been valuable in determining the structure of two metabolites of nandrolone isolated from horse urine

  2. Free acid gel form of β-hydroxy-β-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt.

    Fuller, John C; Sharp, Rick L; Angus, Hector F; Baier, Shawn M; Rathmacher, John A

    2011-02-01

    The leucine metabolite, β-hydroxy-β-methylbutyrate (HMB), is a nutritional supplement that increases lean muscle and strength with exercise and in disease states. HMB is presently available as the Ca salt (CaHMB). The present study was designed to examine whether HMB in free acid gel form will improve HMB availability to tissues. Two studies were conducted and in each study four males and four females were given three treatments in a randomised, cross-over design. Treatments were CaHMB (gelatin capsule, 1 g), equivalent HMB free acid gel swallowed (FASW) and free acid gel held sublingual for 15 s then swallowed (FASL). Plasma HMB was measured for 3 h following treatment in study 1 and 24 h with urine collection in study 2. In both the studies, the times to peak plasma HMB were 128 (sem 11), 38 (sem 4) and 38 (sem 1) min (P HMB excretion was not significantly increased resulting in more HMB retained (P HMB from plasma. In conclusion, HMB free acid gel could improve HMB availability and efficacy to tissues in health and disease.

  3. The relationship of endogenous plasma concentrations of β-Hydroxy β-Methyl Butyrate (HMB) to age and total appendicular lean mass in humans.

    Kuriyan, Rebecca; Lokesh, Deepa P; Selvam, Sumithra; Jayakumar, J; Philip, Mamatha G; Shreeram, Sathyavageeswaran; Kurpad, Anura V

    2016-08-01

    The maintenance of muscle mass and muscle strength is important for reducing the risk of chronic diseases. The age- related loss of muscle mass and strength is associated with adverse outcomes of physical disability, frailty and death. β-Hydroxy β-Methyl Butyrate (HMB), a metabolite of leucine, has beneficial effects on muscle mass and strength under various catabolic conditions. The objectives of the present study were to determine if age- related differences existed in endogenous plasma HMB levels, and to assess if HMB levels correlated to total appendicular lean mass and forearm grip strength. Anthropometry, dietary and physical activity assessment, and the estimation of fasting plasma HMB concentrations and handgrip strength were performed on the 305 subjects (children, young adults and older adults). Lean mass, which serves as a surrogate for muscle mass was measured using dual energy X-ray absorptiometry (DEXA). Mean plasma HMB concentrations were significantly lower with increasing age groups, with children having highest mean HMB concentration (pHMB concentrations. A significant positive correlation between HMB concentrations and appendicular lean mass normalized for body weight (%), appendicular lean mass (r=0.37; pHMB concentrations in young adults (r=0.58; pHMB concentrations in humans and the HMB concentrations were positively correlated with appendicular lean mass and hand grip strength in young adults and older adults group. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters.

    Rathmacher, J A; Nissen, S; Panton, L; Clark, R H; Eubanks May, P; Barber, A E; D'Olimpio, J; Abumrad, N N

    2004-01-01

    Combining the amino acids arginine and glutamine with the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been shown to reverse lean tissue loss in cancer and acquired immunodeficiency syndrome (AIDS) patients. Although each of these nutrients has been shown to be safe, the safety of this mixture has not been reported. Three double-blind studies examined the safety of the combination of HMB, arginine and glutamine on blood chemistries, hematology, emotional profile, and adverse events. Study 1 was conducted in healthy adult males (n = 34), study 2 was in HIV patients with AIDS-associated weight loss (n = 43), and study 3 was in cancer patients with wasting (n = 32). Volunteers were assigned to either a placebo or a mixture of 3 g HMB, 14 g arginine, and 14 g glutamine per day. Across the 3 studies, HMB, arginine, and glutamine supplementation was not associated with any adverse indicators of health. The only significant changes noted were positive indicators of health status. HMB, arginine, and glutamine supplementation was associated with an improvement in emotional profile (p = .05), a decreased feeling of weakness (p = .03), and increased red blood cells, hemoglobin, hematocrit, lymphocytes, and eosinophils (p HMB, arginine, and glutamine supplementation, which was possibly caused by the additional nitrogen consumed or to the fact that ureagenesis is influenced by arginine and glutamine supplementation. These results show that HMB, arginine, and glutamine can be safely used to treat muscle wasting associated with AIDS and cancer.

  5. Organic metabolites produced by Vibrio parahaemolyticus strain ...

    Identification and action of several antibacterial metabolites produced by a fish pathogen Vibrio parahaemolyticus strain An3 from marine ecosystem of Goa has been demonstrated. Antibacterial activity of the crude cell extract of the test bacterium has been evaluated against indicator pathogenic bacterial strains such as ...

  6. Chemical composition, secondary metabolites, in vitro gas ...

    Chemical composition, secondary metabolites, in vitro gas production characteristics and acceptability study of some forage for ruminant feeding in South-Western Nigeria. ... Chemical composition and qualitative analysis of saponins, phenol and steroids of the plants were determined. In vitro gas production (IVGP) was ...

  7. Secondary metabolites from Scorzonera latifolia roots

    Acikara, O. B.; Šmejkal, K.; Cvačka, Josef; Buděšínský, Miloš; Dračínský, Martin; Saltan, G.

    2015-01-01

    Roč. 81, č. 16 (2015), PM167 ISSN 0032-0943. [GA 2015. International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research /63./. 23.08.2015-27.08.2015, Budapest] Institutional support: RVO:61388963 Keywords : medical plant * metabolites * Asteraceae Subject RIV: CB - Analytical Chemistry, Separation

  8. Antibacterial activity of secondary metabolites isolated from ...

    Aghomotsegin

    2015-10-28

    Oct 28, 2015 ... Alternaria spp. are cosmopolitan mould fungi and can be found in soils ... the secondary metabolites products from A. alternata and ..... Zone of inhibition (mm) of test bacterial strains to fungal products and standard antibiotics. Fungal ... marine actinomycetes from pulicat, Muttukadu, and Ennore estuaries.

  9. Identification of a new metabolite of GHB

    Petersen, Ida Nymann; Tortzen, Christian; Kristensen, Jesper Langgaard

    2013-01-01

    Gamma-hydroxybutyric acid (GHB) is an important analyte in clinical and forensic toxicology with a narrow detection window of 3-6 h. In the search of improved detection methods, the existence in vivo of a glucuronated GHB metabolite (GHB-GLUC) was hypothesized. Chemically pure standards of GHB...

  10. Streptopyrrole: An antimicrobial metabolite from Streptomyces armeniacus

    Breinholt, J.; Gürtler, Hanne; Kjær, Anders

    1998-01-01

    A colourless, crystalline metabolite, C14H12ClNO4, named streptopyrrole, has been isolated from submerged fermentation cultures of Streptomyces armeniacus by extraction, followed by chromatographic purification. Its tricyclic molecular framework, seemingly without natural product precedents. as w...

  11. Microbial metabolism part 13 metabolites of hesperetin

    The fungal culture, Mucor ramannianus (ATCC 2628) transformed hesperitin to four metabolites: 4'-methoxy -5, 7, 8, 3'-tetrahydroxyflavanone (8-hydroxyhesperetin), 5, 7, 3', 4'-tetrahydroxyflavanone (eriodictyol), 4'-methoxy-5, 3'-dihydroxyflavanone 7-sulfate (hesperetin 7-sulfate) and 5, 7, 3'-tri...

  12. Human pharmacokinetics of proguanil and its metabolites

    Bygbjerg, Ib Christian; Ravn, P; Rønn, A

    1987-01-01

    The pharmacokinetics of proguanil and its metabolites cycloguanil and p-chlorophenylbiguanide were studied in five healthy volunteers taking 200 mg orally for 14 days. A highly sensitive and specific high-performance liquid chromatographic assay was applied, clearly identifying all three compounds...

  13. para palmito

    Francisco Paulo Chaimsohn

    2007-01-01

    Full Text Available Densidades de siembra, arreglos espaciales y fertilización en pejibaye (Bactris gasipaes cv Diamantes-10 para palmito. La investigación se llevó a cabo en la Estación Experimental Los Diamantes (Guápiles, Costa Rica, el 3 de octubre del 2003, cuyo objetivo fue la evaluación del efecto de diferentes densidades de siembra (3.333, 5.000 y 6.666 plantas/ha, arreglos espaciales, y diversos métodos de fertilización (química, orgánica, sobre el crecimiento de las plantas de pejibaye para producción de palmito. Se consideraron las variables diámetro y altura del tallo primario y el número de hojas y rebrotes como indicadores de producción. El período de evolución abarcó sólo los primeros 25 meses de crecimiento en el campo. El número de hojas, la altura y el diámetro del tallo no mostraron diferencias de respuesta relevantes. Sólo el número de rebrotes disminuyó al aumentar la densidad de la población, cuando se midió a los 15 meses de edad. El efecto de la fertilización se hizo evidente después de la primera cosecha, realizada a los 20 meses, debido al aumento de la competencia entre plantas, ahora más desarrolladas. Fue entonces cuando la fertilización química indujo la producción de un mayor número y vigor de los rebrotes. Sin embargo, las prácticas evaluadas 25 meses después de la siembra, no habían infl uido hasta ese momento en el número de palmitos cosechados, ni tampoco había afectado las características físicas de los sectores foliar y caulinar del palmito.

  14. Circulating prostacyclin metabolites in the dog

    Taylor, B.M.; Shebuski, R.J.; Sun, F.F.

    1983-01-01

    The present study was designed to determine the concentration of prostacyclin (PGI2) metabolites in the blood of the dog. After a bolus i.v. dose of [11 beta- 3 H]PGI2 (5 micrograms/kg) into each of five dogs, blood samples were withdrawn at 0.33, 0.67, 1, 3, 5, 20, 30, 60 and 120 min postdrug administration. Plasma samples were extracted and the radioactive components were analyzed by two-dimensional thin-layer chromatography with autoradiofluorography and radio-high-performance liquid chromatography. The compounds were identified by comparing their mobility with synthetic standards; only parallel responses observed in both tests constituted positive identification. Seven metabolites were identified by these two techniques: 6-keto-prostaglandin (PG)F1 alpha; 6-keto-PGE1; 2,3-dinor-6-keto-PGF 1 alpha; 2,3-dinor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha; and 2,3,18,19-tetranor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha. Several additional compounds, both polar and nonpolar in nature, which did not co-chromatograph with any of our standards were also detected. Early samples consisted predominantly of 6-keto-PGF 1 alpha and other 20-carbon metabolites. By 30 min, the predominant metabolites were the 16- and 18-carbon dicarboxylic acids. By 60 min, 85% of the radioactivity was associated with two unidentified polar compounds. The evidence suggests that 6-keto-PGF 1 alpha probably reflects only the transient levels of freshly entering PGI2 in the circulation, whereas levels of the most polar metabolites (e.g., dihydro-diketo-carboxyl tetranor-PGF 2 alpha) may be a better measure of the overall PGI2 presence due to its longer half-life in circulation

  15. Metabolites of 2,4,4'-tribrominated diphenyl ether (BDE-28) in pumpkin after in vivo and in vitro exposure.

    Yu, Miao; Liu, Jiyan; Wang, Thanh; Sun, Jianteng; Liu, Runzeng; Jiang, Guibin

    2013-01-01

    There is currently limited knowledge on PBDE metabolism in plants although they could play an important role in the environmental transformation of these persistent organic pollutants. In this study, pumpkin (Cucurbita maxima × C. moschata) was chosen as the model to understand the fate of BDE-28 in plants. MeO-tri-BDEs, OH-tri-BDEs, and OH-tri-BDEs were found as metabolites in plant samples of both in vivo hydroponic and in vitro tissue culture exposure. Three MeO-tri-BDEs were further identified as para-substituted metabolites. MeO-BDEs and OH-BDEs, respectively, accounted for about 1.6% and 1.5% (recovery corrected) of initial amount of BDE-28 according to the semiquantitative results. Other PBDEs, especially less brominated PBDEs as impurities in the standard of BDE-28, were also detected. The impurities and evaporation of the standard must be considered when trace metabolites are studied in exposure experiments.

  16. 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

  17. Rationalization and prediction of in vivo metabolite exposures: The role of metabolite kinetics, clearance predictions and in vitro parameters

    Lutz, Justin D.; Fujioka, Yasushi; Isoherranen, Nina

    2010-01-01

    Importance of the field Due to growing concerns over toxic or active metabolites, significant efforts have been focused on qualitative identification of potential in vivo metabolites from in vitro data. However, limited tools are available to quantitatively predict their human exposures. Areas covered in this review Theory of clearance predictions and metabolite kinetics is reviewed together with supporting experimental data. In vitro and in vivo data of known circulating metabolites and their parent drugs was collected and the predictions of in vivo exposures of the metabolites were evaluated. What the reader will gain The theory and data reviewed will be useful in early identification of human metabolites that will circulate at significant levels in vivo and help in designing in vivo studies that focus on characterization of metabolites. It will also assist in rationalization of metabolite-to-parent ratios used as markers of specific enzyme activity. Take home message The relative importance of a metabolite in comparison to the parent compound as well as other metabolites in vivo can only be predicted using the metabolites in vitro formation and elimination clearances, and the in vivo disposition of a metabolite can only be rationalized when the elimination pathways of that metabolite are known. PMID:20557268

  18. 4-Hydroxy estradiol but not 2-hydroxy estradiol induces expression of hypoxia-inducible factor 1α and vascular endothelial growth factor A through phosphatidylinositol 3-kinase/Akt/FRAP pathway in OVCAR-3 and A2780-CP70 human ovarian carcinoma cells

    Gao Ning; Nester, Rebecca A.; Sarkar, Mohamadi A.

    2004-01-01

    Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor composed of HIF-1α and HIF-1β subunits. HIF-1 expression is induced by hypoxia, growth factors, and activation of oncogenes. HIF-1 activates downstream target genes such as vascular endothelial growth factor A (VEGF-A), which plays an important role in tumor progression and angiogenesis. Estrogen exposure is considered to be the major risk factor for ovarian cancer. Estradiol (E2) is usually metabolized by CYP1A1/1A2 and CYP3A4 to the 2-hydroxy estradiol (2-OHE2) and 4-hydroxy estradiol (4-OHE2) in human liver. Many reports have suggested that the formation of 4-OHE2 is important for mammary carcinogenesis. However, the formation of 2-OHE2 may play an important role in exhibiting anticarcinogenic effects. In the present study, we have demonstrated that one of the catechol estrogen metabolites of E2, 4-OHE2, induces HIF-1α and VEGF-A expression at protein level in two human ovarian cancer cell lines, OVCAR-3 and A2780-CP70 cells, in dose- and time-dependent manners, whereas the other catechol estrogen metabolite of E2, 2-OHE2, does not alter HIF-1α and VEGF-A expression. To explore the mechanism of 4-OHE2-induced HIF-1α and VEGF-A expression, we studied whether phosphatidylinositol 3-kinase (PI3K) or mitogen-activated protein kinase (MAPK) signaling pathways are involved in 4-OHE2-induced HIF-1α and VEGF-A expression. Our findings indicate that PI3K inhibitors, LY294002 and wortmannin, inhibited HIF-1α and VEGF-A expression, whereas MAPK inhibitor, PD98059, did not alter HIF-1α and VEGF-A expression induced by 4-OHE2. 4-OHE2, but not 2-OHE2, also induced Akt phosphorylation at Ser473 in dose- and time-dependent manners, and LY294002 and wortmannin inhibited Akt phosphorylation at Ser473 induced by 4-OHE2. Our results also indicated that the mTOR/FRAP inhibitor, rapamycin, inhibited 4-OHE2-induced HIF-1α and VEGF-A expression. These results suggest that the PI3K

  19. Metabolite coupling in genome-scale metabolic networks

    Palsson Bernhard Ø

    2006-03-01

    Full Text Available Abstract Background Biochemically detailed stoichiometric matrices have now been reconstructed for various bacteria, yeast, and for the human cardiac mitochondrion based on genomic and proteomic data. These networks have been manually curated based on legacy data and elementally and charge balanced. Comparative analysis of these well curated networks is now possible. Pairs of metabolites often appear together in several network reactions, linking them topologically. This co-occurrence of pairs of metabolites in metabolic reactions is termed herein "metabolite coupling." These metabolite pairs can be directly computed from the stoichiometric matrix, S. Metabolite coupling is derived from the matrix ŜŜT, whose off-diagonal elements indicate the number of reactions in which any two metabolites participate together, where Ŝ is the binary form of S. Results Metabolite coupling in the studied networks was found to be dominated by a relatively small group of highly interacting pairs of metabolites. As would be expected, metabolites with high individual metabolite connectivity also tended to be those with the highest metabolite coupling, as the most connected metabolites couple more often. For metabolite pairs that are not highly coupled, we show that the number of reactions a pair of metabolites shares across a metabolic network closely approximates a line on a log-log scale. We also show that the preferential coupling of two metabolites with each other is spread across the spectrum of metabolites and is not unique to the most connected metabolites. We provide a measure for determining which metabolite pairs couple more often than would be expected based on their individual connectivity in the network and show that these metabolites often derive their principal biological functions from existing in pairs. Thus, analysis of metabolite coupling provides information beyond that which is found from studying the individual connectivity of individual

  20. Production of 5-hydroxy-7-methoxy-4-methylphthalide in a culture of Penicillium crustosum

    Angela M.M.P. Valente

    Full Text Available The chemical reactions carried out by microorganisms have been used as a tool in modern chemistry. This paper reports the production of mycophenolic acid and a new phthalide by the endophytic fungus Penicillium crustosum obtained from coffee seeds. The fungus was cultivated in a liquid medium for a period of seven days and after that the culture medium was divided into four treatments: A, B, C and D, to which different organic substances were added. Treatment A was maintained as the control to evaluate the occurrence of biotransformation. Organic acids were added to the culture media of treatments B (ferulic and quinic acids and C [cinnamic and 3,4-(methylenedioxy cinnamic acids], and caffeine was added in the treatment D. All these organic compounds were dissolved in DMSO, and the fermentation was maintained for more 13 days, totalizing 20 days. Mycophenolic acid was isolated from the culture with no added acids (treatment A. Mycophenolic acid and a new phthalide, 5-hydroxy-7-methoxy-4-methylphthalide were isolated from treatments B and C, and mycophenolic acid and caffeine (added to the culture medium were isolated from treatment D. The structures were determined by NMR techniques and confirmed by MS and MS/MS techniques.As reações químicas realizadas por microorganismos têm sido utilizadas como uma ferramenta na química moderna. Este artigo relata a produção de ácido micofenólico e uma nova ftalida pelo fungo endofítico Penicillium crustosum obtido a partir de grãos de café. O fungo foi cultivado em meio líquido durante um período de sete dias, e depois disso, o meio de cultura foi dividido em quatro lotes: A, B, C e D, nos quais diferentes substâncias orgânicas foram adicionadas. O lote A foi mantido como controle para avaliar a ocorrência de biotransformação. Os ácidos orgânicos foram adicionados ao meio de cultura dos lotes B (ácidos ferúlico e quínico e C [ácido cinâmico e 3,4-(metilenodioxi cinâmico], e cafe

  1. Metabolite Depletion Affects Flux Profiling of Cell Lines

    Nilsson, A.; Haanstra, J. R.; Teusink, B.

    2018-01-01

    Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation.......Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation....

  2. Ketamine and ketamine metabolites as novel estrogen receptor ligands: Induction of cytochrome P450 and AMPA glutamate receptor gene expression.

    Ho, Ming-Fen; Correia, Cristina; Ingle, James N; Kaddurah-Daouk, Rima; Wang, Liewei; Kaufmann, Scott H; Weinshilboum, Richard M

    2018-04-03

    Major depressive disorder (MDD) is the most common psychiatric illness worldwide, and it displays a striking sex-dependent difference in incidence, with two thirds of MDD patients being women. Ketamine treatment can produce rapid antidepressant effects in MDD patients, effects that are mediated-at least partially-through glutamatergic neurotransmission. Two active metabolites of ketamine, (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-HNK, also appear to play a key role in ketamine's rapid antidepressant effects through the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors. In the present study, we demonstrated that estrogen plus ketamine or estrogen plus active ketamine metabolites displayed additive effects on the induction of the expression of AMPA receptor subunits. In parallel, the expression of estrogen receptor alpha (ERα) was also significantly upregulated. Even more striking, radioligand binding assays demonstrated that [ 3 H]-ketamine can directly bind to ERα (K D : 344.5 ± 13 nM). Furthermore, ketamine and its (2R,6R)-HNK and (2S,6S)-HNK metabolites displayed similar affinity for ERα (IC 50 : 2.31 ± 0.1, 3.40 ± 0.2, and 3.53 ± 0.2 µM, respectively) as determined by [ 3 H]-ketamine displacement assays. Finally, induction of AMPA receptors by either estrogens or ketamine and its metabolites was lost when ERα was knocked down or silenced pharmacologically. These results suggest a positive feedback loop by which estrogens can augment the effects of ketamine and its (2R,6R)-HNK and (2S,6S)-HNK metabolites on the ERα-induced transcription of CYP2A6 and CYP2B6, estrogen inducible enzymes that catalyze ketamine's biotransformation to form the two active metabolites. These observations provide novel insight into ketamine's molecular mechanism(s) of action and have potential implications for the treatment of MDD. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid

    Conti, P; De Amici, M; Bräuner-Osborne, Hans

    2002-01-01

    The synthesis and pharmacology of two potential glutamic acid receptor ligands are described. Preparation of the bicyclic 3-hydroxy-delta2-isoxazoline-cyclopentane derivatives (+/-)-7 and (+/-)-8 was accomplished via 1,3-dipolar cycloaddition of bromonitrile oxide to suitably protected 1-amino......-cyclopent-3-enecarboxylic acids. Their structure was established using a combination of 1H NMR spectroscopy and molecular mechanics calculations carried out on the intermediate cycloadducts (+/-)-11 and (+/-)-12. Amino acid derivatives (+/-)-7 and (+/-)-8 were assayed at ionotropic and metabotropic glutamic...... acid receptor subtypes and their activity compared with that of trans-ACPD and cis-ACPD. The results show that the replacement of the omega-carboxylic group of the model compounds with the 3-hydroxy-delta2-isoxazoline moiety abolishes or reduces drastically the activity at the metabotropic glutamate...

