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Sample records for carbinol

  1. Time evolution of dimethyl carbinol in water vortex rings

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    Omocea, Ioana-Laura; Damian, Iulia-Rodica; Simionescu, Štefan-Mugur; Bǎlan, Corneliu; Mihǎilescu, Mona

    2015-02-01

    The paper is concerned with the experimental study of the time evolution of a single laminar vortex ring generated at the interface between water and dimethyl carbinol. The experiments were performed by the submerged injection with a constant rate of dimethyl carbinol (isopropyl alcohol) in a water tank. The dynamics of the vortex formation was recorded at 1000 fps with a Photron Fastcam SA1 camera, equipped with a microscopic Edmund Optics objective. A symmetrical buoyant vortex ring with an elongated topology was observed at the interface between the two immiscible liquids. The analyses of the time dependence of the vortex rings disclosed three regions for the evolution of the interface: one dominated by inertia force, a transition region and a third region, dominated by buoyancy force.

  2. INDOL-3-CARBINOL IN THE TREATMENT OF BENIGN BREAST DISORDERS

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    E. T. Zulkarnayeva

    2008-01-01

    Full Text Available 123 patients with various forms of fibrocystic mastopathy (n=114 and fibroadenoma of mammry gland (n=9 were enrolled into the study. Indol-3-carbinol (indinol, Close corporation «Mirax-Pharma» was administered in the dose of 300—400 mg per day for 3—6 months. Disappearance of complaints to pain was observed in 35% of patients after 3 months of therapy and in 63% — after 6 months of therapy. Objective signs of fibrocystic mastopathy completely regressed in 9% of patients after 3 months of therapy and in 16% — after 6 month of therapy. Overall considerable improvement of condition or complete cure was seen in 55% of patients after 3 month of treatment and in 92% — after 6 months of therapy. Thus, indinol is highly effective and safe agent for treatment of different types of mastopathy.

  3. The glucosinolate breakdown product indole-3-carbinol acts as an auxin antagonist in roots of Arabidopsis thaliana.

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    Katz, Ella; Nisani, Sophia; Yadav, Brijesh S; Woldemariam, Melkamu G; Shai, Ben; Obolski, Uri; Ehrlich, Marcelo; Shani, Eilon; Jander, Georg; Chamovitz, Daniel A

    2015-05-01

    The glucosinolate breakdown product indole-3-carbinol functions in cruciferous vegetables as a protective agent against foraging insects. While the toxic and deterrent effects of glucosinolate breakdown on herbivores and pathogens have been studied extensively, the secondary responses that are induced in the plant by indole-3-carbinol remain relatively uninvestigated. Here we examined the hypothesis that indole-3-carbinol plays a role in influencing plant growth and development by manipulating auxin signaling. We show that indole-3-carbinol rapidly and reversibly inhibits root elongation in a dose-dependent manner, and that this inhibition is accompanied by a loss of auxin activity in the root meristem. A direct interaction between indole-3-carbinol and the auxin perception machinery was suggested, as application of indole-3-carbinol rescues auxin-induced root phenotypes. In vitro and yeast-based protein interaction studies showed that indole-3-carbinol perturbs the auxin-dependent interaction of Transport Inhibitor Response (TIR1) with auxin/3-indoleacetic acid (Aux/IAAs) proteins, further supporting the possibility that indole-3-carbinol acts as an auxin antagonist. The results indicate that chemicals whose production is induced by herbivory, such as indole-3-carbinol, function not only to repel herbivores, but also as signaling molecules that directly compete with auxin to fine tune plant growth and development.

  4. Serum glutathione transferase does not respond to indole-3-carbinol: A pilot study

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    Daniel R McGrath

    2010-05-01

    Full Text Available Daniel R McGrath1, Hamid Frydoonfar2, Joshua J Hunt3, Chris J Dunkley3, Allan D Spigelman41Ipswich Hospital, Ipswich, UK; 2Hunter Pathology Service, New South Wales; 3Royal Newcastle Centre, Newcastle; 4St Vincent’s Clinical School, Sydney, AustraliaBackground: Despite the well recognized protective effect of cruciferous vegetables against various cancers, including human colorectal cancers, little is known about how this effect is conferred. It is thought that some phytochemicals found only in these vegetables confer the protection. These compounds include the glucosinolates, of which indole-3-carbinol is one. They are known to induce carcinogen-metabolizing (phase II enzymes, including the glutathione S-transferase (GST family. Other effects in humans are not well documented. We wished to assess the effect of indole-3-carbinol on GST enzymes.Methods: We carried out a placebo-controlled human volunteer study. All patients were given 400 mg daily of indole-3-carbinol for three months, followed by placebo. Serum samples were tested for the GSTM1 genotype by polymerase chain reaction. Serum GST levels were assessed using enzyme-linked immunosorbent assay and Western Blot methodologies.Results: Forty-nine volunteers completed the study. GSTM1 genotypes were obtained for all but two volunteers. A slightly greater proportion of volunteers were GSTM1-positive, in keeping with the general population. GST was detected in all patients. Total GST level was not affected by indole-3-carbinol dosing compared with placebo. Although not statistically significant, the GSTM1 genotype affected the serum GST level response to indole-3-carbinol.Conclusion: Indole-3-carbinol does not alter total serum GST levels during prolonged dosing.Keywords: pilot study, colorectal cancer, glutathione transferase, human, indole-3-carbinol

  5. Intermolecular Cross-Acyloin Reactions by Fluoride-Promoted Additions of O-Silyl Thiazolium Carbinols.

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    Mathies, Alex K; Mattson, Anita E; Scheidt, Karl A

    2009-01-01

    The addition of acyl anion equivalents to aliphatic aldehydes (crossed-acyloin reaction) has been developed. Cesium fluoride with isopropanol as solvent promotes the addition of O-silyl thiazolium carbinols to various aliphatic aldehydes in moderate to good yields. These reactions represent a general procedure for the selective coupling of aliphatic aldehydes by an acyl anion reaction which have been problematic until now.

  6. Research on cruciferous vegetables, indole-3-carbinol, and cancer prevention: A tribute to Lee W. Wattenberg.

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    Fujioka, Naomi; Fritz, Vincent; Upadhyaya, Pramod; Kassie, Fekadu; Hecht, Stephen S

    2016-06-01

    Lee W. Wattenberg, who spent his entire career at the University of Minnesota, was a true pioneer in the field of chemoprevention. This paper is a tribute to his groundbreaking research which uncovered the cancer prevention properties of many dietary compounds, including those discussed here in some detail-indole-3-carbinol and diindolylmethane. These compounds occur as glucosinolate conjugates in cruciferous vegetables and are released when one chews or otherwise macerates the vegetable. They have numerous beneficial effects including the ability to prevent cancer in laboratory animals treated with carcinogens. We review some of the early work on indole-3-carbinol and diindolylmethane which spurred subsequent studies on their efficacy and molecular mechanisms of prevention. We also present unique data on field conditions that affect levels of their glucosinolate precursors in vegetables and on the release of diindolylmethane in people who consume cruciferous vegetables.

  7. Effect of 4-methoxyindole-3-carbinol on the proliferation of colon cancer cells in vitro, when treated alone or in combination with indole-3-carbinol.

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    Kronbak, Remy; Duus, Fritz; Vang, Ole

    2010-07-28

    Consumption of cruciferous vegetables and cancer prevention seem to be positively associated. We present an easy two-step synthesis for 4-methoxyindole-3-carbinol (4MeOI3C), the expected breakdown product of 4-methoxyglucobrassicin during ingestion. 4MeOI3C inhibited the proliferation of human colon cancer cells DLD-1 and HCT 116 with IC(50) values of 116 microM and 96 microM, respectively, after 48 h in vitro, and is therefore a more potent inhibitor than indole-3-carbinol (I3C). 4MeOI3C and I3C combined in different molar ratios inhibited proliferation in a nearly additive to slightly synergistic manner. Proliferation was inhibited by 100 microM 4MeOI3C after 48 h without affecting cell cycle phase distribution, indicating an overall-slowdown effect on the cell cycle. However, 200 microM 4MeOI3C caused a very high level of cell death and an accumulation of living cells in the G(0)/G(1) phase, indicating a concentration-dependent mode of action. We conclude that 4MeOI3C might play a role in the cancer preventive effect of cruciferous vegetables.

  8. A Hypothetical Study on Structural aspects of Indole-3-carbinol (I3C by Hyperchem and Arguslab 4 software

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    K. Laxmi

    2016-01-01

    Full Text Available Indole-3-carbinol (I3C is a plant compound derived from glucosinolates, found in cruciferous vegetables. Researchers have indicated that I3C shows great promise as a cancer preventative and hormone-balancing agent. HyperChem 7.5 software was used for quantum mechanical calculations. The geometry optimization was carried out using Ab Initio method. QSAR parameters were generated with semi empirical single point AM1 method. The HOMO and LUMO frontier orbital energies were also computed. Conformational analysis and geometry optimization of Indole-3-carbinol (I3C was performed according to the Hartree-Fock (HF calculation method by ArgusLab 4.0.1 software .The minimum heat of formation is calculated by geometry convergence function by ArgusLab software. PM3 semi empirical quantum mechanical calculations were carried out on structure of Indole-3-carbinol (I3C to obtain the geometries, geometric parameters and thermodynamic parameters. The HOMO and LUMO frontier orbital energies were also computed for the optimized molecule. Electron density surface of IDOX is determined using PM3 geometry with PM3 wavefunciton.

  9. Photodegradation of malachite green and malachite green carbinol under irradiation with different wavelength ranges.

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    Fischer, A R; Werner, P; Goss, K-U

    2011-01-01

    The dye malachite green (MG) is used worldwide as a fungicide in aquaculture. It is a toxic substance which in aqueous solutions is partly converted into its non-ionic colorless form (leucocarbinol). The equilibrium between these two forms is pH-dependent (pK=6.9). To assess the photodegradation of MG under sunlight conditions, both species were irradiated separately in aqueous solutions with different pH values (4.0 and 12.0) using various ultraviolet and visible wavelength ranges (UV/VIS). A 700 W high-pressure mercury lamp with special filters was used. No artificial photooxidizers such as H₂O₂ or TiO₂ were added. MG leucocarbinol proved to be much more sensitive to irradiation than the dye form. Quantum yields Φ were calculated for some wavelength ranges as follows: MG carbinol: Φ((280-312 nm)) is 4.3 × 10⁻³, Φ((313 - 410 nm)) is 5.8 × 10⁻³, and MG dye: Φ((280 - 312 nm)) is 4.8 × 10(-5), Φ((313-365nm)) is 1.1×10⁻⁵, and Φ((> 365nm)) is 0, respectively. Therefore, the solar photolysis of MG is an important sink and primarily depends on the photodegradation of the colorless leucocarbinol. During the irradiation of MG leucocarbinol with wavelengths > 365 nm, an intermediate was formed which has photocatalytical properties.

  10. Intranasal delivery of liposomal indole-3-carbinol improves its pulmonary bioavailability.

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    Song, Jung Min; Kirtane, Ameya R; Upadhyaya, Pramod; Qian, Xuemin; Balbo, Silvia; Teferi, Fitsum; Panyam, Jayanth; Kassie, Fekadu

    2014-12-30

    Indole-3-carbinol (I3C), a constituent of commonly consumed Brassica vegetables, has been shown to have anticancer effects in a variety of preclinical models of lung cancer. However, it has shown only limited efficacy in clinical trials, likely due to its poor oral bioavailability. Intranasal administration of I3C has the potential to enhance the pulmonary accumulation of the drug, thereby improving its availability at the target site of action. In this study, we developed a liposomal formulation of I3C and evaluated its lung delivery and chemopreventive potential in tobacco smoke carcinogen [4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK)]-treated mice. Intranasal administration of I3C liposomes led to a ∼100-fold higher lung exposure of I3C than the oral route of administration. Further, intranasal delivery of liposomal I3C led to a significant reduction (37%; pLiposomal I3C also significantly increased (by 10-fold) the expression of CYP1A1, a cytochrome P450 enzyme known to increase the detoxification of chemical carcinogens by enhancing their metabolism. Overall, our findings demonstrate that intranasal administration of liposomal I3C has the potential to significantly improve the efficacy of I3C for lung cancer chemoprevention.

  11. Indole-3-carbinol inhibits nasopharyngeal carcinoma growth through cell cycle arrest in vivo and in vitro.

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    Zhe Chen

    Full Text Available Nasopharyngeal carcinoma is a common malignant tumor in the head and neck. Because of frequent recurrence and distant metastasis which are the main causes of death, better treatment is needed. Indole-3-carbinol (I3C, a natural phytochemical found in the vegetables of the cruciferous family, shows anticancer effect through various signal pathways. I3C induces G1 arrest in NPC cell line with downregulation of cell cycle-related proteins, such as CDK4, CDK6, cyclin D1 and pRb. In vivo, nude mice receiving I3C protectively or therapeutically exhibited smaller tumors than control group after they were inoculated with nasopharyngeal carcinoma cells. The expression of CDK4, CDK6, cyclin D1 and pRb in preventive treatment group and drug treatment group both decreased compared with the control group. We conclude that I3C can inhibit the growth of NPC in vitro and in vivo by suppressing the expression of CDK and cyclin families. The drug was safe and had no toxic effects on normal tissues and organs.

  12. Indole-3-carbinol, a vegetable phytochemical, inhibits adipogenesis by regulating cell cycle and AMPKα signaling.

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    Choi, Hyeon-Son; Jeon, Hui-Jeon; Lee, Ok-Hwan; Lee, Boo-Yong

    2014-09-01

    Indole-3-carbinol (I3C) is a phytochemical present mainly in cruciferous vegetables. In this study, we investigated the mechanism by which I3C blocks adipogenesis in 3T3-L1 cells, and evaluated the anti-adipogenic effect of I3C in zebrafish. Our data showed that I3C mainly inhibits early differentiation of adipocyte through cell cycle arrest. Inhibition of early differentiation was reflected by down-regulation of early adipogenic factors such as CCAAT-enhancer binding proteins β and δ (C/EBPβ and C/EBPδ), followed by down-regulation of late adipogenic factors such as peroxisome proliferator-activated receptor γ (PPARγ) and C/EBPα, and regulation of signaling molecules. This result was supported by a reduction in triglyceride (TG) levels and TG synthetic enzymes. I3C activated AMP-activated protein kinase α (AMPKα) to inhibit fatty acid synthesis. In addition, an anti-adipogenic effect of I3C was found in zebrafish study. Our data suggest that vegetables-derived I3C could reduce lipid accumulation via various molecular mechanisms in cell.

  13. Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol

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    Okudaira Taeko

    2009-01-01

    Full Text Available Abstract Background Adult T-cell leukemia/lymphoma (ATLL is a malignancy derived from T cells infected with human T-cell leukemia virus type 1 (HTLV-1, and it is known to be resistant to standard anticancer therapies. Indole-3-carbinol (I3C, a naturally occurring component of Brassica vegetables such as cabbage, broccoli and Brussels sprout, is a promising chemopreventive agent as it is reported to possess antimutagenic, antitumorigenic and antiestrogenic properties in experimental studies. The aim of this study was to determine the potential anti-ATLL effects of I3C both in vitro and in vivo. Results In the in vitro study, I3C inhibited cell viability of HTLV-1-infected T-cell lines and ATLL cells in a dose-dependent manner. Importantly, I3C did not exert any inhibitory effect on uninfected T-cell lines and normal peripheral blood mononuclear cells. I3C prevented the G1/S transition by reducing the expression of cyclin D1, cyclin D2, Cdk4 and Cdk6, and induced apoptosis by reducing the expression of XIAP, survivin and Bcl-2, and by upregulating the expression of Bak. The induced apoptosis was associated with activation of caspase-3, -8 and -9, and poly(ADP-ribose polymerase cleavage. I3C also suppressed IκBα phosphorylation and JunD expression, resulting in inactivation of NF-κB and AP-1. Inoculation of HTLV-1-infected T cells in mice with severe combined immunodeficiency resulted in tumor growth. The latter was inhibited by treatment with I3C (50 mg/kg/day orally, but not the vehicle control. Conclusion Our preclinical data suggest that I3C could be potentially a useful chemotherapeutic agent for patients with ATLL.

  14. Assessment of mutagenic potential of propoxur and its modulation by indole-3-carbinol.

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    Agrawal, R C; Mehrotra, N k

    1997-01-01

    Propoxur is a widely used dithiocarbamate pesticide. In the present set of investigations, mutagenicity of propoxur (in formulation) was studied using the micronucleus assay in bone marrow of Swiss mice. Single intraperitoneal (i.p.) administration of 25 mg/kg body weight dose of propoxur, which is a maximum tolerated dose (MTD), significantly induced the micronucleus formation in bone marrow cells after a 24- and 48-hr exposure. A half and a quarter of the MTD (12.5 and 6.25 mg/kg) were found ineffective to induce the micronuclei formation after 24- and 48-hr time periods by the i.p. route. However, the PCE:NCE ratio was inhibited significantly with all the dose levels at both time periods. Oral administration of propoxur at different dose levels also induced micronuclei formation. A single application of 50 and 25 mg/kg dose levels of propoxur, which are MTD and 50% of MTD, also significantly induced micronuclei formation after 24- and 48-hr time periods in bone marrow cells of Swiss mice as compared with solvent control group, whereas a 12.5 mg/kg dose of propoxur was ineffective in inducing micronuclei formation. Single application of indole-3-carbinol (I3C), a glucobrassicin derivative present in cruciferous vegetables, significantly inhibited the propoxur-induced micronuclei formation when it was given at the dose level of 500 mg/kg body weight 48 hr before the single application of propoxur. Therefore, it seems that propoxur is mutagenic in the above test systems and I3C inhibited the mutagenicity of propoxur significantly.

  15. EGFR-dependent Impact of Indol-3-Carbinol on Radiosensitivity 
of Lung Cancer Cells

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    Xiao XIAO

    2012-07-01

    Full Text Available Background and objective Indole-3-carbinol (I3C is a naturally occurring phytochemical found in cruciferous vegetables. The aim of the present study is to investigate the influence of I3C on radiosensitivity in epidermal growth factor receptor (EGFR-positive and EGFR-negative lung cancer cell lines. Methods Human lung adenocarcinoma NIH-H1975 cells and human lung squamous carcinoma NIH-H226 and NIH-H520 cells were routinely cultured in RPMI-1640. MTT assay and clonogenic assay were used to detect cell growth and survival, respectively. Western blot and RT-PRC assay was employed to detect EGFR protein and mRNA expression. Results 5 μmol/L of I3C significantly reduced radiosensitivity of EGFR-positive NIH-H1975 and NIH-H226 cells, but failed to affect radiosensitivity of EGFR-negative NIH-H520 cells. Furthermore, I3C caused an increased expression of total EGFR and pEGFR (Y845 protein in NIH-H1975 and NIH-H226 cell lines, but not in NIH-H520 cell line. A reduction of EGFR expression by EGFR-siRNA significantly inhibited I3C-caused radioresistance in NIH-H1975 cells. Conclusion Our data presented here for the first time demonstrate that I3C reduces radiosensitivity of lung cancer cells by mediating EGFR expression, indicating that EGFR may be an important target for I3C-mediated radioresistance in lung cancer.

  16. Characterization of acute biliary hyperplasia in Fisher 344 rats administered the indole-3-carbinol analog, NSC-743380.

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    Eldridge, Sandy R; Covey, Joseph; Morris, Joel; Fang, Bingliang; Horn, Thomas L; Elsass, Karen E; Hamre, John R; McCormick, David L; Davis, Myrtle A

    2014-12-15

    NSC-743380 (1-[(3-chlorophenyl)-methyl]-1H-indole-3-carbinol) is in early stages of development as an anticancer agent. Two metabolites reflect sequential conversion of the carbinol functionality to a carboxaldehyde and the major metabolite, 1-[(3-chlorophenyl)-methyl]-1H-indole-3-carboxylic acid. In an exploratory toxicity study in rats, NSC-743380 induced elevations in liver-associated serum enzymes and biliary hyperplasia. Biliary hyperplasia was observed 2 days after dosing orally for 2 consecutive days at 100mg/kg/day. Notably, hepatotoxicity and biliary hyperplasia were observed after oral administration of the parent compound, but not when major metabolites were administered. The toxicities of a structurally similar but pharmacologically inactive molecule and a structurally diverse molecule with a similar efficacy profile in killing cancer cells in vitro were compared to NSC-743380 to explore scaffold versus target-mediated toxicity. Following two oral doses of 100mg/kg/day given once daily on two consecutive days, the structurally unrelated active compound produced hepatic toxicity similar to NSC-743380. The structurally similar inactive compound did not, but, lower exposures were achieved. The weight of evidence implies that the hepatotoxicity associated with NSC-743380 is related to the anticancer activity of the parent molecule. Furthermore, because biliary hyperplasia represents an unmanageable and non-monitorable adverse effect in clinical settings, this model may provide an opportunity for investigators to use a short-duration study design to explore biomarkers of biliary hyperplasia.

  17. Encapsulation of indole-3-carbinol and 3'3'-diindolylmethane in zein/carboxymethyl chitosan nanoparticles with controlled release property and improved stability

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    Indole-3-carbinol (I3C) and diindolylmethane (DIM) are two bioactive compounds from Cruciferous vegetables. Their stabilities are the major challenges for their pharmaceutical applications. In this study, zein and zein/carboxymethyl chitosan (zein/CMCS) nanoparticles have been prepared to encapsulat...

  18. Indole-3-carbinol (I3C) increases apoptosis, represses growth of cancer cells, and enhances adenovirus-mediated oncolysis.

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    Chen, Lan; Cheng, Pei-Hsin; Rao, Xiao-Mei; McMasters, Kelly M; Zhou, Heshan Sam

    2014-09-01

    Epidemiological studies suggest that high intake of cruciferous vegetables is associated with a lower risk of cancer. Experiments have shown that indole-3-carbinol (I3C), a naturally occurring compound derived from cruciferous vegetables, exhibits potent anticarcinogenic properties in a wide range of cancers. In this study, we showed that higher doses of I3C (≥400 μM) induced apoptotic cancer cell death and lower doses of I3C (≤200 μM) repressed cancer cell growth concurrently with suppressed expression of cyclin E and its partner CDK2. Notably, we found that pretreatment with low doses of I3C enhanced Ad-mediated oncolysis and cytotoxicity of human carcinoma cells by synergistic upregulation of apoptosis. Thus, the vegetable compound I3C as a dietary supplement may benefit cancer prevention and improve Ad oncolytic therapies.