  4. SYNTHESIS, CHARACTERIZATION AND ANTIOXIDANT ACTIVITY OF 7-HYDROXY-3',4'-DIMETHOXYFLAVONE

    Elfi Susanti VH

    2012-03-01

    Full Text Available Synthesis of flavones and their derivatives has attracted considerable attention due to their significant pharmaceutical effects. 7-hydroxy-3',4'-dimethoxyflavone has been synthesized and its antioxidant activity has been investigated. Flavone was synthesized by oxidative cyclization of chalcone. 2',4'-dihydroxy-3,4-dimethoxychalcone was prepared by Claisen-Schmidt condensation of 2,4-dihydroxyacetophenones with 3,4-dimethoxybenzaldehydes in the presence of aqueous solution of sodium hydroxide and ethanol at room temperature. Oxidative cyclization of 2',4'-dihydroxy-3,4-dimethoxychalcone was done by using I2 catalyst in DMSO to form 7-hydroxy-3',4'-dimethoxyflavone. The synthesized compounds were characterized by means of their UV-Vis, IR, 1H-NMR and 13C-NMR spectral data. The compound was tested for their antioxidant activities by DPPH method.

  5. Phase transition and intramolecular hydrogen bonding in nitro derivatives of ortho-hydroxy acetophenones

    Filarowski, A.; Kochel, A.; Koll, A.; Bator, G.; Mukherjee, S.

    2006-03-01

    The crystal structures of two ortho-hydroxy aryl ketones (5-chloro-3-nitro-2-hydroxyacetophenone, 5-methyl-3-nitro-2-hydroxyacetophenone and the complex 5-chloro-3-nitro-2-hydroxyacetophenone with 2-aminobenzoic acid (anthranilic acid)) were determined by X-ray diffraction. The existence of an intramolecular hydrogen bond of enol character between the hydroxyl and acetyl groups was found by the X-ray method. The enol character was also confirmed by DFT (B3LYP/6-31+G(d,p)) calculations. A phase transition was found at 138 K in 5-chloro-3-nitro-2-hydroxyacetophenone. This phase transition was investigated by differential scanning calorimetry (DSC), dilatometry, and the dielectric method. A study of the nitro-group dynamics in the ortho-hydroxy acetophenones was carried out with DFT (B3LYP/6-31+G(d,p)) calculations.

  6. Synthesis, characterisation and anion exchange properties of copper, magnesium, zinc and nickel hydroxy nitrates

    Biswick, Timothy; Jones, William; Pacuła, Aleksandra; Serwicka, Ewa

    2006-01-01

    Anion exchange reactions of four structurally related hydroxy salts, Cu 2(OH) 3NO 3, Mg 2(OH) 3NO 3, Ni 2(OH) 3NO 3 and Zn 3(OH) 4(NO 3) 2 are compared and trends rationalised in terms of the strength of the covalent bond between the nitrate group and the matrix cation. Powder X-ray diffraction (PXRD), Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA) and elemental analysis are used to characterise the materials. Replacement of the nitrate anions in the zinc and copper salts with benzoate anions is possible although exchange of the zinc salt is accompanied by modification of the layer structure from one where zinc is exclusively six-fold coordinated to a structure where there is both six- and four-fold zinc coordination. Magnesium and nickel hydroxy nitrates, on the other hand, hydrolyse to their respective metal hydroxides.

  7. 2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid

    Johansen, Tommy N; Janin, Yves L; Nielsen, Birgitte

    2002-01-01

    In order to identify new subtype-selective (S)-glutamate (Glu) receptor ligands we have synthesized (RS)-2-amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid [(RS)-TDPA]. Resolution of (RS)-TDPA by chiral chromatography was performed using a Crownpac CR(+) column affording (R)- and (S......)-TDPA of high enantiomeric purity (enantiomeric excess=99.9%). An X-ray crystallographic analysis revealed that the early eluting enantiomer has R-configuration. Both enantiomers showed high affinity as well as high agonist activity at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA...... a remarkably low AMPA receptor stereoselectivity, (S)-TDPA showing the highest affinity and (R)-TDPA the most potent agonist activity. In addition, (S)-TDPA was shown to interact with synaptosomal Glu uptake sites displacing [(3)H](R)-aspartic acid (IC(50 ) approximately 390 microM). An enantiospecific...

  8. Synthesis, vibrational, NMR, quantum chemical and structure-activity relation studies of 2-hydroxy-4-methoxyacetophenone.

    Arjunan, V; Devi, L; Subbalakshmi, R; Rani, T; Mohan, S

    2014-09-15

    The stable geometry of 2-hydroxy-4-methoxyacetophenone is optimised by DFT/B3LYP method with 6-311++G(∗∗) and cc-pVTZ basis sets. The structural parameters, thermodynamic properties and vibrational frequencies of the optimised geometry have been determined. The effects of substituents (hydroxyl, methoxy and acetyl groups) on the benzene ring vibrational frequencies are analysed. The vibrational frequencies of the fundamental modes of 2-hydroxy-4-methoxyacetophenone have been precisely assigned and analysed and the theoretical results are compared with the experimental vibrations. 1H and 13C NMR isotropic chemical shifts are calculated and assignments made are compared with the experimental values. The energies of important MO's, the total electron density and electrostatic potential of the compound are determined. Various reactivity and selectivity descriptors such as chemical hardness, chemical potential, softness, electrophilicity, nucleophilicity and the appropriate local quantities are calculated. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Physiological basis of tingling paresthesia evoked by hydroxy-α-sanshool

    Lennertz, Richard C; Tsunozaki, Makoto; Bautista, Diana M; Stucky, Cheryl L

    2010-01-01

    Hydroxy-α-sanshool, the active ingredient in plants of the prickly ash plant family, induces robust tingling paresthesia by activating a subset of somatosensory neurons. However, the subtypes and physiological function of sanshool-sensitive neurons remain unknown. Here we use the ex vivo skin-nerve preparation to examine the pattern and intensity with which the sensory terminals of cutaneous neurons respond to hydroxy-α-sanshool. We found that sanshool excites virtually all D-hair afferents, a distinct subset of ultra-sensitive light touch receptors in the skin, and targets novel populations of Aβ and C-fiber nerve afferents. Thus, sanshool provides a novel pharmacological tool for discriminating functional subtypes of cutaneous mechanoreceptors. The identification of sanshool-sensitive fibers represents an essential first step in identifying the cellular and molecular mechanisms underlying tingling paresthesia that accompanies peripheral neuropathy and injury. PMID:20335471

  10. Physiological basis of tingling paresthesia evoked by hydroxy-alpha-sanshool.

    Lennertz, Richard C; Tsunozaki, Makoto; Bautista, Diana M; Stucky, Cheryl L

    2010-03-24

    Hydroxy-alpha-sanshool, the active ingredient in plants of the prickly ash plant family, induces robust tingling paresthesia by activating a subset of somatosensory neurons. However, the subtypes and physiological function of sanshool-sensitive neurons remain unknown. Here we use the ex vivo skin-nerve preparation to examine the pattern and intensity with which the sensory terminals of cutaneous neurons respond to hydroxy-alpha-sanshool. We found that sanshool excites virtually all D-hair afferents, a distinct subset of ultrasensitive light-touch receptors in the skin and targets novel populations of Abeta and C fiber nerve afferents. Thus, sanshool provides a novel pharmacological tool for discriminating functional subtypes of cutaneous mechanoreceptors. The identification of sanshool-sensitive fibers represents an essential first step in identifying the cellular and molecular mechanisms underlying tingling paresthesia that accompanies peripheral neuropathy and injury.

  11. N-tert-Butyl-3-hydroxy-5-androstene-17-carboxamide monohydrate

    Jiang-Sheng Li

    2009-07-01

    Full Text Available In the title compound, C24H39NO2·H2O, the A and C rings of the pregnolene derivative sterol adopt chair conformations, with the B ring in a flattened chair conformation and the five-membered ring in an envelope conformation twisted about the C/D ring junction. The N-tert-butylcarboxamide substituent is equatorial. The 3β-hydroxy H atom and one H atom of the water molecule are disordered over two positions with equal occupancies. In the crystal structure, O—H...O hydrogen bonds between the 3β-hydroxy groups of neighbouring molecules form dimers in the bc plane and these dimers are stacked along the a axis by additional O—H...O hydrogen bonds involving the water molecules. The steric effect of the bulky tert-butyl substituent in the carboxamide chain precludes hydrogen-bond formation by the N—H group.

  12. Quinolinium 8-hy-droxy-7-iodo-quinoline-5-sulfonate 0.8-hydrate.

    Smith, Graham

    2012-12-01

    In the crystal structure of the title hydrated quinolinium salt of ferron (8-hy-droxy-7-iodo-quinoline-5-sulfonic acid), C9H7N(+)·C9H5INO4S(-)·0.8H2O, the quinolinium cation is fully disordered over two sites (occupancy factors fixed at 0.63 and 0.37) lying essentially within a common plane and with the ferron anions forming π-π-associated stacks down the b axis [minimum ring centroid separation = 3.462 (6) Å]. The cations and anions are linked into chains extending along c through hy-droxy O-H⋯O and quinolinium N-H⋯O hydrogen bonds to sulfonate O-atom acceptors which are also involved in water O-H⋯O hydrogen-bonding inter-actions along b, giving a two-dimensional network.

  13. Quinolinium 8-hydroxy-7-iodoquinoline-5-sulfonate 0.8-hydrate

    Graham Smith

    2012-12-01

    Full Text Available In the crystal structure of the title hydrated quinolinium salt of ferron (8-hydroxy-7-iodoquinoline-5-sulfonic acid, C9H7N+·C9H5INO4S−·0.8H2O, the quinolinium cation is fully disordered over two sites (occupancy factors fixed at 0.63 and 0.37 lying essentially within a common plane and with the ferron anions forming π–π-associated stacks down the b axis [minimum ring centroid separation = 3.462 (6 Å]. The cations and anions are linked into chains extending along c through hydroxy O—H...O and quinolinium N—H...O hydrogen bonds to sulfonate O-atom acceptors which are also involved in water O—H...O hydrogen-bonding interactions along b, giving a two-dimensional network.

  14. Effect of β-hydroxy-β-methylbutyrate calcium on growth, blood parameters, and carcass qualities of broiler chickens.

    Qiao, X; Zhang, H J; Wu, S G; Yue, H Y; Zuo, J J; Feng, D Y; Qi, G H

    2013-03-01

    Beta-hydroxy-β-methylbutyrate (HMB), the metabolite of leucine, plays an important role in muscle protein metabolism. To investigate the effect of dietary HMB calcium (HMB-Ca) on growth performance, breast muscle development, and serum parameters in broiler chickens, a total of two hundred seventy 1-d-old Arbor Acres male broiler chicks were randomly allotted into 3 dietary treatments supplemented with 0, 0.05%, or 0.1% HMB-Ca during the starter (1 to 21 d) and grower (22 to 42 d) period. The results showed that broilers fed 0.1% HMB-Ca diet had higher ADG during the starter or the whole period, and gain 148 g more BW than the chicks fed the control diet at 42 d of age (P dressing percentage than birds fed the control or 0.05% HMB-Ca diet (P < 0.05). At 42 d of age, 0.1% HMB-Ca increased breast muscle yield than the control and decreased abdominal fat compared with the control or 0.05% HMB-Ca group (P < 0.05). In comparison with the control, feeding 0.1% HMB-Ca increased the triiodothyronine, thyroxine, triiodothyronine/thyroxine ratio and decreased the serum uric acid level at d 21 (P < 0.05). At 42 d of age, serum thyroxine level was elevated in the 0.05% HMB-Ca treatment, and the uric acid concentration was significantly decreased by the 0.1% HMB-Ca-supplemented diet (P < 0.05). Dietary HMB-Ca did not affect the growth hormone or insulin content. This study suggested that dietary supplementation of HMB-Ca improved growth performance, stimulated the breast muscle development, and decreased the abdominal fat deposition in broiler chickens, and the favorable effects were more pronounced in the starter phase. The growth promotion effect of HMB-Ca may be partly related to the increased serum thyroid hormones in broiler chickens.

  15. 25-hydroxy-Vitamin D status: limitations in comparison and clinical interpretation of serum-levels across different assay methods.

    Enko, Dietmar; Fridrich, Leo; Rezanka, Erwin; Stolba, Robert; Ernst, Juliane; Wendler, Iris; Fabian, Daniel; Hauptlorenz, Susanne; Halwachs-Baumann, Gabriele

    2014-01-01

    Background: Over the last decade, clinical interest to evaluate human 25-hydroxy-vitamin D (25[OH]D) serum levels has increased exponentially. In the present study, four chemiluminescence immunoassays (CLIA), one radioimmunoassy (RIA), and one high performance liquid chromatography (HPLC) method were compared and also with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in view of 25(OH)D serum level determination. Methods: For the method comparison, blood samples from 133 consecutive patients were prospectively collected. All participants gave written informed consent for their blood samples to be used in this study. They came to the Department of Nuclear Medicine of the Central Hospital Steyr (Austria) for osteodensidometric measurement as part of their preventive medical check-up. Pearson's correlation coefficients, Bland-Altman plots, and paired t-tests were calculated. Assay-specific reference ranges were considered using blood samples from persons with normal parathormone, calcium, and total-protein values (n = 97). Results: The highest correlation was between the HPLC and the LC-MS/MS method (r = 0.96). The lowest correlation was between the cobas Vitamin D3 assay (Roche) and any of the evaluated assays (r = 0.46 - 0.63). Bland-Altman plots revealed a big negative mean bias in three assays (cobas Vitamin D3 assay [Roche]: -22.8; DiaSorin LIAISON [25[OH]D total CLIA [Diasorin]: -18.4; Diasorin 25[OH]D125 I RIA [Diasorin]: -23.8 [nmol/L]) and a much smaller positive mean bias in the other assays (ClinRep complete 25[OH]D2/D3 HPLC kit [Recipe]: 2.7; ADVIA Centaur Vitamin D total assay [Siemens]: 8.2; IDS total vitamin D assay [Immunodiagnostic Systems]: 12.1 [nmol/L]) compared to the LC-MS/MS method. Meanwhile, the manufacturer has withdrawn the cobas Vitamin D3 assay from the market. Conclusions: Poor antibody specificity with cross-reactivity to other vitamin D metabolites, incomplete extraction of the 25(OH)D analyte from the vitamin D

  16. Identifying diseases-related metabolites using random walk.

    Hu, Yang; Zhao, Tianyi; Zhang, Ningyi; Zang, Tianyi; Zhang, Jun; Cheng, Liang

    2018-04-11

    Metabolites disrupted by abnormal state of human body are deemed as the effect of diseases. In comparison with the cause of diseases like genes, these markers are easier to be captured for the prevention and diagnosis of metabolic diseases. Currently, a large number of metabolic markers of diseases need to be explored, which drive us to do this work. The existing metabolite-disease associations were extracted from Human Metabolome Database (HMDB) using a text mining tool NCBO annotator as priori knowledge. Next we calculated the similarity of a pair-wise metabolites based on the similarity of disease sets of them. Then, all the similarities of metabolite pairs were utilized for constructing a weighted metabolite association network (WMAN). Subsequently, the network was utilized for predicting novel metabolic markers of diseases using random walk. Totally, 604 metabolites and 228 diseases were extracted from HMDB. From 604 metabolites, 453 metabolites are selected to construct the WMAN, where each metabolite is deemed as a node, and the similarity of two metabolites as the weight of the edge linking them. The performance of the network is validated using the leave one out method. As a result, the high area under the receiver operating characteristic curve (AUC) (0.7048) is achieved. The further case studies for identifying novel metabolites of diabetes mellitus were validated in the recent studies. In this paper, we presented a novel method for prioritizing metabolite-disease pairs. The superior performance validates its reliability for exploring novel metabolic markers of diseases.

  17. 40 CFR 159.179 - Metabolites, degradates, contaminants, and impurities.

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Metabolites, degradates, contaminants.../Benefit Information § 159.179 Metabolites, degradates, contaminants, and impurities. (a) Metabolites and... degradation of less than 10 percent in a 30-day period. (b) Contaminants and impurities. The presence in any...

  18. SPE-NMR metabolite sub-profiling of urine

    Jacobs, D.M.; Spiesser, L.; Garnier, M.; Roo, de N.; Dorsten, van F.; Hollebrands, B.; Velzen, van E.; Draijer, R.; Duynhoven, van J.P.M.

    2012-01-01

    NMR-based metabolite profiling of urine is a fast and reproducible method for detection of numerous metabolites with diverse chemical properties. However, signal overlap in the (1)H NMR profiles of human urine may hamper quantification and identification of metabolites. Therefore, a new method has

  19. Are serotonin metabolite levels related to bone mineral density in patients with neuroendocrine tumours?

    Sen Gupta, Piya; Grozinsky-Glasberg, Simona; Drake, William M; Akker, Scott A; Perry, Les; Grossman, Ashley B; Druce, Maralyn R

    2014-02-01

    Bone mineral density (BMD) is influenced by multiple factors. Recent studies have highlighted a possible relationship between serotonin and BMD. Patients with neuroendocrine tumours (NETs) frequently have elevated urinary 5-hydroxy-indoleacetic acid (5-HIAA) levels, a serotonin metabolite. Evaluation of the relationship between 5-HIAA and BMD in patients with NETs may provide insights into the relationship between serotonin and BMD. One-year audit of consecutive patients with NETs within two institutions. Relationships between urinary 5-HIAA and dual X-ray absorptiometry (DEXA)-scan-measured BMD were investigated by group comparisons, correlation and regression. Of 65 patients with NETs, 19 did not participate or were excluded. Of 46 subjects evaluated (48·9% males, 63·8 ± 10·5 years, BMI 26·6 ± 4·4 kg/m(2) ) with 32 gastrointestinal, 9 pancreatic, 3 pulmonary and 2 ovarian NETs, 72·3% had the carcinoid syndrome. Median interval from diagnosis was 4·0 years (IQR 2·0-6·0); 41·3% had osteoporosis and 32·6% osteopaenia (WHO definition). The group with a higher urinary 5-HIAA had a lower hip BMD (total T-score and Z-score), confirmed on individual analysis (Spearman's rank correlation -0·41, P = 0·004; -0·44, P = 0·002, respectively); urinary 5-HIAA was not found to be an independent predictor for BMD on multiple linear regression analysis. These data of patients with NETs with higher serotonin metabolites having a lower BMD at the hip in group and individual comparisons, warrants further evaluation. Urinary 5-HIAA measurement alone cannot be used to predict future BMD. A larger cohort with prospective design including fractures as a clinical outcome will aid these data in determining whether patients with NETs should be subject to targeted osteoporosis prevention. © 2013 John Wiley & Sons Ltd.

  20. Assessment of the oestrogenic activity of the contraceptive progestin levonorgestrel and its non-phenolic metabolites.

    Santillán, R; Pérez-Palacios, G; Reyes, M; Damián-Matsumura, P; García, G A; Grillasca, I; Lemus, A E

    2001-09-14

    Levonorgestrel (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4-gonen-3-one), a potent contraceptive progestin stimulates growth and proliferation of cultured breast cancer cells through a receptor-mediated mechanism, even though levonorgestrel does not bind to the oestrogen receptor (ER). To assess whether the oestrogen-like effects induced by this synthetic progestin are exerted via its metabolic conversion products, we studied the binding affinity of three A-ring levonorgestrel derivatives to the ER and their capability to transactivate an oestrogen-dependent yeast system co-transfected with the human ER gene and oestrogen responsive elements fused to a beta-galactosidase reporter vector. The results demonstrated that the 3beta,5alpha reduced levonorgestrel derivative and to a lesser extent its 3alpha isomer interact with the oestrogen receptor, with a significantly lower relative binding affinity (2.4% and 0.4%, respectively) than that of oestradiol (100%), while levonorgestrel does not. Both levonorgestrel metabolites were able to activate, in a dose-dependent manner, the beta-galactosidase reporter gene in the yeast expression system, an effect that was precluded by a steroidal antioestrogen. The oestrogenic potency of levonorgestrel metabolites was significantly lower (750-fold) than that of oestradiol. Furthermore, high doses of 3beta,5alpha levonorgestrel (2.5 mg/day/6 days) induced an increase of oestrogen-dependent progestin receptor in the anterior pituitary of castrated rats. The overall data offer a plausible explanation for the weak oestrogenic effects induced by high, non-pharmacological doses of levonorgestrel.

  1. Neuropharmacology of 3,4-Methylenedioxypyrovalerone (MDPV), Its Metabolites, and Related Analogs.

    Baumann, Michael H; Bukhari, Mohammad O; Lehner, Kurt R; Anizan, Sebastien; Rice, Kenner C; Concheiro, Marta; Huestis, Marilyn A

    2017-01-01

    3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive component of so-called bath salts products that has caused serious medical consequences in humans. In this chapter, we review the neuropharmacology of MDPV and related analogs, and supplement the discussion with new results from our preclinical experiments. MDPV acts as a potent uptake inhibitor at plasma membrane transporters for dopamine (DAT) and norepinephrine (NET) in nervous tissue. The MDPV formulation in bath salts is a racemic mixture, and the S isomer is much more potent than the R isomer at blocking DAT and producing abuse-related effects. Elevations in brain extracellular dopamine produced by MDPV are likely to underlie its locomotor stimulant and addictive properties. MDPV displays rapid pharmacokinetics when injected into rats (0.5-2.0 mg/kg), with peak plasma concentrations achieved by 10-20 min and declining quickly thereafter. MDPV is metabolized to 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) in vivo, but motor activation produced by the drug is positively correlated with plasma concentrations of parent drug and not its metabolites. 3,4-Catechol-PV is a potent uptake blocker at DAT in vitro but has little activity after administration in vivo. 4-OH-3-MeO-PV is the main MDPV metabolite but is weak at DAT and NET. MDPV analogs, such as α-pyrrolidinovalerophenone (α-PVP), display similar ability to inhibit DAT and increase extracellular dopamine concentrations. Taken together, these findings demonstrate that MDPV and its analogs represent a unique class of transporter inhibitors with a high propensity for abuse and addiction.

  2. Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes

    Philipp Röse

    2015-01-01

    Full Text Available The cobalt(I-catalysed 1,4-hydrovinylation reaction of allyloxytrimethylsilane and allyl alcohol with substituted 1,3-dienes leads to hydroxy-functionalised 1,4-dienes in excellent regio- and diastereoselective fashion. Those 1,4-dienols can be converted into tetrahydrofuran and pyran derivatives under indirect electrochemical conditions generating selenium or iodonium cations. The reactions proceed in good yields and regioselectivities for the formation of single diastereomers.

  3. Determination of polycyclic aromatic hydrocarbons and their oxy-, nitro-, and hydroxy-oxidation products

    Cochran, R.E.; Dongari, N.; Jeong, H.; Beránek, J.; Haddadi, S.; Shipp, J.; Kubátová, A.

    2012-01-01

    Highlights: ► We describe a method for determining PAHs and their oxidation products. ► Solid-phase extraction was used to fractionate PAHs and their oxidation products. ► Gas chromatography–mass spectrometry methods were optimized. ► The developed method was applied to two particulate matter (PM) samples. - Abstract: A sensitive method has been developed for the trace analysis of PAHs and their oxidation products (i.e., nitro-, oxy-, and hydroxy-PAHs) in air particulate matter (PM). Following PM extraction, PAHs, nitro-, oxy-, and hydroxy-PAHs were fractionated using solid phase extraction (SPE) based on their polarities. Gas chromatography–mass spectrometry (GC–MS) conditions were optimized, addressing injection (i.e., splitless time), negative-ion chemical ionization (NICI) parameters, i.e., source temperature and methane flow rate, and MS scanning conditions. Each class of PAH oxidation products was then analyzed using the sample preparation and appropriate ionization conditions (e.g., nitro-PAHs exhibited the greatest sensitivity when analyzed with NICI–MS while hydroxy-PAHs required chemical derivatization prior to GC–MS analysis). The analyses were performed in selected-ion-total-ion (SITI) mode, combining the increased sensitivity of selected-ion monitoring (SIM) with the identification advantages of total-ion current (TIC). The instrumental LODs determined were 6–34 pg for PAHs, 5–36 pg for oxy-PAHs, and 1–21 pg for derivatized hydroxy-PAHs using electron ionization (GC-EI-MS). NICI–MS was found to be a useful tool for confirming the tentative identification of oxy-PAHs. For nitro-PAHs, LODs were 1–10 pg using negative-ion chemical ionization (GC-NICI-MS). The developed method was successfully applied to two types of real-world PM samples, diesel exhaust standard reference material (SRM 2975) and wood smoke PM.

  4. Theoretical investigation of tautomeric equilibrium in ortho-hydroxy phenyl Schiff bases

    Kluba, M.; Lipkowski, P.; Filarowski, A.

    2008-10-01

    This Letter presents a study of the tautomeric equilibrium in ortho-hydroxy phenyl Schiff bases. The influence of substitution and solvent (simulated by the self-consistent reaction field model, SCRF) on the energy barrier of the transition state and on proton transfer is investigated. Dependencies of the HOMA and HOSE aromaticity indices on the molecular, transition state, and proton transfer forms were obtained. The state of chelate chain and phenyl ring aromaticity depending on the tautomeric equilibrium is studied.

  5. Synthesis and Antimicrobial Activity of New Schiff Base Compounds Containing 2-Hydroxy-4-pentadecylbenzaldehyde Moiety

    Gadada Naganagowda

    2014-01-01

    Full Text Available Various novel Schiff base compounds have been synthesized by reaction of 2-hydroxy-4-pentadecylbenzaldehyde with substituted benzothiophene-2-carboxylic acid hydrazide and different substituted aromatic or heterocyclic amines in the presence of acetic acid in ethanol. The structures of all these compounds were confirmed by elemental analysis, IR, 1H-NMR, 13C-NMR, and mass spectral data and have been screened for antibacterial and antifungal activity.

  6. Novel Topical Photodynamic Therapy of Prostate Carcinoma Using Hydroxy-aluminum Phthalocyanine Entrapped in Liposomes

    Sutoris, K.; Rakušan, J.; Karásková, M.; Mattová, J.; Beneš, J.; Nekvasil, Miloš; Ježek, Petr; Zadinová, M.; Poučková, P.; Větvička, D.

    2013-01-01

    Roč. 33, č. 4 (2013), s. 1563-1568 ISSN 0250-7005 R&D Projects: GA MPO(CZ) 2A-1TP1/026; GA MŠk(CZ) OE09026; GA TA ČR(CZ) TA01010781 Institutional support: RVO:67985823 Keywords : PC prostate carcinomas * LNCaP * liposomes * hydroxy-aluminum phthalocyanine * photodynamic therapy Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.872, year: 2013

  7. [The research of 10-hydroxy-2-decenoic acid on experiment hyperlipoidemic rat].

    Xu, Donghui; Mei, Xueting; Xu, Shibo

    2002-05-01

    To study the pharmacological effect of 10-hydroxy-2-decenoic acid(10-HDA) in experiment hyperlipoidemic rat. Preventive and therapeutic effects of 10-HDA were tested on hyperlioidemic rat model induced by high fat food. 10-HDA could reduce the content of TC, TG and beta-lioprotein, raise the content of HDL, which showed 10-HDA had preventive and therapeutic effects on hyperlipoidemic rat. 10-HDA was functional factor of preventive and therapeutic effects of royal jelly on hyperlipoidemia.

  8. The functional property of royal jelly 10-hydroxy-2-decenoic acid as a melanogenesis inhibitor

    Peng, Chi-Chung; Sun, Hui-Tzu; Lin, I-Ping; Kuo, Ping-Chung; Li, Jen-Chieh

    2017-01-01

    Background It has been reported that royal jelly would reduce melanin synthesis and inhibit the expression of melanogensis related proteins and genes. In this study, we evaluate the anti-melanogenic and depigmenting activity of 10-hydroxy-2-decenoic acid (10-HDA) from royal jelly of Apis mellifera. Methods In this study, we assesses the 10-HDA whitening activity in comparison with the changes in the intracellular tyrosinase activity, melanin content and melanin production related protein levl...

  9. Effect of hydroxy (HHO) gas addition on gasoline engine performance and emiss

    Mohamed M. EL-Kassaby; Yehia A. Eldrainy; Mohamed E. Khidr; Kareem I. Khidr

    2016-01-01

    The objective of this work was to construct a simple innovative HHO generation system and evaluate the effect of hydroxyl gas HHO addition, as an engine performance improver, into gasoline fuel on engine performance and emissions. HHO cell was designed, fabricated and optimized for maximum HHO gas productivity per input power. The optimized parameters were the number of neutral plates, distance between them and type and quantity of two catalysts of Potassium Hydroxide (KOH) and sodium hydroxi...

  10. Characterisation of equine satellite cell transcriptomic profile response to ?-hydroxy-?-methylbutyrate (HMB)

    Szcze?niak, Katarzyna A.; Ciecierska, Anna; Ostaszewski, Piotr; Sadkowski, Tomasz

    2016-01-01

    ?-Hydroxy-?-methylbutyrate (HMB) is a popular ergogenic aid used by human athletes and as a supplement to sport horses, because of its ability to aid muscle recovery, improve performance and body composition. Recent findings suggest that HMB may stimulate satellite cells and affect expressions of genes regulating skeletal muscle cell growth. Despite the scientific data showing benefits of HMB supplementation in horses, no previous study has explained the mechanism of action of HMB in this spe...

  11. Conversion of beta-methylbutyric acid to beta-hydroxy-beta-methylbutyric acid by Galactomyces reessii.

    Lee, I Y; Nissen, S L; Rosazza, J P

    1997-01-01

    beta-Hydroxy-beta-methylbutyric acid (HMB) has been shown to increase strength and lean mass gains in humans undergoing resistance-exercise training. HMB is currently marketed as a calcium salt of HMB, and thus, environmentally sound and inexpensive methods of manufacture are being sought. This study investigates the microbial conversion of beta-methylbutyric acid (MBA) to HMB by cultures of Galactomyces reessii. Optimal concentrations of MBA were in the range of 5 to 20 g/liter for HMB produ...

  12. International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)

    Wilson, Jacob M; Fitschen, Peter J; Campbell, Bill; Wilson, Gabriel J; Zanchi, Nelo; Taylor, Lem; Wilborn, Colin; Kalman, Douglas S; Stout, Jeffrey R; Hoffman, Jay R; Ziegenfuss, Tim N; Lopez, Hector L; Kreider, Richard B; Smith-Ryan, Abbie E; Antonio, Jose

    2013-01-01

    Abstract Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB) as a nutritional supplement. The ISSN has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. 2. If consuming HMB, an athlete will benefit from consuming the supplement in close pro...

  13. Polynuclear Iron-Oxo/Hydroxy Complexes of Ketoacidoximate Ligands: Synthesis, Structures and Conversion to Ferric Oxide

    Davaasuren, Bambar; Khanderi, Jayaprakash; Rothenberger, Alexander

    2017-01-01

    The polynuclear iron-oxo/hydroxy complexes containing ketoacidoximate ligands described in this report are [Fe3(μ3-O){O2C-C(C6H5)=NOCH3}6(py)3] (1) (py=pyridine), [Fe2(μ3-O){O2C-C(CH2-C6H5)=NO}2(H2O)(CH3OH)]2 (2) and [{Fe(μ2-OH)(O2C-C(CH3)=NO

  14. Thermochemical and Theoretical Studies of 2-Hydroxyquinoxaline, 2,3-Dihydroxyquinoxaline, and 2-Hydroxy-3-methylquinoxaline

    Ribeiro da Silva, M. A. V.; Matos, M. A. R.; Rio, Carolina; Miranda, M. S.; Morais, V. M. F.

    2000-01-01

    The standard (p° = 0.1 MPa) molar enthalpies of formation for crystalline 2-hydroxyquinoxaline, 2,3-dihydroxyquinoxaline, and 2-hydroxy-3-methylquinoxaline were derived from the standard molar enthalpies of combustion, in oxygen, at T = 298.15 K, measured by static bomb combustion calorimetry. The standard molar enthalpies of sublimation, at T = 298.15 K, of the three compounds were measured by Calvet microcalorimetry. The derived standard molar enthalpies of formation in the gaseous phase ar...

  15. Preparation of 2H- and 13C-labelled precursors of 2-hydroxy-1, 3-butadiene

    Turecek, F.

    1987-01-01

    2-exo-Vinylbicyclo[2.2.1]hept-5-en-2-ols, specifically labelled with 2 H at C-3 and in the vinyl group were prepared from bicyclo[2.2.1]hept-5-en-2-one in several steps. [4- 13 C]oct-1-en-3-one was prepared in five steps from 13 CO 2 . These compounds serve as precursors for the preparation of specifically labelled neutral and ionized 2-hydroxy-1, 3-butadienes. (author)

  16. Bio-Catalytic Structural Transformation of Anti-cancer Steroid, Drostanolone Enanthate with Cephalosporium aphidicola and Fusarium lini, and Cytotoxic Potential Evaluation of Its Metabolites against Certain Cancer Cell Lines

    M. Iqbal Choudhary

    2017-12-01

    Full Text Available In search of selective and effective anti-cancer agents, eight metabolites of anti-cancer steroid, drostanolone enanthate (1, were synthesized via microbial biotransformation. Enzymes such as reductase, oxidase, dehydrogenase, and hydrolase from Cephalosporium aphidicola, and Fusarium lini were likely involved in the biotransformation of 1 into new metabolites at pH 7.0 and 26°C, yielding five new metabolites, 2α-methyl-3α,14α,17β-trihydroxy-5α-androstane (2, 2α-methyl-7α-hydroxy-5α-androstan-3,17-dione (3, 2-methylandrosta-11α-hydroxy-1, 4-diene-3,17-dione (6, 2-methylandrosta-14α-hydroxy-1,4-diene-3,17-dione (7, and 2-methyl-5α-androsta-7α-hydroxy-1-ene-3,17-dione (8, along with three known metabolites, 2α-methyl-3α,17β-dihydroxy-5α-androstane (4, 2-methylandrosta-1, 4-diene-3,17-dione (5, and 2α-methyl-5α-androsta-17β-hydroxy-3-one (9, on the basis of NMR, and HREI-MS data, and single-crystal X-ray diffraction techniques. Interestingly, C. aphidicola and F. lini were able to catalyze hydroxylation only at alpha positions of 1. Compounds 1–9 showed a varying degree of cytotoxicity against HeLa (human cervical carcinoma, PC3 (human prostate carcinoma, H460 (human lung cancer, and HCT116 (human colon cancer cancer cell lines. Interestingly, metabolites 4 (IC50 = 49.5 ± 2.2 μM, 5 (IC50 = 39.8 ± 1.5 μM, 6 (IC50 = 40.7 ± 0.9 μM, 7 (IC50 = 43.9 ± 2.4 μM, 8 (IC50 = 19.6 ± 1.4 μM, and 9 (IC50 = 25.1 ± 1.6 μM were found to be more active against HeLa cancer cell line than the substrate 1 (IC50 = 54.7 ± 1.6 μM. Similarly, metabolites 2 (IC50 = 84.6 ± 6.4 μM, 3 (IC50 = 68.1 ± 1.2 μM, 4 (IC50 = 60.4 ± 0.9 μM, 5 (IC50 = 84.0 ± 3.1 μM, 6 (IC50 = 58.4 ± 1.6 μM, 7 (IC50 = 59.1 ± 2.6 μM, 8 (IC50 = 51.8 ± 3.4 μM, and 9 (IC50 = 57.8 ± 3.2 μM were identified as more active against PC-3 cancer cell line than the substrate 1 (IC50 = 96.2 ± 3.0 μM. Metabolite 9 (IC50 = 2.8 ± 0.2 μM also showed potent anticancer

  17. Conformational analysis of 2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) by NMR and molecular modeling

    Ferreira, Marcelle de S.; Figueroa-Villar, Jose D., E-mail: jdfv2009@gmail.com [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Dept. de Quimica. Grupo de Medicina Quimica

    2014-05-15

    2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-ones) with para and ortho-R groups on the benzene ring were prepared and studied by nuclear magnetic resonance (NMR) and molecular modeling to determine their conformational exchanges. Experimental and calculated results indicated conformational interconversions in these compounds by rotation of benzene ring and slow movement of dimedone rings, leading to intramolecular hydrogen bond length variation. The presence of one R group at the ortho position on the benzene ring modifies conformational exchange, leading to disappearance of one intramolecular hydrogen bond and superposition of diverse NMR signals. The correlation of σ{sub p} values with chemical shifts, angles and atomic charges confirms that para-R groups electronic properties are involved in conformational exchange and chemical shift variance. These results will be used to study the interaction of these compounds with bio-molecules and their use as starting materials for design and synthesis of new bioactive agents. (author)

  18. [3-hydroxy-3-methylglutaric aciduria and recurrent Reye-like syndrome].

    Eirís, J; Ribes, A; Fernández-Prieto, R; Rodríguez-García, J; Rodríguez-Segade, S; Castro-Gago, M

    1998-06-01

    3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is an inborn error of ketogenesis and Leucine catabolism. HMG-CoA lyase catalyses the final step in leucine degradation, converting HMG-CoA to acetyl-CoA and acetoacetic acid. Clinical manifestations include hepatomegaly, lethargy or coma and apnoea. Biochemically there is a characteristic absence of ketosis with hypoglycemia, acidosis, hipertransaminasemia and variable hyperammoniemia. The urinary organic acid profile includes elevated concentrations of 3-hydroxy-3-isovaleric, 3-hydroxy-3-methylglutaric, 3-methylglutaconic and 3-methylglutaric acids. Here, we report the case of a 17-year-old girl who presented in both ten months and five years of age a clinical picture characterized by lethargy leading to apnea and coma, hepatomegaly, hypoglycemia, metabolic acidosis, hyperammoniemia, elevated serum transaminases and absence of ketonuria. Diagnostic of Reye syndrome was suggested by hystopathologic finding of hepatic steatosis and clinical and biochemical data. As of 11 years old, laboratory investigations revealed carnitine deficiency and characteristic aciduria. Confirmatory enzyme diagnosis revealing deficiency of HMG-CoA lyase was made in cultured fibroblasts. Our report constitutes an example of the presentation of HMG-CoA lyase deficiency as recurrent Reye-like syndrome.

  19. Facile Synthesis of 3-Aryl-3-hydroxy-2-oxindoles from 2-Arylindoles

    Moon, Hye Ran; Roh, Hwa Jung; Kim, Jae Nyoung [Chonnam National University, Gwangju (Korea, Republic of); Lee, Sangku [Korea Research Institute of Bioscience and Biotechnology, Chungju (Korea, Republic of)

    2016-07-15

    An efficient synthetic route of 3-aryl-3-hydroxy-2-oxindoles has been developed from 2-arylindoles. The procedure provides a brand-new synthetic method of 3-aryl-3-hydroxy-2-oxindoles from readily available starting materials in high yields. We reported an aerobic transition metal-free synthesis of 2,3-diarylindoles via an oxidative nucleophilic substitution of hydrogen (ONSH) pathway from 2-arylindoles and nitroarenes. As an example, the reaction of 2-phenylindole (1a) and 1,3-dinitrobenzene in DMSO in the presence of Cs{sub 2}CO{sub 3} under O{sub 2} balloon atmosphere afforded 2,3-diarylindole in good yield (78%) in short time, as shown in Scheme 1. During the study, we found the formation of 3-phenyl-3-hydroxy-2-oxindole (2a), albeit in moderate yield (41%), under the same reaction condition for a long time (8 h) without 1,3-dinitrobenzene. Based on the experimental results, the reaction mechanism for the conversion of 1a to 2a is proposed, as shown in Scheme 2. The indole anion I was converted to 3-hydroxyindolenine intermediate III via the hydroperoxide intermediate II. Subsequently, III was changed to an epoxide intermediate IV under basic condition, and a following semipinacol type rearrangement of IV would produce 3-phenyloxindole VI. A subsequent aerobic oxidation of VI would produce 2a.

  20. Field evaluation of 3-hydroxy-2-hexanone and ethanol as attractants for the cerambycid beetle pest of vineyards, Xylotrechus arvicola.

    Rodríguez-González, Álvaro; Sánchez-Maíllo, Esteban; Peláez, Horacio J; González-Núñez, Manuel; Hall, David R; Casquero, Pedro A

    2017-08-01

    The beetle Xylotrechus arvicola (Coleoptera: Cerambycidae) is a serious pest of vineyards in the Iberian Peninsula. In previous work, the male beetles, but not females, were shown to produce (R)-3-hydroxy-2-hexanone, and female beetles were attracted to this compound in a laboratory bioassay. In this study, release rates of 3-hydroxy-2-hexanone from different dispensers were measured in the laboratory, and the attractiveness of these to X. arvicola adults was determined in trapping tests in three traditional wine-growing regions in Spain. As a result of laboratory experiments, for field experiments 3-hydroxy-2-hexanone was formulated as 100 μL in a polyethylene sachet (50 mm × 50 mm × 250 µm), and ethanol was formulated as 1 mL in a polyethylene press-seal bag (76 mm × 57 mm ×50 µm). Field catches were similar at all three study sites. Catches in traps baited with 3-hydroxy-2-hexanone alone were not significantly different from those in unbaited control traps, but catches in traps baited with 3-hydroxy-2-hexanone and ethanol in separate sachets, with 3-hydroxy-2-hexanone and ethanol in the same sachet or with ethanol alone were significantly greater than those in control traps. These results confirm that the beetles are attracted to ethanol, and the addition of 3-hydroxy-2-hexanone does not seem to make any difference. Attraction of females for the male-produced compound (R)-3-hydroxy-2-hexanone has been observed in laboratory but not in field experiments. Traps baited with ethanol are highly attractive to both sexes of adults of X. arvicola, and these can be used for improved monitoring of the adult emergence and for population control by mass trapping. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  1. High-intensity interval training and β-hydroxy-β-methylbutyric free acid improves aerobic power and metabolic thresholds

    Robinson, Edward H; Stout, Jeffrey R; Miramonti, Amelia A; Fukuda, David H; Wang, Ran; Townsend, Jeremy R; Mangine, Gerald T; Fragala, Maren S; Hoffman, Jay R

    2014-01-01

    Background Previous research combining Calcium β-hydroxy-β-methylbutyrate (CaHMB) and running high-intensity interval training (HIIT) have shown positive effects on aerobic performance measures. The purpose of this study was to examine the effect of β-hydroxy-β-methylbutyric free acid (HMBFA) and cycle ergometry HIIT on maximal oxygen consumption (VO2peak), ventilatory threshold (VT), respiratory compensation point (RCP) and time to exhaustion (Tmax) in college-aged men and women. Methods Thi...

  2. Carbamoyl anion-initiated cascade reaction for stereoselective synthesis of substituted α-hydroxy-β-amino amides.

    Lin, Chao-Yang; Ma, Peng-Ju; Sun, Zhao; Lu, Chong-Dao; Xu, Yan-Jun

    2016-01-18

    A carbamoyl anion-initiated cascade reaction with acylsilanes and imines has been used to rapidly construct substituted α-hydroxy-β-amino amides. The Brook rearrangement-mediated cascade allows the formation of two C-C bonds and one O-Si bond in a single pot. Using this approach, a range of α-aryl α-hydroxy-β-amino amides has been synthesized in high yields with excellent diastereoselectivities.

  3. Anti-inflammatory effects of secondary metabolites isolated from the marine-derived fungal strain Penicillium sp. SF-5629.

    Ngan, Nguyen Thi Thanh; Quang, Tran Hong; Kim, Kwan-Woo; Kim, Hye Jin; Sohn, Jae Hak; Kang, Dae Gill; Lee, Ho Sub; Kim, Youn-Chul; Oh, Hyuncheol

    2017-03-01

    After the chemical investigation of the ethyl acetate extract of the marine-derived fungal strain Penicillium sp. SF-5629, the isolation and structural elucidation of eight secondary metabolites, including (3R,4S)-6,8-dihydroxy-3,4,7-trimethylisocoumarin (1), (3S,4S)-sclerotinin A (2), penicitrinone A (3), citrinin H1 (4), emodin (5), ω-hydroxyemodin (6), 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (7), and 3,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (8) were carried out. Evaluation of the anti-inflammatory activity of these metabolites showed that 4 inhibited nitric oxide and prostaglandin E2 production in lipopolysaccharide-stimulated BV2 microglia, with IC 50 values of 8.1 ± 1.9 and 8.0 ± 2.8 μM, respectively. The inhibitory function of 4 was confirmed based on decreases in inducible nitric oxide synthesis and cyclooxygenase-2 gene expression. In addition, 4 was found to suppress the phosphorylation of inhibitor kappa B-α, interrupt the nuclear translocation of nuclear factor kappa B, and decrease the activation of p38 mitogen-activated protein kinase.

  4. Structure, function and carcinogenicity of metabolites of methylated and non-methylated polycyclic aromatic hydrocarbons: a comprehensive review.

    Flesher, James W; Lehner, Andreas F

    2016-01-01

    The Unified Theory of PAH Carcinogenicity accommodates the activities of methylated and non-methylated polycyclic aromatic hydrocarbons (PAHs) and states that substitution of methyl groups on meso-methyl substituted PAHs with hydroxy, acetoxy, chloride, bromide or sulfuric acid ester groups imparts potent cancer producing properties. It incorporates specific predictions from past researchers on the mechanism of carcinogenesis by methyl-substituted hydrocarbons, including (1) requirement for metabolism to an ArCH2X type structure where X is a good leaving group and (2) biological substitution of a meso-methyl group at the most reactive center in non-methylated hydrocarbons. The Theory incorporates strong inferences of Fieser: (1) The mechanism of carcinogenesis involves a specific metabolic substitution of a hydrocarbon at its most reactive center and (2) Metabolic elimination of a carcinogen is a detoxifying process competitive with that of carcinogenesis and occurring by a different mechanism. According to this outlook, chemical or biochemical substitution of a methyl group at the reactive meso-position of non-methylated hydrocarbons is the first step in the mechanism of carcinogenesis for most, if not all, PAHs and the most potent metabolites of PAHs are to be found among the meso methyl-substituted hydrocarbons. Some PAHs and their known or potential metabolites and closely related compounds have been tested in rats for production of sarcomas at the site of subcutaneous injection and the results strongly support the specific predictions of the Unified Theory.