  19. Characterization of acute biliary hyperplasia in Fisher 344 Rats administered the Indole-3-Carbinol Analog, NSC-743380

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    Eldridge, Sandy R.; Covey, Joseph; Morris, Joel [Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, 20892 (United States); Fang, Bingliang [The University of Texas MD Anderson Cancer Center, Houston, TX, 77030 (United States); Horn, Thomas L. [IIT Research Institute, Chicago, IL, 60616 (United States); Elsass, Karen E. [Battelle Columbus, Columbus, OH, 43201 (United States); Hamre, John R. [Investigative Toxicology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702 (United States); McCormick, David L. [IIT Research Institute, Chicago, IL, 60616 (United States); Davis, Myrtle A., E-mail: myrtledavis@mail.nih.gov [Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, 20892 (United States)

    2014-12-15

    NSC-743380 (1-[(3-chlorophenyl)-methyl]-1H-indole-3-carbinol) is in early stages of development as an anticancer agent. Two metabolites reflect sequential conversion of the carbinol functionality to a carboxaldehyde and the major metabolite, 1-[(3-chlorophenyl)-methyl]-1H-indole-3-carboxylic acid. In an exploratory toxicity study in rats, NSC-743380 induced elevations in liver-associated serum enzymes and biliary hyperplasia. Biliary hyperplasia was observed 2 days after dosing orally for 2 consecutive days at 100 mg/kg/day. Notably, hepatotoxicity and biliary hyperplasia were observed after oral administration of the parent compound, but not when major metabolites were administered. The toxicities of a structurally similar but pharmacologically inactive molecule and a structurally diverse molecule with a similar efficacy profile in killing cancer cells in vitro were compared to NSC-743380 to explore scaffold versus target-mediated toxicity. Following two oral doses of 100 mg/kg/day given once daily on two consecutive days, the structurally unrelated active compound produced hepatic toxicity similar to NSC-743380. The structurally similar inactive compound did not, but, lower exposures were achieved. The weight of evidence implies that the hepatotoxicity associated with NSC-743380 is related to the anticancer activity of the parent molecule. Furthermore, because biliary hyperplasia represents an unmanageable and non-monitorable adverse effect in clinical settings, this model may provide an opportunity for investigators to use a short-duration study design to explore biomarkers of biliary hyperplasia. - Highlights: • NSC-743380 induced biliary hyperplasia in rats. • Toxicity of NSC-743380 appears to be related to its anticancer activity. • The model provides an opportunity to explore biomarkers of biliary hyperplasia.

  20. Suppression of Inflammatory Mediators by Cruciferous Vegetable-Derived Indole-3-Carbinol and Phenylethyl Isothiocyanate in Lipopolysaccharide-Activated Macrophages

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    Jo-Ting Tsai

    2010-01-01

    Full Text Available This study was aimed to examine the effects of indole-3-carbinol (I3C and β-phenylethyl isothiocyanate (PEITC, bioactive components present in cruciferous vegetable, on the production of inflammatory mediators, including nitric oxide (NO, tumor necrosis factor-α (TNF-α and interleukin-10 (IL-10, in lipopolysaccharide- (LPS- stimulated RAW 264.7 macrophages. Possible mechanisms of the NO-inhibitory effects were also explored. The results indicated that I3C and PEITC inhibited NO production, and this suppression was associated with decreased production of TNF-α and IL-10 by activated macrophages. In addition, I3C suppressed NO production even after the inducible nitric oxide synthase (iNOS protein had been produced, but such an inhibitory effect was not observed in cells treated with PEITC. Furthermore, both compounds reduced the NO contents generated from an NO donor in a cell-free condition, suggesting that the increased NO clearance may have contributed to the NO-inhibitory effects. In summary, both I3C and PEITC possessed antiinflammatory effects by inhibiting the productions of NO, TNF-α, and IL-10, although the NO-inhibitory effects may have involved in different mechanisms.

  1. Evaluation of antiulcer activity of indole-3-carbinol and/or omeprazole on aspirin-induced gastric ulcer in rats.

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    El-Shinnawy, Nashwa A; Abd-Elmageid, Samira A; Alshailabi, Eda M A

    2014-05-01

    The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing.

  2. 3,3′-Diindolylmethane, but not indole-3-carbinol, inhibits histone deacetylase activity in prostate cancer cells

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    Beaver, Laura M., E-mail: beaverl@onid.orst.edu [Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331 (United States); School of Biological and Population Health Sciences, Oregon State University, 103 Milam Hall, Corvallis, OR 97331 (United States); Yu, Tian-Wei, E-mail: david.yu@oregonstate.edu [Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331 (United States); Sokolowski, Elizabeth I., E-mail: sokolowe@onid.orst.edu [School of Biological and Population Health Sciences, Oregon State University, 103 Milam Hall, Corvallis, OR 97331 (United States); Williams, David E., E-mail: david.williams@oregonstate.edu [Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331 (United States); Department of Environmental and Molecular Toxicology, Oregon State University, 1007 Agriculture and Life Sciences Building, Corvallis, OR 97331 (United States); Dashwood, Roderick H., E-mail: rod.dashwood@oregonstate.edu [Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331 (United States); Department of Environmental and Molecular Toxicology, Oregon State University, 1007 Agriculture and Life Sciences Building, Corvallis, OR 97331 (United States); Ho, Emily, E-mail: Emily.Ho@oregonstate.edu [Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331 (United States); School of Biological and Population Health Sciences, Oregon State University, 103 Milam Hall, Corvallis, OR 97331 (United States)

    2012-09-15

    Increased consumption of cruciferous vegetables is associated with a reduced risk of developing prostate cancer. Indole-3-carbinol (I3C) and 3,3′-diindolylmethane (DIM) are phytochemicals derived from cruciferous vegetables that have shown promise in inhibiting prostate cancer in experimental models. Histone deacetylase (HDAC) inhibition is an emerging target for cancer prevention and therapy. We sought to examine the effects of I3C and DIM on HDACs in human prostate cancer cell lines: androgen insensitive PC-3 cells and androgen sensitive LNCaP cells. I3C modestly inhibited HDAC activity in LNCaP cells by 25% but no inhibition of HDAC activity was detected in PC-3 cells. In contrast, DIM significantly inhibited HDAC activity in both cell lines by as much as 66%. Decreases in HDAC activity correlated with increased expression of p21, a known target of HDAC inhibitors. DIM treatment caused a significant decrease in the expression of HDAC2 protein in both cancer cell lines but no significant change in the protein levels of HDAC1, HDAC3, HDAC4, HDAC6 or HDAC8 was detected. Taken together, these results show that inhibition of HDAC activity by DIM may contribute to the phytochemicals' anti-proliferative effects in the prostate. The ability of DIM to target aberrant epigenetic patterns, in addition to its effects on detoxification of carcinogens, may make it an effective chemopreventive agent by targeting multiple stages of prostate carcinogenesis. -- Highlights: ► DIM inhibits HDAC activity and decreases HDAC2 expression in prostate cancer cells. ► DIM is significantly more effective than I3C at inhibiting HDAC activity. ► I3C has no effect on HDAC protein expression. ► Inhibition of HDAC activity by DIM is associated with increased p21 expression. ► HDAC inhibition may be a novel epigenetic mechanism for cancer prevention with DIM.

  3. Differential modulation of dibenzo[def,p]chrysene transplacental carcinogenesis: Maternal diets rich in indole-3-carbinol versus sulforaphane

    Energy Technology Data Exchange (ETDEWEB)

    Shorey, Lyndsey E.; Madeen, Erin P. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States); Atwell, Lauren L.; Ho, Emily [Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States); School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331 (United States); Löhr, Christiane V. [Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States); College of Veterinary Medicine, Oregon State University, Corvallis, OR, 97331 (United States); Pereira, Clifford B. [Department of Statistics, Oregon State University, Corvallis, OR, 97331 (United States); Dashwood, Roderick H. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States); Williams, David E., E-mail: david.williams@oregonstate.edu [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States)

    2013-07-01

    Cruciferous vegetable components have been documented to exhibit anticancer properties. Targets of action span multiple mechanisms deregulated during cancer progression, ranging from altered carcinogen metabolism to the restoration of epigenetic machinery. Furthermore, the developing fetus is highly susceptible to changes in nutritional status and to environmental toxicants. Thus, we have exploited a mouse model of transplacental carcinogenesis to assess the impact of maternal dietary supplementation on cancer risk in offspring. In this study, transplacental and lactational exposure to a maternal dose of 15 mg/Kg B.W. of dibenzo[def,p]chrysene (DBC) resulted in significant morbidity of offspring due to an aggressive T-cell lymphoblastic lymphoma. As in previous studies, indole-3-carbinol (I3C, feed to the dam at 100, 500 or 1000 ppm), derived from cruciferous vegetables, dose-dependently reduced lung tumor multiplicity and also increased offspring survival. Brussels sprout and broccoli sprout powders, selected for their relative abundance of I3C and the bioactive component sulforaphane (SFN), respectively, surprisingly enhanced DBC-induced morbidity and tumorigenesis when incorporated into the maternal diet at 10% wt/wt. Purified SFN, incorporated in the maternal diet at 400 ppm, also decreased the latency of DBC-dependent morbidity. Interestingly, I3C abrogated the effect of SFN when the two purified compounds were administered in equimolar combination (500 ppm I3C and 600 ppm SFN). SFN metabolites measured in the plasma of neonates positively correlated with exposure levels via the maternal diet but not with offspring mortality. These findings provide justification for further study of the safety and bioactivity of cruciferous vegetable phytochemicals at supplemental concentrations during the perinatal period. - Highlights: • Dietary supplementation may modulate cancer risk in a mouse model of lymphoma. • Cruciferous vegetables may not contain sufficient I3C

  4. Characterization of the N-methoxyindole-3-carbinol (NI3C)–Induced Cell Cycle Arrest in Human Colon Cancer Cell Lines

    DEFF Research Database (Denmark)

    Neave, Antje S.; Sarup, Sussi; Seidelin, Michel;

    2005-01-01

    of cellular proliferation, NI3C caused an accumulation of HCT-116 cells in the G2/M phase, in contrast to I3C, which led to an accumulation of the colon cells in G0/G1 phase. Furthermore, NI3C delays the G1-S phase transition of synchronized HCT-116 cells. The indole-mediated cell-cycle arrest may be related......Recent results have shown that indole-3-carbinol (I3C) inhibits the cellular growth of human cancer cell lines. In some cruciferous vegetables, another indole, N-methoxyindole-3-carbinol (NI3C), is found beside I3C. Knowledge about the biological effects of NI3C is limited. The aim of the present...... study was to show the effect of NI3C on cell growth of two human colon cancer cell lines, DLD-1 and HCT-116. For the first time it is shown that NI3C inhibits cellular growth of DLD-1 and HCT-116 and that NI3C is a more potent inhibitor of cell proliferation than I3C. In addition to the inhibition...

  5. Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

    Directory of Open Access Journals (Sweden)

    Gescher Andreas

    2003-01-01

    Full Text Available Abstract Background Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines. Methods Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO2 from 14C-labelled substrate, and polyamine levels were measured by HPLC. Results I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G2/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration. Conclusion While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative

  6. Attenuation of Carcinogenesis and the Mechanism Underlying by the Influence of Indole-3-carbinol and Its Metabolite 3,3′-Diindolylmethane: A Therapeutic Marvel

    Directory of Open Access Journals (Sweden)

    V. L. Maruthanila

    2014-01-01

    Full Text Available Rising evidence provides credible support towards the potential role of bioactive products derived from cruciferous vegetables such as broccoli, cauliflower, kale, cabbage, brussels sprouts, turnips, kohlrabi, bok choy, and radishes. Many epidemiological studies point out that Brassica vegetable protects humans against cancer since they are rich sources of glucosinolates in addition to possessing a high content of flavonoids, vitamins, and mineral nutrients. Indole-3-carbinol (I3C belongs to the class of compounds called indole glucosinolate, obtained from cruciferous vegetables, and is well-known for tits anticancer properties. In particular, I3C and its dimeric product, 3,3′-diindolylmethane (DIM, have been generally investigated for their value against a number of human cancers in vitro as well as in vivo. This paper reviews an in-depth study of the anticancer activity and the miscellaneous mechanisms underlying the anticarcinogenicity thereby broadening its therapeutic marvel.

  7. LC-MS/MS quantification of sulforaphane and indole-3-carbinol metabolites in human plasma and urine after dietary intake of selenium-fortified broccoli.

    Science.gov (United States)

    Hauder, Johanna; Winkler, Stefanie; Bub, Achim; Rüfer, Corinna E; Pignitter, Marc; Somoza, Veronika

    2011-08-10

    This study aimed at developing a sensitive LC-MS/MS method for the quantification of sulforaphane (SFN) and indole-3-carbinol metabolites in plasma and urine after dietary intake of regular and selenium-fertilized broccoli using stable isotope dilution analysis. In a three-armed, placebo-controlled, randomized human intervention study with 76 healthy volunteers, 200 g of regular (485 μg of total glucosinolates and <0.01 μg of selenium per gram fresh weight) or selenium-fertilized broccoli (589 μg of total glucosinolates and 0.25 μg of selenium per gram fresh weight) was administered daily for 4 weeks. Glucoraphanin and glucobrassicin metabolites quantified in plasma and urine were SFN-glutathione, SFN-cysteine, SFN-cysteinylglycine, SFN-acetylcysteine, and indole-3-carboxaldehyde, indole-3-carboxylic acid, and ascorbigen, respectively. Dietary intake of selenium-fertilized broccoli increased serum selenium concentration analyzed by means of atomic absorption spectroscopy by up to 25% (p < 0.001), but affected neither glucosinolate concentrations in broccoli nor their metabolite concentrations in plasma and urine compared to regular broccoli.

  8. Inhibition of cell proliferation and in vitro markers of angiogenesis by indole-3-carbinol, a major indole metabolite present in cruciferous vegetables.

    Science.gov (United States)

    Wu, Hsiao-Ting; Lin, Shyh-Hsiang; Chen, Yue-Hwa

    2005-06-29

    A variety of studies have suggested a cancer protective role of cruciferous vegetables. In the present study, we investigated the effect of indole-3-carbinol (I3C), a major indole metabolite in cruciferous vegetables, on cell proliferation and in vitro markers of angiogenesis in phorbol myristate acetate (PMA)-stimulated endothelial EA hy926 cells. The results showed that I3C inhibited the growth of EA hy926 cells in a concentration-dependent manner. The capillary-like tube formation by PMA-activated endothelial cells was significantly suppressed by I3C, and such inhibition was associated with decreased vascular endothelial growth factor (VEGF) and increased interleukin-8 (IL-8) secretion, but not with the expression of VEGF receptor-2 protein. Additionally, gelatin zymography analysis indicated that I3C suppressed activities of matrix metalloproteinases-2 (MMP-2) and MMP-9 stimulated by PMA. These results suggest that the dietary I3C may be useful in the treatment of human cancers and angiogenic diseases.

  9. Cooperative antiproliferative signaling by aspirin and indole-3-carbinol targets microphthalmia-associated transcription factor gene expression and promoter activity in human melanoma cells.

    Science.gov (United States)

    Poindexter, Kevin M; Matthew, Susanne; Aronchik, Ida; Firestone, Gary L

    2016-04-01

    Antiproliferative signaling of combinations of the nonsteroidal anti-inflammatory drug acetylsalicylic acid (aspirin) and indole-3-carbinol (I3C), a natural indolecarbinol compound derived from cruciferous vegetables, was investigated in human melanoma cells. Melanoma cell lines with distinct mutational profiles were sensitive to different extents to the antiproliferative response of aspirin, with oncogenic BRAF-expressing G361 cells and wild-type BRAF-expressing SK-MEL-30 cells being the most responsive. I3C triggered a strong proliferative arrest of G361 melanoma cells and caused only a modest decrease in the proliferation of SK-MEL-30 cells. In both cell lines, combinations of aspirin and I3C cooperatively arrested cell proliferation and induced a G1 cell cycle arrest, and nearly ablated protein and transcript levels of the melanocyte master regulator microphthalmia-associated transcription factor isoform M (MITF-M). In melanoma cells transfected with a -333/+120-bp MITF-M promoter-luciferase reporter plasmid, treatment with aspirin and I3C cooperatively disrupted MITF-M promoter activity, which accounted for the loss of MITF-M gene products. Mutational analysis revealed that the aspirin required the LEF1 binding site, whereas I3C required the BRN2 binding site to mediate their combined and individual effects on MITF-M promoter activity. Consistent with LEF1 being a downstream effector of Wnt signaling, aspirin, but not I3C, downregulated protein levels of the Wnt co-receptor LDL receptor-related protein-6 and β-catenin and upregulated the β-catenin destruction complex component Axin. Taken together, our results demonstrate that aspirin-regulated Wnt signaling and I3C-targeted signaling pathways converge at distinct DNA elements in the MITF-M promoter to cooperatively disrupt MITF-M expression and melanoma cell proliferation.

  10. Natural indoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression

    Energy Technology Data Exchange (ETDEWEB)

    Busbee, Philip B.; Nagarkatti, Mitzi; Nagarkatti, Prakash S., E-mail: prakash@mailbox.sc.edu

    2014-01-01

    Staphylococcal enterotoxin B (SEB) is a potent exotoxin produced by the Staphylococcus aureus. This toxin is classified as a superantigen because of its ability to directly bind with MHC-II class molecules followed by activation of a large proportion of T cells bearing specific Vβ-T cell receptors. Commonly associated with classic food poisoning, SEB has also been shown to induce toxic shock syndrome, and is also considered to be a potential biological warfare agent because it is easily aerosolized. In the present study, we assessed the ability of indole-3-carbinol (I3C) and one of its byproducts, 3,3′-diindolylmethane (DIM), found in cruciferous vegetables, to counteract the effects of SEB-induced activation of T cells in mice. Both I3C and DIM were found to decrease the activation, proliferation, and cytokine production by SEB-activated Vβ8{sup +} T cells in vitro and in vivo. Interestingly, inhibitors of histone deacetylase class I (HDAC-I), but not class II (HDAC-II), showed significant decrease in SEB-induced T cell activation and cytokine production, thereby suggesting that epigenetic modulation plays a critical role in the regulation of SEB-induced inflammation. In addition, I3C and DIM caused a decrease in HDAC-I but not HDAC-II in SEB-activated T cells, thereby suggesting that I3C and DIM may inhibit SEB-mediated T cell activation by acting as HDAC-I inhibitors. These studies not only suggest for the first time that plant-derived indoles are potent suppressors of SEB-induced T cell activation and cytokine storm but also that they may mediate these effects by acting as HDAC inhibitors. - Highlights: • I3C and DIM reduce SEB-induced T cell activation and inflammatory cytokines. • Inhibiting class I HDACs reduces T cell activation and inflammatory cytokines. • Inhibiting class II HDACs increases T cell activation and inflammatory cytokines. • I3C and DIM selectively reduce mRNA expression of class I HDACs. • Novel use and mechanism to counteract

  11. Ultraviolet radiation-induced non-melanoma skin cancer in the Crl:SKH1:hr-BR hairless mouse: augmentation of tumor multiplicity by chlorophyllin and protection by indole-3-carbinol.

    Science.gov (United States)

    Cope, R B; Loehr, C; Dashwood, R; Kerkvliet, N I

    2006-05-01

    Over 1 million new cases of ultraviolet radiation-induced non-melanoma skin cancers (NMSC) per year now occur in the USA and the incidence of these diseases continues to increase. New preventative strategies are required. The hypothesis tested was that dietary administration of the putative cancer chemopreventatives sodium-copper-chlorophyllin (Chlor) or indole-3-carbinol (I3C) would inhibit UV-induced skin carcinogenesis in the Crl:SKH1:hr-BR hairless mouse. Groups of 20 mice were pre-fed isocaloric/isonutritive 20% corn-oil AIN-76a based diets that contained either Chlor (1.52 g%), I3C (5.08 g%) or no chemopreventative (control) for 2 weeks followed by exposure of their dorsal skin to a 10 week incremental, sub-erythemal, carcinogenic simulated solar UV exposure regime. Feeding was continued for the duration of the experiment. Matched non-UV exposed dietary groups were also included in the experimental design. The diets had no significant (p > 0.05) effect on body weight, feed consumption, cutaneous methanol-extractable UV photoprotective substances or on cutaneous UV-reflective characteristics. By day 180, UV-irradiated mice fed the Chlor had a significantly (p 0.05) affect UV-induced systemic suppression of contact hypersensitivity responses. These results demonstrate augmentation of the UV-induced cutaneous carcinogenic process by dietary chlorophyllin and protection from this carcinogenic process by indole-3-carbinol via mechanisms that do not involve changes in skin optical properties, modulation of photoimmunosuppression or caloric/nutrient effects.

  12. Indole-3-carbinol induces a rat liver glutathione transferase subunit (Yc2) with high activity toward aflatoxin B1 exo-epoxide. Association with reduced levels of hepatic aflatoxin-DNA adducts in vivo.

    Science.gov (United States)

    Stresser, D M; Williams, D E; McLellan, L I; Harris, T M; Bailey, G S

    1994-01-01

    Aflatoxin B1 (AFB1), a metabolite of the grain mold Aspergillus flavus, is a potent hepatocarcinogen and widespread contaminant of human food supplies. AFB1-induced tumors or preneoplastic lesions in experimental animals can be inhibited by cotreatment with several compounds, including indole-3-carbinol (I3C), a component of cruciferous vegetables, and the well-known Ah receptor agonist beta-naphthoflavone (BNF). This study examines the influence of these two agents on the AFB1-glutathione detoxication pathway and AFB1-DNA adduction in rat liver. After 7 days of feeding approximately equally inhibitory doses of I3C (0.2%) or BNF (0.04%) alone or in combination, male Fischer 344 rats were administered [3H]AFB1 (0.5 mg/kg, 480 microCi/kg) intraperitoneally and killed 2 hr later. All three experimental diets inhibited in vivo AFB1-DNA adduction (BNF, 46%; I3C, 68%; combined, 51%). Based on Western blots using antibodies specific for the glutathione S-transferase (GST), subunit Yc2 (subunit 10) appeared to be substantially elevated by the diets containing I3C (I3C diet, 4.0-fold increase in band density; combined diet, 2.8-fold). The BNF diet appeared to elevate Yc2 to a lesser extent (2.2-fold increase in band density).(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Antiangiogenic effects of indole-3-carbinol and 3,3'-diindolylmethane are associated with their differential regulation of ERK1/2 and Akt in tube-forming HUVEC.

    Science.gov (United States)

    Kunimasa, Kazuhiro; Kobayashi, Tomomi; Kaji, Kazuhiko; Ohta, Toshiro

    2010-01-01

    We previously reported that indole-3-carbinol (I3C), found in cruciferous vegetables, suppresses angiogenesis in vivo and in vitro. However, the underlying molecular mechanisms still remain unclear. Antiangiogenic effects of its major metabolite, 3,3'-diindolylmethane (DIM), also have not been fully elucidated. In this study, we investigated the effects of these indoles on angiogenesis and tested a hypothesis that I3C and DIM inhibit angiogenesis and induce apoptosis by affecting angiogenic signal transduction in human umbilical vein endothelial cells (HUVEC). We found that I3C and DIM at 25 micromol/L significantly inhibited tube formation and only DIM induced a significant increase in apoptosis in tube-forming HUVEC. DIM showed a stronger antiangiogenic activity than I3C. At the molecular level, I3C and DIM markedly inactivated extracellular signal-regulated kinase 1/2 (ERK1/2) and the inhibitory effect of DIM was significantly greater than that of I3C. DIM treatment also resulted in activation of the caspase pathway and inactivation of Akt, whereas I3C did not affect them. These results indicate that I3C and DIM had a differential potential in the regulation of the 2 principal survival signals, ERK1/2 and Akt, in endothelial cells. We also demonstrated that pharmacological inhibition of ERK1/2 and/or Akt was enough to inhibit tube formation and induce caspase-dependent apoptosis in tube-forming HUVEC. We conclude that both I3C and DIM inhibit angiogenesis at least in part via inactivation of ERK1/2 and that inactivation of Akt by DIM is responsible for its stronger antiangiogenic effects than those of I3C.