  5. Identification of drug metabolites in human plasma or serum integrating metabolite prediction, LC-HRMS and untargeted data processing

    Jacobs, P.L.; Ridder, L.; Ruijken, M.; Rosing, H.; Jager, N.G.L.; Beijnen, J.H.; Bas, R.R.; Dongen, W.D. van

    2013-01-01

    Background: Comprehensive identification of human drug metabolites in first-in-man studies is crucial to avoid delays in later stages of drug development. We developed an efficient workflow for systematic identification of human metabolites in plasma or serum that combines metabolite prediction,

  6. Docking Studies and Anti-inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids

    Ivan O. Juranic

    2008-03-01

    Full Text Available The article describes a two-step synthesis of diastereomeric 3-hydroxy-2-methyl-3-(4-biphenylylbutanoic acids. In the first step an intermediate α-bromo propanoicacid 1-ethoxyethyl ester was synthesized. The second step is a new modified Reformatskyreaction in presence of Zn in tetrahydrofuran (THF at –5 to 10 °C between the previouslysynthesized intermediate and 4-acetylbiphenyl. Synthesis of the other studied β-hydroxy-β-arylpropanoic acids has already been reported. These β-hydroxy-β-arylpropanoic acidsbelong to the arylpropanoic acid class of compounds, structurally similar to the NSAIDssuch as ibuprofen. The anti-inflammatory activity and gastric tolerability of thesynthesized compounds were evaluated. Molecular docking experiments were carried outto identify potential COX-2 inhibitors among the β-hydroxy-β-aryl-alkanoic acids class.The results indicate that all compounds possess significant anti-inflammatory activity afteroral administration and that the compounds 2-(9-(9-hydroxy-fluorenyl-2-methylpropanoic acid (5 and 3-hydroxy-3,3-diphenyl-propanoic acid (3 possess thestrongest anti-inflammatory activity, comparable to that of ibuprofen, a standard NSAID,and that none of tested substances or ibuprofen produced any significant gastric lesions.

  7. Effect of temperature and hydroxy-Al interlayers on Cs selectivity and fixation in river suspensions and soils. Final report

    Zelazny, L.W.; Martens, D.C.; El-Prince, A.M.; Rich, C.I.

    1978-01-01

    The adsorption of 137/sub Cs/ by sediments from the Savannah River Plant follows a theoretically expected linear relationship between ln Kd and l/T where kd and T are the equilibrium distribution coefficient and the temperature in kelvins, respectively. The slope of these plots decreases after removal of hydroxy Al interlayers. Hydroxy Al interlayers thus make Cs + adsorption more temperature dependent. The phenomenon is explained by considering hydroxy Al interlayers as a source of hydronium ions H 3 O + , which compete with Cs for exchange positions in wedge zones. An increase in temperature favors an increase in H 3 O ions, which in turn favors less adsorption of Cs + . Aside from their thermal effect the positively charged hydroxy aluminum polymeric groups drastically decrease the cation exchange capacity and, consequently, the adsorption of cesium. The adsorption of trace radioactive cesium by sediments from the Savannah River Plant area also follows a theoretically expected linear relationship between ln Kd and the pH of the equilibrium solution. Theoretically, the slope of these plots is proportional to the fraction of surface area occupied by pH dependent charges. Experimentally, the slope becomes zero after removal of hydroxy Al interlayers. Hydroxy Al interlayers are thus the main source for the pH dependent charges, making Cs + adsorption pH dependent also

  8. Concentrations of isoflavones and their metabolites in the blood of pregnant and non-pregnant heifers fed soy bean.

    Woclawek-Potocka, Izabela; Piskula, Mariusz Krzysztof; Bah, Mamadou; Siemieniuch, Marta Jolanta; Korzekwa, Anna; Brzezicka, Edyta; Skarzynski, Dariusz Jan

    2008-10-01

    The present study compared the changes in isoflavones (daidzein and genistein) and their metabolite (equol and para-ethyl-phenol) concentrations in the blood plasma of cyclic and pregnant heifers after feeding with soy bean. Twelve healthy heifers were divided into three groups: cyclic heifers (days 8-12 of the estrous cycle; control group; n=4), an early pregnancy group (2 months pregnant; n=4) and a late pregnancy group (8 months pregnant; n=4). All heifers were fed a single dose of 2.5 kg of soy bean and then blood samples were taken from the jugular vein for 8 h at predetermined intervals. The concentrations of soy bean-derived isoflavones and their active metabolites were measured in the blood plasma on an HPLC system. In the blood plasma of the early- and late-pregnant heifers, we found lower concentrations and time-dependent decreases in daidzein and genistein in comparison to cyclic heifers (P0.05). In conclusion, physiological status (cyclicity or pregnancy) of the females influenced the concentrations of isoflavone metabolites in the blood plasma of the heifers. The stage of pregnancy affects isoflavone absorption, biotransformation and metabolism differently and results in higher concentrations of active metabolites of isoflavones during early pregnancy in comparison to their lower concentrations during late pregnancy. Therefore, we surmise that cows are more sensitive to active isoflavone metabolite actions during early pregnancy than cyclic heifers and heifers in late pregnancy.

  9. The neurotoxicity of pyridinium metabolites of haloperidol

    Agnieszka Górska

    2015-10-01

    Full Text Available Haloperydol is a butyrophenone, typical neuroleptic agent characterized as a high antipsychotics effects in the treatment of schizophrenia and in palliative care to alleviation many syndromes, such as naursea, vomiting and delirium. Clinical problems occurs during and after administration of the drug are side effects, particularly extrapyrramidal symptoms (EPS. The neurotoxicity of haloperydol may be initiated by the cationic metabolites of haloperydol, HPP+, RHPP+, formed by oxidation and reduction pathways. These metabolites are transported by human organic cation transporters (hOCT to several brain structures for exapmle, in substantia nigra, striatum, caudate nucleus, hippocampus. After reaching the dopaminergic neurons inhibits mitochondrial complex I, evidence for free radical involvement, thus leading to neurodegeneration.

  10. Vitamin D metabolites in human milk

    Weisman, Y.; Bawnik, J.C.; Eisenberg, Z.; Spirer, Z.

    1982-01-01

    The concentrations of unconjugated 25-OHD, 24, 25(OH)2D, and 1,25(OH)2D were measured in human milk by competitive protein-binding radioassays following successive preparative Sephadex LH-20 chromatography and HPLC. The mean (+/- SE) concentration of 25-OHD was 0.37 +/- 0.03 ng/ml, of 24,25(OH)2D was 24.8 +/- 1.9 pg/ml, and of 1,25(OH)2D was 2.2 +/-0.1 pg/ml. The concentration of 25-OHD3 in milk as determined by HPLC and UV detection at 254 nm was 0.27 +/- 0.08 ng/ml. The milk concentrations of vitamin D metabolites did not correlate with the maternal serum 25-OHD levels. The total amounts of unconjugated vitamin D metabolites correspond to the known low bioassayable vitamin D antirachitic activity in human milk

  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. 7-N-Acetylcysteine-pyrrole conjugate-A potent DNA reactive metabolite of pyrrolizidine alkaloids.

    He, Xiaobo; Ma, Liang; Xia, Qingsu; Fu, Peter P

    2016-10-01

    Plants containing pyrrolizidine alkaloids (PAs) are widespread throughout the world and are the most common poisonous plants affecting livestock, wildlife, and humans. PAs require metabolic activation to form reactive dehydropyrrolizidine alkaloids (dehydro-PAs) that are capable of alkylating cellular DNA and proteins, form (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA and DHP-protein adducts, and lead to cytotoxicity, genotoxicity, and tumorigenicity. In this study, we determined that the metabolism of riddelliine and monocrotaline by human and rat liver microsomes in the presence of N-acetylcysteine both produced 7-N-acetylcysteine-DHP (7-NAC-DHP) and DHP. Reactions of 7-NAC-DHP with 2'-deoxyguanosine (dG), 2'-deoxyadenosine (dA), and calf thymus DNA in aqueous solution followed by enzymatic hydrolysis yielded DHP-dG and/or DHP-dA adducts. These results indicate that 7-NAC-DHP is a reactive metabolite that can lead to DNA adduct formation. Copyright © 2016. Published by Elsevier B.V.

  13. 7-N-Acetylcysteine-pyrrole conjugate—A potent DNA reactive metabolite of pyrrolizidine alkaloids

    Xiaobo He

    2016-10-01

    Full Text Available Plants containing pyrrolizidine alkaloids (PAs are widespread throughout the world and are the most common poisonous plants affecting livestock, wildlife, and humans. PAs require metabolic activation to form reactive dehydropyrrolizidine alkaloids (dehydro-PAs that are capable of alkylating cellular DNA and proteins, form (±-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP-DNA and DHP-protein adducts, and lead to cytotoxicity, genotoxicity, and tumorigenicity. In this study, we determined that the metabolism of riddelliine and monocrotaline by human and rat liver microsomes in the presence of N-acetylcysteine both produced 7-N-acetylcysteine-DHP (7-NAC-DHP and DHP. Reactions of 7-NAC-DHP with 2′-deoxyguanosine (dG, 2′-deoxyadenosine (dA, and calf thymus DNA in aqueous solution followed by enzymatic hydrolysis yielded DHP-dG and/or DHP-dA adducts. These results indicate that 7-NAC-DHP is a reactive metabolite that can lead to DNA adduct formation.

  14. Role of metabolites of cyclophosphamide in cardiotoxicity

    Kurauchi, Koichiro; Nishikawa, Takuro; Miyahara, Emiko; Okamoto, Yasuhiro; Kawano, Yoshifumi

    2017-01-01

    Background The dose-limiting toxic effect of cyclophosphamide (CY) is cardiotoxicity. The pathogenesis of myocardial damage is poorly understood, and there is no established means of prevention. In previous studies, we suggested that for CY-induced cardiotoxicity, whereas acrolein is the key toxic metabolite, carboxyethylphosphoramide mustard (CEPM) is protective. We sought to verify that acrolein is the main cause of cardiotoxicity and to investigate whether aldehyde dehydrogenase (ALDH), wh...

  15. Fungal Anticancer Metabolites: Synthesis Towards Drug Discovery.

    Barbero, Margherita; Artuso, Emma; Prandi, Cristina

    2018-01-01

    Fungi are a well-known and valuable source of compounds of therapeutic relevance, in particular of novel anticancer compounds. Although seldom obtainable through isolation from the natural source, the total organic synthesis still remains one of the most efficient alternatives to resupply them. Furthermore, natural product total synthesis is a valuable tool not only for discovery of new complex biologically active compounds but also for the development of innovative methodologies in enantioselective organic synthesis. We undertook an in-depth literature searching by using chemical bibliographic databases (SciFinder, Reaxys) in order to have a comprehensive insight into the wide research field. The literature has been then screened, refining the obtained results by subject terms focused on both biological activity and innovative synthetic procedures. The literature on fungal metabolites has been recently reviewed and these publications have been used as a base from which we consider the synthetic feasibility of the most promising compounds, in terms of anticancer properties and drug development. In this paper, compounds are classified according to their chemical structure. This review summarizes the anticancer potential of fungal metabolites, highlighting the role of total synthesis outlining the feasibility of innovative synthetic procedures that facilitate the development of fungal metabolites into drugs that may become a real future perspective. To our knowledge, this review is the first effort to deal with the total synthesis of these active fungi metabolites and demonstrates that total chemical synthesis is a fruitful means of yielding fungal derivatives as aided by recent technological and innovative advancements. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. New antitumour fungal metabolites from Alternaria porri.

    Phuwapraisirisan, Preecha; Rangsan, Jakaphan; Siripong, Pongpan; Tip-Pyang, Santi

    2009-01-01

    Chemical investigation of the onion pathogenic fungus Alternaria porri resulted in the isolation of two new phthalides named zinnimide (2) and deprenylzinnimide (8), along with a new bianthraquinone, alterporriol F (10). The structures of the new metabolites were characterised by spectroscopic analysis and chemical degradation. Of the new compounds isolated, alterporriol F was highly cytotoxic towards HeLa and KB cells, with IC(50) values of 6.5 and 7.0 microg mL(-1).

  17. The evaluation of 25-hydroxy vitamin D, calcium, phosphate and alkaline phosphatase levels in epileptic children under antiepileptic medication

    Keyhani doost Z

    2011-01-01

    Full Text Available "n 800x600 Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 st1":*{behavior:url(#ieooui } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} Background: Epilepsy is a common disease in the pediatric neurology. There are frequent anti-epileptic drugs which are used in management of epilepsy. Anti-epileptic drugs may have some complications on bone and vitamin-D metabolism. In this study we aimed to evaluate vitamin-D metabolism in epileptic children."n"nMethods: The study was a prospective and cross sectional one. A total 89 epileptic children who were taking anti-epileptic drugs for longer than six months with no underlying disorder in Imam Khomeini and Bahrami Hospitals in Tehran, Iran were enrolled in our study"n"nResults: Forty nine boys and 40 girls were enrolled in this study; mean age of the patients was 7.8±2.1 years. Mean duration of anti-epileptic drug therapy was 2.3 years (SD=0.4, 70 of patients were under monotherapy and 19 were under polytherapy. None of the patients had signs of rickets. Serum calcium and phosphor levels were within normal ranges. Serum alkaline phosphates levels were increased more than two times in 43%. 42% had vitamin-D deficiency (25-OH Vit D<10 ng/ml and another 33% had vitamin-D insufficiency (10<25-oh Vit D<20 ng/ml. 29 patients (32% were taking prophylactic supplemental Vit D (200-400 IU/day. There was significant difference between patients taking supplemental vitamin-D as prophylaxis and patients who did not (p=0.04. There was no significant difference in vitamin-D levels between patients according to age, gender or different drugs."n"nConclusion: Periodic

  18. Synthesis of 7-hydroxy-4'-methoxyflavanone and 7-hydroxy-4'-methoxyflavone as a candidate anticancer against cervical (HeLa) cancer cell and colon (WiDr) cancer cell by in vitro

    Matsjeh, Sabirin; Anwar, Chairil; Solikhah, Eti Nurwening; Farah, Harra Ismi; Nurfitria, Kurnia

    2017-03-01

    The compound 7-hydroxy-4'-methoxyflavanone and 7-hydroxy-4'-methoxyflavone have been synthesized through cyclization reaction of 2 ', 4'-dihydroxy-4-methoxychalcone (1,3-diphenyl-2-propene-1-one). The 2 ', 4'-dihydroxy-4-methoxychalcone were synthesized through Claisen-Schmidt condensation from 2,4-dihydroxyacetophenone and 4-methoxybenzaldehyde (anisaldehyde) in aqueous KOH as a catalyst in ethanol. The 7-hydroxy-4'-methoxyflavanone has been synthesized through cyclization reaction of 2 ', 4'-dihydroxy-4-methoxychalcone by Oxa-Michael addition reaction with sulfuric acid as a catalyst in ethanol. The 7-hydroxy-4'-methoxyflavone has been synthesized through oxidative cyclization reaction of 2 ', 4'-dihydroxy-4-methoxychalcone using I2 in DMSO as a catalyst with a mole ratio (1: 1) mol. All these producets were characterized by FT-IR, GC-MS, and 1H-NMR and 13C-NMR spectrometer. Both of these compounds were tested citotoxycity activity as an anticancer against cervical and colon cancer cells (HeLa and WiDr cell lines) using MTT assay in vitro. Dose series given test solution concentration on HeLa and WiDr cells starting from 0,78; 1,56; 3,12; 6,25; 12,50; 25; 50 and 100 µg/mL with a long incubation treatment for 24 hours. The results study showed that the 7-hydroxy-4'-methoxyflavanone as bright yellow crystals with a melting point 172-174 ° C and a yield of 56.67% and the 7-hydroxy-4'-methoxyflavone as bright yellow crystals with a yield of 88, 31%, and a melting point of 263-265 ° C. The test results cytotoxic 7-hydroxy-4-methoxyflavone showed active against HeLa cells with IC50 value of 25.73 µg/mL and was quite active in the WiDr cells with IC50 value of 83.75 µg/mL. The result of the activity of 7-hydroxy-4-methoxyflavanone show active cytotoxic activity against HeLa and WiDr cell growth with IC50 value of 40.13 µg/mL and 37.85 µg/mL. IC50 value indicated that 7-hydroxy-4'-methoxyflavone and 7-hydroxy-4'-methoxyflavanone potential as inhibitors in HeLa and

  19. Profiling ABA metabolites in Nicotiana tabacum L. leaves by ultra-performance liquid chromatography-electrospray tandem mass spectrometry.

    Turecková, Veronika; Novák, Ondrej; Strnad, Miroslav

    2009-11-15

    We have developed a simple method for extracting and purifying (+)-abscisic acid (ABA) and eight ABA metabolites--phaseic acid (PA), dihydrophaseic acid (DPA), neophaseic acid (neoPA), ABA-glucose ester (ABAGE), 7'-hydroxy-ABA (7'-OH-ABA), 9'-hydroxy-ABA (9'-OH-ABA), ABAaldehyde, and ABAalcohol--before analysis by a novel technique for these substances, ultra-performance liquid chromatography-electrospray ionisation tandem mass spectrometry (UPLC-ESI-MS/MS). The procedure includes addition of deuterium-labelled standards, extraction with methanol-water-acetic acid (10:89:1, v/v), simple purification by Oasis((R)) HLB cartridges, rapid chromatographic separation by UPLC, and sensitive, accurate quantification by MS/MS in multiple reaction monitoring modes. The detection limits of the technique ranged between 0.1 and 1 pmol for ABAGE and ABA acids in negative ion mode, and 0.01-0.50 pmol for ABAGE, ABAaldehyde, ABAalcohol and the methylated acids in positive ion mode. The fast liquid chromatographic separation and analysis of ABA and its eight measured derivatives by UPLC-ESI-MS/MS provide rapid, accurate and robust quantification of most of the substances, and the low detection limits allow small amounts of tissue (1-5mg) to be used in quantitative analysis. To demonstrate the potential of the technique, we isolated ABA and its metabolites from control and water-stressed tobacco leaf tissues then analysed them by UPLC-ESI-MS/MS. Only ABA, PA, DPA, neoPA, and ABAGE were detected in the samples. PA was the most abundant analyte (ca. 1000 pmol/g f.w.) in both the control and water-stressed tissues, followed by ABAGE and DPA, which were both present at levels ca. 5-fold lower. ABA levels were at least 100-fold lower than PA concentrations, but they increased following the water stress treatment, while ABAGE, PA, and DPA levels decreased. Overall, the technique offers substantial improvements over previously described methods, enabling the detailed, direct study of

  20. Phthalate Metabolites, Consumer Habits and Health Effects

    Peter Wallner

    2016-07-01

    Full Text Available Phthalates are multifunctional chemicals used in a wide variety of consumer products. The aim of this study was to investigate whether levels of urinary phthalate metabolites in urine samples of Austrian mothers and their children were associated with consumer habits and health indicators. Within an Austrian biomonitoring survey, urine samples from 50 mother-child pairs of five communities (two-stage random stratified sampling were analysed. The concentrations of 14 phthalate metabolites were determined, and a questionnaire was administered. Monoethyl phthalate (MEP, mono-n-butyl phthalate (MnBP, mono-isobutyl phthalate (MiBP, monobenzyl phthalate (MBzP, mono-(2-ethylhexyl phthalate (MEHP, mono-(2-ethyl-5-hydroxyhexyl phthalate (5OH-MEHP, mono-(2-ethyl-5-oxohexyl phthalate (5oxo-MEHP, mono-(5-carboxy-2-ethylpentyl phthalate (5cx-MEPP, and 3-carboxy-mono-propyl phthalate (3cx-MPP could be quantified in the majority of samples. Significant correlations were found between the use of hair mousse, hair dye, makeup, chewing gum, polyethylene terephthalate (PET bottles and the diethyl phthalate (DEP metabolite MEP. With regard to health effects, significant associations of MEP in urine with headache, repeated coughing, diarrhoea, and hormonal problems were observed. MBzP was associated with repeated coughing and MEHP was associated with itching.

  1. Natural metabolites for parasitic weed management.

    Vurro, Maurizio; Boari, Angela; Evidente, Antonio; Andolfi, Anna; Zermane, Nadjia

    2009-05-01

    Compounds of natural origin, such as phytotoxins produced by fungi or natural amino acids, could be used in parasitic weed management strategies by interfering with the early growth stages of the parasites. These metabolites could inhibit seed germination or germ tube elongation, so preventing attachment to the host plant, or, conversely, stimulate seed germination in the absence of the host, contributing to a reduction in the parasite seed bank. Some of the fungal metabolites assayed were very active even at very low concentrations, such as some macrocyclic trichothecenes, which at 0.1 microM strongly suppressed the germination of Orobanche ramosa L. seeds. Interesting results were also obtained with some novel toxins, such as phyllostictine A, highly active in reducing germ tube elongation and seed germination both of O. ramosa and of Cuscuta campestris Yuncker. Among the amino acids tested, methionine and arginine were particularly interesting, as they were able to suppress seed germination at concentrations lower than 1 mM. Some of the fungal metabolites tested were also able to stimulate the germination of O. ramosa seeds. The major findings in this research field are described and discussed.

  2. Phthalate Metabolites, Consumer Habits and Health Effects.

    Wallner, Peter; Kundi, Michael; Hohenblum, Philipp; Scharf, Sigrid; Hutter, Hans-Peter

    2016-07-15

    Phthalates are multifunctional chemicals used in a wide variety of consumer products. The aim of this study was to investigate whether levels of urinary phthalate metabolites in urine samples of Austrian mothers and their children were associated with consumer habits and health indicators. Within an Austrian biomonitoring survey, urine samples from 50 mother-child pairs of five communities (two-stage random stratified sampling) were analysed. The concentrations of 14 phthalate metabolites were determined, and a questionnaire was administered. Monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-(5-carboxy-2-ethylpentyl) phthalate (5cx-MEPP), and 3-carboxy-mono-propyl phthalate (3cx-MPP) could be quantified in the majority of samples. Significant correlations were found between the use of hair mousse, hair dye, makeup, chewing gum, polyethylene terephthalate (PET) bottles and the diethyl phthalate (DEP) metabolite MEP. With regard to health effects, significant associations of MEP in urine with headache, repeated coughing, diarrhoea, and hormonal problems were observed. MBzP was associated with repeated coughing and MEHP was associated with itching.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Formation of malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE) in fish and fish oil during dynamic gastrointestinal in vitro digestion.

    Larsson, Karin; Harrysson, Hanna; Havenaar, Robert; Alminger, Marie; Undeland, Ingrid

    2016-02-01

    Marine lipids contain a high proportion of polyunsaturated fatty acids (PUFA), including the characteristic long chain (LC) n-3 PUFA. Upon peroxidation these lipids generate reactive products, such as malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE), which can form covalent adducts with biomolecules and thus are regarded as genotoxic and cytotoxic. PUFA peroxidation can occur both before and after ingestion. The aim of this study was to determine what levels of MDA, HHE and HNE can evolve in the gastric and intestinal lumen after ingesting meals containing fish or fish oil using a dynamic gastrointestinal (GI) model (TIM). The impact of the fish muscle matrix, lipid content, fish species, and oven baking on GI oxidation was evaluated. MDA and HHE concentrations in gastric lumen increased for all meals during digestion, with the highest level found with herring mince; ∼ 25 μM MDA and ∼ 850 nM HHE. Aldehyde concentrations reached in intestinal lumen during digestion of fish containing meals were generally lower than in gastric lumen, while isolated herring oils (bulk and emulsified) generated higher MDA and HHE values in intestinal lumen compared to gastric lumen. Based on aldehyde levels in gastric lumen, meals containing herring lipids were ranked: raw herring (17% lipid) = baked herring (4% lipid) > raw herring (4% lipid) ≫ herring oil emulsion > herring oil. Herring developed higher concentrations of MDA and HHE during gastric digestion compared to salmon, which initially contained lower levels of oxidation products. Cooked salmon generated higher MDA concentrations during digestion than raw salmon. Low levels of HNE were observed during digestion of all test meals, in accordance with the low content of n-6 PUFA in fish lipids.

  8. The synthesis and characterization of 7-hydroxy-4-methylcoumarin and the investigation of the fluorescence properties of its 7-hydroxy-4-methylcoumarin-chitosan films

    Wahyuningrum, Deana; Zulqarnaen, Muhammad; Suendo, Veinardi

    2014-03-01

    Chitosan fluorescent films containing 7-hydroxy-4-methylcoumarin (7H4MC) have been successfully prepared. Used chitosan was obtained from chitin isolated from skin of tiger prawns (Penaeus monodon) through the deproteination, demineralization, and deacetylation process. The yields of chitin and chitosan are 10.66% and 23.83%, respectively. The chitosan has 55.00% degree of deacetylation based on FTIR spectroscopy. Average molecular mass of chitosan which was determined by Ostwald viscometry method is 8.55 × 106 g/mol. The 7H4MC was synthesized from resorcinol and ethyl acetoacetate using amberlyst-15 as catalyst based on Pechmann reaction with chemical yields of 90.01% and the melting point of 189-190°C. The FTIR, 1H-NMR, and 13C-NMR spectroscopies confirmed the structure which corresponds to the structure of 7H4MC. The films of chitosan containing 7H4MC were prepared by solvent evaporation method in 2% (v/v) acetic acid. The 7H4MC content in each film was 0% (blank), 0.2%, 0.4%, 0.6%, and 0.8% (w/w). The UV-Vis spectrum of 7H4MC in methanol showed λmax at 235 and 337 nm. The observed fluorescence is the fluorescence color of cyan. The excitation wavelengths are 200, 235, 275, 337, and 365 nm. The highest intensity of cyan color fluorescence of chitosan containing 7H4MC films was obtained at the concentration of 0.2% of 7-hydroxy-4-methylcoumarin at the excitation wavelength of 275 nm.

  9. Simultaneous Analysis of Malondialdehyde, 4-Hydroxy-2-hexenal, and 4-Hydroxy-2-nonenal in Vegetable Oil by Reversed-Phase High-Performance Liquid Chromatography.

    Ma, Lukai; Liu, Guoqin

    2017-12-27

    A group of toxic aldehydes such as, malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE), and 4-hydroxy-2-nonenal (HNE) have been found in various vegetable oils and oil-based foods. Then simultaneous determination of them holds a great need in both the oil chemistry field and food field. In the present study, a simple and efficient analytical method was successfully developed for the simultaneous separation and detection of MDA, HHE, and HNE in vegetable oils by reversed-phase-high-performance liquid chromatography (RP-HPLC) coupled with photodiode array detector (PAD) at dual-channel detection mode. The effect of various experimental factors on the extraction performance, such as coextraction solvent system, butylated hydroxytoluene addition, and trichloroacetic acid addition were systematically investigated. Results showed that the linear ranges were 0.02-10.00 μg/mL for MDA, 0.02-4.00 μg/mL for HHE, and 0.03-4.00 μg/mL for HNE with the satisfactory correlation coefficient of >0.999 for all detected aldehydes. The limit of detection (LOD) and limit of quantification (LOQ) of MDA, HHE, and HNE were ∼0.021and 0.020 μg/mL, ∼0.009 and 0.020 μg/mL, and ∼0.014 and 0.030 μg/mL, respectively. Their recoveries were 99.64-102.18%, 102.34-104.61%, and 98.87-103.04% for rapeseed oil and 96.38-98.05%, 96.19-101.34%, and 96.86-99.04% for French fries, separately. Under the selected conditions, the developed methods was successfully applied to the simultaneous determination of MDA, HHE, and HNE in different tested vegetable oils. The results indicated that this method could be employed for the quality assessment of vegetable oils.

  10. The synthesis and characterization of 7-hydroxy-4-methylcoumarin and the investigation of the fluorescence properties of its 7-hydroxy-4-methylcoumarin-chitosan films

    Wahyuningrum, Deana, E-mail: deana@chem.itb.ac.id [Organic Chemistry Research Division, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132 (Indonesia); Zulqarnaen, Muhammad [Chemistry Study Program, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132 (Indonesia); Suendo, Veinardi [Inorganic and Physical Chemistry Research Division, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132 (Indonesia)

    2014-03-24

    Chitosan fluorescent films containing 7-hydroxy-4-methylcoumarin (7H4MC) have been successfully prepared. Used chitosan was obtained from chitin isolated from skin of tiger prawns (Penaeus monodon) through the deproteination, demineralization, and deacetylation process. The yields of chitin and chitosan are 10.66% and 23.83%, respectively. The chitosan has 55.00% degree of deacetylation based on FTIR spectroscopy. Average molecular mass of chitosan which was determined by Ostwald viscometry method is 8.55 × 10{sup 6} g/mol. The 7H4MC was synthesized from resorcinol and ethyl acetoacetate using amberlyst-15 as catalyst based on Pechmann reaction with chemical yields of 90.01% and the melting point of 189–190°C. The FTIR, {sup 1}H–NMR, and {sup 13}C–NMR spectroscopies confirmed the structure which corresponds to the structure of 7H4MC. The films of chitosan containing 7H4MC were prepared by solvent evaporation method in 2% (v/v) acetic acid. The 7H4MC content in each film was 0% (blank), 0.2%, 0.4%, 0.6%, and 0.8% (w/w). The UV-Vis spectrum of 7H4MC in methanol showed λ{sub max} at 235 and 337 nm. The observed fluorescence is the fluorescence color of cyan. The excitation wavelengths are 200, 235, 275, 337, and 365 nm. The highest intensity of cyan color fluorescence of chitosan containing 7H4MC films was obtained at the concentration of 0.2% of 7-hydroxy-4-methylcoumarin at the excitation wavelength of 275 nm.

  11. Metabolism of trans, trans-muconaldehyde, a cytotoxic metabolite of benzene, in mouse liver by alcohol dehydrogenase Adh1 and aldehyde reductase AKR1A4

    Short, Duncan M.; Lyon, Robert; Watson, David G.; Barski, Oleg A.; McGarvie, Gail; Ellis, Elizabeth M.

    2006-01-01

    The reductive metabolism of trans, trans-muconaldehyde, a cytotoxic metabolite of benzene, was studied in mouse liver. Using an HPLC-based stopped assay, the primary reduced metabolite was identified as 6-hydroxy-trans, trans-2,4-hexadienal (OH/CHO) and the secondary metabolite as 1,6-dihydroxy-trans, trans-2,4-hexadiene (OH/OH). The main enzymes responsible for the highest levels of reductase activity towards trans, trans-muconaldehyde were purified from mouse liver soluble fraction first by Q-sepharose chromatography followed by either blue or red dye affinity chromatography. In mouse liver, trans, trans-muconaldehyde is predominantly reduced by an NADH-dependent enzyme, which was identified as alcohol dehydrogenase (Adh1). Kinetic constants obtained for trans, trans-muconaldehyde with the native Adh1 enzyme showed a V max of 2141 ± 500 nmol/min/mg and a K m of 11 ± 4 μM. This enzyme was inhibited by pyrazole with a K I of 3.1 ± 0.57 μM. Other fractions were found to contain muconaldehyde reductase activity independent of Adh1, and one enzyme was identified as the NADPH-dependent aldehyde reductase AKR1A4. This showed a V max of 115 nmol/min/mg and a K m of 15 ± 2 μM and was not inhibited by pyrazole

  12. Urinary phthalate and phthalate alternative metabolites and isoprostane among couples undergoing fertility treatment.

    Wu, Haotian; Olmsted, Alexandra; Cantonwine, David E; Shahsavari, Shahin; Rahil, Tayyab; Sites, Cynthia; Pilsner, J Richard

    2017-02-01

    Epidemiological data suggest associations between phthalate exposures to a variety of adverse reproductive outcomes including reduced sperm quality and reproductive success. While mechanisms of these associations are not fully elucidated, oxidative stress has been implicated as a potential mediator. We examined associations of urinary metabolites of phthalates and phthalate alternative plasticizers with oxidative stress among couples seeking fertility treatment. Seventeen urinary plasticizer metabolites and 15-F2t isoprostane, a biomarker of oxidative stress, were quantified in spot samples from 50 couples seeking fertility treatment who enrolled in the Sperm Environmental Epigenetics and Development Study during 2014-2015. In multivariable analyses, percent change in isoprostane was positively associated with interquartile range increases for the oxidative metabolites of di-2-ethylhexyl phthalate, [mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP; 20.0%, p=0.02), mono-2-ethyl-5-oxohexyl phthalate (MEOHP; 24.1%, p=0.01), and mono-2-ethyl-5-carboxypentyl phthalate (MECPP; 24.1%, p=0.004)], mono-isobutyl phthalate (MiBP; 17.8%, p=0.02), mono-hydroxyisobutyl phthalate (MHiBP; 27.5%, p=0.003), and cyclohexane-1,2-dicarboxylic acid mono-hydroxy-isononyl ester (MHINCH; 32.3%, p=0.002). Stratification of participants by sex revealed that isoprostane was positively associated with MHiBP (41.4%, p=0.01) and monocarboxy-isononyl phthalate (MCNP; 26.0%, p=0.02) among females and MEOHP (35.8%, p=0.03), MiBP (29.2%, p=0.01), MHiBP (34.7%, p=0.007) and MHINCH (49.0%, p=0.002) among males. Our results suggest that exposure to phthalates and phthalate replacements are associated with higher levels of oxidative stress in a sex-specific manner. Additional studies are needed to replicate our findings and to examine the potential health implications of the use of phthalates and alternative phthalates in consumer end products. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Metabolism of para-aminophenol by rat hepatocytes.

    Yan, Z; Nikelly, J G; Killmer, L; Tarloff, J B

    2000-08-01

    Autoxidation of para-aminophenol (PAP) has been proposed to account for the selective nephrotoxicity of this compound. However, other studies suggest that hepatic metabolites of PAP rather than the parent compound may be responsible for renal damage. These studies were designed to investigate PAP metabolism in isolated hepatocytes. We synthesized several proposed metabolites for analysis by HPLC/mass spectrometry and compared those results with HPLC/mass spectrometric analyses of metabolites found after incubating hepatocytes with PAP. Hepatocytes prepared from male Sprague-Dawley rats were incubated in Krebs-Henseleit buffer at 37 degrees C for 5 h with 2.3 mM PAP under an atmosphere of 5% CO2/95% O2. Aliquots were withdrawn at 0.1 h of incubation and then hourly through 5 h of incubation. Reactions were terminated by the addition of acetonitrile. Hepatocyte viability was unaltered with PAP present in the incubation medium. We found that hepatocytes converted PAP to two major metabolites (PAP-GSH conjugates and PAP-N-acetylcysteine conjugates) and several minor metabolites [PAP-O-glucuronide, acetaminophen (APAP), APAP-O-glucuronide, APAP-GSH conjugates, and 4-hydroxyformanilide]. Preincubating hepatoyctes with 1-aminobenzotriazole, an inhibitor of cytochromes P450, did not alter the pattern of PAP metabolism. In conclusion, we found that PAP was metabolized in hepatocytes predominantly to PAP-GSH conjugates and PAP-N-acetylcysteine conjugates in sufficient quantities to account for the nephrotoxicity of PAP.

  14. Antibacterial activity of sulfamethoxazole transformation products (TPs): general relevance for sulfonamide TPs modified at the para position.

    Majewsky, Marius; Wagner, Danny; Delay, Markus; Bräse, Stefan; Yargeau, Viviane; Horn, Harald

    2014-10-20

    Sulfonamide antibiotics undergo transformation in the aquatic environment through biodegradation, photolysis, or hydrolysis. In this study, the residual antibacterial activity of 11 transformation products (TPs) of sulfamethoxazole (SMX) was investigated with regard to their in vitro growth and luminescence inhibition on Vibrio fischeri (30 min and 24 h exposure). Two transformation products, 4-hydroxy-SMX and N(4)-hydroxy-acetyl-SMX, were synthesized in-house and confirmed by nuclear magnetic resonance and high-resolution mass spectrometry. Results of individual compound experiments showed that TPs modified at the para amino group still exhibit clear antibacterial effects, whereas TPs resulting from breakdown of the SMX structure lost this mechanism of action. 4-NO2- and 4-OH-SMX were found to inhibit growth to a clearly greater extent than the parent compound, SMX. In contrast, the N(4)-acetyl- and N(4)-hydroxy-acetyl-derivatives retain less than 10 and 5% of the effect of SMX on growth and luminescence inhibition, respectively. The effect of a mixture of para-modified TPs was observed to be additive. Considering the homologous series of sulfa drugs widely prescribed and their common mechanism of action, the potential environmental impact must consider the total amount of sulfonamide antibiotics and their derivative TPs, which might end up in a water body. Extrapolating the results obtained here for the para TPs of SMX to other sulfa drugs and determining the persistence and occurrence of these compounds in the aquatic environment is required for improved risk assessment.

  15. Effect of Terbuthylazine-2-hydroxy at Environmental Concentrations on Early Life Stages of Common Carp (Cyprinus carpio L.

    Josef Velisek

    2014-01-01

    Full Text Available The aim of the study was to investigate effects of the triazine’s herbicide terbuthylazine-2-hydroxy on early life stage of common carp (Cyprinus carpio L. through antioxidant indices, mortality, growth, development, and histopathology. Based on accumulated mortality in the experimental groups, lethal concentrations of terbuthylazine-2-hydroxy were estimated at 35-day LC50 = 10.9 mg/L terbuthylazine-2-hydroxy. By day 15, fish were exposed to 3.5 mg/L and by day 26, fish were exposed to 0.0029 mg/L; real environmental concentration in Czech rivers, 0.07 mg/L, 1.4 mg/L, and 3.5 mg/L terbuthylazine-2-hydroxy, showed significantly lower mass and total length compared with controls. Based on inhibition of growth in the experimental groups, lowest observed effect concentration (LOEC = 0.002 mg/L terbuthylazine-2-hydroxy and no observed effect concentration (NOEC = 0.0001 mg/L terbuthylazine-2-hydroxy. No significant negative effects on hatching or embryo viability were demonstrated at the concentrations tested, but significant differences in early ontogeny among groups were noted. Fish from the two highest tested concentrations showed a dose-related delay in development compared with the controls. Total superoxide dismutase (SOD activity was significant lower in all groups testedly for terbuthylazine-2-hydroxy compared with the control group. At concentrations of 1.4 and 3.5 mg/L damage to caudal kidney tubules when compared to control fish was found.

  16. 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.

  17. Metabolite damage and repair in metabolic engineering design.

    Sun, Jiayi; Jeffryes, James G; Henry, Christopher S; Bruner, Steven D; Hanson, Andrew D

    2017-11-01

    The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects. Copyright © 2017 International Metabolic Engineering Society. All rights reserved.

  18. Metabolite damage and repair in metabolic engineering design

    Sun, Jiayi; Jeffryes, James G.; Henry, Christopher S.; Bruner, Steven D.; Hanson, Andrew D.

    2017-11-01

    The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects.

  19. Thermogenic effects of sibutramine and its metabolites

    Connoley, Ian P; Liu, Yong-Ling; Frost, Ian; Reckless, Ian P; Heal, David J; Stock, Michael J

    1999-01-01

    The thermogenic activity of the serotonin and noradrenaline reuptake inhibitor sibutramine (BTS 54524; Reductil) was investigated by measuring oxygen consumption (VO2) in rats treated with sibutramine or its two pharmacologically-active metabolites. Sibutramine caused a dose-dependent rise in VO2, with a dose of 10 mg kg−1 of sibutramine or its metabolites producing increases of up to 30% that were sustained for at least 6 h, and accompanied by significant increases (0.5–1.0°C) in body temperature. Based on the accumulation in vivo of radiolabelled 2-deoxy-[3H]-glucose, sibutramine had little or no effect on glucose utilization in most tissues, but caused an 18 fold increase in brown adipose tissue (BAT). Combined high, non-selective doses (20 mg kg−1) of the β-adrenoceptor antagonists, atenolol and ICI 118551, inhibited completely the VO2 response to sibutramine, but the response was unaffected by low, β1-adrenoceptor-selective (atenolol) or β2-adrenoceptor-selective (ICI 118551) doses (1 mg kg−1). The ganglionic blocking agent, chlorisondamine (15 mg kg−1), inhibited completely the VO2 response to the metabolites of sibutramine, but had no effect on the thermogenic response to the β3-adrenoceptor-selective agonist BRL 35135. Similar thermogenic responses were produced by simultaneous injection of nisoxetine and fluoxetine at doses (30 mg kg−1) that had no effect on VO2 when injected individually. It is concluded that stimulation of thermogenesis by sibutramine requires central reuptake inhibition of both serotonin and noradrenaline, resulting in increased efferent sympathetic activation of BAT thermogenesis via β3-adrenoceptor, and that this contributes to the compound's activity as an anti-obesity agent. PMID:10217544

  20. Analysis of arsenical metabolites in biological samples.

    Hernandez-Zavala, Araceli; Drobna, Zuzana; Styblo, Miroslav; Thomas, David J

    2009-11-01

    Quantitation of iAs and its methylated metabolites in biological samples provides dosimetric information needed to understand dose-response relations. Here, methods are described for separation of inorganic and mono-, di-, and trimethylated arsenicals by thin layer chromatography. This method has been extensively used to track the metabolism of the radionuclide [(73)As] in a variety of in vitro assay systems. In addition, a hydride generation-cryotrapping-gas chromatography-atomic absorption spectrometric method is described for the quantitation of arsenicals in biological samples. This method uses pH-selective hydride generation to differentiate among arsenicals containing trivalent or pentavalent arsenic.

  1. Practical synthesis of methyl 7-(3-hydroxy-5-oxocyclopent-1-en-1-yl-heptanoate

    Xinpeng Jiang

    2017-07-01

    Full Text Available The key intermediate of misoprostol, methyl 7-(3-hydroxy-5-oxocyclopent-1-en-1-yl-heptanoate was prepared from commercially available suberic acid in 40% yield over five steps. The key step involved a ZnCl2 catalyzed Friedel-Crafts reaction between furan and 2,9-oxonanedione. Sulfuric acid catalyzed methylation of 8-(furan-2-yl-8-oxooctanoic acid followed by sequential reduction and ZnCl2 catalyzed Piancatelli rearrangement resulted in the formation of the key intermediate of misoprostol.

  2. Effect of hydroxy (HHO) gas addition on performance and exhaust emissions in compression ignition engines

    Yilmaz, Ali Can; Uludamar, Erinc; Aydin, Kadir [Department of Mechanical Engineering, Cukurova University, 01330 Adana (Turkey)

    2010-10-15

    In this study, hydroxy gas (HHO) was produced by the electrolysis process of different electrolytes (KOH{sub (aq)}, NaOH{sub (aq)}, NaCl{sub (aq)}) with various electrode designs in a leak proof plexiglass reactor (hydrogen generator). Hydroxy gas was used as a supplementary fuel in a four cylinder, four stroke, compression ignition (CI) engine without any modification and without need for storage tanks. Its effects on exhaust emissions and engine performance characteristics were investigated. Experiments showed that constant HHO flow rate at low engine speeds (under the critical speed of 1750 rpm for this experimental study), turned advantages of HHO system into disadvantages for engine torque, carbon monoxide (CO), hydrocarbon (HC) emissions and specific fuel consumption (SFC). Investigations demonstrated that HHO flow rate had to be diminished in relation to engine speed below 1750 rpm due to the long opening time of intake manifolds at low speeds. This caused excessive volume occupation of hydroxy in cylinders which prevented correct air to be taken into the combustion chambers and consequently, decreased volumetric efficiency was inevitable. Decreased volumetric efficiency influenced combustion efficiency which had negative effects on engine torque and exhaust emissions. Therefore, a hydroxy electronic control unit (HECU) was designed and manufactured to decrease HHO flow rate by decreasing voltage and current automatically by programming the data logger to compensate disadvantages of HHO gas on SFC, engine torque and exhaust emissions under engine speed of 1750 rpm. The flow rate of HHO gas was measured by using various amounts of KOH, NaOH, NaCl (catalysts). These catalysts were added into the water to diminish hydrogen and oxygen bonds and NaOH was specified as the most appropriate catalyst. It was observed that if the molality of NaOH in solution exceeded 1% by mass, electrical current supplied from the battery increased dramatically due to the too much

  3. Natural 4-Hydroxy-2,5-dimethyl-3(2H)-furanone (Furaneol®)

    Wilfried Schwab

    2013-01-01

    4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF, furaneol®) and its methyl ether 2,5-dimethyl-4-methoxy-3(2H)-furanone (DMMF) are import aroma chemicals and are considered key flavor compounds in many fruit. Due to their attractive sensory properties they are highly appreciated by the food industry. In fruits 2,5-dimethyl-3(2H)-furanones are synthesized by a series of enzymatic steps whereas HDMF is also a product of the Maillard reaction. Numerous methods for the synthetic preparation of these c...

  4. 1,5-Bis(2-hydroxy-3-methoxybenzylidenecarbonohydrazide methanol 0.47-solvate

    Mouhamadou Moustapha Sow

    2014-04-01

    Full Text Available In the title compound, C17H18N4O5·0.47CH3OH, the virtually planar (r.m.s. deviation = 0.128 Å carbonohydrazide molecule is located on a twofold axis and conformation of its C=N bonds is E. There are short intramolecular O—H...N hydrogen bonds between the hydroxy groups and hydrazide N atoms. In the crystal, bifurcated N—H...(O,O hydrogen bonds assemble the carbonohydrazide molecules into a three-dimensional network. There are C2 symmetric voids in this network, 47% of which are occupied by disordered methanol molecules.