  14. Indole-3-carbinol induces cMYC and IAP-family downmodulation and promotes apoptosis of Epstein-Barr virus (EBV)-positive but not of EBV-negative Burkitt's lymphoma cell lines.

    Science.gov (United States)

    Perez-Chacon, Gema; de Los Rios, Cristobal; Zapata, Juan M

    2014-11-01

    Indole-3-carbinol (I3C) is a natural product found in broadly consumed plants of the Brassica genus, such as broccoli, cabbage, and cauliflower, which exhibits anti-tumor effects through poorly defined mechanisms. I3C can be orally administered and clinical trials have demonstrated that I3C and derivatives are safe in humans. In this study we show that I3C efficiently induces apoptosis in cell lines derived from EBV-positive Burkitt's lymphomas (virus latency I/II), while it does not have any cytotoxic activity against EBV-negative Burkitt's lymphomas and immortalized EBV-infected lymphoblastoid cell lines (virus latency III). The effect of I3C in EBV-positive Burkitt's lymphoma is very specific, since only I3C and its C6-methylated derivative, but not other 3-substituted indoles, have an effect on cell viability. I3C treatment caused apoptosis characterized by loss of mitochondria membrane potential and caspase activation. I3C alters the expression of proteins involved in the control of apoptosis and transcription regulation in EBV-positive Burkitt's lymphoma cell lines. Among those, cMYC, cIAP1/2 and XIAP downmodulation at mRNA and protein level precede apoptosis induction, thus suggesting a role in I3C cytotoxicity. We also showed that I3C and, more particularly, its condensation dimer 3,3'-diindolylmethane (DIM) prolonged survival and reduced tumor burden of mice xenotransplanted with EBV-positive Burkitt's lymphoma Daudi cells. In summary these results, together with previous reports from clinical trials indicating the lack of toxicity in humans of I3C and derivatives, support the use of these compounds as a new therapeutic approach for treating patients with endemic (EBV-positive) Burkitt's lymphoma.

  15. Tumors from rats given 1,2-dimethylhydrazine plus chlorophyllin or indole-3-carbinol contain transcriptional changes in beta-catenin that are independent of beta-catenin mutation status.

    Science.gov (United States)

    Wang, Rong; Dashwood, W Mohaiza; Bailey, George S; Williams, David E; Dashwood, Roderick H

    2006-10-10

    Tumors induced in the rat by 1,2-dimethylhydrazine (DMH) contain mutations in beta-catenin, but the spectrum of such mutations can be influenced by phytochemicals such as chlorophyllin (CHL) and indole-3-carbinol (I3C). In the present study, we determined the mutation status of beta-catenin in more than 50 DMH-induced colon tumors and small intestine tumors, and compared this with the concomitant expression of beta-catenin mRNA using quantitative real-time RT-PCR analysis. In total, 19/57 (33%) of the tumors harbored mutations in beta-catenin, and 14/19 (74%) of the genetic changes substituted amino acids adjacent to Ser33, a key site for phosphorylation and beta-catenin degradation. These tumors were found to express a 10-fold range of beta-catenin mRNA levels, independent of the beta-catenin mutation status and phytochemical exposure, i.e. CHL or I3C given post-initiation. However, beta-catenin mRNA levels were strongly correlated with mRNA levels of c-myc, c-jun and cyclin D1, which are targets of beta-catenin/Tcf signaling. Tumors with the highest levels of beta-catenin mRNA often had over-expressed beta-catenin protein, and those with lower beta-catenin mRNA typically had low beta-catenin protein expression, but there were exceptions (high beta-catenin mRNA/low beta-catenin protein, or vice versa). We conclude that DMH-induced mutations stabilize beta-catenin protein in tumors, which increase c-myc, c-jun and cyclin D1, but there also can be over-expression of beta-catenin itself at the mRNA level, contributing to high beta-catenin protein levels. Similar findings have been reported in primary human colon cancers and their liver metastases, compared with matched normal-looking tissue. Thus, further studies are warranted on the mechanisms that upregulate beta-catenin at the transcriptional level in human and rodent colon cancers.

  16. 吲哚-3-甲醇对肺癌细胞放射敏感性的EGFR依赖性调节%EGFR-dependent Impact of Indol-3-Carbinol on Radiosensitivity of Lung Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    肖骁; 孟庆慧; 徐加英; 焦旸; Eliot M Rosen; 樊赛军

    2012-01-01

    背景与目的 吲哚-3-甲醇(indole-3-carbinol,I3C)是十字花科蔬菜中一种主要的有效植物化学物质,且具有防癌和抗癌作用.本研究旨在观察I3C是否影响表皮生长因子受体(epidermal growth factor receptor,EGFR )表达水平不同的肺癌细胞放射敏感性.方法 采用MTT和克隆形成实验方法分别检测肺癌细胞的生长和存活率;siRNA转染方法降低细胞中EGFR蛋白表达水平;Western blot和RT-PCR法分别测定EGFR蛋白和mRNA的表达.结果 采用无明显毒副作用的5 μmol/L剂量的I3C预处理明显降低了EGFR表达阳性的人肺腺癌H1975和人肺鳞癌H226细胞对γ-射线照射的放射敏感性,而I3C对EGFR表达阴性的人肺鳞癌NIH-H520细胞的放射敏感性则影响非常小.Western blot结果显示I3C可以增加H1975和H226细胞中EGFR蛋白的表达水平和Y845位点磷酸化水平.EGFR siRNA降低了NIH-H1975细胞中EGFR蛋白的表达,增加了细胞的放射敏感性,并有效地降低和抑制了I3C导致的细胞耐辐射效应.结论 我们的研究结果首次证实I3C可以通过调节EGFR表达和磷酸化水平从而影响肺癌细胞的放射治疗敏感性,提示EGFR可能是I3C影响肺癌放射治疗敏感性的重要靶蛋白.%Background and objective Indole-3-carbinol (I3C) is a naturally occurring phytochemical found in cruciferous vegetables. The aim of the present study is to investigate the influence of 13C on radiosensitivity in epidermal growth factor receptor (EGFR)-positive and EGFR-negative lung cancer cell lines. Methods Human lung adenocard-noma NIH-H197S cells and human lung squamous carcinoma NIH-H226 and NIH-H520 cells were routinely cultured in RPMI-1640. MTT assay and donogenic assay were used to detect cell growth and survival, respectively. Western blot and RT-PRC assay was employed to detect EGFR protein and mRNA expression. Results 5 祄ol/L of I3C significantly reduced radiosensitivity of EGFR-positive NIH-H197S and NIH-H226

  17. Therapeutic effects of indole-3-carbinol on multiple hepatotoxic factors-induced liver fibrosis in rats%吲哚-3-原醇对复合因素所致肝纤维化大鼠的治疗作用及部分机制研究

    Institute of Scientific and Technical Information of China (English)

    高爱梅; 平洁; 汪晖

    2011-01-01

    目的 观察吲哚-3-原醇(I3C)对复合因素诱导肝纤维化大鼠的治疗作用并探讨其可能机制.方法 采用复合因素(CCl4、酒精、高脂低蛋白饲料)制备大鼠肝纤维化模型,用I3C治疗10 d后,检测大鼠肝组织的羟脯氨酸(Hyp)、超氧化物歧化酶(SOD)、丙二醛(MDA)的含量;通过HE及Masson三色染色,观察肝脏病理学改变及胶原含量改变;免疫组化法观察肝脏中α-平滑肌肌动蛋白(α-SMA)的表达;Western blot检测肝组织中基质金属蛋白-2(MMP-2)的表达.结果 与模型对照组比较,I3C治疗组肝组织Hyp含量降低,SOD活性升高,以大剂量(12 mg·kg-1)组明显(P<0.01),MMP-2蛋白表达升高;病理学改变尤其是胶原纤维的沉积明显减轻(P<0.05),α-SMA表达也降低.结论 I3C可促进复合因素所致大鼠肝纤维化模型的恢复,其机制与降低肝组织氧化应激、减少活化HSC数量以及促进基质胶原降解有关.%Aim To investigate the effects of indole-3carbinol ( I3C ) on multiple hepatotoxic factors-induced liver fibrosis in rats and its possible mechanism. Methods Male Wistar rats were divided randomly into six groups , a normal control group , a model control group ,a I3C control group and fibrotic groups treated with three different doses of I3C. The fibrotic model was induced by multiple hepatotoxic factors, including carbon tetrachloride. ethanol and high fat/low proteins for 4 weeks . After completing models , rats in treatment groups were administered I3C 3. 6 and 12 mg · kg-1 through intraperitoneal injection, daily for 10 days.Hepatic activity of superoxide dismutase ( SOD ), hepatic malondialdehyde ( MDA ) and hepatic hydroxy proline ( Hyp ) content were determined. The liver histology and immunohistochemistry with a-smooth muscle actin ( α-SMA ) were assayed. Meanwhile. the expression of matrix metalloproteinases-2 ( MMP-2 ) in liver was analyzed by Western blot. Results Compared with the fibrosis control group, hepatic

  18. Stepwise modification of titanium alkoxy chloride compounds by pyridine carbinol.

    Science.gov (United States)

    Boyle, Timothy J; Ottley, Leigh Anna M; Rodriguez, Mark A; Sewell, Robin M; Alam, Todd M; McIntyre, Sarah K

    2008-11-17

    The stepwise modifications of stoichiometric mixtures of titanium chloride (TiCl 4) and titanium iso-propoxide (Ti(OPr (i)) 4) by 2-pyridine methanol (H-OPy) led to the isolation of a systematically varied, novel family of compounds. The 3:1 reaction mixture of Ti(OPr (i)) 4:TiCl 4 yielded [Cl(OPr (i)) 2Ti(mu-OPr (i))] 2 ( 1). Modification of 1 with 1 and 2 equiv of H-OPy produced [Cl(OPr (i)) 2Ti(mu c-OPy)] 2 ( 2, where mu c = chelating bridge) and "(OPy) 2TiCl(OPr (i))" ( 3, not crystallographically characterized), respectively. Altering the Ti(OPr (i)) 4 to TiCl 4 stoichiometry to 1:1 led to isolation and identification of another dimeric species [Cl 2(OPr (i))Ti(mu-OPr (i))] 2 ( 4). Upon modification with 1 equiv of H-OPy, [Cl 2(OPr (i))Ti(mu c-OPy)] 2 ( 5) was isolated from toluene and (OPy)TiCl 2(OPr (i))(py) ( 6) from py. An additional equivalent of H-OPy led to the monomeric species (OPy) 2TiCl 2 ( 7). Because of the low solubility and similarity in constructs of these compounds, additional analytical data, such as the beryllium dome or BeD-XRD powder analyses, were used to verify the bulk samples, which were found to be in agreement with the single crystal structures.

  19. Effects of ultraviolet-B laser irradiation on lens α-crystallin and protection of indole-3-carbinol to chaperone activity of α-crystallin%紫外线-B激光照射对α晶状体蛋白的影响及3-吲哚甲醇对其分子伴侣活性的保护作用

    Institute of Scientific and Technical Information of China (English)

    张钦; 曹晓光; 裴雪婷; 鲍永珍

    2012-01-01

    与色氨酸代谢产物N-甲酰犬尿氨酸(N-FK)的荧光强度呈正相关(R2=0.949).CAT热凝聚实验表明,加入50 μmol/L和100μmol/L的I3C后,各强度的激光照射组α晶状体蛋白的相对A360值均明显高于对照组,差异有统计学意义(P=0.000);α晶状体蛋白分子伴侣功能下降幅度低于对照组,差异有统计学意义(P=0.000).分子伴侣活性随着激光照射能量的增加与不加入I3C的α晶状体蛋白相比降低变慢.结论 紫外线-B激光照射可以造成α晶状体蛋白分子结构的变化及分子伴侣活性的降低,I3C对于α晶状体蛋白分子伴侣活性具有保护作用.%Background Ultraviolet radiation is one of factors of the formation of age-related cataract.Indole-3-carbinol(I3C) is a plant chemical material with inhibitory effect on oxidative-induced cell damage and formation of amyloid fibrils,and the oxidative damage and amyloid fibrils are associated with cataract.However,the relationship between I3C and α-crystallin is in study. Objective This study was to evaluate the effects of ultraviolet-B laser irradiation on the secondary structure of α-crystallin and to explore the protection of I3C to chaperone activity of α-crystallin. Methods The fresh eyeballs were obtained from 1-year-old cattle to prepare the purified lens α-crystallin by gel chromatography.α-Crystallin was isolated from cattle lenses using gel chromatography.The purified α-crystallin was collected using fast protein liquid chromatography ( FPLC ) and exposed to 1:308 nmultraviolet-B at different irradiation intensities ( 23.75,118.75,475.00,1187.50,2375.00,4750.00,11 875.00,23 750.00 mJ/cm2 ) and then to ultraviolet-B 2:308 nm with irradiation intensities of 28 535.00,6730.00,3435.00,1910.00,1040.00 mJ/cm2.Ultraviolet-absorbance spectra,tryptophan fluorescence and N-formylkynurenine (N-FK)fluorescence spectra of both irradiated and non-irradiated α-crystallin were measured.I3C at the concentrations of 50 μmol/L and

  20. Effect of 4-methoxyindole-3-carbinol on the proliferation of colon cancer cells in vitro, when treated alone or in combination with indole-3-carbinol

    DEFF Research Database (Denmark)

    Kronbak, Remy; Duus, Fritz; Vang, Ole

    2010-01-01

    synergistic manner. Proliferation was inhibited by 100 microM 4MeOI3C after 48 h without affecting cell cycle phase distribution, indicating an overall-slowdown effect on the cell cycle. However, 200 microM 4MeOI3C caused a very high level of cell death and an accumulation of living cells in the G(0)/G(1...

  1. Studies and Applications of Metals for the Synthesis of Carbinols, Amides and Carbohydrates

    DEFF Research Database (Denmark)

    Osztrovszky, Gyorgyi

    the carbonyl addition was found to be faster or comparable to the protonation by the reagent. Project 2: Ruthenium catalyzed synthesis of amides from primary alcohols and amines The direct synthesis of amides from alcohols and amines with the simultaneous liberation of dihydrogen was previously discovered...... for the amidation. These two systems do not show any significant differences in reactivity indicating that the same catalytically active species is operating. Project 3: Synthesis of a trisaccharide probe as a putative dengue virus receptor At the Institute for Glycomics major research has been devoted to identify...

  2. Synthesis, stereochemistry, and pharmacology of some new (3-quinuclidyl) diheteroaryl-and aryl heteroaryl carbinols

    Energy Technology Data Exchange (ETDEWEB)

    Arbuzova, O.R.; Mikhlina, E.E.; Tupikina, S.M.; Turchin, K.F.; Zhirnikova, M.L.

    1986-11-01

    The investigation of the antisecretory and antiulcer activity was performed on hybrid male rats. The influence of the compounds on the gastric secretory function was determined by the method of Shai in the modification of Meyer. Gastric ulcers were induced in the rats by the single ip application of 30 mg of histamine. The data obtained indicate that compound (Ic.HCI) shows antisecretory action. Analysis relating to the chemical shifts of protons induced by Eu (DPM)/sub 3/ in the difuryl and dithienyl derivatives indicates that the other two substituents at c/sub 9/ can be determined correspondingly from the concurrence of difference of the signs of the shifts induced for the rotons of the given substituent.

  3. Enhanced photostability, radical scavenging and antitumor activity of indole-3-carbinol-loaded rose hip oil nanocapsules.

    Science.gov (United States)

    Gehrcke, Mailine; Giuliani, Laura Minussi; Ferreira, Luana Mota; Barbieri, Allanna Valentini; Sari, Marcel Henrique Marcondes; da Silveira, Elita Ferreira; Azambuja, Juliana Hofstatter; Nogueira, Cristina Wayne; Braganhol, Elizandra; Cruz, Letícia

    2017-05-01

    This study aimed to develop poly(ε-caprolactone) nanocapsules loaded with indole-3-cabinol (I3C) using rose hip oil (RHO) or medium chain triglycerides (MCT) as oil core. In vitro radical scavenging activity (DPPH method), hemolysis, and antitumor effects on breast (MCF-7) and glioma (C6) cells were conducted. Preformulation evaluations revealed that RHO is suitable to prepare the nanocapsules considering the log P determination and dissolution/swelling experiments of polymer films. The nanocapsules were prepared and presented adequate physicochemical characteristics as mean size around 250nm, polydispersity index values oil core (RHO or MCT) on these parameters. However, the photodegradation study demonstrated that RHO nanocapsules showed less degree of I3C degradation in comparison to MCT nanocapsules. The in vitro release profile showed that both nanocapsule suspensions demonstrated an initial burst effect followed by a prolonged I3C release. In addition, the formulations were considered hemocompatibles at 10μg/mL and showed an enhanced radical scavenging activity in comparison to free I3C. Moreover, nanocapsules prepared with RHO increased about two times the antitumor effect of I3C on MCF-7 and C6 cells without significant reduction of astrocyte cell viability. In conclusion, nanocapsule formulations developed in this study might be considered promising for cancer treatment.

  4. Tandem diastereo- and enantioselective preparation of aryl and alkyl cyclopropyl carbinols with three adjacent stereocenters using perhydrobenzoxazines and diethylzinc.

    Science.gov (United States)

    Infante, Rebeca; Nieto, Javier; Andrés, Celia

    2014-01-14

    The enantio- and diastereoselective one-pot ethylation/cyclopropanation is efficiently promoted by a chiral perhydrobenzoxazine. The catalytic system tolerates a wide range of di- and trisubstituted α,β-unsaturated aldehydes and has been found to be highly diastereo- and enantioselective. Enals leading to intermediates lacking allylic strain or with either A(1,2) or A(1,3) strain afford the corresponding syn hydroxycyclopropanes very selectively. While α-methyl enals are successfully ethylated/cyclopropanated, the presence of bulky substituents at the alpha position of the enal constitutes a limitation to the substrate scope. The use of 1,1-diiodoethane allows the obtention of the corresponding enantioenriched cyclopropylcarbinol, which bears carbon-substituents at all three positions of the ring, with good enantiocontrol, although moderate diastereoselectivity. A procedure for the asymmetric one-pot arylation/cyclopropanation of enals is proposed, which involves the use of triarylboroxin, diethylzinc and diiodomethane.

  5. A combination of indol-3-carbinol and genistein synergistically induces apoptosis in human colon cancer HT-29 cells by inhibiting Akt phosphorylation and progression of autophagy

    Directory of Open Access Journals (Sweden)

    Watanabe Hirotsuna

    2009-11-01

    Full Text Available Abstract Background The chemopreventive effects of dietary phytochemicals on malignant tumors have been studied extensively because of a relative lack of toxicity. To achieve desirable effects, however, treatment with a single agent mostly requires high doses. Therefore, studies on effective combinations of phytochemicals at relatively low concentrations might contribute to chemopreventive strategies. Results Here we found for the first time that co-treatment with I3C and genistein, derived from cruciferous vegetables and soy, respectively, synergistically suppressed the viability of human colon cancer HT-29 cells at concentrations at which each agent alone was ineffective. The suppression of cell viability was due to the induction of a caspase-dependent apoptosis. Moreover, the combination effectively inhibited phosphorylation of Akt followed by dephosphorylation of caspase-9 or down-regulation of XIAP and survivin, which contribute to the induction of apoptosis. In addition, the co-treatment also enhanced the induction of autophagy mediated by the dephosphorylation of mTOR, one of the downstream targets of Akt, whereas the maturation of autophagosomes was inhibited. These results give rise to the possibility that co-treatment with I3C and genistein induces apoptosis through the simultaneous inhibition of Akt activity and progression of the autophagic process. This possibility was examined using inhibitors of Akt combined with inhibitors of autophagy. The combination effectively induced apoptosis, whereas the Akt inhibitor alone did not. Conclusion Although in vivo study is further required to evaluate physiological efficacies and toxicity of the combination treatment, our findings might provide a new insight into the development of novel combination therapies/chemoprevention against malignant tumors using dietary phytochemicals.

  6. Indole-3-carbinol and 3’, 3’-diindolylmethane modulate androgen effect up-regulation on C-C chemokine ligand 2 and monocyte attraction to prostate cancer cells

    Science.gov (United States)

    Inflammation has a role in prostate tumorigenesis. Recruitment of inflammatory monocytes to the tumor site is mediated by C-C chemokine ligand 2 (CCL2) through binding to its receptor CCR2. We hypothesized that androgen could modulate CCL2 expression in hormone-responsive prostate cancer cells, and ...

  7. The Role of SDF-1alpha and CXCR4 in Metastatic Breast Cancer

    Science.gov (United States)

    2006-08-01

    cancer cells. Nutr Cancer 2004;48:84–94. 5. Rahman KM, Aranha O, Glazyrin A, Chinni SR, Sarkar FH. Translocation of Bax to mitochondria induces...KM, Aranha O, Sarkar FH. Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in non- tumorigenic breast epithelial cells. Nutr Cancer...Rahman KM, Aranha O, Glazyrin A, et al. Translocation of Bax to mitochondria induces apoptotic cell death in indole-3-carbinol (I3C) treated breast

  8. Phytochemicals from cruciferous vegetables, epigenetics, and prostate cancer prevention.

    Science.gov (United States)

    W Watson, Gregory; M Beaver, Laura; E Williams, David; H Dashwood, Roderick; Ho, Emily

    2013-10-01

    Epidemiological evidence has demonstrated a reduced risk of prostate cancer associated with cruciferous vegetable intake. Follow-up studies have attributed this protective activity to the metabolic products of glucosinolates, a class of secondary metabolites produced by crucifers. The metabolic products of glucoraphanin and glucobrassicin, sulforaphane, and indole-3-carbinol respectively, have been the subject of intense investigation by cancer researchers. Sulforaphane and indole-3-carbinol inhibit prostate cancer by both blocking initiation and suppressing prostate cancer progression in vitro and in vivo. Research has largely focused on the anti-initiation and cytoprotective effects of sulforaphane and indole-3-carbinol through induction of phases I and II detoxification pathways. With regards to suppressive activity, research has focused on the ability of sulforaphane and indole-3-carbinol to antagonize cell signaling pathways known to be dysregulated in prostate cancer. Recent investigations have characterized the ability of sulforaphane and indole-3-carbinol derivatives to modulate the activity of enzymes controlling the epigenetic status of prostate cancer cells. In this review, we will summarize the well-established, "classic" non-epigenetic targets of sulforaphane and indole-3-carbinol, and highlight more recent evidence supporting these phytochemicals as epigenetic modulators for prostate cancer chemoprevention.