  5. Electronic structure and magnetism in transition metals doped 8-hydroxy-quinoline aluminum.

    Baik, Jeong Min; Shon, Yoon; Lee, Seung Joo; Jeong, Yoon Hee; Kang, Tae Won; Lee, Jong-Lam

    2008-10-15

    We report the room-temperature ferromagnetism in transition metals (Co, Ni)-doped 8-hydroxy-quinoline aluminum (Alq3) by thermal coevaporation of high purity metal and Alq3 powders. For 5% Co-doped Alq3, a maximum magnetization of approximately 0.33 microB/Co at 10 K was obtained and ferromagnetic behavior was observed up to 300 K. The Co atoms interact chemically with O atoms and provide electrons to Alq3, forming new states acting as electron trap sites. From this, it is suggested that ferromagnetism may be associated with the strong chemical interaction of Co atoms and Alq3 molecules.

  6. Ethyl 4-chloro-2′-fluoro-3-hydroxy-5-methylbiphenyl-2-carboxylate

    Muhammad Adeel

    2011-09-01

    Full Text Available In the title compound, C16H14ClFO3, the dihedral angle between the mean planes of the two benzene rings is 71.50 (5°. Due to an intramolecular O—H...O hydrogen bond between the hydroxy group and the carbonyl O atom of the ethyl ester group, the ethyl ester group lies within the ring plane. The crystal structure is consolidated by intermolecular C—H...O and C—H...F interactions.

  7. Amide-transforming activity of Streptomyces: possible application to the formation of hydroxy amides and aminoalcohols.

    Yamada, Shinya; Miyagawa, Taka-Aki; Yamada, Ren; Shiratori-Takano, Hatsumi; Sayo, Noboru; Saito, Takao; Takano, Hideaki; Beppu, Teruhiko; Ueda, Kenji

    2013-07-01

    To develop an efficient bioconversion process for amides, we screened our collection of Streptomyces strains, mostly obtained from soil, for effective transformers. Five strains, including the SY007 (NBRC 109343) and SY435 (NBRC 109344) of Streptomyces sp., exhibited marked conversion activities from the approximately 700 strains analyzed. These strains transformed diverse amide compounds such as N-acetyltetrahydroquinoline, N-benzoylpyrrolidine, and N-benzoylpiperidine into alcohols or N,O-acetals with high activity and regioselectivity. N,O-acetal was transformed into alcohol by serial tautomerization and reduction reactions. As such, Streptomyces spp. can potentially be used for the efficient preparation of hydroxy amides and aminoalcohols.

  8. Concise and Straightforward Asymmetric Synthesis of a Cyclic Natural Hydroxy-Amino Acid

    Mario J. Simirgiotis

    2014-11-01

    Full Text Available An enantioselective total synthesis of the natural amino acid (2S,4R,5R-4,5-di-hydroxy-pipecolic acid starting from D-glucoheptono-1, 4-lactone is presented. The best sequence employed as a key step the intramolecular nucleophilic displacement by an amino function of a 6-O-p-toluene-sulphonyl derivative of a methyl D-arabino-hexonate and involved only 12 steps with an overall yield of 19%. The structures of the compounds synthesized were elucidated on the basis of comprehensive spectroscopic (NMR and MS and computational analysis.

  9. Influence of (9Z)-12-hydroxy-9-dodecenoic acid and methyl jasmonate on plant protein phosphorylation.

    Tarchevsky, I A; Karimova, F G; Grechkin, A N; Moukhametchina, N U

    2000-12-01

    The products of the lipoxygenase pathway, methyl jasmonic acid (MeJA) and (9Z)-12-hydroxy-9-dodecenoic acid (HDA), hardly changed the relative level of phosphorylated polypeptides (RLPPs) during 2 h of incubation: 15 and 17 kDa RLPPs were enhanced by HDA, but decreased by MeJA. RLPPs of 73 and 82 kDa were increased by both compounds. MeJA and HDA treatment induced specific and unspecific effects in some RLPPs. It was shown that HDA and MeJA increased protein kinase activity in the presence of 1 microM cAMP.

  10. Ring-substituted 4-Hydroxy-1H-quinolin-2-ones: Preparation and Biological Activity

    Jiri Dohnal

    2009-03-01

    Full Text Available In the study, a series of twelve ring-substituted 4-hydroxy-1H-quinolin-2-one derivatives were prepared. The procedures for synthesis of the compounds are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity and tested for their photosynthesis-inhibiting activity using spinach (Spinacia oleracea L. chloroplasts. All the synthesized compounds were also evaluated for antifungal activity using in vitro screening with eight fungal strains. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed, as well as their structure-activity relationships (SAR.

  11. [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.

  12. Analysis of Hydroxy Fatty Acids from the Pollen of Brassica campestris L. var. oleifera DC. by UPLC-MS/MS

    Nian-Yun Yang

    2013-01-01

    Full Text Available Ultraperformance liquid chromatography coupled with negative electrospray tandem mass spectrometry (UPLC-ESI-MS/MS was used to determine 7 hydroxy fatty acids in the pollen of Brassica campestris L. var. oleifera DC. All the investigated hydroxy fatty acids showed strong deprotonated molecular ions [M–H]−, which underwent two major fragment pathways of the allyl scission and the β-fission of the alcoholic hydroxyl group. By comparison of their molecular ions and abundant fragment ions with those of reference compounds, they were tentatively assigned as 15,16-dihydroxy-9Z,12Z-octadecadienoic acid (1, 10,11,12-trihydroxy-(7Z,14Z-heptadecadienoic acid (2, 7,15,16-trihydroxy-9Z,12Z-octadecadienoic acid (3, 15,16-dihydroxy-9Z,12Z-octadecadienoic acid (4, 15-hydroxy-6Z,9Z,12Z-octadecatrienoic acid (5, 15-hydroxy-9Z,12Z- octadecadienoic acid (6, and 15-hydroxy-12Z-octadecaenoic acid (7, respectively. Compounds 3, 5, and 7 are reported for the first time.

  13. A latex metabolite benefits plant fitness under root herbivore attack

    Huber, M.; Epping, J.; Gronover, C.S.; Fricke, J.; Aziz, Z.; Brillatz, T.; Swyers, M.; Köllner, T.G.; Vogel, H.; Hammerbacher, A.; Triebwasser-Freese, D.; Robert, C.A.M.; Verhoeven, K.; Preite, V.; Gershenzon, J.

    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 n...

  14. Novel pyrazine metabolites found in polymyxin biosynthesis by Paenibacillus polymyxa

    Beck, Hans Christian; Hansen, Anne M; Lauritsen, Frants R

    2003-01-01

    A complex mixture of methyl-branched alkyl-substituted pyrazines was found in the growth medium of the polymyxin-producing bacterium Paenibacillus polymyxa, and of these, seven are new natural compounds. A total of 19 pyrazine metabolites were identified. The dominant metabolite was 2...... supplementation. The other pyrazine metabolites, all related pyrazines with either one, two or three alkyl substituents, were identified by means of their mass spectral data and/or co-elution with authentic standards....

  15. Cyanobacteria as Cell Factories to Produce Plant Secondary Metabolites

    Xue, Yong; He, Qingfang

    2015-01-01

    Cyanobacteria represent a promising platform for the production of plant secondary metabolites. Their capacity to express plant P450 proteins, which have essential functions in the biosynthesis of many plant secondary metabolites, makes cyanobacteria ideal for this purpose, and their photosynthetic capability allows cyanobacteria to grow with simple nutrient inputs. This review summarizes the advantages of using cyanobacteria to transgenically produce plant secondary metabolites. Some techniq...

  16. Interaction and Transport of Methamphetamine and its Primary Metabolites by Organic Cation and Multidrug and Toxin Extrusion Transporters.

    Wagner, David J; Sager, Jennifer E; Duan, Haichuan; Isoherranen, Nina; Wang, Joanne

    2017-07-01

    Methamphetamine is one of the most abused illicit drugs with roughly 1.2 million users in the United States alone. A large portion of methamphetamine and its metabolites is eliminated by the kidney with renal clearance larger than glomerular filtration clearance. Yet the mechanism of active renal secretion is poorly understood. The goals of this study were to characterize the interaction of methamphetamine and its major metabolites with organic cation transporters (OCTs) and multidrug and toxin extrusion (MATE) transporters and to identify the major transporters involved in the disposition of methamphetamine and its major metabolites, amphetamine and para -hydroxymethamphetamine ( p -OHMA). We used cell lines stably expressing relevant transporters to show that methamphetamine and its metabolites inhibit human OCTs 1-3 (hOCT1-3) and hMATE1/2-K with the greatest potencies against hOCT1 and hOCT2. Methamphetamine and amphetamine are substrates of hOCT2, hMATE1, and hMATE2-K, but not hOCT1 and hOCT3. p -OHMA is transported by hOCT1-3 and hMATE1, but not hMATE2-K. In contrast, organic anion transporters 1 and 3 do not interact with or transport these compounds. Methamphetamine and its metabolites exhibited complex interactions with hOCT1 and hOCT2, suggesting the existence of multiple binding sites. Our studies suggest the involvement of the renal OCT2/MATE pathway in tubular secretion of methamphetamine and its major metabolites and the potential of drug-drug interactions with substrates or inhibitors of the OCTs. This information may be considered when prescribing medications to suspected or known abusers of methamphetamine to mitigate the risk of increased toxicity or reduced therapeutic efficacy. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  17. Exometabolomic Analysis of Cross-Feeding Metabolites.

    Lubbe, Andrea; Bowen, Benjamin P; Northen, Trent

    2017-10-04

    Microbial consortia have the potential to perform complex, industrially important tasks. The design of microbial consortia requires knowledge of the substrate preferences and metabolic outputs of each member, to allow understanding of potential interactions such as competition and beneficial metabolic exchange. Here, we used exometabolite profiling to follow the resource processing by a microbial co-culture of two biotechnologically relevant microbes, the bacterial cellulose degrader Cellulomonas fimi, and the oleaginous yeast Yarrowia lipolytica. We characterized the substrate preferences of the two strains on compounds typically found in lignocellulose hydrolysates. This allowed prediction that specific sugars resulting from hemicellulose polysaccharide degradation by C. fimi may serve as a cross-feeding metabolites to Y. lipolytica in co-culture. We also showed that products of ionic liquid-treated switchgrass lignocellulose degradation by C. fimi were channeled to Y. lipolytica in a co-culture. Additionally, we observed metabolites, such as shikimic acid accumulating in the co-culture supernatants, suggesting the potential for producing interesting co-products. Insights gained from characterizing the exometabolite profiles of individual and co-cultures of the two strains can help to refine this interaction, and guide strategies for making this an industrially viable co-culture to produce valuable products from lignocellulose material.

  18. Urinary estrogen metabolites and breast cancer

    Dallal, Cher M; Stone, Roslyn A; Cauley, Jane A

    2013-01-01

    Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16a-hydroxyestrone (16a-OHE1......), and their ratio (2:16a-OHE1) in relation to breast cancer risk. ¿Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using...... premenopausal 2:16a-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16a-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvs...

  19. Reparation and Immunomodulating Properties of Bacillus sp. Metabolites from Permafrost.

    Kalenova, L F; Melnikov, V P; Besedin, I M; Bazhin, A S; Gabdulin, M A; Kolyvanova, S S

    2017-09-01

    An ointment containing metabolites of Bacillus sp. microorganisms isolated from permafrost samples was applied onto the skin wound of BALB/c mice. Metabolites isolated during culturing of Bacillus sp. at 37°C produced a potent therapeutic effect and promoted wound epithelialization by 30% in comparison with the control (ointment base) and by 20% in comparison with Solcoseryl. Treatment with Bacillus sp. metabolites stimulated predominantly humoral immunity, reduced the time of wound contraction and the volume of scar tissue, and promoted complete hair recovery. These metabolites can be considered as modulators of the wound process with predominance of regeneration mechanisms.

  20. 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.

  1. Novel pyrazine metabolites found in polymyxin biosynthesis by Paenibacillus polymyxa

    Beck, Hans Christian; Hansen, Anne M; Lauritsen, Frants R

    2003-01-01

    A complex mixture of methyl-branched alkyl-substituted pyrazines was found in the growth medium of the polymyxin-producing bacterium Paenibacillus polymyxa, and of these, seven are new natural compounds. A total of 19 pyrazine metabolites were identified. The dominant metabolite was 2,5-diisoprop......A complex mixture of methyl-branched alkyl-substituted pyrazines was found in the growth medium of the polymyxin-producing bacterium Paenibacillus polymyxa, and of these, seven are new natural compounds. A total of 19 pyrazine metabolites were identified. The dominant metabolite was 2...

  2. Reactive oxygen species via redox signaling to PI3K/AKT pathway contribute to the malignant growth of 4-hydroxy estradiol-transformed mammary epithelial cells.

    Victor O Okoh

    Full Text Available The purpose of this study was to investigate the effects of 17-β-estradiol (E2-induced reactive oxygen species (ROS on the induction of mammary tumorigenesis. We found that ROS-induced by repeated exposures to 4-hydroxy-estradiol (4-OH-E2, a predominant catechol metabolite of E2, caused transformation of normal human mammary epithelial MCF-10A cells with malignant growth in nude mice. This was evident from inhibition of estrogen-induced breast tumor formation in the xenograft model by both overexpression of catalase as well as by co-treatment with Ebselen. To understand how 4-OH-E2 induces this malignant phenotype through ROS, we investigated the effects of 4-OH-E2 on redox-sensitive signal transduction pathways. During the malignant transformation process we observed that 4-OH-E2 treatment increased AKT phosphorylation through PI3K activation. The PI3K-mediated phosphorylation of AKT in 4-OH-E2-treated cells was inhibited by ROS modifiers as well as by silencing of AKT expression. RNA interference of AKT markedly inhibited 4-OH-E2-induced in vitro tumor formation. The expression of cell cycle genes, cdc2, PRC1 and PCNA and one of transcription factors that control the expression of these genes - nuclear respiratory factor-1 (NRF-1 was significantly up-regulated during the 4-OH-E2-mediated malignant transformation process. The increased expression of these genes was inhibited by ROS modifiers as well as by silencing of AKT expression. These results indicate that 4-OH-E2-induced cell transformation may be mediated, in part, through redox-sensitive AKT signal transduction pathways by up-regulating the expression of cell cycle genes cdc2, PRC1 and PCNA, and the transcription factor - NRF-1. In summary, our study has demonstrated that: (i 4-OH-E2 is one of the main estrogen metabolites that induce mammary tumorigenesis and (ii ROS-mediated signaling leading to the activation of PI3K/AKT pathway plays an important role in the generation of 4-OH-E2

  3. Simultaneous determination of LSD and 2-oxo-3-hydroxy LSD in hair and urine by LC-MS/MS and its application to forensic cases.

    Jang, Moonhee; Kim, Jihyun; Han, Inhoi; Yang, Wonkyung

    2015-11-10

    Lysergic acid diethylamide (LSD) is administered in low dosages, which makes its detection in biological matrices a major challenge in forensic toxicology. In this study, two sensitive and reliable methods based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) were established and validated for the simultaneous determination of LSD and its metabolite, 2-oxo-3-hydroxy-LSD (O-H-LSD), in hair and urine. Target analytes in hair were extracted using methanol at 38°C for 15h and analyzed by LC-MS/MS. For urine sample preparation, liquid-liquid extraction was performed. Limits of detection (LODs) in hair were 0.25pg/mg for LSD and 0.5pg/mg for O-H-LSD. In urine, LODs were 0.01 and 0.025ng/ml for LSD and O-H-LSD, respectively. Method validation results showed good linearity and acceptable precision and accuracy. The developed methods were applied to authentic specimens from two legal cases of LSD ingestion, and allowed identification and quantification of LSD and O-H-LSD in the specimens. In the two cases, LSD concentrations in hair were 1.27 and 0.95pg/mg; O-H-LSD was detected in one case, but its concentration was below the limit of quantification. In urine samples collected from the two suspects 8 and 3h after ingestion, LSD concentrations were 0.48 and 2.70ng/ml, respectively, while O-H-LSD concentrations were 4.19 and 25.2ng/ml, respectively. These methods can be used for documenting LSD intake in clinical and forensic settings. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Genome-Wide Identification and Comparative Analysis of the 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase (HMGR Gene Family in Gossypium

    Wei Liu

    2018-01-01

    Full Text Available Terpenes are the largest and most diverse class of secondary metabolites in plants and play a very important role in plant adaptation to environment. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR is a rate-limiting enzyme in the process of terpene biosynthesis in the cytosol. Previous study found the HMGR genes underwent gene expansion in Gossypium raimondii, but the characteristics and evolution of the HMGR gene family in Gossypium genus are unclear. In this study, genome-wide identification and comparative study of HMGR gene family were carried out in three Gossypium species with genome sequences, i.e., G. raimondii, Gossypium arboreum, and Gossypium hirsutum. In total, nine, nine and 18 HMGR genes were identified in G. raimondii, G. arboreum, and G. hirsutum, respectively. The results indicated that the HMGR genes underwent gene expansion and a unique gene cluster containing four HMGR genes was found in all the three Gossypium species. The phylogenetic analysis suggested that the expansion of HMGR genes had occurred in their common ancestor. There was a pseudogene that had a 10-bp deletion resulting in a frameshift mutation and could not be translated into functional proteins in G. arboreum and the A-subgenome of G. hirsutum. The expression profiles of the two pseudogenes showed that they had tissue-specific expression. Additionally, the expression pattern of the pseudogene in the A-subgenome of G. hirsutum was similar to its paralogous gene in the D-subgenome of G. hirsutum. Our results provide useful information for understanding cytosolic terpene biosynthesis in Gossypium species.

  5. β-Hydroxy-β-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats

    Hao, Yanlei; Jackson, Janna R.; Wang, Yan; Edens, Neile; Pereira, Suzette L.

    2011-01-01

    β-Hydroxy-β-methylbutyrate (HMB) is a leucine metabolite shown to reduce protein catabolism in disease states and promote skeletal muscle hypertrophy in response to loading exercise. In this study, we evaluated the efficacy of HMB to reduce muscle wasting and promote muscle recovery following disuse in aged animals. Fisher 344×Brown Norway rats, 34 mo of age, were randomly assigned to receive either Ca-HMB (340 mg/kg body wt) or the water vehicle by gavage (n = 32/group). The animals received either 14 days of hindlimb suspension (HS, n = 8/diet group) or 14 days of unloading followed by 14 days of reloading (R; n = 8/diet group). Nonsuspended control animals were compared with suspended animals after 14 days of HS (n = 8) or after R (n = 8). HMB treatment prevented the decline in maximal in vivo isometric force output after 2 wk of recovery from hindlimb unloading. The HMB-treated animals had significantly greater plantaris and soleus fiber cross-sectional area compared with the vehicle-treated animals. HMB decreased the amount of TUNEL-positive nuclei in reloaded plantaris muscles (5.1% vs. 1.6%, P HMB did not significantly alter Bcl-2 protein abundance compared with vehicle treatment, HMB decreased Bax protein abundance following R, by 40% and 14% (P HMB-treated reloaded plantaris and soleus muscles, compared with vehicle-treated animals. HMB reduced cleaved caspase-9 by 14% and 30% (P HMB was unable to prevent unloading-induced atrophy, it attenuated the decrease in fiber area in fast and slow muscles after HS and R. HMB's ability to protect against muscle loss may be due in part to putative inhibition of myonuclear apoptosis via regulation of mitochondrial-associated caspase signaling. PMID:21697520

  6. Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review.

    Wilson, Gabriel J; Wilson, Jacob M; Manninen, Anssi H

    2008-01-03

    The leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been extensively used as an ergogenic aid; particularly among bodybuilders and strength/power athletes, who use it to promote exercise performance and skeletal muscle hypertrophy. While numerous studies have supported the efficacy of HMB in exercise and clinical conditions, there have been a number of conflicting results. Therefore, the first purpose of this paper will be to provide an in depth and objective analysis of HMB research. Special care is taken to present critical details of each study in an attempt to both examine the effectiveness of HMB as well as explain possible reasons for conflicting results seen in the literature. Within this analysis, moderator variables such as age, training experience, various states of muscle catabolism, and optimal dosages of HMB are discussed. The validity of dependent measurements, clustering of data, and a conflict of interest bias will also be analyzed. A second purpose of this paper is to provide a comprehensive discussion on possible mechanisms, which HMB may operate through. Currently, the most readily discussed mechanism has been attributed to HMB as a precursor to the rate limiting enzyme to cholesterol synthesis HMG-coenzyme A reductase. However, an increase in research has been directed towards possible proteolytic pathways HMB may operate through. Evidence from cachectic cancer studies suggests that HMB may inhibit the ubiquitin-proteasome proteolytic pathway responsible for the specific degradation of intracellular proteins. HMB may also directly stimulate protein synthesis, through an mTOR dependent mechanism. Finally, special care has been taken to provide future research implications.

  7. β–Hydroxy β–Methylbutyrate Improves Dexamethasone-Induced Muscle Atrophy by Modulating the Muscle Degradation Pathway in SD Rat

    Choi, Yeon Ja; Park, Min Hi; Jang, Eun Ji; Park, Chan Hum; Yoon, Changshin; Kim, Nam Deuk; Kim, Mi Kyung; Chung, Hae Young

    2014-01-01

    Skeletal muscle atrophy results from various conditions including high levels of glucocorticoids, and β–hydroxy β–methylbutyrate (HMB; a metabolite of leucine) is a potent therapeutical supplement used to treat various muscle disorders. Recent studies have demonstrated that HMB inhibits dexamethasone-induced atrophy in cultured myotubes, but its effect on dexamethasone-induced muscle atrophy has not been determined in vivo. In the present study, we investigated the effect of HMB on dexamethasone-induced muscle atrophy in rats. Treatment with dexamethasone weakened grip strengths and increased muscle damage as determined by increased serum creatine kinase levels and by histological analysis. Dexamethasone treatment also reduced both soleus and gastrocnemius muscle masses. However, HMB supplementation significantly prevented reductions in grip strengths, reduced muscle damage, and prevented muscle mass and protein concentration decrease in soleus muscle. Biochemical analysis demonstrated that dexamethasone markedly increased levels of MuRF1 protein, which causes the ubiquitination and degradation of MyHC. Indeed, dexamethasone treatment decreased MyHC protein expression and increased the ubiquitinated-MyHC to MyHC ratio. However, HMB supplementation caused the down-regulations of MuRF1 protein and of ubiquitinated-MyHC. Furthermore, additional experiments provided evidence that HMB supplementation inhibited the nuclear translocation of FOXO1 induced by dexamethasone, and showed increased MyoD expression in the nuclear fractions of soleus muscles. These findings suggest that HMB supplementation attenuates dexamethasone-induced muscle wasting by regulating FOXO1 transcription factor and subsequent MuRF1 expression. Accordingly, our results suggest that HMB supplementation could be used to prevent steroid myopathy. PMID:25032690

  8. Effects of beta-hydroxy-beta-methylbutyrate (HMB on exercise performance and body composition across varying levels of age, sex, and training experience: A review

    Wilson Jacob M

    2008-01-01

    Full Text Available Abstract The leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB has been extensively used as an ergogenic aid; particularly among bodybuilders and strength/power athletes, who use it to promote exercise performance and skeletal muscle hypertrophy. While numerous studies have supported the efficacy of HMB in exercise and clinical conditions, there have been a number of conflicting results. Therefore, the first purpose of this paper will be to provide an in depth and objective analysis of HMB research. Special care is taken to present critical details of each study in an attempt to both examine the effectiveness of HMB as well as explain possible reasons for conflicting results seen in the literature. Within this analysis, moderator variables such as age, training experience, various states of muscle catabolism, and optimal dosages of HMB are discussed. The validity of dependent measurements, clustering of data, and a conflict of interest bias will also be analyzed. A second purpose of this paper is to provide a comprehensive discussion on possible mechanisms, which HMB may operate through. Currently, the most readily discussed mechanism has been attributed to HMB as a precursor to the rate limiting enzyme to cholesterol synthesis HMG-coenzyme A reductase. However, an increase in research has been directed towards possible proteolytic pathways HMB may operate through. Evidence from cachectic cancer studies suggests that HMB may inhibit the ubiquitin-proteasome proteolytic pathway responsible for the specific degradation of intracellular proteins. HMB may also directly stimulate protein synthesis, through an mTOR dependent mechanism. Finally, special care has been taken to provide future research implications.

  9. Simultaneous quantitation of atorvastatin and its two active metabolites in human plasma by liquid chromatography/(– electrospray tandem mass spectrometry

    Pankaj Partani

    2014-02-01

    Full Text Available A sensitive, accurate and selective liquid chromatography–tandem mass spectrometry method (LC–MS/MS was developed and validated for the simultaneous quantitation of atorvastatin (AT and its equipotent hydroxyl metabolites, 2-hydroxy atorvastatin (2-AT and 4-hydroxy atorvastatin (4-AT, in human plasma. Electrospray ionization (ESI interface in negative ion mode was selected to improve the selectivity and the sensitivity required for this application. Additionally, a solid phase extraction (SPE step was performed to reduce any ion-suppression and/or enhancement effects. The separation of all compounds was achieved in less than 6 min using a C18 reverse-phase fused-core® column and a mobile phase, composed of a mixture of 0.005% formic acid in water:acetonitrile:methanol (35:25:40, v/v/v, in isocratic mode at a flow rate of 0.6 mL/min. The method has lower limit of quantitation (LLOQ of 0.050 ng/mL for all analytes. The method has shown tremendous reproducibility, with intra- and inter-day precision less than 6.6%, and intra- and inter-day accuracy within ±4.3% of nominal values, for all analytes, and has proved to be highly reliable for the analysis of clinical samples. Keywords: Atorvastatin, LC–MS/MS, Solid phase extraction, Pharmacokinetics, Method validation

  10. Chaetopyranin, a benzaldehyde derivative, and other related metabolites from Chaetomium globosum, an endophytic fungus derived from the marine red alga Polysiphonia urceolata.

    Wang, Song; Li, Xiao-Ming; Teuscher, Franka; Li, Dong-Li; Diesel, Arnulf; Ebel, Rainer; Proksch, Peter; Wang, Bin-Gui

    2006-11-01

    Cultivation of the endophytic fungus Chaetomium globosum, which was isolated from the inner tissue of the marine red alga Polysiphonia urceolata, resulted in the isolation of chaetopyranin (1), a new benzaldehyde secondary metabolite. Ten known compounds were also isolated, including two benzaldehyde congeners, 2-(2',3-epoxy-1',3'-heptadienyl)-6-hydroxy-5-(3-methyl-2-butenyl)benzaldehyde (2) and isotetrahydroauroglaucin (3), two anthraquinone derivatives, erythroglaucin (4) and parietin (5), five asperentin derivatives including asperentin (6, also known as cladosporin), 5'-hydroxy-asperentin-8-methylether (7), asperentin-8-methyl ether (8), 4'-hydroxyasperentin (9), and 5'-hydroxyasperentin (10), and the prenylated diketopiperazine congener neoechinulin A (11). The structures of these compounds were determined on the basis of their spectroscopic data analysis (1H, 13C, 1H-1H COSY, HMQC, and HMBC NMR, as well as low- and high-resolution mass experiments). To our knowledge, compound 1 represents the first example of a 2H-benzopyran derivative of marine algal-derived fungi as well as of the fungal genus Chaetomium. Each isolate was tested for its DPPH (1,1-diphenyl-2-picrylhydrazyl) radical-scavenging property. Compounds 1-4 were found to have moderate activity. Chaetopyranin (1) also exhibited moderate to weak cytotoxic activity toward several tumor cell lines.

  11. 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.

  12. (-)-6 alpha hydroxy polyanthellian A - A novel antifouling diterpenoid from the Indian soft coral Cladiella krempfi (Hickson)

    LimnaMol, V.P.; Raveendran, T.V.; Parameswaran, P.S.; Kunnath, R.J.; Rajamohanan, P.R.

    shifts of (-)-6α-hydroxy polyanthellin A and polyanthellin A C- No (-)-6α-hydroxy polyanthellin A Polyanthellin A δ c δ h δ c δ h 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 41... 3 4 5 6 7 8 9 1011 12 13 14 15 16 17 18 19 20 H H O CH 3 CH 3 Fig.3. (-)-6α-hydroxy polyanthellin A A 0 20 40 60 80 100 Control 6.25 12.5 25 50 100 Concentration (μg/ml) % A c t i v i t y B 0 20 40 60 80 100 Control 6.25 12.5 25 50 100...

  13. Synthesis of new 3-(2-aminothiazol-4-yl-4-hydroxy-2H-chromen-2-one derivatives

    S. SUKDOLAK

    2006-06-01

    Full Text Available Aminothiazole derivatives of 4-hydroxy-2H-chromen-2-one were prepared by the Hantzsch reaction1 using 3-(2-bromoacetyl-4-hydroxy-2H-chromen-2-one and thiourea derivatives. Starting compound for this synthesis 3-(2-bromoacetyl-4-hydroxy- 2H-chromen-2-one (1 was prepared previously.2 Also, for this synthesis we used thiourea derivatives (2a–j as compounds which possess groups with biological activity. Reactions are carried out in refluxing ethanol for a period of 30 – 45 min. Final products (3a–j are obtained in a high yield. Chemical structure of the obtained compounds was confirmed by elemental and structural analysis (IR and 1H NMR spectroscopy.

  14. Proton-transfer compounds of 8-hydroxy-7-iodoquinoline-5-sulfonic acid (ferron) with 4-chloroaniline and 4-bromoaniline.

    Smith, Graham; Wermuth, Urs D; Healy, Peter C

    2007-07-01

    The crystal structures of the proton-transfer compounds of ferron (8-hydroxy-7-iodoquinoline-5-sulfonic acid) with 4-chloroaniline and 4-bromoaniline, namely 4-chloroanilinium 8-hydroxy-7-iodoquinoline-5-sulfonate monohydrate, C(6)H(7)ClN(+) x C(9)H(5)INO(4)S(-) x H(2)O, and 4-bromoanilinium 8-hydroxy-7-iodoquinoline-5-sulfonate monohydrate, C(6)H(7)BrN(+) x C(9)H(5)INO(4)S(-) x H(2)O, have been determined. The compounds are isomorphous and comprise sheets of hydrogen-bonded cations, anions and water molecules which are extended into a three-dimensional framework structure through centrosymmetric R(2)(2)(10) O-H...N hydrogen-bonded ferron dimer interactions.

  15. Spectroscopic studies, antimicrobial activities and crystal structures of N-(2-hydroxy-3-methoxybenzalidene)1-aminonaphthalene

    Ünver, Hüseyin; Yıldız, Mustafa; Dülger, Başaran; Özgen, Özen; Kendi, Engin; Durlu, Tahsin Nuri

    2005-03-01

    Schiff base N-(2-hydroxy-3-methoxybenzalidene)1-aminonaphthalene has been synthesized from the reaction of 2-hydroxy-3-methoxybenzaldehyde with 1-aminonaphthalene. The compound were characterized by elemental analysis, FT-IR, 1H NMR, 13C NMR and UV-visible techniques. The UV-visible spectra of the Schiff base were studied in polar and nonpolar solvents in acidic and basic media. The structure of the compound has been examined cyrstallographically. There are two independent molecules in the asymmetric unit. It crystallizes in the monoclinic space group P21/c, with unit cell parameters: a=14, 602(2), b=5,800(1), c=16, 899(1) Å, V=1394.4(2) Å 3, Dx=1.321 g cm -3 and Z=4. The crystal structure was solved by direct methods and refined by full-matrix least squares to a find R=0.041 of for 1179 observed reflections. The title compound's antimicrobial activities also have been studied. The antimicrobial activities of the ligand has been screened in vitro against the organisms Escherichia coli ATCC 11230, Staphylococcus aureus ATCC 6538, Klebsiella pneumoniae UC57, Micrococcus luteus La 2971, Proteus vulgaris ATCC 8427, Pseudomonas aeruginosa ATCC 27853, Mycobacterium smegmatis CCM 2067, Bacillus cereus ATCC 7064 and Listeria monocytogenes ATCC 15313, the yeast cultures Candida albicans ATCC 10231, Kluyveromyces fragilis NRRL 2415, Rhodotorula rubra DSM 70403, Debaryomyces hansenii DSM 70238 and Hanseniaspora guilliermondii DSM 3432.

  16. Design of Novel 4-Hydroxy-chromene-2-one Derivatives as Antimicrobial Agents

    Milan Mladenović

    2010-06-01

    Full Text Available This paper presents the design of novel 4-hydroxy-chromene-2 one derivatives, based on previously obtained minimal inhibitory concentration values (MICs, against twenty four microorganism cultures, Gram positive and negative bacteria and fungi. Two of our compounds, 3b (MIC range 130–500 μg/mL and 9c (31.25–62.5 μg/mL, presented high potential antimicrobial activity. The compound 9c had equal activity to the standard ketoconazole (31.25 μg/mL against M. mucedo. Enlarged resistance of S. aureus, E. coli and C. albicans on the effect of potential drugs and known toxicity of coumarin antibiotics, motivated us to establish SAR and QSAR models of activity against these cultures and correlate biological activity, molecular descriptors and partial charges of functional groups to explain activity and use for the design of new compounds. The QSAR study presents essential relation of antimicrobial activity and dominant substituents, 4-hydroxy, 3-acetyl and thiazole functional groups, also confirmed through molecular docking. The result was ten new designed compounds with much improved predicted inhibition constants and average biological activity.

  17. Four Thermochromic o-Hydroxy Schiff Bases of α-Aminodiphenylmethane: Solution and Solid State Study

    Marija Zbačnik

    2017-01-01

    Full Text Available More than a hundred years after the first studies of the photo- and thermochromism of o-hydroxy Schiff bases (imines, it is still an intriguing topic that fascinates several research groups around the world. The reasons for such behavior are still under investigation, and this work is a part of it. We report the solution-based and mechanochemical synthesis of four o-hydroxy imines derived from α-aminodiphenylmethane. The thermochromic properties were studied for the single crystal and polycrystalline samples of the imines. The supramolecular impact on the keto-enol tautomerism in the solid state was studied using SCXRD and NMR, while NMR spectroscopy was used for the solution state. All four imines are thermochromic, although the color changes of the single crystals are not as strong as of the polycrystalline samples. One of the imines shows negative thermochromism, and that one is in keto-amine tautomeric form, both in the solid state as in solution.

  18. Kinetic and thermodynamic analysis of 10-hydroxy-camptothecin hydrolysis at physiological pH

    Kunadharaju, Sasank [Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201 (United States); Savva, Michalakis [Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201 (United States)], E-mail: msavva@liu.edu

    2008-09-15

    To derive accurately the thermodynamic parameters governing the hydrolysis of the lactone ring at physiological pH, a derivative spectrophotometric technique was used for the simultaneous estimation of lactone and carboxylate forms of the 10-hydroxy-camptothecin (10-HC). Validation of the analytical method was done with respect to reproducibility, percent recovery, and level of detection. Hydrolysis of the lactone ring of 10-HC followed a 1st order decay with a rate constant equal to (0.0281 {+-} 0.001) min{sup -1} in PBS at pH 7.4 and at a temperature of 310 K. The activation energy for the hydrolysis reaction as calculated from the Arrhenius equation was (79.41 {+-} 0.92) kJ . mol{sup -1}, whereas the enthalpy and entropy of hydrolysis of 10-hydroxy-camptothecin were on average 12.45 kJ . mol{sup -1} and 52.37 J . K{sup -1} . mol{sup -1}, respectively. The positive enthalpy and entropy values of the 10-HC-lactone hydrolysis indicate that the reaction is endothermic and entropically driven.

  19. Atrazine sorption by hydroxy-interlayered clays and their organic complexes.

    Indraratne, Srimathie P; Farenhorst, Annemieke; Goh, Tee Boon

    2008-01-01

    This study examined the sorption of atrazine by hydroxy-Fe interlayered montmorillonite (FeMt) and its hydroquinone (FeMtHQ), citrate (FeMtCt) and catechol (FeMtCC) complexes as well as by hydroxy-Al interlayered montmorillonite (AlMt) and its hydroquinone (AlMtHQ) and citrate (AlMtCt) complexes. Found among the clays were sorption distribution coefficients (K(d)) ranging from 24 to 123 mL g(-1) and maximum sorption (M) ranging from 2.2 to 16.8 microg g(-1). Both K(d) and M decreased in the order of FeMtCC > FeMtHQ > AlMtHQ > (AlMt = FeMt) > (AlMtCt = FeMtCt). The pH was negatively correlated with both K(d) (r = -0.90, p 0.96, p 0.94, p AlMt). This suggests that functional groups of Fe-OH and Al-OH in FeMt and AlMt reduced the available sorption sites for atrazine by making complexes with citrate ions while forming FeMtCt and AlMtCt. The atrazine was sorbed through the hydrophobic interactions with organic compound surfaces as well as through H-bonding and ionic bonding with clay-mineral surfaces.

  20. Green synthesis of monodisperse silver nanoparticles using hydroxy propyl methyl cellulose

    Dong, Chunfa; Zhang, Xianglin, E-mail: hust_zxl@mail.hust.edu.cn; Cai, Hao

    2014-01-15

    Graphical abstract: -- Highlights: • Synthesis of silver nanoparticles using hydroxy propyl methyl cellulose is reported. • HPMC and glucose are used as capping agent and reducing agent respectively. • It is the first time to use HPMC for synthesis of silver nanoparticles. • The small, spherical and well-dispersed particle is observed in the range of 3–17 nm. • The green method can be extended to other noble metals. -- Abstract: A simple and environmentally friendly method for the synthesis of highly stable and small sized silver nanoparticles with narrow distribution from 3 nm to 17 nm is reported. Silver nitrate, hydroxy propyl methyl cellulose (HPMC) and glucose, were used as silver precursor, capping agents and reducing agents respectively. The formation of silver nanoparticles was observed by change of color from colorless to wine red. The silver nanoparticles were characterized by transmission electron microscopy (TEM), UV–visible spectroscopy (UV–vis), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR). The results demonstrated that the obtained metallic nanoparticles were single crystalline silver nanoparticles capped with HPMC. The effects of the reaction time, reaction temperature and the concentration of silver ion and reducing agents on the particle size were investigated. A possible formation mechanism was proposed. The method may be extended to other noble metal for other technological applications such as additional medicinal, industrial applications.

  1. Green synthesis of monodisperse silver nanoparticles using hydroxy propyl methyl cellulose

    Dong, Chunfa; Zhang, Xianglin; Cai, Hao

    2014-01-01

    Graphical abstract: -- Highlights: • Synthesis of silver nanoparticles using hydroxy propyl methyl cellulose is reported. • HPMC and glucose are used as capping agent and reducing agent respectively. • It is the first time to use HPMC for synthesis of silver nanoparticles. • The small, spherical and well-dispersed particle is observed in the range of 3–17 nm. • The green method can be extended to other noble metals. -- Abstract: A simple and environmentally friendly method for the synthesis of highly stable and small sized silver nanoparticles with narrow distribution from 3 nm to 17 nm is reported. Silver nitrate, hydroxy propyl methyl cellulose (HPMC) and glucose, were used as silver precursor, capping agents and reducing agents respectively. The formation of silver nanoparticles was observed by change of color from colorless to wine red. The silver nanoparticles were characterized by transmission electron microscopy (TEM), UV–visible spectroscopy (UV–vis), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR). The results demonstrated that the obtained metallic nanoparticles were single crystalline silver nanoparticles capped with HPMC. The effects of the reaction time, reaction temperature and the concentration of silver ion and reducing agents on the particle size were investigated. A possible formation mechanism was proposed. The method may be extended to other noble metal for other technological applications such as additional medicinal, industrial applications

  2. Synthesis of Linezolid Metabolites PNU-142300 and PNU-142586 toward the Exploration of Metabolite-Related Events.

    Hanaya, Kengo; Matsumoto, Kazuaki; Yokoyama, Yuta; Kizu, Junko; Shoji, Mitsuru; Sugai, Takeshi

    2017-01-01

    Linezolid (1) is an oxazolidinone antibiotic that is partially metabolized in vivo via ring cleavage of its morpholine moiety to mainly form two metabolites, PNU-142300 (2) and PNU-142586 (3). It is supposed that accumulation of 2 and 3 in patients with renal insufficiency may cause thrombocytopenia, one of the adverse effects of linezolid. However, the poor availability of 2 and 3 has hindered further investigation of the clinical significance of the accumulation of these metabolites. In this paper, we synthesized metabolites 2 and 3 via a common synthetic intermediate, 4; this will encourage further exploration of events related to these metabolites and lead to improved clinical use of linezolid.

  3. 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.

  4. 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

  5. 4-Hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as potent anti-tumor agents.

    Hayakawa, Ichiro; Shioya, Rieko; Agatsuma, Toshinori; Furukawa, Hidehiko; Naruto, Shunji; Sugano, Yuichi

    2004-01-19

    Based on the structure of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which exhibits selective cytotoxicity against a tumorigenic cell line, (2,4-dimethoxyphenyl)-(4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)-methanone (18m) was designed and synthesized as a biologically stable derivative containing no ester group. Although the potency of 18m was almost the same as our initial hit compound 1, 18m is expected to last longer in the human body as an anticancer agent.

  6. Complete 1H and 13C NMR assignments and anti fungal activity of two 8-hydroxy flavonoids in mixture

    Johann, Susana; Smania Junior, Artur; Branco, Alexsandro

    2007-01-01

    A mixture of the two new flavonols 8-hydroxy-3, 4', 5, 6, 7-pentamethoxyflavone (1) and 8-hydroxy-3, 3', 4', 5, 6, 7-hexamethoxyflavone (2) was isolated from a commercial sample of Citrus aurantifolia. An array of one- ( 1 H NMR, { 1 H} -13 C NMR, and APT -13 C NMR) and two-dimensional NMR techniques (COSY, NOESY, HMQC and HMBC) was used to achieve the structural elucidation and the complete 1 H and 13 C chemical shift assignments of these natural compounds. In addition, the antifungal activity of these compounds against phytopathogenic and human pathogenic fungi was investigated. (author)

  7. A new high-performance liquid chromatography-tandem mass spectrometry method for the determination of paclitaxel and 6α-hydroxy-paclitaxel in human plasma: Development, validation and application in a clinical pharmacokinetic study.

    Bianca Posocco

    Full Text Available Paclitaxel belongs to the taxanes family and it is used, alone or in multidrug regimens, for the therapy of several solid tumours, such as breast-, lung-, head and neck-, and ovarian cancer. Standard dosing of chemotherapy does not take into account the many inter-patient differences that make drug exposure highly variable, thus leading to the insurgence of severe toxicity. This is particularly true for paclitaxel considering that a relationship between haematological toxicity and plasma exposure was found. Therefore, in order to treat patients with the correct dose of paclitaxel, improving the overall benefit-risk ratio, Therapeutic Drug Monitoring is necessary. In order to quantify paclitaxel and its main metabolite, 6α-hydroxy-paclitaxel, in patients' plasma, we developed a new, sensitive and specific HPLC-MS/MS method applicable to all paclitaxel dosages used in clinical routine. The developed method used a small volume of plasma sample and is based on quick protein precipitation. The chromatographic separation of the analytes was achieved with a SunFire™ C18 column (3.5 μM, 92 Å, 2,1 x 150 mm; the mobile phases were 0.1% formic acid/bidistilled water and 0.1% formic acid/acetonitrile. The electrospray ionization source worked in positive ion mode and the mass spectrometer operated in selected reaction monitoring mode. Our bioanalytical method was successfully validated according to the FDA-EMA guidelines on bioanalytical method validation. The calibration curves resulted linear (R2 ≥0.9948 over the concentration ranges (1-10000 ng/mL for paclitaxel and 1-1000 ng/mL for 6α-hydroxy-paclitaxel and were characterized by a good accuracy and precision. The intra- and inter-day precision and accuracy were determined on three quality control concentrations for paclitaxel and 6α-hydroxy-paclitaxel and resulted respectively <9.9% and within 91.1-114.8%. In addition, to further verify the assay reproducibility, we tested this method by re

  8. Atualizações sobre beta-hidroxi-beta-metilbutirato: suplementação e efeitos sobre o catabolismo de proteínas New findings on beta-hydroxy-beta-methylbutyirate: supplementation and effects on the protein catabolism

    Everson Araújo Nunes

    2008-04-01

    Full Text Available O beta-hidroxi-beta-metilbutirato, metabólito do aminoácido leucina, vem sendo utilizado como suplemento alimentar, em situações específicas, com o intuito de aumentar ou manter a massa isenta de gordura. Os relatos dos efeitos do beta-hidroxi-beta-metilbutirato em estudos recentes fizeram crescer as expectativas sobre sua utilização em casos patológicos. Também foram demonstrados melhores resultados, quando da sua ingestão, no treinamento de força em indivíduos iniciantes e em idosos. Em humanos o beta-hidroxi-beta-metilbutirato tem sido usado como agente anti-catabólico, e em modelos animais foi demonstrado ser eficaz em inibir a atividade de vias proteolíticas em células musculares de indivíduos caquéticos in vitro e in vivo. Os mecanismos participantes desses processos envolvem: a inibição da atividade do sistema ubiquitina proteossoma ATP-dependente, a inibição de vias de sinalização com participação da proteína quinase C-alfa e a diminuição da concentração citoplasmática do fator nuclear - kappa B livre, eventos relacionados ao decréscimo da proteólise em células musculares.The leucine metabolite beta-hydroxy-beta-methylbutyrate has been used as a nutritional supplement in specific situations to prevent losing or to increase lean mass. Recent studies showed interesting results of beta-hydroxy-beta-methylbutyrate supplementation in certain disease states. Better results have also been demonstrated when it is taken by starters or old individuals doing strength training. In humans, beta-hydroxy-beta-methylbutyrate has been used as an anticatabolic agent and in animal models it has been demonstrated to be effective in inhibiting the activity of the proteolytic pathways in muscle cells of extremely weak individuals in vivo and in vitro. The mechanisms that participate in this process involve: inhibition of the ATP-ubiquitin-proteasome pathway, inhibition of the signalization pathways involving protein kinase C

  9. Enteral B-hydroxy-B-methylbutyrate supplementation increases protein synthesis in skeletal muscle of neonatal pigs

    Many low-birth weight infants are at risk for poor growth due to an inability to achieve adequate protein intake. Administration of the amino acid leucine stimulates protein synthesis in skeletal muscle of neonates. To determine the effects of enteral supplementation of the leucine metabolite B-hydr...