  9. Palladium-catalyzed cyclization/Heck- and cyclization/conjugate-addition-type sequences in the preparation of polysubstituted furans.

    Science.gov (United States)

    Aurrecoechea, José M; Durana, Aritz; Pérez, Elena

    2008-05-02

    Palladium-catalyzed heterocyclization-coupling sequences have been developed starting from buta-1,2,3-trienyl carbinols and electron-deficient alkenes. Polysubstituted furans are formed where the heterocyclic ring originates from the elements of the butatrienyl carbinol while the electron-deficient olefin is incorporated as a C-3 substituent. In most cases, the reaction proceeds via a Heck-type pathway leading to the efficient formation of 3-vinylfurans. However, couplings with methyl vinyl ketone display a divergent behavior to afford selectively either Heck- or hydroarylation-type products depending on reaction conditions.

  10. Molecular Effects of 13C/DIM in Prostate Cancer

    Science.gov (United States)

    2007-04-01

    Neurosci, 19:7476–85. Rahman KM, Aranha O, Glazyrin A et al. 2000. Translocation of Bax to mitochondria induces apoptotic cell death in indole-3-carbinol...I3C) treated breast cancer cells. Oncogene, 19:5764–71. Rahman KW, Aranha O, Sarkar FH. 2003. Indole-3-Carbinol (I3C) induces apoptosis in...K. M., Aranha , O., Glazyrin, A., Chinni, S. R. & Sarkar, F. H. (2000) Translocation of Bax to mitochondria induces apoptotic cell death in indole-3

  11. Chemosensitization of Breast Cancer Cells to Chemotherapeutic Agents by 3,3’-Diindolylmethane (DIM)

    Science.gov (United States)

    2007-08-01

    cancer cells. Front Biosci 2005;10:236-43. 34. Rahman KM, Aranha O, Sarkar FH. Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in...by AKT and NF-kappaB pathways in prostate cancer cells. Front Biosci 2005;10:236-43. 27. Rahman KM, Aranha O, Sarkar FH. Indole-3-carbinol (I3C...breast cancer cells. Cancer research 1999;59:1244-51. 45. Rahman KM, Aranha O, Glazyrin A, Chinni SR, Sarkar FH. Translocation of Bax to mitochondria

  12. Chemosensitization of Breast Cancer Cells to Chemotherapeutic Agents by 3,3’diindolylmethane (DIM)

    Science.gov (United States)

    2006-08-01

    during I3C-induced apopto- sis in breast cancer cells. Nutr Cancer 2004;48:84–94. 5. Rahman KM, Aranha O, Glazyrin A, Chinni SR, Sarkar FH...Biochem Mol Biol 2002;80:191–201. 7. Rahman KM, Aranha O, Sarkar FH. Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in non- tumorigenic...1011–9. 24. Rahman KM, Aranha O, Glazyrin A, et al. Translocation of Bax to mitochondria induces apoptotic cell death in indole-3-carbinol (I3C) treated

  13. Facile synthesis of (S)-beta-hydroxy-beta-trichloromethylated aromatic ketones by the regioselective ring cleavage of chiral beta-trichloromethyl-beta-propiolactone under the Friedel-Crafts conditions

    NARCIS (Netherlands)

    Fujisawa, T; Ito, T; Fujimoto, K; Shimizu, M; Wynberg, H; Staring, EGJ

    1997-01-01

    The reaction of enantiomerically pure beta-trichloromethyl-beta-propiolactone (1) as a chiral building block with an aromatic compound in the presence of Lewis acid provided an acylated product with a chiral trichloromethyl carbinol moiety. The acylated product was used as an effective chiral syntho

  14. Recentes aplicações sintéticas de compostos orgânicos tricloro(bromometila substituídos Recent synthetic applications of trichloro(bromomethyl containing organic compounds

    Directory of Open Access Journals (Sweden)

    Fabrício Gava Menezes

    2010-01-01

    Full Text Available This review presents the recent applications of some trihalomethyl carbinols, α,α,α-trihalogenated carbonyl compounds and trichloro(bromomethyl-containing heterocycles, acting as high versatile synthetic precursors in organic chemistry, based on the last 10 years' literature.

  15. The kinetic of key phytochemical compounds of non-heading and heading leafy Brassica oleracea landraces as affected by traditional cooking methods

    NARCIS (Netherlands)

    Giambanelli, Elisa; Verkerk, Ruud; Antuono, D' L.F.; Oliviero, Teresa

    2016-01-01

    BACKGROUND: Kales are often a key ingredient of traditional foods, containing high amounts of indolic glucosinolates (precursors of indole-3-carbinol and ascorbigen), carotenoids and phenolics. The present trend to associate traditional foods crops with health-promoting properties suggested to in

  16. Synthesis of Peramine, an Anti-insect Defensive Alkaloid Produced by Endophytic Fungi of Cool Season Grasses.

    Science.gov (United States)

    Nelli, Matthew R; Scheerer, Jonathan R

    2016-04-22

    A seven-step synthesis of peramine, which required three chromatographic separations, is described. Key to the synthesis is an enolate alkylation of a pyrrole-fused diketopiperazine, reduction of the acyl pyrrole, and dehydration of the intermediate pyrrolyl carbinol to establish the pyrrolopyrazine core of peramine.

  17. Inhibitory Ah Receptor-Androgen Receptor Crosstalk in Prostate Cancer

    Science.gov (United States)

    2006-02-01

    8217-Diindolylmethane induces apoptosis in human cancer cells. Biochem Biophys Res Commun 1996; 228:153- 158. 24. Rahman KM, Aranha O, Glazyrin A, Chinni SR...8217-diindolylmethane (DIM) in human breast cancer cells. Biochem Pharmacol 2002; 63:1085-1097. 28. Rahman KM, Aranha O, Sarkar FH. Indole-3-carbinol (I3C) induces

  18. Prototropic processes in benzaurins. 19F and 1H NMR spectra of fluoro- and methylsubstituted 4-hydroxyphenyl-diphenylcarbinols, related fuchsones and benzaurins

    DEFF Research Database (Denmark)

    Hansen, Poul Erik; Peregudov, Alexander S.; Kravtsov, Dmitii N.;

    2011-01-01

    Tautomerism of benzaurins and hydration are studied. 1H and 19F chemical shifts have been determined for a number of substituted 4-hydroxyphenyl-diphenyl carbinols containing fluorine in a 3-, 3*- or 4*-position, and for similar compounds containing additional methyl groups in a position of 3, 3*...

  19. Defense Technical Information Center Thesaurus

    Science.gov (United States)

    2000-10-01

    Carbinols Euglenophyta Algeria Cortisol Hydrophytes BT North Africa+ Cyclohexanols Pyrrophyta Ethanols Rhodophyta Algin Glycerols Seaweed use Alginic... crustaceans havingCytomegalovirus BT Ionosphere+ imperfect segmentation; very large BT Herpetic viruses+ biramous antennae that are the Dacron chief...Nonsequential NT Algeria electric field strength or energy Egypt+ flux). Nonskid materials Libya RT Langmuir Blodgett films BT Materials Morocco BT Optics

  20. JPRS Report, Science & Technology, USSR: Materials Science

    Science.gov (United States)

    2007-11-02

    dithiophosphoric acid), and frother-reagents (T-66 etalon, hexyl alcohols, terpene alcohols, pine oil, Methylisobutyl carbinol MIBC). References 2...degassing aluminum alloys has been developed, namely use of a metal capable of absorbing gas, specifically hydrogen dissolved in the aluminum melt

  1. Berberine alkaloid: Quantum chemical study of different forms by the DFT and MP2 methods

    Science.gov (United States)

    Danilov, V. I.; Dailidonis, V. V.; Hovorun, D. M.; Kurita, N.; Murayama, Y.; Natsume, T.; Potopalsky, A. I.; Zaika, L. A.

    2006-10-01

    The stable structures and electronic properties for the berberine cation as well as possible ammonium, carbinol and amino-aldehyde forms of protoberberine salts in the presence of hydroxyl ions were investigated by the B3LYP/6-31G(d,p) and MP2/6-31++G(d,p) methods. The geometry optimizations by both methods lead to the nonplanar propeller-twisted and buckled structure for the all forms. The obtained bond lengths and bond angles agree with the experimental values. The comparison of total energies elucidates that the amino-aldehyde form is the most preferable tautomer in gas phase, while the carbinol form is less stable. The least stable tautomer is the ammonium form.

  2. Antimicrobial activity of selected phytochemicals against Escherichia coli and Staphylococcus aureus and their biofilms

    OpenAIRE

    2014-01-01

    Bacteria can be resistant to multiple antibiotics and we are fast approaching a time when antibiotics will not work on some bacterial infections. New antimicrobial compounds are urgently necessary. Plants are considered the greatest source to obtain new antimicrobials. This study aimed to assess the antimicrobial activity of four phytochemicals—7-hydroxycoumarin (7-HC), indole-3-carbinol (I3C), salicylic acid (SA) and saponin (SP)—against Escherichia coli and Staphylococcus aureus, either as...

  3. Expression of Metabolic and Apoptotic Genes During Treatment With Chemopreventive Agents for Breast Cancer

    Science.gov (United States)

    2005-07-01

    Minneapolis, MN. Cancer -preventive properties of the components of cruciferous vegetables including indoles have been studied extensively. 3,3...carbinol (13C) is a product of autolysis from glucobrassicin in cruciferous vegetables . It is condensed to 3,3’-diindolylmethane (DIM) and other products in...AD Award Number: DAMD17-01-1-0332 TITLE: Expression of Metabolic and Apoptotic Genes During Treatment with Chemopreventive Agents for Breast Cancer

  4. Nature's chemicals and synthetic chemicals: comparative toxicology.

    OpenAIRE

    Ames, B N; Profet, M; Gold, L S

    1990-01-01

    The toxicology of synthetic chemicals is compared to that of natural chemicals, which represent the vast bulk of the chemicals to which humans are exposed. It is argued that animals have a broad array of inducible general defenses to combat the changing array of toxic chemicals in plant food (nature's pesticides) and that these defenses are effective against both natural and synthetic toxins. Synthetic toxins such as dioxin are compared to natural chemicals, such as indole carbinol (in brocco...

  5. Asymmetric 1,4-bis(ethynylbicyclo[2.2.2]octane rotators via monocarbinol functionalization. Ready access to polyrotors

    Directory of Open Access Journals (Sweden)

    Cyprien Lemouchi

    2015-10-01

    Full Text Available Asymmetric rotators with a 1,4-bis(ethynylbicyclo[2.2.2]octane (BCO core are needed for engineering crystalline arrays of functional molecular rotors. Their synthesis uses carbinol, 2-methyl-3-butyn-2-ol, as a protecting group because of its polar character and its ability to sustain orthogonal functionalization with the further advantage of being readily removed. The synthesis in good yields of unprecedented asymmetric rotors and polyrotors demonstrates the efficiency of this strategy.

  6. The anticarcinogen 3,3'-diindolylmethane is an inhibitor of cytochrome P-450.

    Science.gov (United States)

    Stresser, D M; Bjeldanes, L F; Bailey, G S; Williams, D E

    1995-08-01

    Dietary indole-3-carbinol inhibits carcinogenesis in rodents and trout. Several mechanisms of inhibition may exist. We reported previously that 3,3'-diindolylmethane, an in vivo derivative of indole-3-carbinol, is a potent noncompetitive inhibitor of trout cytochrome P450 (CYP) 1A-dependent ethoxyresorufin O-deethylase with Ki values in the low micromolar range. We now report a similar potent inhibition by 3,3'-diindolylmethane of rat and human CYP1A1, human CYP1A2, and rat CYP2B1 using various CYP-specific or preferential activity assays. 3,3'-Diindolylmethane also inhibited in vitro CYP-mediated metabolism of the ubiquitous food contaminant and potent hepatocarcinogen, aflatoxin B1. There was no inhibition of cytochrome c reductase. In addition, we found 3,3'-diindolylmethane to be a substrate for rat hepatic microsomal monooxygenase(s) and tentatively identified a monohydroxylated metabolite. These observations indicate that 3,3'-diindolylmethane can inhibit the catalytic activities of a range of CYP isoforms from lower and higher vertebrates in vitro. This broadly based inhibition of CYP-mediated activation of procarcinogens may be an indole-3-carbinol anticarcinogenic mechanism applicable to all species, including humans.

  7. Conversion of 2,3-butanediol to butadiene

    Energy Technology Data Exchange (ETDEWEB)

    Lilga, Michael A.; Frye, Jr, John G.; Lee, Suh-Jane; Albrecht, Karl O.

    2016-09-06

    A composition comprising 2,3-butanediol is dehydrated to methyl vinyl carbinol and/or 1,3-butadiene by exposure to a catalyst comprising (a) M.sub.xO.sub.y wherein M is a rare earth metal, a group IIIA metal, Zr, or a combination thereof, and x and y are based upon an oxidation state of M, or (b) M.sup.3.sub.a(PO.sub.4).sub.b where M.sup.3 is a group IA, a group IIA metal, a group IIIA metal, or a combination thereof, and a and b are based upon the oxidation state of M.sup.3. Embodiments of the catalyst comprising M.sub.xO.sub.y may further include M.sup.2, wherein M.sup.2 is a rare earth metal, a group IIA metal, Zr, Al, or a combination thereof. In some embodiments, 2,3-butanediol is dehydrated to methyl vinyl carbinol and/or 1,3-butadiene by a catalyst comprising M.sub.xO.sub.y, and the methyl vinyl carbinol is subsequently dehydrated to 1,3-butadiene by exposure to a solid acid catalyst.

  8. Effects of cruciferous vegetable consumption on urinary metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in singapore chinese.

    Science.gov (United States)

    Hecht, Stephen S; Carmella, Steven G; Kenney, Patrick M J; Low, Siew-Hong; Arakawa, Kazuko; Yu, Mimi C

    2004-06-01

    Vegetable consumption, including cruciferous vegetables, is protective against lung cancer, but the mechanisms are poorly understood. The purpose of this study was to investigate the effects of cruciferous vegetable consumption on the metabolism of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in smokers. The study was carried out in Singapore Chinese, whose mean daily intake of cruciferous vegetables is three times greater than that of people in the United States. Eighty-four smokers provided urine samples and were interviewed about dietary habits using a structured questionnaire, which included questions on consumption of nine commonly consumed cruciferous vegetables. Samples of these vegetables obtained in Singapore markets at three different times of year were analyzed for glucosinolates. Urine was analyzed for metabolites of NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Glucs). Glucobrassicins, which release indole-3-carbinols on chewing, were the major glucosinolates in seven of the nine cruciferous vegetables, accounting for 70.0% to 93.2% of all glucosinolates in these vegetables. There was a significant correlation (P = 0.01) between increased consumption of glucobrassicins and decreased levels of NNAL in urine after adjustment for number of cigarettes smoked per day; similar trends were observed for NNAL-Glucs (P = 0.08) and NNAL plus NNAL-Glucs (P = 0.03). These results are consistent with those of previous studies, which demonstrate that indole-3-carbinol decreases levels of urinary NNAL probably by inducing hepatic metabolism of NNK. The results are discussed with respect to the known chemopreventive activity of indole-3-carbinol against lung tumorigenesis by NNK in mice and the effects of isothiocyanates, which are also formed on consumption of cruciferous vegetables, on NNK metabolism. The results of this study demonstrate the complexities in assessing effects of

  9. Complex of Burkholderia cepacia lipase with transition state analogue of 1-phenoxy-2-acetoxybutane: biocatalytic, structural and modelling study.

    Science.gov (United States)

    Luić, M; Tomić, S; Lescić, I; Ljubović, E; Sepac, D; Sunjić, V; Vitale, L; Saenger, W; Kojic-Prodić, B

    2001-07-01

    In a series of four racemic phenoxyalkyl-alkyl carbinols, 1-phenoxy-2-hydroxybutane (1) is enantioselectively acetylated by Burkholderia cepacia (formerly Pseudomonas cepacia) lipase with an E value > or = 200, whereas for the other three racemates E was found to be analogue with a tetrahedral P-atom, (R(P),S(P))-O-(2R)-(1-phenoxybut-2-yl)methylphosphonic acid chloride was prepared and crystallized in complex with B. cepacia lipase. The X-ray structure of the complex was determined, allowing to compare the conformation of the inhibitor with results of molecular modelling.

  10. Synthesis of tritiated 1-alpha-methadol and 1-alpha-acetylmethadol

    Energy Technology Data Exchange (ETDEWEB)

    Thang, D.C.; Nam, N.H.; Pontikis, R. (Institut National de la Sante et de la Recherche Medicale (INSERM), Hopital Fernand Widal, 75 - Paris (France)); Pichat, L. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Service des Molecules Marquees)

    1982-04-01

    dl-Methadone was resolved by crystallization of its ammonium d- ..cap alpha.. -bromocamphor-..pi..-sulfonate salt to give d-methadone. The latter in ethyl acetate solution was reduced with tritium gas to 1-..cap alpha..-methadol /sup 3/H in presence of Adams platinum oxide at normal temperature and pressure. Acetylation of 1-..cap alpha..-carbinol hydrochloride by means of acetyl chloride afforded 1-..cap alpha..-acetylmethadol /sup 3/H, specific activity: 20 Ci/mMole. The positions and extent of tritium labelling were determined by /sup 3/H NMR spectroscopy.

  11. Asymmetric synthesis and biological evaluation of natural or bioinspired cytotoxic C2-symmetrical lipids with two terminal chiral alkynylcarbinol pharmacophores.

    Science.gov (United States)

    Listunov, Dymytrii; Fabing, Isabelle; Saffon-Merceron, Nathalie; Gaspard, Hafida; Volovenko, Yulian; Maraval, Valérie; Chauvin, Remi; Génisson, Yves

    2015-06-05

    Bidirectional syntheses of C2-symmetrical lipids embedding two terminal alkynylcarbinol pharmacophores are reported. Naturally occurring chiral alkenylalkynylcarbinol units were generated using Pu's procedure for enantioselective addition of terminal alkynes to aldehydes, allowing the first asymmetric synthesis of (3R,4E,16E,18R)-icosa-4,16-diene-1,19-diyne-3,18-diol, isolated from Callyspongia pseudoreticulata. Two synthetic analogues embedding the recently uncovered (S)-dialkynylcarbinol pharmacophore were secured using Carreira's procedure adapted to ynal substrates. The dramatic effect of the carbinol configuration on cytotoxicity was confirmed with submicromolar IC50 values against HCT116 cells.

  12. Molecular Effects of I3C/DIM in Prostate Cancer Cells

    Science.gov (United States)

    2005-04-01

    959-965. nisms: implications for therapy in pancreatic cancer. J. Am. Coll. Surg. 198: 38. Rahman, K. M., Aranha , 0., Glazyrin, A., Chinni, S. R...inducible by hypoxia. FEBS 39. Rahman, K. M., Aranha , 0. & Sarkar, F. H. (2003) Indole-3-carbinol Lett. 530: 186-190. (13C) induces apoptosis in...85] J.N. Davis, N. Muqim, M. Bhuiyan, 0. Kucuk, K.J. Pienta, [97] S.A. Alhasan, 0. Aranha , F.H. Sarkar, Genistein elicits F.H. Sarkar, Inhibition

  13. Influence of fermentation on glucosinolates and glucobrassicin degradation products in sauerkraut.

    Science.gov (United States)

    Palani, Kalpana; Harbaum-Piayda, Britta; Meske, Diana; Keppler, Julia Katharina; Bockelmann, Wilhelm; Heller, Knut J; Schwarz, Karin

    2016-01-01

    A systematic investigation was carried out on the influence of fermentation on glucosinolates and their degradation products from fresh raw cabbage, throughout fermentation at 20 °C and storage at 4 °C. Glucosinolates were degraded dramatically between Day 2 and 5 of fermentation and by Day 7 there was no detectable amount of glucosinolates left. Fermentation led to formation of potential bioactive compounds ascorbigen (13.0 μmol/100 g FW) and indole-3-carbinol (4.52 μmol/100g FW) with their higher concentrations from Day 5 to Day 9. However, during storage indole-3-carbinol slowly degraded to 0.68 μmol/100 g FW, while ascorbigen was relatively stable from Week 4 until Week 8 at 6.78 μmol/100 g FW. In contrast, the content of indole-3-acetonitrile decreased rapidly during fermentation from 3.6 to 0.14 μmol/100 g FW. The results imply a maximum of health beneficial compounds after fermentation (7-9 days) in contrast to raw cabbage or stored sauerkraut.

  14. A Comparative Study on the Effect of Flotation Reagents on Growth and Iron Oxidation Activities of Leptospirillum ferrooxidans and Acidithiobacillus ferrooxidans

    Directory of Open Access Journals (Sweden)

    Mohammad Jafari

    2016-12-01

    Full Text Available Recently, extraction of metals from different resources using a simple, efficient, and low-cost technique-known as bioleaching-has been widely considered, and has turned out to be an important global technology. Leptospirillum ferrooxidans and Acidithiobacillus (Thiobacillus ferrooxidans are ubiquitous bacteria in the biomining industry. To date, the effects of commercial flotation reagents on the biooxidation activities of these bacteria have not been thoroughly studied. This investigation, by using various systematic measurement methods, studied the effects of various collectors and frothers (collectors: potassium amylxanthate, potassium isobutyl-xanthate, sodium ethylxanthate, potassium isopropylxanthate, and dithiophosphate; and frothers: pine oil and methyl isobutyl carbinol on L. ferrooxidans and A. ferrooxidans activities. In general, results indicate that in the presence of these collectors and frothers, L. ferrooxidans is less sensitive than T. ferrooxidans. In addition, the inhibition effect of collectors on both bacteria is recommended in the following order: for the collectors, potassium isobutyl-xanthate > dithiophosphate > sodium ethylxanthate > potassium isobutyl-xanthate > potassium amylxanthate; and for the frothers, methyl isobutyl carbinol > pine oil. These results can be used for the optimization of biometallurgical processes or in the early stage of a process design for selection of flotation reagents.