  10. Encapsulates for Food Bioconversions and Metabolite Production

    Breguet, Véronique; Vojinovic, Vojislav; Marison, Ian W.

    The control of production costs in the food industry must be very strict as a result of the relatively low added value of food products. Since a wide variety of enzymes and/or cells are employed in the food industry for starch processing, cheese making, food preservation, lipid hydrolysis and other applications, immobilization of the cells and/or enzymes has been recognized as an attractive approach to improving food processes while minimizing costs. This is due to the fact that biocatalyst immobilization allows for easier separation/purification of the product and reutilization of the biocatalyst. The advantages of the use of immobilized systems are many, and they have a special relevance in the area of food technology, especially because industrial processes using immobilized biosystems are usually characterized by lower capital/energy costs and better logistics. The main applications of immobilization, related to the major processes of food bioconversions and metabolite production, will be described and discussed in this chapter.

  11. Formation of reactive metabolites from benzene

    Snyder, R.; Jowa, L.; Witz, G.; Kalf, G.; Rushmore, T.

    1986-01-01

    Rat liver mitoplasts were incubated first with [ 3 H]dGTP, to form DNA labeled in G, and then with [ 14 C]benzene. The DNA was isolated and upon isopycnic density gradient centrifugation in CsCl yielded a single fraction of DNA labeled with both [ 3 H] and [ 14 C]. These data are consistent with the covalent binding of one or more metabolites of benzene to DNA. The DNA was enzymatically hydrolyzed to deoxynucleosides and chromatographed to reveal at least seven deoxyguanosine adducts. Further studies with labeled deoxyadenine revealed one adduct on deoxyadenine. [ 3 H]Deoxyguanosine was reacted with [ 14 C]hydroquinone or benzoquinone. The product was characterized using uv, fluorescence, mass and NMR spectroscopy. A proposed structure is described. (orig.)

  12. 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...

  13. Methionine Metabolites in Patients With Sepsis.

    Wexler, Orren; Gough, Michael S; Morgan, Mary Anne M; Mack, Cynthia M; Apostolakos, Michael J; Doolin, Kathleen P; Mooney, Robert A; Arning, Erland; Bottiglieri, Teodoro; Pietropaoli, Anthony P

    2018-01-01

    Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.

  14. A Latex Metabolite Benefits Plant Fitness under Root Herbivore Attack

    Huber, M.; Epping, Janina; Schulze Gronover, C.; Fricke, Julia; Aziz, Zohra; Brillatz, Théo; Swyers, Michael; Kollner, T.G.; Vogel, H.; Hammerbacher, Almuth; Triebwasser-Freese, Daniella; Robert, Christelle A.M.; Verhoeven, K.J.F.; Preite, V.; Gershenzon, J.; Erb, M.

    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

  15. Pharmacokinetics of ifosfamide and some metabolites in children

    Kaijser, G. P.; de Kraker, J.; Bult, A.; Underberg, W. J.; Beijnen, J. H.

    1998-01-01

    The pharmacokinetics of ifosfamide and some metabolites in children was investigated. The patients received various doses of ifosfamide, mostly by continuous infusion, over several days. The penetration of ifosfamide and its metabolites into the cerebrospinal fluid was also studied in four cases.

  16. Effect of metabolites produced by Trichoderma species against ...

    Metabolites released from Trichoderma viride, T. polysporum, T. hamatum and T. aureoviride were tested in culture medium against Ceratocystis paradoxa, which causes black seed rot in oil palm sprouted seeds. The Trichoderma metabolites had similar fungistatic effects on the growth of C. paradoxa except those from T.

  17. Prototype of an intertwined secondary-metabolite supercluster

    Phillipp Wiemann; Chun-Jun. Guo; Jonathan M. Palmer; Relebohile Sekonyela; Clay C.C. Wang; Nancy P. Keller

    2013-01-01

    The hallmark trait of fungal secondary-metabolite gene clusters is well established, consisting of contiguous enzymatic and often regulatory gene(s) devoted to the production of a metabolite of a specific chemical class. Unexpectedly, we have found a deviation from this motif in a subtelomeric region of Aspergillus fumigatus. This region, under the...

  18. Metabolite characterization in serum samples from normal healthy ...

    Metabolite characterization in serum samples from normal healthy human subjects by 1H and 13C NMR spectroscopy. D Misra, U Bajpai. Abstract. One and two dimensional NMR spectroscopy has been employed to characterize the various metabolites of serum control healthy samples. Two dimensional heteronuclear ...

  19. Leach and mold resistance of essential oil metabolites

    Carol A. Clausen; Vina W. Yang

    2011-01-01

    Purified primary metabolites from essential oils were previously shown to be bioactive inhibitors of mold fungi on unleached Southern pine sapwood, either alone or in synergy with a second metabolite. This study evaluated the leachability of these compounds in Southern pine that was either dip- or vacuum-treated. Following laboratory leach tests, specimens were...

  20. UV-guided isolation of fungal metabolites by HSCCC

    Dalsgaard, P.W.; Nielsen, K.F.; Larsen, Thomas Ostenfeld

    2005-01-01

    Analytical standardised reversed phase liquid chromatography (RPLC) data can be helpful in finding a suitable solvent combination for isolation of fungal metabolites by high-speed counter current chromatography. Analysis of the distribution coefficient (K-D) of fungal metabolites in a series...... peptides from a crude fungal extract....

  1. Aspergillus flavus secondary metabolites: more than just aflatoxins

    Aspergillus flavus is best known for producing the family of potent carcinogenic secondary metabolites known as aflatoxins. However, this opportunistic plant and animal pathogen also produces numerous other secondary metabolites, many of which have also been shown to be toxic. While about forty of t...

  2. Synthesis of an Albendazole Metabolite: Characterization and HPLC Determination

    Mahler, Graciela; Davyt, Danilo; Gordon, Sandra; Incerti, Marcelo; Nunez, Ivana; Pezaroglo, Horacio; Scarone, Laura; Serra, Gloria; Silvera, Mauricio; Manta, Eduardo

    2008-01-01

    In this laboratory activity, students are introduced to the synthesis of an albendazole metabolite obtained by a sulfide oxidation reaction. Albendazole as well as its metabolite, albendazole sulfoxide, are used as anthelmintic drugs. The oxidation reagent is H[subscript 2]O[subscript 2] in acetic acid. The reaction is environmental friendly,…

  3. 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

  4. Loss of metabolites from monkey striatum during PET with FDOPA

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  5. Yeast synthetic biology for high-value metabolites.

    Dai, Zhubo; Liu, Yi; Guo, Juan; Huang, Luqi; Zhang, Xueli

    2015-02-01

    Traditionally, high-value metabolites have been produced through direct extraction from natural biological sources which are inefficient, given the low abundance of these compounds. On the other hand, these high-value metabolites are usually difficult to be synthesized chemically, due to their complex structures. In the last few years, the discovery of genes involved in the synthetic pathways of these metabolites, combined with advances in synthetic biology tools, has allowed the construction of increasing numbers of yeast cell factories for production of these metabolites from renewable biomass. This review summarizes recent advances in synthetic biology in terms of the use of yeasts as microbial hosts for the identification of the pathways involved in the synthesis, as well as for the production of high-value metabolites. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  6. (1) H-MRS processing parameters affect metabolite quantification

    Bhogal, Alex A; Schür, Remmelt R; Houtepen, Lotte C

    2017-01-01

    investigated the influence of model parameters and spectral quantification software on fitted metabolite concentration values. Sixty spectra in 30 individuals (repeated measures) were acquired using a 7-T MRI scanner. Data were processed by four independent research groups with the freedom to choose their own...... + NAAG/Cr + PCr and Glu/Cr + PCr, respectively. Metabolite quantification using identical (1) H-MRS data was influenced by processing parameters, basis sets and software choice. Locally preferred processing choices affected metabolite quantification, even when using identical software. Our results......Proton magnetic resonance spectroscopy ((1) H-MRS) can be used to quantify in vivo metabolite levels, such as lactate, γ-aminobutyric acid (GABA) and glutamate (Glu). However, there are considerable analysis choices which can alter the accuracy or precision of (1) H-MRS metabolite quantification...

  7. Urinary excretion of androgen metabolites, comparison with excretion of radioactive metabolites after injection of [4-14C]testosterone

    Deslypere, J.P.; Sayed, A.; Vermeulen, A.; Wiers, P.W.

    1981-01-01

    The influence of age on the metabolic pattern of [4- 14 C]testosterone was studied in 20 young and 8 elderly males and compared to the metabolic pattern of endogenous androgens; the latter was also studied in 16 young and 8 elderly women. In both young and elderly males, androsterone and aetiocholanolone glucuronide represent 65% of [4- 14 C]testosterone metabolites: together with their suephoconjugates as well as with 5α- and 5β-androstane-3α, 17β-diol they represent even more than 75% of total urinary metabolites. The 5α/5β ratio of metabolites of [4- 14 C]testosterone was significantly (P 14 C]testosterone metabolites was generally higher than the ratio of metabolites of endogenous androgens, suggesting that the transformation of T to ring A saturated metabolites occurs at least partially in another compartment than the transformation of DHEA to these metabolites. For both [4- 14 C]testosterone and endogenous androgen metabolites we observed a statistically significant reduction of the 5α/5β ratio with age, a general phenomenon in both males and females. This reduction concern also 11-OH-androst-4-ene-3.17-dione metabolism. Neither sex hormone levels, nor specific binding seems to determine this age dependent shift; neither is there convincing evidence for latent hypothyroisism or liver dysfunction in the elderly. An age associated primary decrease of the 5α-reductase activity seems the most likely explanation. (author)

  8. Antibacterial activity and characterization of secondary metabolites isolated from mangrove plant Avicennia officinalis

    Valentin Bhimba B; J Meenupriya; Elsa Lycias Joel; D Edaya Naveena; Suman kumar; M Thangaraj

    2010-01-01

    Objective:To explore antibacterial activity and characterization of secondary metabolites isolated from mangrove plant Avicennia officinalis (A. officinalis). Methods:In the present study the leaf extracts of A. officinalis were examined for its antibacterial potential using five different solvents against some reference strains of human pathogenic bacteria for the crude extract. Maximum activity was observed for ethyl acetate and hence different concentrations like 15μL, 25μL, and 50μL of ethyl extracts was checked for its antibacterial activity. Partial purification of crude extract was carried by column chromatography and fractions were analyzed using gas chromatography-mass spectrometry (GC-MS) to identify compounds. Results:The crude ethyl acetate extracts of A. officinalis showed remarkable antibacterial activity with zones of inhibition of 13 mm against Eschericia coli (E. coli) and 11 mm against Staphylococcus aureus (S. aureus). Fraction 13 (ethyl acetate÷methanol=8÷2) as the most potent one against with the minimal inhibitory concentration of 30 mm against E. coli and 25 mm against S. aureus. The GC-MS resultsof active column fraction (F13) revealed that the active principals were a mixture of hydroxy-4 methoxybenzoic acid, diethyl phthalate, oleic acid. Conclusions:The leaf extracts with proven antibacterial effects can clearly be directed towards cancer treatment as to inhibiting cancer cell growth. The limited number of test organisms owes to a constraint of resource. So, the effect of strong bursts of leaf extracts on human pathogenic bacteria should further be tested on a wide range of test organisms.

  9. Pharmacokinetics of lansoprazole and its main metabolites after single intravenous doses in healthy Chinese subjects.

    Zhang, Dan; Yang, Man; Liu, Man; Zhang, Yanan; Wang, Xiaolin; Xiao, Xue; Liu, Huichen

    2012-11-01

    The aim of the study was to evaluate the pharmacokinetics (PK) of lansoprazole (LPZ) and its main metabolites 5'-hydroxy lansoprazole (HLPZ) and lansoprazole sulphone (LPZS) after single intravenous (i.v.) doses of LPZ in healthy Chinese subjects, and the relationship between the cytochrome P450 (CYP) 2C19 phenotypes and the plasma concentrations of LPZS at the time-points in the elimination phase of LPZ. Twelve subjects were given lansoprazole by i.v. infusion. Blood samples were collected at designated time points up to 24 h. Plasma concentrations of LPZ, HLPZ and LPZS were quantified by a selective and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. After single i.v. doses of 15, 30 and 60 mg LPZ, C(max) and area under the plasma concentration-time curve (AUC(0-t)) of LPZ were 725 ± 151, 1480 ± 190, 3130 ± 480 µg · L(-1) and 1690 ± 1210, 3630 ± 2530, 8080 ± 4550 µg · h · L(-1), respectively. LPZ was generally well tolerated in healthy Chinese subjects, and displayed linear PK in the range of 15-60 mg. There were significant differences in the elimination of LPZ and the formation of LPZS between the single CYP2C19 poor metabolizer (PM) and the CYP2C19 extensive metabolizers (EM). The concentration of LPZS at the time-points in the elimination phase of LPZ could be monitored for CYP2C19 phenotyping. As a probe drug for CYP2C19 phenotyping, LPZ for injection might be more suitable than LPZ oral formulations.

  10. Pharmacokinetics of detomidine and its metabolites following intravenous and intramuscular administration in horses.

    Grimsrud, K N; Mama, K R; Thomasy, S M; Stanley, S D

    2009-04-01

    Detomidine is commonly used i.v. for sedation and analgesia in horses, but the pharmacokinetics and metabolism of this drug have not been well described. To describe the pharmacokinetics of detomidine and its metabolites, 3-hydroxy-detomidine (OH-detomidine) and detomidine 3-carboxylic acid (COOH-detomidine), after i.v. and i.m. administration of a single dose to horses. Eight horses were used in a balanced crossover design study. In Phase 1, 4 horses received a single dose of i.v. detomidine, administered 30 microg/kg bwt and 4 a single dose i.m. 30 microg/kg bwt. In Phase 2, treatments were reversed. Plasma detomidine, OH-detomidine and COOH-detomidine were measured at predetermined time points using liquid chromatography-mass spectrometry. Following i.v. administration, detomidine was distributed rapidly and eliminated with a half-life (t1/2(el)) of approximately 30 min. Following i.m. administration, detomidine was distributed and eliminated with t1/2(el) of approximately one hour. Following, i.v. administration, detomidine clearance had a mean, median and range of 12.41, 11.66 and 10.10-18.37 ml/min/kg bwt, respectively. Detomidine had a volume of distribution with the mean, median and range for i.v. administration of 470, 478 and 215-687 ml/kg bwt, respectively. OH-detomidine was detected sooner than COOH-detomidine; however, COOH-detomidine had a much greater area under the curve. These pharmacokinetic parameters provide information necessary for determination of peak plasma concentrations and clearance of detomidine in mature horses. The results suggest that, when a longer duration of plasma concentration is warranted, the i.m. route should be considered.

  11. Steady-state metabolite concentrations reflect a balance between maximizing enzyme efficiency and minimizing total metabolite load.

    Naama Tepper

    Full Text Available Steady-state metabolite concentrations in a microorganism typically span several orders of magnitude. The underlying principles governing these concentrations remain poorly understood. Here, we hypothesize that observed variation can be explained in terms of a compromise between factors that favor minimizing metabolite pool sizes (e.g. limited solvent capacity and the need to effectively utilize existing enzymes. The latter requires adequate thermodynamic driving force in metabolic reactions so that forward flux substantially exceeds reverse flux. To test this hypothesis, we developed a method, metabolic tug-of-war (mTOW, which computes steady-state metabolite concentrations in microorganisms on a genome-scale. mTOW is shown to explain up to 55% of the observed variation in measured metabolite concentrations in E. coli and C. acetobutylicum across various growth media. Our approach, based strictly on first thermodynamic principles, is the first method that successfully predicts high-throughput metabolite concentration data in bacteria across conditions.

  12. 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...

  13. Mitochondrial localization of the mevalonate pathway enzyme 3-Hydroxy-3-methyl-glutaryl-CoA reductase in the Trypanosomatidae

    Pena Diaz, Javier; Montalvetti, Andrea; Flores, Carmen-Lisset

    2004-01-01

    3-Hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) is a key enzyme in the sterol biosynthesis pathway, but its subcellular distribution in the Trypanosomatidae family is somewhat controversial. Trypanosoma cruzi and Leishmania HMGRs are closely related in their catalytic domains to bacterial and eu...

  14. On the formation of C2H5O2+ ions having the structure of hydroxy-protonated acetic acid

    Terlouw, J.K.; Koster, C.G. de; Levsen, K.

    1984-01-01

    Experiments are reported which are best explained in terms of the formation of the long-sought hydroxy-protonated acetic acid, CH3C(O)OH2- This C2 H5O2+ species, generated upon dissociative ionization of 2,4-dihydroxy-2-methylpentane (consecutive losses of CH3. and C3H6), is characterized by a

  15. Synthesis and Biological Evaluation of 2-Hydroxy-3-[(2-aryloxyethylamino]propyl 4-[(Alkoxycarbonylamino]benzoates

    Jan Tengler

    2013-01-01

    Full Text Available A series of twenty substituted 2-hydroxy-3-[(2-aryloxyethylamino]propyl 4-[(alkoxycarbonylamino]benzoates were prepared and characterized. As similar compounds have been described as potential antimycobacterials, primary in vitro screening of the synthesized carbamates was also performed against two mycobacterial species. 2-Hydroxy-3-[2-(2,6-dimethoxyphenoxyethylamino]-propyl 4-(butoxycarbonylaminobenzoate hydrochloride, 2-hydroxy-3-[2-(4-methoxyphenoxyethylamino]-propyl 4-(butoxycarbonylaminobenzoate hydrochloride, and 2-hydroxy-3-[2-(2-methoxyphenoxyethylamino]-propyl 4-(butoxycarbonylaminobenzoate hydrochloride showed higher activity against M. avium subsp. paratuberculosis and M. intracellulare than the standards ciprofloxacin, isoniazid, or pyrazinamide. Cytotoxicity assay of effective compounds was performed using the human monocytic leukaemia THP-1 cell line. Compounds with predicted amphiphilic properties were also tested for their effects on the rate of photosynthetic electron transport (PET in spinach (Spinacia oleracea L. chloroplasts. All butyl derivatives significantly stimulated the rate of PET, indicating that the compounds can induce conformational changes in thylakoid membranes resulting in an increase of their permeability and so causing uncoupling of phosphorylation from electron transport.

  16. One-Pot Catalyst-Free Synthesis of β- and γ-Hydroxy Sulfides using Diaryliodonium Salts and Microwave Irradiation

    A facile one-pot high-yield protocol is described for the preparation of β- and γ-hydroxy sulfides directly from diaryliodonium salts, potassium thiocyanate, and ethane-1,2-diol (ethylene glycol)/propane-1,3-diol (β-propylene glycol) without the need for any additional catalyst o...

  17. Fatty Acids are Key in 4-Hydroxy-2-Nonenal-Mediated Activation of Uncoupling Proteins 1 and 2

    Malingriaux, E. A.; Rupprecht, A.; Gille, L.; Jovanovic, O.; Ježek, Petr; Jabůrek, Martin; Pohl, E. E.

    2013-01-01

    Roč. 8, č. 10 (2013), e77786 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP302/10/0346 Institutional support: RVO:67985823 Keywords : mitochondrial uncoupling proteins * 4-hydroxy-2-nonenal * fatty acids Subject RIV: EA - Cell Biology Impact factor: 3.534, year: 2013

  18. Formation and persistence of DNA adducts from the carcinogen N-hydroxy-2-acetylaminofluorene in rat mammary gland in vivo

    Allaben, W.T.; Weis, C.C.; Fullerton, N.F.; Beland, F.A.

    1983-01-01

    The rat mammary carcinogen, N-hydroxy-2-acetylaminofluorene (N-hydroxy-2-AAF), has been proposed to be metabolically activated by mammary cytosolic N,O-acetyltransferase to a DNA binding species. To test this hypothesis, adult female Sprague-Dawley derived CD rats were treated, i.p., with 4.0 mg/kg [ring- 3 H]N-hydroxy-2-AAF. After 4 h, 1, 3, 14, and 28 days, the animals were killed, the mammary epithelium DNA was isolated and the carcinogen-deoxyribonucleoside adducts present were analyzed by high pressure liquid chromatography. At each time, only one adduct was detected and it was chromatographically identical to N-(deoxyguanosin-8-yl)-2-aminofluorene. The level of the adduct was maximal at 4 h (1.5 adducts/10(6) nucleotides) and then decreased, following first order kinetics with a t1/2 of 14.2 days. The detection of a single non-acetylated aminofluorene adduct is consistent with N,O-acyltransferase being involved in the metabolic activation of N-hydroxy-2-AAF in the rat mammary gland

  19. Synthesis of α-hydroxy-ω-amino poly(ethylene oxide) and its use in reaction injection moulding (RIM)

    Loontjens, Ton J.A.; Scholtens, Boudewijn J.R.; Belt, Wil J.W.; Frisch, Kurt C.; Wong, Shaio-wen

    1993-01-01

    Computer simulations show that oligomers with two different terminal groups with dissimilar reactivities for isoeyanates give a delayed viscosity rise in polyurethanes. This is a desired behaviour for RIM processes. Therefore, an α-hydroxy-ω-amino poly(ethylene oxide) (HAPEO) has been prepared. The

  20. Organic Solvent-Tolerant Marine Microorganisms as Catalysts for Kinetic Resolution of Cyclic β-Hydroxy Ketones

    Chen, B.; Liu, Hui; Zeferino Ribeiro De Souza, F.; Liu, Lan

    2017-01-01

    Chiral cyclic β-hydroxy ketones represent key motifs in the production of natural products of biological interest. Although the molecules are structurally simple, they require cumbersome synthetic steps to get access to them and their synthesis remains a challenge in organic chemistry. In this