  15. Beneficial and adverse effects of chemopreventive agents

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Mu; Park, Kwang-Kyun

    2003-03-01

    The beneficial and adverse effects of some chemopreventive agents, such as Vitamins A, C, E, beta-carotene, indole-3-carbinol, capsaicin, garlic, and aloe are reviewed. Two large randomized trials with a lung cancer endpoint, the Alpha-Tocopherol, Beta-Carotene (ATBC) Prevention Study and the Beta-Carotene and Retinol Efficacy Trial (CARET), suggested that antioxidants might be harmful in smokers. However, the results of the Linxian study and of the ATBC or the CARET studies were significantly different in this respect, and therefore, the relationship between antioxidant and carcinogenesis remains open to debate. Indole-3-carbinol has cancer promoting activities in the colon, thyroid, pancreas, and liver, whereas capsaicin alters the metabolism of chemical carcinogens and may promote carcinogenesis at high doses. Organosulfur compounds and selenium from garlic have no or a little enhancing effect on cancer promotion stage. Information upon chemopreventive mechanisms that inhibit carcinogenesis is imperfect, although the causes and natures of certain human cancers are known. Therefore, definitive preventive guidelines should be carefully offered for various types of tumors, which properly consider ethnic variations, and the efficacies and the safety of chemopreventive agents.

  16. Current principles of effective therapy for ovarian cancer

    Directory of Open Access Journals (Sweden)

    L. A. Ashrafyan

    2015-01-01

    Full Text Available In spite of all of modern medicine»s advances, ovarian cancer (OC mortality remains to be incommensurably high and to hold the lead among gynecological cancers. The initial cause of this deplorable statistics is the absence of a clear concept of the pathogenesis of OC and hence the justified prevention and methodology of early diagnosis of the disease; in this connection, therapy that proves to be ineffective is frequently used by medical oncologists in their daily practice. As a consequence, there is a high proportion of its further progression: the rates of early and late recurrences were about 30 and 60–65 %, respectively; most of which are drug resistant to further chemotherapy cycles. By taking into account these strikingly modest statistics, it becomes apparent that oncologists desire to make changes in the existing treatment regimen to achieve meaningful results. To use target drugs is one of these promising areas owing to new views on the concept of the pathogenesis of OC.Nevertheless, considering a wide variety of the signaling cascades and molecules, which are involved in the process of carcinogenesis, even target compounds, if they have only one point of application, cannot always produce their desirable therapeutic effect and their co-administration is responsible for high toxicity. In this light, the most effective drugs are indole-3-carbinol and epigallocathechin-3-gallate, which virtually cause no adverse reactions and can block various molecular targets at different levels of the mechanism of malignant transformation. Based on L. A. Ashrafyan, s concept of two pathogenetic variants of sporadic OC (2009 and on the recent findings in molecular biology and epigenetics, the incorporation of the above medications into the standard treatment regimen for OC should increase survival rates and change the nature of recurrence by that of more locally advanced forms. On this basis, a clinical trial was carried out to study

  17. The balance of estrogen metabolites in breast cancer and the ways of its correction

    Directory of Open Access Journals (Sweden)

    L. A. Ashrafyan

    2015-01-01

    Full Text Available Background. A clear relationship is now found between the activity of estrogen metabolites and the development of tumors in estrogen-dependent tissues. Many international and Russian studies could identify a number of compounds involved in the regulation of estrogen metabolites. Indole-3-carbinol is one of these compounds that correct a ratio of 2-hydroxyestrone (2-OHE1 to 16-OHE1. It is a phytonutrient that is contained in Cruciferous vegetables and has antitumor activity. Our investigations used highly purified indole-3-carbinol (Indinol. The ability to identify the role of metabolic syndrome, by applying the current methodological approaches, allowed us to study the effect of highly purified indole-3-carbinol on the level of expression of estrogen metabolites and to attempt to expand views on procedures to prevent and treat breast tumors. Materials and methods. A total of 136 women were comprehensively examined; of them 44 patients formed a group of those with morphologically verified hormone-independent breast cancer (BC and 42 patients were a group of those with hormone-dependent BC. A control group included 50 women without signs of breast disease. In all the patients, body mass index was calculated; the ratio of urinary estrogen metabolites (2-ОНЕ1/16α-ОНЕ1 was quantified; and biopsy specimens and operative material were histologically and immunohistologically studied. Results. The BC patients were noted to have the high expression of 16α-OHE1 and the low values of 2-OHE1 (ratio, 0.42 as compared to the control group (2.09, which was an important component of metabolic syndrome. The BC patients had the high level of concomitant endocrine metabolic disturbances with the high body mass index, which reflected the clinical manifestation of metabolic syndrome. Indinol used to treat both hormone-dependent and hormone-independent BC showed an antimetabolic effect that was most pronounced 6 months later. Conclusion. Thus, early correction

  18. Avaliação da reação foto-fenton na decomposição de resíduos de carrapaticida Evaluation of the photo-fenton reaction in the decomposition of tick residues

    Directory of Open Access Journals (Sweden)

    Caio Fernando Gromboni

    2007-04-01

    Full Text Available Experimental procedures based on factorial design and surface response methodology were applied to establishe experimental conditions for the decomposition of a 1:400 (v/v Supocade® (chlorfenvinphos 13.8% and cypermethrin 2.6% solution, used to control cattle ticks. Experiments exploring photo-oxidative reactions were performed with and without UV radiation, fixing exposition time and pesticide volume, and varying the oxidant mixture. The use of 3.6 mmol L-1 Fe2+ plus 1.9 mol L-1 H2O2 plus UV radiation provided destruction of 94% of the original carbon content and reduction of aromatic, aliphatic and carbinolic compounds, evaluated by determination of residual carbon content by ICP OES and NMR analysis.

  19. Treatment of recurrent respiratory papillomatosis lung involvement by cidofovir infusion.

    Science.gov (United States)

    Rivière, Frédéric; Gille, Thomas; Le Tinier, Jean Yves; Gharbi, Nourredine; Khalil, Antoine; Wislez, Marie; Cadranel, Jacques

    2011-02-01

    Lung parenchyma involvement in recurrent respiratory papillomatosis (RRP) is rare, can be severe, and has variable outcomes. Although several reports have described the effects of different drugs (interferon alpha, indol-3-carbinol, cidofovir, etc.), there is no standard treatment for lung involvement in respiratory papillomatosis. We discuss herein the controversial effectiveness of cidofovir in light of a new observation of respiratory papillomatosis involving lung parenchyma. The reported case is one of rare pulmonary involvement in RRP and shows the effectiveness of intravenous cidofovir alone on symptoms, high-resolution computed tomography abnormalities, and pulmonary function tests. Aggravation after stopping cidofovir may also be interpreted as an indirect argument for the effectiveness of cidofovir in this case.

  20. Bioavailability of Glucosinolates and Their Breakdown Products: Impact of Processing

    Science.gov (United States)

    Barba, Francisco J.; Nikmaram, Nooshin; Roohinejad, Shahin; Khelfa, Anissa; Zhu, Zhenzhou; Koubaa, Mohamed

    2016-01-01

    Glucosinolates are a large group of plant secondary metabolites with nutritional effects, and are mainly found in cruciferous plants. After ingestion, glucosinolates could be partially absorbed in their intact form through the gastrointestinal mucosa. However, the largest fraction is metabolized in the gut lumen. When cruciferous are consumed without processing, myrosinase enzyme present in these plants hydrolyzes the glucosinolates in the proximal part of the gastrointestinal tract to various metabolites, such as isothiocyanates, nitriles, oxazolidine-2-thiones, and indole-3-carbinols. When cruciferous are cooked before consumption, myrosinase is inactivated and glucosinolates transit to the colon where they are hydrolyzed by the intestinal microbiota. Numerous factors, such as storage time, temperature, and atmosphere packaging, along with inactivation processes of myrosinase are influencing the bioavailability of glucosinolates and their breakdown products. This review paper summarizes the assimilation, absorption, and elimination of these molecules, as well as the impact of processing on their bioavailability. PMID:27579302

  1. Cardiac remodeling during and after renin-angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats

    DEFF Research Database (Denmark)

    Heijnen, Bart Fj; Pelkmans, Leonie Pj; Danser, Ah Jan

    2013-01-01

    . Hypertrophic genes were highly upregulated, whereas in substantial activation a fibrotic response was absent. Four weeks after withdrawal of I3C, (pro)renin levels were normalized in all IHR. While in adult IHR BP returned to normal, hypertension was sustained in young IHR. Despite the latter, myocardial...... administration of indole-3-carbinol (I3C). Young (four-weeks old) and adult (30-weeks old) IHR were fed I3C for four weeks (leading to systolic BP >200 mmHg). RAS-stimulation was stopped and animals were followed-up for a consecutive period. Cardiac function and geometry was determined echocardiographically...... hypertrophy was fully regressed in both young and adult IHR. We conclude that (pro)renin-induced severe hypertension in IHR causes an age-independent fully reversible myocardial concentric hypertrophic remodeling, despite a continued elevated BP in young IHR....

  2. Cooperative titanocene and phosphine catalysis: accelerated C-X activation for the generation of reactive organometallics.

    Science.gov (United States)

    Fleury, Lauren M; Kosal, Andrew D; Masters, James T; Ashfeld, Brandon L

    2013-01-18

    The study presented herein describes a reductive transmetalation approach toward the generation of Grignard and organozinc reagents mediated by a titanocene catalyst. This method enables the metalation of functionalized substrates without loss of functional group compatibility. Allyl zinc reagents and allyl, vinyl, and alkyl Grignard reagents were generated in situ and used in the addition to carbonyl substrates to provide the corresponding carbinols in yields up to 99%. It was discovered that phosphine ligands effectively accelerate the reductive transmetalation event to enable the metalation of C-X bonds at temperatures as low as -40 °C. Performing the reactions in the presence of chiral diamines and amino alcohols led to the enantioselective allylation of aldehydes.

  3. Evaluation of the photo-fenton reaction in the decomposition of tick residues; Avaliacao da reacao foto-fenton na decomposicao de residuos de carrapaticida

    Energy Technology Data Exchange (ETDEWEB)

    Gromboni, Caio Fernando; Ferreira, Antonio Gilberto [Universidade Federal de Sao Carlos, SP (Brazil). Dept. de Quimica; Kamogawa, Marcos Yassuo [Sao Paulo Univ., Piracicaba, SP (Brazil). Escola Superior de Agricultura Luiz de Queiroz. Dept. de Ciencias Exatas; Nogueira, Ana Rita de Araujo [Embrapa Pecuaria Sudeste, Sao Carlos, SP (Brazil)]. E-mail: anarita@cppse.embrapa.br

    2007-03-15

    Experimental procedures based on factorial design and surface response methodology were applied to establish experimental conditions for the decomposition of a 1:400 (v/v) Supocade (chlorfenvinphos 13.8% and cypermethrin 2.6%) solution, used to control cattle ticks. Experiments exploring photo-oxidative reactions were performed with and without UV radiation, fixing exposition time and pesticide volume, and varying the oxidant mixture. The use of 3.6 mmol L{sup -1} Fe{sup 2+} plus 1.9 mol L-1 H{sub 2}O{sub 2} plus UV radiation provided destruction of 94% of the original carbon content and reduction of aromatic, aliphatic and carbinolic compounds, evaluated by determination of residual carbon content by ICP OES and NMR analysis. (author)

  4. A New Asymmetric α-Amido-hydroxyalkylation Mediated by SmI2

    Institute of Scientific and Technical Information of China (English)

    ZHENG Xiao; FENG Chen-Guo; HUNG Pei-Qiang

    2004-01-01

    Polyhydroxylated indolizidine alkaloids, such as castanospermine (Ⅰ) and swainsonine (H)are of longstanding interest due to their powerful glycosidase inhibitory activity. Asymmetric hydroxyatkylation via α-amido carbanions to form C-C bands would provide a convenient approach to these compounds.In continuation of our efforts in developing asyrmmetric o-amido-hydroxyalkylation method,1 we report a new SmI2 mediated flexible asymmetric α-amido-hydroxyalkylation method. Starting from the known (S)-3-hydroxy-2-pyrrolidinone 1,2 sulfide 2 and 3 were prepared. SmI2-mediated reductive metallation of these sulfides followed by reaction with ketones or aldehydes under Barbier conditions provided C2 hydroxyalkylated products 4 in yields ranged from 30% to 83%. High C2/C3 trans diastereoselectivity and mediocre diastereoselectivity at newly formed carbinolic center have been observed. The present method will open an avenue for the asymmetric synthesis of polyhydroxylated indolizidine alkaloids.

  5. Harnessing the fruits of nature for the development of multi-targeted cancer therapeutics.

    Science.gov (United States)

    Sarkar, Fazlul H; Li, Yiwei

    2009-11-01

    Cancer cells exhibit deregulation in multiple cellular signaling pathways. Therefore, treatments using specific agents that target only one pathway usually fail in cancer therapy. The combination treatments using chemotherapeutic agents with distinct molecular mechanisms are considered more promising for higher efficacy; however, using multiple agents contributes to added toxicity. Emerging evidence has shown that some "natural products" such as isoflavones, indole-3-carbinol (I3C) and its in vivo dimeric product 3,3'-diindolylmethane (DIM), and curcumin among many others, have growth inhibitory and apoptosis inducing effects on human and animal cancer cells mediated by targeting multiple cellular signaling pathways in vitro without causing unwanted toxicity in normal cells. Therefore, these non-toxic "natural products" from natural resources could be useful in combination with conventional chemotherapeutic agents for the treatment of human malignancies with lower toxicity and higher efficacy. In fact, recently increasing evidence from pre-clinical in vivo studies and clinical trials have shown some success in support of the use of rational design of multi-targeted therapies for the treatment of cancers using conventional chemotherapeutic agents in combination with "natural products". These studies have provided promising results and further opened-up newer avenues for cancer therapy. In this review article, we have succinctly summarized the known effects of "natural products" especially by focusing on isoflavones, indole-3-carbinol (I3C) and its in vivo dimeric product 3,3'-diindolylmethane (DIM), and curcumin, and provided a comprehensive view on the molecular mechanisms underlying the principle of cancer therapy using combination of "natural products" with conventional therapeutics.

  6. Estimating the total TEQ in human blood from naturally-occurring vs. anthropogenic dioxins. A dietary study

    Energy Technology Data Exchange (ETDEWEB)

    Connor, K. [Exponent, Natick, MA (United States); Harris, M. [Exponent, Houston, TX (United States); Edwards, M. [Exponent, Bellevue, WA (United States); Chu, A.; Clark, G. [XDS, Inc., Durham, NC (United States); Finley, B. [Exponent, Santa Rosa, CA (United States)

    2004-09-15

    Numerous naturally-occurring compounds in the human diet can bind to the aryl hydrocarbon, or dioxin receptor (AhR) and activate the AhR signaling pathway. These compounds include certain indole carbinols and their derivatives, heterocyclic aromatic amines, flavonoids, carotinoids, vitamin A derivatives (retinoids), and tryptophan metabolites. Several researchers have suggested that the daily dietary intake of these ''endodioxins'', in terms of a TCDD-equivalency (TEQ) is likely to be far greater than that associated with daily background intake of anthropogenic dioxins. The purpose of this study was to provide preliminary data for evaluating whether dietary endodioxins may in fact be significant contributors to the non-PCDD/F and PCB fraction of the blood TEQ. This was accomplished by measuring the total bioassay (CALUX {sup registered}) TEQ in the blood of several volunteers under various dietary regimens. Specifically, blood samples were collected from volunteers who maintained a baseline diet, which was relatively free of vegetables, followed by a diet enriched in endodioxin-containing vegetables. The background blood levels of PCDD/Fs and PCBs were measured for each volunteer at the beginning of the study in order to establish a baseline TEQ for each participant. To provide a measure of study sensitivity, CALUX {sup registered} analysis was also performed on blood samples from volunteers who took an off-the-shelf indole-3-carbinole (I3C) supplement. I3C is the main dietary ICZ precursor and could be expected to increase the levels of this endodioxin in blood.

  7. Determination of crystal violet in water by direct solid phase spectrophotometry after rotating disk sorptive extraction.

    Science.gov (United States)

    Manzo, Valentina; Navarro, Orielle; Honda, Luis; Sánchez, Karen; Inés Toral, M; Richter, Pablo

    2013-03-15

    The microextraction of crystal violet (CV) from water samples into polydimethylsiloxane (PDMS) using the rotating disk sorptive extraction (RDSE) technique was performed. The extracting device was a small Teflon disk that had an embedded miniature magnetic stirring bar and a PDMS (560 μL) film attached to one side of the disk using double-sided tape. The extraction involves a preconcentration of CV into the PDMS, where the analyte is then directly quantified using solid phase spectrophotometry at 600 nm. Different chemical and extraction device-related variables were studied to achieve the best sensitivity for the determination. The optimum extraction was performed at pH 14 because under this condition, CV is transformed to the neutral and colorless species carbinol, which can be quantitatively transferred to the PDMS phase. Although the colorless species is the chemical form extracted in the PDMS, an intense violet coloration appeared in the phase because the -OH bond in the carbinol molecule is weakened through the formation of hydrogen bonds with the oxygen atoms of the PDMS, allowing the resonance between the three benzene rings to compensate for the charge deficit on the central carbon atom of the molecule. The accuracy and precision of the method were evaluated in river water samples spiked with 10 and 30 μg L(-1) of CV, yielding a relative standard deviation of 6.2% and 8.4% and a recovery of 98.4% and 99.4%, respectively. The method detection limit was 1.8 μg L(-1) and the limit of quantification was 5.4 μg L(-1), which can be decreased if the sample volume is increased.

  8. Effects of common ingredients in EPDM insulation on thermal decomposition behaviors of dicumyl peroxide as crosslinking agent%EPDM绝热层常用组分对交联剂DCP热分解行为的影响

    Institute of Scientific and Technical Information of China (English)

    王明超; 马新刚; 凌玲; 胡伟; 罗岚; 聂松; 王敏

    2013-01-01

    采用热重-差示扫描量热法(TG-DSC)和气相色谱-质谱法(GC-MS)分别研究了白炭黑、硬脂酸和氧化镁对过氧化二异丙苯(DCP)的热分解特性和热分解产物的影响,还研究了白炭黑和硬脂酸对DCP热分解影响的机理.结果表明,白炭黑对DCP的热分解具有催化作用,显著降低DCP热分解活化能,催化DCP热解产物α,α-二甲基苄醇发生脱水反应生成α-甲基苯乙烯,同时加剧β-消除反应生成α-甲基苯乙酮;硬脂酸对DCP热分解峰温以及活化能无显著影响,但具有微弱催化α,α-二甲基苄醇脱水生成α-甲基苯乙烯和加剧β-消除反应生成α-甲基苯乙酮的作用;氧化镁对DCP热分解行为几乎没有影响.%The effects of silica,stearic acid and magnesium oxide on thermal decomposition of dicumyl peroxide (DCP) and its decomposition products were investigated by means of thermal gravimetry-differential scanning calorimetry (TG-DSC) and gas chromatography-mass spectrum (GC-MS)respectively.The influence mechanism of silica and stearic acid on thermal decomposition of DCP were also analyzed.Results show that silica has catalytic effect on thermal decomposition of DCP,and can obviously reduce the activation energy for thermal decomposition of DCP.It was found that silica can also catalyze α,α-phenyl dimethyl carbinol to become α-methylstyrene,and can accelerateβ-eliminate reaction to produce α-acetophenone; Stearic acid has little effect on peak temperature and activation energy of DCP thermal decomposition reation,however,it has weak influence to catalyze α,α-phenyl dimethyl carbinol to α-methylstyrene,and accelerateβ-eliminate reaction;Magnesium oxide (MgO) has little effect on thermal decomposition of DCP.

  9. Reactions of cumene hydroperoxide mixed with sodium hydroxide.

    Science.gov (United States)

    Hou, Hung-Yi; Shu, Chi-Min; Tsai, Tung-Lin

    2008-04-15

    Decomposition of cumene hydroperoxide (CHP) was undertaken in a free radical chain reaction. The peroxyl group is very active and unstable, while the remainder of the molecule is inert. CHP reacted with various concentrations of dilute sodium hydroxide as a catalyst to cleave at ambient and decomposition temperature. The products were verified by GC/MS, and were quantitatively analyzed by chromatography. CHP cleaved heterolytic with NaOH at 250 degrees C, whose major product was dimethylphenyl carbinol (DMPC); however, the main products become acetophenone and alpha-methylstyrene by cleaved homolytic pathway. The catalytic concentrations of NaOH significantly affected the branch ratios of DMPC under decomposition. Based on the experimental results, a radical cleavage mechanism was proposed. To sum up, the reaction parameters, such as temperature, Lewis base, etc., could affect the incompatibilities and decomposition pathways for proper CHP cleavage process. In addition, exothermic onset temperatures (T0) and heat of decomposition (Delta Hd) of incompatible mixtures and CHP itself were studied by differential scanning calorimetry (DSC). Comparisons of T0, Delta Hd and peak power were assessed to corroborate the severity of thermal hazards. From the decay rate of CHP concentration, the reaction order was determined to be 0.5, and the Arrhenius parameters were measured as Ea=92.1 kJ/mol and frequency factor A=2.42 x 10(10)min(-1).

  10. Enantioselective synthesis of α-phenyl- and α-(dimethylphenylsilyl)alkylboronic esters by ligand mediated stereoinductive reagent-controlled homologation using configurationally labile carbenoids.

    Science.gov (United States)

    Barsamian, Adam L; Wu, Zhenhua; Blakemore, Paul R

    2015-03-28

    Chain extension of boronic esters by the action of configurationally labile racemic lithium carbenoids in the presence of scalemic bisoxazoline ligands was explored for the enantioselective synthesis of the two title product classes. Enantioenriched 2° carbinols generated by oxidative work-up (NaOOH) of initial α-phenylalkylboronate products were obtained in 35-83% yield and 70-96% ee by reaction of B-alkyl and B-aryl neopentyl glycol boronates with a combination of O-(α-lithiobenzyl)-N,N-diisopropylcarbamate and ligand 3,3-bis[(4S)-4,5-dihydro-4-isopropyloxazol-2-yl] pentane in toluene solvent (-78 °C to rt) with MgBr2·OEt2 additive. Enantioenriched α-(dimethylsilylphenylsilyl)alkylboronates were obtained in 35-69% yield and 9-57% ee by reaction of B-alkyl pinacol boronates with a combination of lithio(dimethylphenylsilyl)methyl 2,4,6-triisopropylbenzoate and ligand 2,2-bis[(4S)-4,5-dihydro-4-isopropyloxazol-2-yl]propane in cumene solvent (-45 °C to -95 °C to rt). The stereochemical outcome of the second type of reaction depended on the temperature history of the organolithium·ligand complex indicating that the stereoinduction mechanism in this case involves some aspect of dynamic thermodynamic resolution.

  11. Biodegradation of malachite green by Pseudomonas sp. strain DY1 under aerobic condition: characteristics, degradation products, enzyme analysis and phytotoxicity.

    Science.gov (United States)

    Du, Lin-Na; Wang, Sheng; Li, Gang; Wang, Bing; Jia, Xiao-Ming; Zhao, Yu-Hua; Chen, Yun-Long

    2011-03-01

    Malachite green (MG), a widely-used and recalcitrant dye, has been confirmed to be carcinogenic and mutagenic against many organisms. The main objective of this study is to investigate the capability of Pseudomonas sp. strain DY1 to decolorize MG, and to explore the possible mechanism. The results showed that this strain demonstrated high decolorizing capability (90.3-97.2%) at high concentrations of MG (100-1,000 mg/l) under shaking condition within 24 h. In static conditions, lower but still effective decolorization (78.9-84.3%) was achieved. The optimal pH and temperature for the decolorization was pH 6.6 and 28-30°C, respectively. Mg(2+) and Mn(2+) (1 mM) were observed to significantly enhance the decolorization. The intermediates of the MG degradation under aerobic condition identified by UV-visible, GC-MS and LC-MS analysis included malachite green carbinol, (dimethyl amino-phenyl)-phenyl-methanone, N,N-dimethylaniline, (methyl amino-phenyl)-phenyl-methanone, (amino phenyl)-phenyl methanone and di-benzyl methane. The enzyme analysis indicated that Mn-peroxidase, NADH-DCIP and MG reductase were involved in the biodegradation of MG. Moreover, phytotoxicity of MG and detoxification for MG by the strain were observed. Therefore, this strain could be potentially used for bioremediation of MG.

  12. A systematic review on recurrent respiratory papillomatosis: clinical effect and duration of benefit of different treatment modalities

    Directory of Open Access Journals (Sweden)

    Elina Kiverniti

    2011-12-01

    Full Text Available The aim of this study is to compare different modalities used for the treatment of recurrent respiratory papillomatosis (RRP in adults and children in terms of their clinical effect and the duration of benefit. Systematic review of papers was written in the English language and published between 1977 and 2007. Outcomes are number of patients with a clinical response and length of time the response lasted for. We found 28 useful studies. There were 1,045 subjects, 416 children and 339 adults who underwent different treatments for RRP between 1976 and 2007. The methods used consisted of cidofovir, interferon, surgical excision, indole-3-carbinol, acyclovir, mumps vaccine, and photodynamic therapy. 62.5% of patients had a complete response on cidofovir (11 studies, 45.14% on interferon (8 studies, 33.33% on I3C (2 studies, 44.36% after surgery (5 studies, 77.55% after the mumps vaccine (1 study, 100% on acyclovir (1 study, and 9.09% after photodynamic therapy (1 study. The effect of different modalities lasted between 9 and 27 months. In conclusion, it is impossible to reach any reliable conclusions as to which method is the most durable and effective. There is a great need for randomised control multicentre trials on the treatment of RRP, so that reliable results can be produced.

  13. Conventional Chiralpak ID vs. capillary Chiralpak ID-3 amylose tris-(3-chlorophenylcarbamate)-based chiral stationary phase columns for the enantioselective HPLC separation of pharmaceutical racemates.

    Science.gov (United States)

    Ahmed, Marwa; Gwairgi, Marina; Ghanem, Ashraf

    2014-11-01

    A comparative enantioselective analysis using immobilized amylose tris-(3-chlorophenylcarbamate) as chiral stationary phase in conventional high-performance liquid chromatography (HPLC) with Chiralpak ID (4.6 mm ID × 250 mm, 5 µm silica gel) and micro-HPLC with Chiralpak ID-3 (0.30 mm ID × 150 mm, 3 µm silica gel) was conducted. Pharmaceutical racemates of 12 pharmacological classes, namely, α- and β-blockers, anti-inflammatory drugs, antifungal drugs, dopamine antagonists, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, diuretics, antihistaminics, anticancer drugs, and antiarrhythmic drugs were screened under normal phase conditions. The effect of an organic modifier on the analyte retentions and enantiomer recognition was investigated. Baseline separation was achieved for 1-acenaphthenol, carprofen, celiprolol, cizolirtine carbinol, miconazole, tebuconazole, 4-hydroxy-3-methoxymandelic acid, 1-indanol, 1-(2-chlorophenyl)ethanol, 1-phenyl-2-propanol, flavanone, 6-hydroxyflavanone, 4-bromogluthethimide, and pentobarbital on the 4.6 mm ID packed with a 5 µm silica column using conventional HPLC. Nonetheless, baseline separation was achieved for aminoglutethimide, naftopidil, and thalidomide on the 0.3 mm ID packed with a 3 µm silica capillary column.

  14. Molecular and Merrifield supported chiral diamines for enantioselective addition of ZnR2 (R = Me, Et) to ketones.

    Science.gov (United States)

    Calvillo-Barahona, Mercedes; Cordovilla, Carlos; Genov, Miroslav N; Martínez-Ilarduya, Jesús M; Espinet, Pablo

    2013-10-28

    Chiral 1,2-ethylenediamines have been previously reported as active catalysts in the enantioselective addition reactions of ZnR2 to either methyl- or trifluoromethyl-ketones. Subtle changes in the molecular structure of different catalysts are described herein and lead to a dramatic effect in their catalytic activity. From these findings, we demonstrate the selective reactivity of the ligands used in the addition of ZnR2 (R = Me, Et) to methyl- and trifluoromethyl-ketones offering an enantioselective access either to chiral non-fluorinated alcohols or to chiral fluorinated tertiary alcohols. Considering the importance of the chiral trifluoromethyl carbinol fragment in several biologically active compounds, we have extended the scope of the addition reaction of ZnEt2 to several trifluoromethylketones catalyzed by (R,R)-1,2-diphenylethylenediamine derivatives. This work explores a homogeneous approach that provides excellent yields and very high ee and the use of a heterogenized tail-tied ligand affording moderate ee, high yields and allowing an easier handling and recycling.

  15. Ground and excited state properties of high performance anthocyanidin dyes-sensitized solar cells in the basic solutions

    Energy Technology Data Exchange (ETDEWEB)

    Prima, Eka Cahya [Advanced Functional Material Laboratory, Engineering Physics, Institut Teknologi Bandung (Indonesia); Computational Material Design and Quantum Engineering Laboratory, Engineering Physics, Institut Teknologi Bandung (Indonesia); International Program on Science Education, Universitas Pendidikan Indonesia (Indonesia); Yuliarto, Brian; Suyatman, E-mail: yatman@tf.itb.ac.id [Advanced Functional Material Laboratory, Engineering Physics, Institut Teknologi Bandung (Indonesia); Dipojono, Hermawan Kresno [Computational Material Design and Quantum Engineering Laboratory, Engineering Physics, Institut Teknologi Bandung (Indonesia)

    2015-09-30

    The aglycones of anthocyanidin dyes were previously reported to form carbinol pseudobase, cis-chalcone, and trans-chalcone due to the basic levels. The further investigations of ground and excited state properties of the dyes were characterized using density functional theory with PCM(UFF)/B3LYP/6-31+G(d,p) level in the basic solutions. However, to the best of our knowledge, the theoretical investigation of their potential photosensitizers has never been reported before. In this paper, the theoretical photovoltaic properties sensitized by dyes have been successfully investigated including the electron injections, the ground and excited state oxidation potentials, the estimated open circuit voltages, and the light harvesting efficiencies. The results prove that the electronic properties represented by dyes’ LUMO-HOMO levels will affect to the photovoltaic performances. Cis-chalcone dye is the best anthocyanidin aglycone dye with the electron injection spontaneity of −1.208 eV, the theoretical open circuit voltage of 1.781 V, and light harvesting efficiency of 56.55% due to the best HOMO-LUMO levels. Moreover, the ethanol solvent slightly contributes to the better cell performance than the water solvent dye because of the better oxidation potential stabilization in the ground state as well as in the excited state. These results are in good agreement with the known experimental report that the aglycones of anthocyanidin dyes in basic solvent are the high potential photosensitizers for dye-sensitized solar cell.

  16. JM47, a cyclic tetrapeptide HC-toxin analogue from a marine Fusarium species.

    Science.gov (United States)

    Jiang, Zhong; Barret, Marc-Olivier; Boyd, Kenneth G; Adams, David R; Boyd, Alan S F; Burgess, J Grant

    2002-05-01

    The known metabolite, enniatin B, and a cyclic tetrapeptide, JM47, which is a new natural product, were extracted from brown rice cultures of a marine fungus, identified as a Fusarium species, isolated from the marine alga Codium fragile. NMR studies, including 15N HMQC and 15N HMBC, established the structure of JM47 as cyclo(Ala-Ala-Aoh-Pro), where Aoh is the amino acid, (2S,9S)-2-amino-8-oxo-9-hydroxydecanoic acid. The absolute stereochemistry of the Aoh side chain carbinol centre was determined using Mosher ester methodology. Analysis of NOESY data assisted by molecular modelling revealed an alternating L-, D-, L-, D-configuration for the tetrapeptide core. The absolute stereochemistry of the core was determined by acidic hydrolysis and chiral TLC analysis of the proline residue. JM47 belongs to the HC-toxin family of cyclic tetrapeptides which possess a 2-amino-8-oxo-9,10-epoxydecanoic acid residue in place of the Aoh unit. This is the first report of an analogue of HC-toxin from a marine Fusarium species.

  17. Predicting the physiological relevance of in vitro cancer preventive activities of phytochemicals

    Institute of Scientific and Technical Information of China (English)

    Lynne M HOWELLS; Elena P MOISEEVA; Christopher P NEAL; Bethany E FOREMAN; Catherine K ANDREADI; Yi-yang SUN; E Ann HUDSON; Margaret M MANSON

    2007-01-01

    There is growing interest in the ability of phytochemicals to prevent chronic diseases, such as cancer and heart disease. However, some of these agents have poor bioavailability and many of the in-depth studies into their mechanisms of action have been carried out in vitro using doses which are unachievable in humans. In order to optimize the design of chemopreventive treatment, it is impor-tant to determine which of the many reported mechanisms of action are clinically relevant. In this review we consider the physiologically achievable doses for afew of the best studied agents (indole-3-carbinol, diindolylmethane, curcumin,epigallocatechin-3-gallate and resveratrol) and summarize the data derived froms tudies using these low concentrations in cell culture. We then cite examples of in vitro effects which have been observed in vivo. Finally, the ability of agent combinations to act synergistically or antagonistically is considered. We con-clude that each of the compounds shows an encouraging range of activities in vitro at concentrations which are likely to be physiologically relevant. There arealso many examples of in vivo studies which validate in vitro observations. An important consideration is that combinations of agents can result in significant activity at concentrations where any single agent is inactive. Thus, for each of the compounds reviewed here, in vitro studies have provided useful insights into their mechanisms of action in humans. However, data are lacking on the full range of activities at low doses in vitro and the benefits or otherwise of combinations invivo.

  18. Indolo[3,2-b]carbazole inhibits gap junctional intercellular communication in rat primary hepatocytes and acts as a potential tumor promoter

    DEFF Research Database (Denmark)

    Herrmann, Susan; Seidelin, Michel; Bisgaard, Hanne Cathrine

    2002-01-01

    Indole-3-carbinol (I3C) is a naturally occurring substance that shows anti-carcinogenic properties in animal models. Besides its clear anti-carcinogenic effects, some studies indicate that I3C may sometimes act as a tumor promoter. Indolo[3,2-b]carbazole (ICZ), which is formed in the acidic...... environment of the stomach after intake of I3C, has a similar structure to, and shares biological effects with, the well-known tumor promoter 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD). Therefore, we hypothesized that ICZ could be responsible for the potential tumor-promoting activity of I3C. The aim...... of the present study was to investigate the effect of ICZ on gap junctional intercellular communication (GJIC) in primary cultured rat hepatocytes co-cultured with the rat liver epithelial cell line WB-F344. Indolo[3,2-b]carbazole inhibited GJIC in the rat hepatocytes in a dose- and time-dependent manner...

  19. Anomalous thickness variation of the foam films stabilized by weak non-ionic surfactants.

    Science.gov (United States)

    Qu, Xuan; Wang, Liguang; Karakashev, Stoyan I; Nguyen, Anh V

    2009-09-15

    The constant thickness (H) of metastable free films of various non-ionic surfactant solutions was measured at surfactant concentrations less than the critical micelle concentrations or solubility limits with fixed 5x10(-5) M sodium chloride (NaCl) serving as the background electrolyte. The surfactants include n-pentanol, n-octanol, methyl isobutyl carbinol (MIBC), polypropylene glycol (PPG-400), tetraethylene glycol monooctyl ether (C(8)E(4)), and tetraethylene glycol monodecyl ether (C(10)E(4)). H was interferometrically measured. For each surfactant in this study, the H-versus-surfactant-concentration curve finds a peak at a concentration around 5x10(-6)-1x10(-5) M and a valley at a higher concentration. The measured H values were compared to those predicted from the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, which considers solely the contribution from electrostatic double-layer repulsion with van der Waals attraction being neglected in the present work. In determining the double-layer repulsion, the ionic strength was determined from the electrolytic conductivity measurement of the film-forming solutions and the surface potential was estimated from the zeta-potential measurement of air bubbles. It was found that the DLVO theory failed to explain the thickness variance with surfactant concentration, implying that additional non-DLVO attractive forces might be required to explain the experimental results. Finally, the possible origins of these attractive forces were discussed.

  20. Effects of Film Elasticity and Surface Forces on the Stability of Foams and Lamellae Films in the Presence of Non-ionic Surfactants

    Science.gov (United States)

    Wang, Liguang; Yoon, Roe-Hoan

    2008-07-01

    This paper describes the basic factors affecting the stability of the foam films produced in the presence of nonionic surfactants such as n-pentanol, n-octanol, methyl isobutyl carbinol (MIBC), and polypropylene glycol (PPG). We used a model developed by Wang and Yoon (Colloids and Surfaces A: Physicochem. Eng. Aspects 282-283, 84-91 (2006)) to calculate the Gibbs elasticity of the lamellae films. In addition, we used the thin film pressure balance (TFPB) technique to measure film thicknesses. The results were used to determine the disjoining pressures in the thin lamellae (foam) films formed between air bubbles, which are relevant forces governing the final drainage stage of foam films before reaching either equilibrium or rupture. The film elasticity and surface forces data were then compared with the foam stabilities measured in the present work in the presence of the various surfactants. It was found that foam stabilities are controlled both by film elasticity and by surface forces, the relative contributions of each changing with surfactant type and concentration. In general, surface forces play a more important role at relatively low surfactant concentrations, while elasticity plays a more important role at higher concentrations. At the surfactant additions usually employed in the mining industry, MIBC stabilizes foams by increasing disjoining pressures, while PPG-400 stabilizes foams by increasing film elasticity.

  1. Activation of thiazide-sensitive co-transport by angiotensin II in the cyp1a1-Ren2 hypertensive rat.

    Directory of Open Access Journals (Sweden)

    Ali Ashek

    Full Text Available Transgenic rats with inducible expression of the mouse Ren2 gene were used to elucidate mechanisms leading to the development of hypertension and renal injury. Ren2 transgene activation was induced by administration of a naturally occurring aryl hydrocarbon, indole-3-carbinol (100 mg/kg/day by gastric gavage. Blood pressure and renal parameters were recorded in both conscious and anesthetized (butabarbital sodium; 120 mg/kg IP rats at selected time-points during the development of hypertension. Hypertension was evident by the second day of treatment, being preceded by reduced renal sodium excretion due to activation of the thiazide-sensitive sodium-chloride co-transporter. Renal injury was evident after the first day of transgene induction, being initially limited to the pre-glomerular vasculature. Mircoalbuminuria and tubuloinsterstitial injury developed once hypertension was established. Chronic treatment with either hydrochlorothiazide or an AT1 receptor antagonist normalized sodium reabsorption, significantly blunted hypertension and prevented renal injury. Urinary aldosterone excretion was increased ≈ 20 fold, but chronic mineralocorticoid receptor antagonism with spironolactone neither restored natriuretic capacity nor prevented hypertension. Spironolactone nevertheless ameliorated vascular damage and prevented albuminuria. This study finds activation of sodium-chloride co-transport to be a key mechanism in angiotensin II-dependent hypertension. Furthermore, renal vascular injury in this setting reflects both barotrauma and pressure-independent pathways associated with direct detrimental effects of angiotensin II and aldosterone.

  2. Cytochrome P450s from the fall armyworm (Spodoptera frugiperda): responses to plant allelochemicals and pesticides.

    Science.gov (United States)

    Giraudo, M; Hilliou, F; Fricaux, T; Audant, P; Feyereisen, R; Le Goff, G

    2015-02-01

    Spodoptera frugiperda is a polyphagous lepidopteran pest that encounters a wide range of toxic plant metabolites in its diet. The ability of this insect to adapt to its chemical environment might be explained by the action of major detoxification enzymes such as cytochrome P450s (or CYP). Forty-two sequences coding for P450s were identified and most of the transcripts were found to be expressed in the midgut, Malpighian tubules and fat body of S. frugiperda larvae. Relatively few P450s were expressed in the established cell line Sf9. In order to gain information on how these genes respond to different chemical compounds, larvae and Sf9 cells were exposed to plant secondary metabolites (indole, indole-3-carbinol, quercetin, 2-tridecanone and xanthotoxin), insecticides (deltamethrin, fipronil, methoprene, methoxyfenozide) or model inducers (clofibrate and phenobarbital). Several genes were induced by plant chemicals such as P450s from the 6B, 321A and 9A subfamilies. Only a few genes responded to insecticides, belonging principally to the CYP9A family. There was little overlap between the response in vivo measured in the midgut and the response in vitro in Sf9 cells. In addition, regulatory elements were detected in the promoter region of these genes. In conclusion, several P450s were identified that could potentially be involved in the adaptation of S. frugiperda to its chemical environment.

  3. A Possible Association of Diindolylmethane with Pulmonary Embolism and Deep Venous Thrombosis

    Science.gov (United States)

    Moualla, Maan

    2016-01-01

    Introduction. 3,3′-Diindolylmethane is available as a supplement in the United States for “cancer prevention” and “augmentation of physical fitness.” A derivative of indole-3-carbinol found in plants, diindolylmethane, binds to receptors associated with the sex steroid pathways and has unclear effects on estrogen and androgen physiology. We present a patient who had been taking diindolylmethane and developed right lower extremity deep venous thrombosis and bilateral pulmonary embolism. Case Presentation. A 65-year-old man presented with swelling, erythema, and warmth of his right lower extremity for three to four weeks. He had been taking diindolylmethane one tablet daily for three to four months. Risk factors for venous thromboembolism included tobacco use, personal history of possible pulmonary embolism, body mass index, and age. Imaging studies found extensive deep venous thrombosis in his right lower extremity and bilateral pulmonary embolism with probable right middle lobe infarction. Follow-up imaging showed chronic deep venous thrombosis in his right lower extremity. Discussion. As suggested in this single case, patients who take diindolylmethane may be at greater risk for venous thromboembolism. Further reports and studies are necessary in order to elucidate this possible association. Clinicians should question patients about supplements in the setting of venous thromboembolism. PMID:28050169

  4. Aldol Reactions of Axially Chiral 5-Methyl-2-(o-arylimino-3-(o-aryl-thiazolidine-4-ones

    Directory of Open Access Journals (Sweden)

    Sule Erol Gunal

    2016-06-01

    Full Text Available Axially chiral 5-methyl-2-(o-arylimino-3-(o-aryl-thiazolidine-4-ones have been subjected to aldol reactions with benzaldehyde to produce secondary carbinols which have been found to be separable by HPLC on a chiral stationary phase. Based on the reaction done on a single enantiomer resolved via a chromatographic separation from a racemic mixture of 5-methyl-2-(α-naphthylimino-3-(α-naphthyl-thiazolidine-4-one by HPLC on a chiral stationary phase, the aldol reaction was shown to proceed via an enolate intermediate. The axially chiral enolate of the thiazolidine-4-one was found to shield one face of the heterocyclic ring rendering face selectivity with respect to the enolate. The selectivities observed at C-5 of the ring varied from none to 11.5:1 depending on the size of the ortho substituent. Although the aldol reaction proceeded with a lack of face selectivity with respect to benzaldehyde, recrystallization returned highly diastereomerically enriched products.

  5. Vegetables, fruit, and cancer prevention: a review.

    Science.gov (United States)

    Steinmetz, K A; Potter, J D

    1996-10-01

    In this review of the scientific literature on the relationship between vegetable and fruit consumption and risk of cancer, results from 206 human epidemiologic studies and 22 animal studies are summarized. The evidence for a protective effect of greater vegetable and fruit consumption is consistent for cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon. The types of vegetables or fruit that most often appear to be protective against cancer are raw vegetables, followed by allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes. Substances present in vegetables and fruit that may help protect against cancer, and their mechanisms, are also briefly reviewed; these include dithiolthiones, isothiocyanates, indole-3-carbinol, allium compounds, isoflavones, protease inhibitors, saponins, phytosterols, inositol hexaphosphate, vitamin C, D-limonene, lutein, folic acid, beta carotene, lycopene, selenium, vitamin E, flavonoids, and dietary fiber. Current US vegetable and fruit intake, which averages about 3.4 servings per day, is discussed, as are possible noncancer-related effects of increased vegetable and fruit consumption, including benefits against cardiovascular disease, diabetes, stroke, obesity, diverticulosis, and cataracts. Suggestions for dietitians to use in counseling persons toward increasing vegetable and fruit intake are presented.

  6. Phase I metabolism of 3-methylindole, an environmental pollutant, by hepatic microsomes from carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Zlabek, Vladimir; Burkina, Viktoriia; Borrisser-Pairó, Francesc; Sakalli, Sidika; Zamaratskaia, Galia

    2016-05-01

    We studied the in vitro metabolism of 3-methylindole (3MI) in hepatic microsomes from fish. Hepatic microsomes from juvenile and adult carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss) were included in the study. Incubation of 3MI with hepatic microsomes revealed the time-dependent formation of two major metabolites, 3-methyloxindole (3MOI) and indole-3-carbinol (I3C). The rate of 3MOI production was similar in both species at both ages. No differences in kinetic parameters were observed (p = 0.799 for Vmax, and p = 0.809 for Km). Production of I3C was detected only in the microsomes from rainbow trout. Km values were similar in juvenile and adult fish (p = 0.957); Vmax was higher in juvenile rainbow trout compared with adults (p = 0.044). In rainbow trout and carp, ellipticine reduced formation of 3MOI up to 53.2% and 81.9% and ketoconazole up to 65.8% and 91.3%, respectively. The formation of I3C was reduced by 53.7% and 51.5% in the presence of the inhibitors ellipticine and ketoconazole, respectively. These findings suggest that the CYP450 isoforms CYP1A and CYP3A are at least partly responsible for 3MI metabolism. In summary, 3MI is metabolised in fish liver to 3MOI and I3C by CYP450, and formation of these metabolites might be species-dependent.

  7. Rh(I)-catalyzed transformation of propargyl vinyl ethers into (E,Z)-dienals: stereoelectronic role of trans effect in a metal-mediated pericyclic process and a shift from homogeneous to heterogeneous catalysis during a one-pot reaction.

    Science.gov (United States)

    Vidhani, Dinesh V; Krafft, Marie E; Alabugin, Igor V

    2014-01-01

    The combination of experiments and computations reveals unusual features of stereoselective Rh(I)-catalyzed transformation of propargyl vinyl ethers into (E,Z)-dienals. The first step, the conversion of propargyl vinyl ethers into allene aldehydes, proceeds under homogeneous conditions via a "cyclization-mediated" mechanism initiated by Rh(I) coordination at the alkyne. This path agrees well with the small experimental effects of substituents on the carbinol carbon. The key feature revealed by the computational study is the stereoelectronic effect of the ligand arrangement at the catalytic center. The rearrangement barriers significantly decrease due to the greater transfer of electron density from the catalytic metal center to the CO ligand oriented trans to the alkyne. This effect increases electrophilicity of the metal and lowers the calculated barriers by 9.0 kcal/mol. Subsequent evolution of the catalyst leads to the in situ formation of Rh(I) nanoclusters that catalyze stereoselective tautomerization. The intermediacy of heterogeneous catalysis by nanoclusters was confirmed by mercury poisoning, temperature-dependent sigmoidal kinetic curves, and dynamic light scattering. The combination of experiments and computations suggests that the initially formed allene-aldehyde product assists in the transformation of a homogeneous catalyst (or "a cocktail of catalysts") into nanoclusters, which in turn catalyze and control the stereochemistry of subsequent transformations.

  8. Drift flux modelling for a two-phase system in a flotation column

    Energy Technology Data Exchange (ETDEWEB)

    Vandenberghe, J.; Choung, J.; Xu, Z.; Masliyah, J. [Alberta Univ., Edmonton, AB (Canada). Dept. of Chemical and Materials Engineering

    2005-04-01

    Mineral and coal industries use flotation columns to improve recovery, upgrade products, save energy and reduce scale. Flotation columns are a proven process equipment that are adaptable to computer process control and offer flexible operation. Once gas is introduced to the bottom of the flotation column, bubbles form and rise throughout the pulp. Hydrophobic particles in the pulp attache to the bubbles, making the density of the bubble particle aggregates less than that of the medium. The bubble zone and the froth zone are the 2 main zones of a flotation column. This study applied the drift flux analysis to a wide range of operating conditions of a two-phase system column in order develop a better empirical relation that can predict the bubbly and froth zone characteristics. Tests were performed with process water taken from a bitumen extraction process at Syncrude Canada Limited with aqueous solutions having low concentrations of methyl isobutyl carbinol at 7.8 or 15.5 ppm. A new correlation for the drift flux system characteristic curve was discovered in this study. The new correlation is applicable for a bubble Reynolds number range of 5 to 70. The numerical equation for this correlation was presented. The bubble and froth zones have different hydrodynamics. Therefore, the method for calculating the Reynolds number in the bubble zone may not be suitable for the froth zone. Therefore, a new equation was proposed to accommodate a wider operating range. 16 refs., 1 tab., 13 figs.

  9. Dehydration and Stabilization of a Reactive Tertiary Hydroxyl Group in Solid Oral Dosage Forms of BMS-779788.

    Science.gov (United States)

    Adams, Monica L; Sharma, Vijayata; Gokhale, Madhushree; Huang, Yande; Stefanski, Kevin; Su, Ching; Hussain, Munir A

    2016-04-01

    BMS-779788 contains a reactive tertiary hydroxyl attached to a weakly basic imidazole ring. Propensity of the carbinol toward dehydration to yield the corresponding alkene, BMS-779788-ALK, was evaluated. Elevated levels of BMS-779788-ALK were observed in excipient compatibility samples. Stability studies revealed that BMS-779788 degrades to BMS-779788-ALK in capsules and tablets prepared by both dry and wet granulation processes. An acid-catalyzed dehydration mechanism, in which the heterocyclic core contributes resonance stability to the cationic intermediate via charge transfer to the imidazole ring, was proposed. Therefore, neutralization via a buffered (pH 7.0) granulating solution was used to mitigate dehydration. Solution studies revealed degradation of BMS-779788 to BMS-779788-ALK over the pH range of 1-7.5. Reversibility was confirmed by initiating reactions with BMS-779788-ALK over the same pH range. Accordingly, a simple reversible scheme can be used to describe reactions initiated with either BMS-779788 or BMS-779788-ALK. To eliminate potential for charge delocalization across the heterocycle and probe the degradation mechanism, the imidazole ring of BMS-779788 was methylated (BMS-779788-Me). The propensity for acid-catalyzed dehydration was then evaluated. The acid stability of BMS-779788-Me confirmed that the heterocyclic core contributes to reactivity liability of the tertiary hydroxyl.

  10. Intestinal inflammation and the diet:Is food friend or foe?

    Institute of Scientific and Technical Information of China (English)

    Bryant W Megna; Patrick R Carney; Gregory D Kennedy

    2016-01-01

    Inflammatory bowel disease(IBD) is a chronic intestinal illness of autoimmune origin affecting millions across the globe. The most common subtypes include ulcerative colitis(UC) and Crohn’s disease. While many medical treatments for IBD exist,none come without the risk of significant immunosuppression and in general do not have benign side effect profiles. Surgical intervention exists only as radical resection for medically refractory UC. There exists a dire need for novel treatments that target the inherent pathophysiologic disturbances of IBD,rather than global immune suppression. One avenue of investigation that could provide such an agent is the interaction between certain dietary elements and the aryl hydrocarbon receptor(AHR). The AHR is a cytosolic transcription factor with a rich history in environmental toxicant handling,however,recently a role has emerged for the AHR as a modulator of the gastrointestinal immune system. Studies have come to elucidate these effects to include the enhancement of Th cell subset differentiation,interactions between enteric flora and the luminal wall,and modulation of inflammatory interleukin and cytokine signaling. This review highlights advancements in our understanding of AHR activity in the digestive tract and how this stimulation may be wrought by certain dietary "micronutriceuticals",namely indole-3-carbinol(I3C) and its derivatives. Greater clarity surrounding these dynamics could lead to a novel diet-derived agonist of the AHR which is not only non-toxic,but also efficacious in the amelioration of clinical IBD.

  11. Mechanisms and Therapeutic Implications of Cell Death Induction by Indole Compounds

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Aamir; Sakr, Wael A.; Rahman, KM Wahidur, E-mail: kmrahman@med.wayne.edu [Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201 (United States)

    2011-07-19

    Indole compounds, obtained from cruciferous vegetables, are well-known for their anti-cancer properties. In particular, indole-3-carbinol (I3C) and its dimeric product, 3,3′-diindolylmethane (DIM), have been widely investigated for their effectiveness against a number of human cancers in vitro as well as in vivo. These compounds are effective inducers of apoptosis and the accumulating evidence documenting their ability to modulate multiple cellular signaling pathways is a testimony to their pleiotropic behavior. Here we attempt to update current understanding on the various mechanisms that are responsible for the apoptosis-inducing effects by these compounds. The significance of apoptosis-induction as a desirable attribute of anti-cancer agents such as indole compounds cannot be overstated. However, an equally intriguing property of these compounds is their ability to sensitize cancer cells to standard chemotherapeutic agents. Such chemosensitizing effects of indole compounds can potentially have major clinical implications because these non-toxic compounds can reduce the toxicity and drug-resistance associated with available chemotherapies. Combinational therapy is increasingly being realized to be better than single agent therapy and, through this review article, we aim to provide a rationale behind combination of natural compounds such as indoles with conventional therapeutics.

  12. Cruciferous vegetables: cancer protective mechanisms of glucosinolate hydrolysis products and selenium.

    Science.gov (United States)

    Keck, Anna-Sigrid; Finley, John W

    2004-03-01

    Dietetic professionals urge Americans to increase fruit and vegetable intakes. The American Institute of Cancer Research estimates that if the only dietary change made was to increase the daily intake of fruits and vegetables to 5 servings per day, cancer rates could decline by as much as 20%. Among the reasons cited for this health benefit are that fruits and vegetables are excellent sources of fiber, vitamins, and minerals. They also contain nonnutritive components that may provide substantial health benefits beyond basic nutrition. Examples of the latter are the glucosinolate hydrolysis products, sulforaphane, and indole-3-carbinol. Epidemiological studies provide evidence that the consumption of cruciferous vegetables protects against cancer more effectively than the total intake of fruits and vegetables. This review describes the anticarcinogenic bioactivities of glucosinolate hydrolysis products, the mineral selenium derived from crucifers, and the mechanisms by which they protect against cancer. These mechanisms include altered estrogen metabolism, protection against reactive oxygen species, altered detoxification by induction of phase II enzymes, decreased carcinogen activation by inhibition of phase I enzymes, and slowed tumor growth and induction of apoptosis.

  13. Mechanisms and Therapeutic Implications of Cell Death Induction by Indole Compounds

    Directory of Open Access Journals (Sweden)

    KM Wahidur Rahman

    2011-07-01

    Full Text Available Indole compounds, obtained from cruciferous vegetables, are well-known for their anti-cancer properties. In particular, indole-3-carbinol (I3C and its dimeric product, 3,3´-diindolylmethane (DIM, have been widely investigated for their effectiveness against a number of human cancers in vitro as well as in vivo. These compounds are effective inducers of apoptosis and the accumulating evidence documenting their ability to modulate multiple cellular signaling pathways is a testimony to their pleiotropic behavior. Here we attempt to update current understanding on the various mechanisms that are responsible for the apoptosis-inducing effects by these compounds. The significance of apoptosis-induction as a desirable attribute of anti-cancer agents such as indole compounds cannot be overstated. However, an equally intriguing property of these compounds is their ability to sensitize cancer cells to standard chemotherapeutic agents. Such chemosensitizing effects of indole compounds can potentially have major clinical implications because these non-toxic compounds can reduce the toxicity and drug-resistance associated with available chemotherapies. Combinational therapy is increasingly being realized to be better than single agent therapy and, through this review article, we aim to provide a rationale behind combination of natural compounds such as indoles with conventional therapeutics.

  14. Inhibition of aberrant proliferation and induction of apoptosis in pre-neoplastic human mammary epithelial cells by natural phytochemicals.

    Science.gov (United States)

    Katdare, M; Osborne, M P; Telang, N T

    1998-01-01

    Aberrant proliferation and modulated apoptosis leading to impaired cellular homeostasis represent crucial early events in the multi-step carcinogenic process. Regulation of these perturbed biomarkers may predict efficacious prevention of cancer development. Present experiments on non-cancerous human mammary epithelial 184-B5 cells were designed to examine whether i) exposure to suspect environmental human carcinogen Benzo (a) pyrene (BP) alters the status of cell proliferation and apoptosis and ii) BP-induced alterations are modulated in response to select natural phytochemicals that inhibit rodent mammary tumorigenesis. Flow cytometric analysis, cellular immunoreactivity to proliferation specific and apoptosis specific gene products and anchorage-dependent colony formation represented quantitative endpoints. Cruciferous glucosinolate indole-3-carbinol (I3C), tea polyphenol (-) epigallo catechin gallate (EGCC) and soy isoflavone genistein (GEN) represented the chemopreventive test compounds. A single 24 h exposure to 39 lM BP resulted in a 50% decrease (P=0.02) in the ratio of quiescent (Q=G0) to proliferative (P=S + M) population in part due to increase in aberrantly proliferative cells. The BP-initiated cells also exhibited an 87.8% inhibition (P=0. 0001) in confluency-associated apoptosis and a concomitant decrease in cellular immunoreactivity to wild-type p53. Simultaneous treatment of cultures with BP + I3C, BP + EGCG and BP + GEN resulted in a 1.8- to 3.4-fold increase (Pp53 immunoreactivity (Pp53 dependent apoptosis.

  15. A Possible Association of Diindolylmethane with Pulmonary Embolism and Deep Venous Thrombosis

    Directory of Open Access Journals (Sweden)

    Peter V. Bui

    2016-01-01

    Full Text Available Introduction. 3,3′-Diindolylmethane is available as a supplement in the United States for “cancer prevention” and “augmentation of physical fitness.” A derivative of indole-3-carbinol found in plants, diindolylmethane, binds to receptors associated with the sex steroid pathways and has unclear effects on estrogen and androgen physiology. We present a patient who had been taking diindolylmethane and developed right lower extremity deep venous thrombosis and bilateral pulmonary embolism. Case Presentation. A 65-year-old man presented with swelling, erythema, and warmth of his right lower extremity for three to four weeks. He had been taking diindolylmethane one tablet daily for three to four months. Risk factors for venous thromboembolism included tobacco use, personal history of possible pulmonary embolism, body mass index, and age. Imaging studies found extensive deep venous thrombosis in his right lower extremity and bilateral pulmonary embolism with probable right middle lobe infarction. Follow-up imaging showed chronic deep venous thrombosis in his right lower extremity. Discussion. As suggested in this single case, patients who take diindolylmethane may be at greater risk for venous thromboembolism. Further reports and studies are necessary in order to elucidate this possible association. Clinicians should question patients about supplements in the setting of venous thromboembolism.

  16. Chemical Composition, Antimicrobial and Antioxidant Activities of the Volatile Oil of Ganoderma pfeifferi Bres

    Directory of Open Access Journals (Sweden)

    Mohamed Al-Fatimi

    2016-04-01

    Full Text Available In a first study of the volatile oil of the mushroom basidiomycete Ganoderma pfeifferi Bres., the chemical composition and antimicrobial and antioxidant activities of the oil were investigated. The volatile oil was obtained from the fresh fruiting bodies of Ganoderma pfeifferi Bres. By hydrodistillation extraction and analyzed by GC-MS. The antimicrobial activity of the oil was evaluated against five bacteria strains and two types of fungi strains, using disc diffusion and broth microdilution methods. In addition, the antioxidant activity of the oil was determined using DPPH assay. Four volatile compounds representing 90.5% of the total oil were identified. The majority of the essential oil was dominated by 1-octen-3-ol (amyl vinyl carbinol 1 (73.6% followed by 1-octen-3-ol acetate 2 (12.4%, phenylacetaldehyde 3 (3.0% and 6-camphenol 4 (1.5%. The results showed that the Gram-positive bacteria species are more sensitive to the essential oil than Gram-negative bacteria. The oil showed strong antimicrobial activity against Staphylococcus aureus as well as Candida albicans. Moreover, the oil exhibited strong radical scavenging activity in the DPPH assay. This first report on the chemical composition and biological properties of G. pfeifferi volatile oil makes its pharmaceutical uses rational and provides a basis in the biological and phytochemical investigations of the volatile oils of Ganodermataceae species.

  17. Final Report: Photo-Directed Molecular Assembly of Multifunctional Inorganic Materials

    Energy Technology Data Exchange (ETDEWEB)

    B.G. Potter, Jr.

    2010-10-15

    This final report details results, conclusions, and opportunities for future effort derived from the study. The work involved combining the molecular engineering of photoactive Ti-alkoxide systems and the optical excitation of hydrolysis and condensation reactions to influence the development of the metal-oxygen-metal network at the onset of material formation. Selective excitation of the heteroleptic alkoxides, coupled with control of alkoxide local chemical environment, enabled network connectivity to be influenced and formed the basis for direct deposition and patterning of Ti-oxide-based materials. The research provided new insights into the intrinsic photoresponse and assembly of these complex, alkoxide molecules. Using a suite of electronic, vibrational, and nuclear spectroscopic probes, coupled with quantum chemical computation, the excitation wavelength and fluence dependence of molecular photoresponse and the nature of subsequent hydrolysis and condensation processes were probed in pyridine-carbinol-based Ti-alkoxides with varied counter ligand groups. Several methods for the patterning of oxide material formation were demonstrated, including the integration of this photoprocessing approach with conventional, dip-coating methodologies.

  18. The in Silico Approach to Identify a Unique Plant-Derived Inhibitor Against E6 and E7 Oncogenic Proteins of High-Risk Human Papillomavirus 16 and 18

    Directory of Open Access Journals (Sweden)

    Kumar

    2016-05-01

    Full Text Available Background Globally, the human papillomavirus (HPV remains the foremost cause of cancer mortality among women. There is a need to identify natural anti-cancerous compounds that can fight against life-threatening infections by HPV. Various kinds of natural plant-originated compounds have been used in the traditional system of medicine for cancer therapy. Different studies have reported the effective inhibition of HPV infection enacted by certain natural compounds. Out of all the different HPV types, HPV-16 and 18 are the ones mainly associated with causing cervical cancer; furthermore, the E6 and E7 oncoproteins of these two high-risk HPV types typically interact with tumor protein 53 (p53 and retinoblastoma tumor suppressor proteins (pRb of human host which consequent to cancer formation. Objectives The goal of this study is to identify unique plant-originated compounds to utilize in order to combat the high-risk human papillomavirus oncoproteins using docking measures. Materials and Methods Twelve natural compounds jaceosidin, withaferin A, curcumin, epigallocatechin-3-gallate (EGCG, artemisinin, gingerol, ursolic acid, ferulic acid, berberin, silymarin, resveratrol, and indol-3-carbinol were docked against E6 and E7 oncoproteins of high-risk HPV types 16 and 18 using a protein-ligand docking software called AutoDock4.2. Results Out of these 12 natural compounds, withaferin A was found to inhibit all four oncoproteins with minimum binding energy. Conclusions These in silico findings indicate that withaferin A may be used as a common drug for cervical cancer caused by high-risk HPV types, perhaps by restoring the normal functions of tumor suppressor proteins.

  19. Aqueous Biphasic Systems for the Synthesis of Formates by Catalytic CO2 Hydrogenation: Integrated Reaction and Catalyst Separation for CO2 -Scrubbing Solutions.

    Science.gov (United States)

    Scott, Martin; Blas Molinos, Beatriz; Westhues, Christian; Franciò, Giancarlo; Leitner, Walter

    2017-03-22

    Aqueous biphasic systems were investigated for the production of formate-amine adducts by metal-catalyzed CO2 hydrogenation, including typical scrubbing solutions as feedstocks. Different hydrophobic organic solvents and ionic liquids could be employed as the stationary phase for cis-[Ru(dppm)2 Cl2 ] (dppm=bis-diphenylphosphinomethane) as prototypical catalyst without any modification or tagging of the complex. The amines were found to partition between the two phases depending on their structure, whereas the formate-amine adducts were nearly quantitatively extracted into the aqueous phase, providing a favorable phase behavior for the envisaged integrated reaction/separation sequence. The solvent pair of methyl isobutyl carbinol (MIBC) and water led to the most practical and productive system and repeated use of the catalyst phase was demonstrated. The highest single batch activity with a TOFav of approximately 35 000 h(-1) and an initial TOF of approximately 180 000 h(-1) was achieved in the presence of NEt3 . Owing to higher stability, the highest productivities were obtained with methyl diethanolamine (Aminosol CST 115) and monoethanolamine (MEA), which are used in commercial scale CO2 -scrubbing processes. Saturated aqueous solutions (CO2 overpressure 5-10 bar) of MEA could be converted into the corresponding formate adducts with average turnover frequencies up to 14×10(3)  h(-1) with an overall yield of 70 % based on the amine, corresponding to a total turnover number of 150 000 over eleven recycling experiments. This opens the possibility for integrated approaches to carbon capture and utilization.

  20. Tether-directed synthesis of highly substituted oxasilacycles via an intramolecular allylation employing allylsilanes

    Directory of Open Access Journals (Sweden)

    Cox Liam R

    2007-02-01

    Full Text Available Abstract Background Using a silyl tether to unite an aldehyde electrophile and allylsilane nucleophile into a single molecule allows a subsequent Lewis-acid-mediated allylation to proceed in an intramolecular sense and therefore receive all the benefits associated with such processes. However, with the ability to cleave the tether post allylation, a product that is the result of a net intermolecular reaction can be obtained. In the present study, four diastereoisomeric β-silyloxy-α-methyl aldehydes, which contain an allylsilane tethered through the β-carbinol centre, have been prepared, in order to probe how the relative configuration of the two stereogenic centres affects the efficiency and selectivity of the intramolecular allylation. Results Syn-aldehydes, syn-4a and syn-4b, both react poorly, affording all four possible diastereoisomeric oxasilacycle products. In contrast, the anti aldehydes anti-4a and anti-4b react analogously to substrates that lack substitution at the α-site, affording only two of the four possible allylation products. Conclusion The outcome of the reaction with anti-aldehydes is in accord with reaction proceeding through a chair-like transition state (T.S.. In these systems, the sense of 1,3-stereoinduction can be rationalised by the aldehyde electrophile adopting a pseudoaxial orientation, which will minimise dipole-dipole interactions in the T.S. The 1,4-stereoinduction in these substrates is modest and seems to be modulated by the R substituent in the starting material. In the case of the syn-substrates, cyclisation through a chair T.S. is unlikely as this would require the methyl substituent α to the reacting carbonyl group to adopt an unfavourable pseudoaxial position. It is therefore proposed that these substrates react through poorly-defined T.S.s and consequently exhibit essentially no stereoselectivity.

  1. Enantioselective nano liquid chromatographic separation of racemic pharmaceuticals: a facile one-pot in situ preparation of lipase-based polymer monoliths in capillary format.

    Science.gov (United States)

    Ahmed, Marwa; Ghanem, Ashraf

    2014-11-01

    New affinity monolithic capillary columns of 150 µm internal diameter were prepared in situ fused glass capillary via either immobilization or encapsulation of Candida antarctica lipase B (CALB) on or within polymer monoliths, respectively. The immobilized lipase-based monoliths were prepared via copolymerization of 19.1% monomers (8.9% MMA and 10.2% GMA), 19.8% EDMA, and 61.1% porogens (54.2% formamide and 6.9% 1-propanol) w/w or 20% GMA, 20% EDMA, and 60% porogens (51.6% cyclohexanol and 8.4% 1-dodecanol) in the presence of AIBN (1%) as a radical initiator. This was followed by pumping a solution of lipase through the capillaries and rinsing with potassium phosphate buffer. On the other hand, the encapsulated lipase-based monoliths were prepared via copolymerization of 20% monomers (GMA), 20% EDMA, and 60% porogens (48% 1-propanol, 6% 1,4-butanediol) or 16.4% monomers (16% BuMA, 0.4% SPMA), 23.6% EDMA, and 60% porogens (36% 1-propanol, 18% 1,4-butanediol along with 6% lipase aqueous solution in potassium phosphate buffer. The prepared capillary columns were investigated for the enantioselective nano liquid chromatographic separation of a set of different classes of racemic pharmaceuticals, namely, α- and β-blockers, antiinflammatory drugs, antifungal drugs, dopamine antagonists, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, diuretics, antihistaminics, anticancer drugs, and antiarrhythmic drugs. Run-to-run repeatability was quite satisfactory. The encapsulated lipase-based capillary monolith showed better enantioselective separations of most of the investigated compounds. Baseline separation was achieved for alprenolol, atenolol, bromoglutithimide, carbuterol, chloropheneramine, cizolertine carbinol, 4-hydroxy-3-methoxymandelic acid, desmethylcizolertine, nomifensine, normetanephrine, and sulconazole under reversed phase chromatographic conditions. A speculation about the understanding of the chiral recognition mechanism of

  2. Synergy among phytochemicals within crucifers: does it translate into chemoprotection?

    Science.gov (United States)

    Wallig, Matthew A; Heinz-Taheny, Kathleen M; Epps, Donna L; Gossman, Tamara

    2005-12-01

    The association between cruciferous vegetables and cancer prevention has been linked to glucosinolate derivatives. These phytochemicals enhance endogenous detoxification, leading to inactivation of potential carcinogens before initiation occurs. Two derivatives, indole-3-carbinol (I3C) and 1-cyano-2-hydroxy-3-butene (crambene) were shown in rats to induce a synergistic enhancement of detoxification enzyme activity. To follow up on these findings, a short-term carcinogenicity study using aflatoxin B1 (AFB(1)) was performed in which male F344 rats were fed diets supplemented with these 2 compounds alone or in combination. Groups included a negative control group (no AFB(1), crambene, or I3C), a crambene group (diet 0.150% crambene), an I3C group (diet 0.165% I3C), a high-dose group (diet 0.150% crambene, 0.165% I3C) a low-dose group (diet 0.030% crambene, 0.033% I3C), and a positive control group (AFB(1) treatment only). AFB(1) was administered after 2 wk of dietary pretreatment. Liver sections were scored for lesions including karyomegaly, apoptosis, and biliary hyperplasia and evaluated for expression of the preneoplastic marker glutathione S-transferase-pi (GSTP). I3C and crambene groups were protected against AFB(1) toxicity whereas the low-dose group was not. The high-dose group had scores close to those of the negative controls. For log(10) transformed 2- and 3-dimensional GSTP data, the high-dose group demonstrated synergistic reduction in GSTP-positive area and an additive reduction in GSTP-positive volume compared with the crambene and I3C groups. The low-dose group had no effect. In conclusion, high combination dietary doses of I3C and crambene demonstrated enhanced protection from AFB(1). Low combination doses, as might be realistically in the diet, were not effective.

  3. HPLC Separation and Determination of Carotenoids in Ipomoea batatas%HPLC分离测定红心薯中类胡萝卜素

    Institute of Scientific and Technical Information of China (English)

    吉宏武; 施兆鹏

    2001-01-01

    The carotenoids from Ipomoea batatas were separated and determined by HPLC. Results show that the main carotenoids in Ipomoea batatas can be successfully separated in 10min with detection at 440nm by extracting the sample in hexane -acetone-ethanol-toluene and 40% potassium hydroxide methanol for twelve hours ,employing Nova-Pak C18 stainliss steel column (3.9×150 mm),using acetonitrile -chloroform-methyl carbinol (83∶15∶2)as flow phase, applying linear gradient eluting with the rate of flow, with the temperature of column at 25 ℃.Four kinds of main carotenoids from Ipomoea batatas were determined by external standards.%应用高效液相色谱法分离和测定红心薯中类胡萝卜素.样品制备采用已烷-丙酮-乙腈-甲苯混合溶剂与40%氢氧化钾甲醇溶液浸提、皂化的方法,使用Nova-Pak C18不锈钢柱,乙腈-三氯甲烷-叔丁醇作三元流动相,流量线性梯度洗脱等色谱条件,在440 nm波长下检测,红心薯中主要类胡萝卜素得到了较好的分离.以外标定量法对红心薯中的4种主要类胡萝卜素(β-胡萝卜素,叶黄质,堇黄质,新黄质)进行了定量,结果较为满意.

  4. Molecular targets of dietary agents for prevention and therapy of cancer.

    Science.gov (United States)

    Aggarwal, Bharat B; Shishodia, Shishir

    2006-05-14

    While fruits and vegetables are recommended for prevention of cancer and other diseases, their active ingredients (at the molecular level) and their mechanisms of action less well understood. Extensive research during the last half century has identified various molecular targets that can potentially be used not only for the prevention of cancer but also for treatment. However, lack of success with targeted monotherapy resulting from bypass mechanisms has forced researchers to employ either combination therapy or agents that interfere with multiple cell-signaling pathways. In this review, we present evidence that numerous agents identified from fruits and vegetables can interfere with several cell-signaling pathways. The agents include curcumin (turmeric), resveratrol (red grapes, peanuts and berries), genistein (soybean), diallyl sulfide (allium), S-allyl cysteine (allium), allicin (garlic), lycopene (tomato), capsaicin (red chilli), diosgenin (fenugreek), 6-gingerol (ginger), ellagic acid (pomegranate), ursolic acid (apple, pears, prunes), silymarin (milk thistle), anethol (anise, camphor, and fennel), catechins (green tea), eugenol (cloves), indole-3-carbinol (cruciferous vegetables), limonene (citrus fruits), beta carotene (carrots), and dietary fiber. For instance, the cell-signaling pathways inhibited by curcumin alone include NF-kappaB, AP-1, STAT3, Akt, Bcl-2, Bcl-X(L), caspases, PARP, IKK, EGFR, HER2, JNK, MAPK, COX2, and 5-LOX. The active principle identified in fruit and vegetables and the molecular targets modulated may be the basis for how these dietary agents not only prevent but also treat cancer and other diseases. This work reaffirms what Hippocrates said 25 centuries ago, let food be thy medicine and medicine be thy food.

  5. 顶空气相色谱-质谱联用法分析灵芝发酵物中的挥发性物质%Head-space gas chromatographic analysis for the volatile flavor compounds from Ganoderma lucidum submerged-cultured broth

    Institute of Scientific and Technical Information of China (English)

    刘高强; 王晓玲

    2007-01-01

    采用顶空-气相色谱-质谱联用法对灵芝发酵物的风味物质进行了定性和定量测定.结果表明,灵芝发酵物中至少含有31种风味物质.对其中21种主要成分进行了鉴定,这些物质大多是酮类、醇类和内酯类化合物.所有物质中4,5-二氢-3,5-二甲基-2-呋喃酮的含量最高,达64.12%.此外,3-戊烯-2-酮和戊基乙烯基原醇是已知的食品香料成分.结果有助于初步理解灵芝发酵物产生清淡香味的原因.%The volatile flavor from Ganoderma lucidum submerged-cultured broth was investigated by head-space gas chromatography-mass spectrometry (GC-MS). More than thirty different volatile flavor compounds from the broth were detected, and twenty-one compounds were identified, which were mainly ketones, alcohols and lactones. Among all the compounds detected in the broth, the compound with its characteristic retention peaks at 22.41min was 4,5-dihydro-3,5-dimethyl-2-furanone, and its content was 64.12% of the total content of all the volatile flavor compounds. In addition, 3-penten-2-one and amyl vinyl carbinol with their characteristic retention peaks at 9.78min and 18.10min, respectively, were the known food spice substances.The results were useful to preliminarily understand the mechanism of light aroma emitted from the submerged-cultured broth of G. lucidum.

  6. Attenuation of multi-targeted proliferation-linked signaling by 3,3'-diindolylmethane (DIM): from bench to clinic.

    Science.gov (United States)

    Banerjee, Sanjeev; Kong, Dejuan; Wang, Zhiwei; Bao, Bin; Hillman, Gilda G; Sarkar, Fazlul H

    2011-01-01

    Emerging evidence provide credible support in favor of the potential role of bioactive products derived from ingesting cruciferous vegetables such as broccoli, brussel sprouts, cauliflower and cabbage. Among many compounds, 3,3'-diindolylmethane (DIM) is generated in the acidic environment of the stomach following dimerization of indole-3-carbinol (I3C) monomers present in these classes of vegetables. Both I3C and DIM have been investigated for their use in preventing, inhibiting, and reversing the progression of cancer - as a chemopreventive agent. In this review, we summarize an updated, wide-ranging pleiotropic anti-tumor and biological effects elicited by DIM against tumor cells. It is unfeasible to point one single target as basis of cellular target of action of DIM. We emphasize key cellular and molecular events that are effectively modulated in the direction of inducing apoptosis and suppressing cell proliferation. Collectively, DIM orchestrates signaling through Ah receptor, NF-κB/Wnt/Akt/mTOR pathways impinging on cell cycle arrest, modulation of key cytochrome P450 enzymes, altering angiogenesis, invasion, metastasis and epigenetic behavior of cancer cells. The ability of DIM to selectively induce tumor cells to undergo apoptosis has been observed in preclinical models, and thus it has been speculated in improving the therapeutic efficacy of other anticancer agents that have diverse molecular targets. Consequently, DIM has moved through preclinical development into Phase I clinical trials, thereby suggesting that DIM could be a promising and novel agent either alone or as an adjunct to conventional therapeutics such as chemo-radio and targeted therapies. An important development has been the availability of DIM formulation with superior bioavailability for humans. Therefore, DIM appears to be a promising chemopreventive agent or chemo-radio-sensitizer for the prevention of tumor recurrence and/or for the treatment of human malignancies.

  7. The role dietary of bioactive compounds on the regulation of histone acetylases and deacetylases: a review.

    Science.gov (United States)

    Vahid, F; Zand, H; Nosrat-Mirshekarlou, E; Najafi, R; Hekmatdoost, A

    2015-05-10

    Nutrigenomics is an area of epigenomics that explores and defines the rapidly evolving field of diet-genome interactions. Lifestyle and diet can significantly influence epigenetic mechanisms, which cause heritable changes in gene expression without changes in DNA sequence. Nutrient-dependent epigenetic variations can significantly affect genome stability, mRNA and protein expression, and metabolic changes, which in turn influence food absorption and the activity of its constituents. Dietary bioactive compounds can affect epigenetic alterations, which are accumulated over time and are shown to be involved in the pathogenesis of age-related diseases such as diabetes, cancer, and cardiovascular disease. Histone acetylation is an epigenetic modification mediated by histone acetyl transferases (HATs) and histone deacetylases (HDACs) critically involved in regulating affinity binding between the histones and DNA backbone. The HDAC-mediated increase in histone affinity to DNA causes DNA condensation, preventing transcription, whereas HAT-acetylated chromatin is transcriptionally active. HDAC and HAT activities are reported to be associated with signal transduction, cell growth and death, as well as with the pathogenesis of various diseases. The aim of this review was to evaluate the role of diet and dietary bioactive compounds on the regulation of HATs and HDACs in epigenetic diseases. Dietary bioactive compounds such as genistein, phenylisothiocyanate, curcumin, resveratrol, indole-3-carbinol, and epigallocatechin-3-gallate can regulate HDAC and HAT activities and acetylation of histones and non-histone chromatin proteins, and their health benefits are thought to be attributed to these epigenetic mechanisms. The intake of dietary compounds that regulate epigenetic modifications can provide significant health effects and may prevent various pathological processes involved in the development of cancer and other life-threatening diseases.

  8. Intrarenal alterations of the angiotensin-converting enzyme type 2/angiotensin 1-7 complex of the renin-angiotensin system do not alter the course of malignant hypertension in Cyp1a1-Ren-2 transgenic rats.

    Science.gov (United States)

    Husková, Zuzana; Kopkan, Libor; Červenková, Lenka; Doleželová, Šárka; Vaňourková, Zdeňka; Škaroupková, Petra; Nishiyama, Akira; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz; Kramer, Herbert J; Červenka, Luděk

    2016-04-01

    The role of the intrarenal renin-angiotensin system (RAS) in the pathophysiology of malignant hypertension is not fully understood. Accumulating evidence indicates that the recently discovered vasodilator axis of the RAS, angiotensin-converting enzyme (ACE) type 2 (ACE2)/angiotensin 1-7 (ANG 1-7), constitutes an endogenous system counterbalancing the hypertensiogenic axis, ACE/angiotensin II (ANG II)/AT1 receptor. This study aimed to evaluate the role of the intrarenal vasodilator RAS axis in the pathophysiology of ANG II-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. ANG II-dependent malignant hypertension was induced by 13 days' dietary administration of indole-3-carbinol (I3C), a natural xenobiotic that activates the mouse renin gene in Cyp1a1-Ren-2 transgenic rats. It was hypothesized that pharmacologically-induced inhibition of the ACE2/ANG 1-7 complex should aggravate, and activation of this axis should attenuate, the course of ANG II-dependent malignant hypertension. Blood pressure (BP) was monitored by radiotelemetry. ACE2 inhibitor (DX 600, 0.2 μg/day) and ACE2 activator (DIZE, 1 mg/day) were administrated via osmotic minipumps. Even though ACE2 inhibitor significantly decreased and ACE2 activator increased intrarenal ANG 1-7 concentrations, the course of BP, as well as of albuminuria, cardiac hypertrophy and renal glomerular damage, were not altered. It was shown that intrarenal alterations in the ACE2/ANG 1-7 complex did not significantly modify the course of malignant hypertension in I3C-induced Cyp1a1-Ren-2 transgenic rats. Thus, in our experimental setting alterations of this intrarenal vasodilator complex of the RAS do not significantly modify the form of malignant hypertension that clearly depends on the inappropriately increased activity of the ACE/ANG II/AT1 receptor axis.

  9. Skatole (3-Methylindole Is a Partial Aryl Hydrocarbon Receptor Agonist and Induces CYP1A1/2 and CYP1B1 Expression in Primary Human Hepatocytes.

    Directory of Open Access Journals (Sweden)

    Martin Krøyer Rasmussen

    Full Text Available Skatole (3-methylindole is a product of bacterial fermentation of tryptophan in the intestine. A significant amount of skatole can also be inhaled during cigarette smoking. Skatole is a pulmonary toxin that induces the expression of aryl hydrocarbon receptor (AhR regulated genes, such as cytochrome P450 1A1 (CYP1A1, in human bronchial cells. The liver has a high metabolic capacity for skatole and is the first organ encountered by the absorbed skatole; however, the effect of skatole in the liver is unknown. Therefore, we investigated the impact of skatole on hepatic AhR activity and AhR-regulated gene expression. Using reporter gene assays, we showed that skatole activates AhR and that this is accompanied by an increase of CYP1A1, CYP1A2 and CYP1B1 expression in HepG2-C3 and primary human hepatocytes. Specific AhR antagonists and siRNA-mediated AhR silencing demonstrated that skatole-induced CYP1A1 expression is dependent on AhR activation. The effect of skatole was reduced by blocking intrinsic cytochrome P450 activity and indole-3-carbinole, a known skatole metabolite, was a more potent inducer than skatole. Finally, skatole could reduce TCDD-induced CYP1A1 expression, suggesting that skatole is a partial AhR agonist. In conclusion, our findings suggest that skatole and its metabolites affect liver homeostasis by modulating the AhR pathway.

  10. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis.

    Science.gov (United States)

    Higdon, Jane V; Delage, Barbara; Williams, David E; Dashwood, Roderick H

    2007-03-01

    Cruciferous vegetables are a rich source of glucosinolates and their hydrolysis products, including indoles and isothiocyanates, and high intake of cruciferous vegetables has been associated with lower risk of lung and colorectal cancer in some epidemiological studies. Glucosinolate hydrolysis products alter the metabolism or activity of sex hormones in ways that could inhibit the development of hormone-sensitive cancers, but evidence of an inverse association between cruciferous vegetable intake and breast or prostate cancer in humans is limited and inconsistent. Organizations such as the National Cancer Institute recommend the consumption of five to nine servings of fruits and vegetables daily, but separate recommendations for cruciferous vegetables have not been established. Isothiocyanates and indoles derived from the hydrolysis of glucosinolates, such as sulforaphane and indole-3-carbinol (I3C), have been implicated in a variety of anticarcinogenic mechanisms, but deleterious effects also have been reported in some experimental protocols, including tumor promotion over prolonged periods of exposure. Epidemiological studies indicate that human exposure to isothiocyanates and indoles through cruciferous vegetable consumption may decrease cancer risk, but the protective effects may be influenced by individual genetic variation (polymorphisms) in the metabolism and elimination of isothiocyanates from the body. Cooking procedures also affect the bioavailability and intake of glucosinolates and their derivatives. Supplementation with I3C or the related dimer 3,3'-diindolylmethane (DIM) alters urinary estrogen metabolite profiles in women, but the effects of I3C and DIM on breast cancer risk are not known. Small preliminary trials in humans suggest that I3C supplementation may be beneficial in treating conditions related to human papilloma virus infection, such as cervical intraepithelial neoplasia and recurrent respiratory papillomatosis, but larger randomized

  11. Activation of AMP-activated protein kinase by 3,3'-Diindolylmethane (DIM is associated with human prostate cancer cell death in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Di Chen

    Full Text Available There is a large body of scientific evidence suggesting that 3,3'-Diindolylmethane (DIM, a compound derived from the digestion of indole-3-carbinol, which is abundant in cruciferous vegetables, harbors anti-tumor activity in vitro and in vivo. Accumulating evidence suggests that AMP-activated protein kinase (AMPK plays an essential role in cellular energy homeostasis and tumor development and that targeting AMPK may be a promising therapeutic option for cancer treatment in the clinic. We previously reported that a formulated DIM (BR-DIM; hereafter referred as B-DIM with higher bioavailability was able to induce apoptosis and inhibit cell growth, angiogenesis, and invasion of prostate cancer cells. However, the precise molecular mechanism(s for the anti-cancer effects of B-DIM have not been fully elucidated. In the present study, we investigated whether AMP-activated protein kinase (AMPK is a molecular target of B-DIM in human prostate cancer cells. Our results showed, for the first time, that B-DIM could activate the AMPK signaling pathway, associated with suppression of the mammalian target of rapamycin (mTOR, down-regulation of androgen receptor (AR expression, and induction of apoptosis in both androgen-sensitive LNCaP and androgen-insensitive C4-2B prostate cancer cells. B-DIM also activates AMPK and down-regulates AR in androgen-independent C4-2B prostate tumor xenografts in SCID mice. These results suggest that B-DIM could be used as a potential anti-cancer agent in the clinic for prevention and/or treatment of prostate cancer regardless of androgen responsiveness, although functional AR may be required.

  12. Does postmenopausal estrogen administration increase the risk of breast cancer? Contributions of animal, biochemical, and clinical investigative studies to a resolution of the controversy.

    Science.gov (United States)

    Zumoff, B

    1998-01-01

    two synergistic steps: a. Eliminating alcohol consumption, or at least keeping it well below an average of 5 grams daily (equivalent to 2/3 ounce of whiskey or 3 ounces of wine). b. Diminishing the capacity to 16 alpha-hydroxylate estradiol, either through pharmacological agents such as indole-3-carbinol or through increased consumption of cruciferous vegetables. It is concluded that despite the inherent ability of postmenopausal estrogen therapy to increase the risk of breast cancer in theory, the increased risk can be eliminated in practice by minimizing or eliminating consumption of alcohol and ingesting pharmacological or dietary agents that reduce the 16 alpha-hydroxylation of estradiol.

  13. Nutrition and primary prevention of breast cancer: foods, nutrients and breast cancer risk.

    Science.gov (United States)

    Hanf, Volker; Gonder, Ulrike

    2005-12-01

    that should be regular constituents in our meals. Lignans from traditionally made sourdough rye bread, linseed/flaxseed and berries are local sources of potentially canceroprotective phyto-estrogens. Furthermore, indole-3-carbinol rich cabbage species might contribute to BC protection by diet. Nevertheless, clear cut recommendations for or against single nutrients or secondary plant metabolites are not yet possible, lacking sufficient data on individual bioavailability, safety and long term outcome. BC prevention by dietary means therefore relies on an individually tailored mixed diet, rich in basic foods and traditional manufacturing and cooking methods.

  14. Study of different routes to develop asymmetric double decker silsesquioxane (DDSQ)

    Science.gov (United States)

    Attanayake, Gayanthi Kumari

    on studies of different routes to an asymmetric DDSQ cage. DDSQ molecules possess a higher symmetry. Breaking the symmetry and selective functionalization of the DDSQ molecule would be highly desirable to fine tune the physical properties. Different routes were studied to develop an asymmetric DDSQ cage. One route is monoprotection of a hydroxyl group from four symmetrical hydroxyl groups present in the DDSQ cage using McDougal chemistry. This chemistry was applied to DDSQ cage, DDSQ(Me)(OH) and DDSQ(Me)(Hydroxypropyl)(carbinol system). The second attempt was hindering one side of the DDSQ cage using an immobilized surface. Different surface immobilized reagents such as "Red-Sil" (Reducing Silica) and Merrifield resinwere analyzed in this project as screening surfaces.

  15. Ecologically appropriate xenobiotics induce cytochrome P450s in Apis mellifera.

    Directory of Open Access Journals (Sweden)

    Reed M Johnson

    Full Text Available BACKGROUND: Honey bees are exposed to phytochemicals through the nectar, pollen and propolis consumed to sustain the colony. They may also encounter mycotoxins produced by Aspergillus fungi infesting pollen in beebread. Moreover, bees are exposed to agricultural pesticides, particularly in-hive acaricides used against the parasite Varroa destructor. They cope with these and other xenobiotics primarily through enzymatic detoxificative processes, but the regulation of detoxificative enzymes in honey bees remains largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: We used several approaches to ascertain effects of dietary toxins on bee susceptibility to synthetic and natural xenobiotics, including the acaricide tau-fluvalinate, the agricultural pesticide imidacloprid, and the naturally occurring mycotoxin aflatoxin. We administered potential inducers of cytochrome P450 enzymes, the principal biochemical system for Phase 1 detoxification in insects, to investigate how detoxification is regulated. The drug phenobarbital induces P450s in many insects, yet feeding bees with phenobarbital had no effect on the toxicity of tau-fluvalinate, a pesticide known to be detoxified by bee P450s. Similarly, no P450 induction, as measured by tau-fluvalinate tolerance, occurred in bees fed xanthotoxin, salicylic acid, or indole-3-carbinol, all of which induce P450s in other insects. Only quercetin, a common pollen and honey constituent, reduced tau-fluvalinate toxicity. In microarray comparisons no change in detoxificative gene expression was detected in phenobarbital-treated bees. However, northern blot analyses of guts of bees fed extracts of honey, pollen and propolis showed elevated expression of three CYP6AS P450 genes. Diet did not influence tau-fluvalinate or imidacloprid toxicity in bioassays; however, aflatoxin toxicity was higher in bees consuming sucrose or high-fructose corn syrup than in bees consuming honey. CONCLUSIONS/SIGNIFICANCE: These results

  16. 谷氨酸锌螯合物的制备及测定新方法%Preparation of zinc-glutamate chelate and the new method for mensuration

    Institute of Scientific and Technical Information of China (English)

    邢颖; 段庆波; 黄国发; 杨野; 赵竹青

    2011-01-01

    Zinc-glutamate chelate was synthesized from glutamic acid and zinc sulfate. Highly pure solid chelates of araino acids with zinc were separated using precipitation fractionation by adding organic solvent. The optimum manufacture conditions for chelates synthesis were evaluated based on the chelation rate. The result showed that the best conditions of chelate were pH 6. 5, chelation could take place at WC for 30 min. The optimum conditions of determine were as follows; carbinol and concentrated chelate solution with 10: 1 apart the highly pure chelates of zinc-glutamate chelate, dissolved by 20% sul-furcacid. The chelation rate was up to 80%. And the qualitative test all showed the reaction of chelation take place. This test showed that synthesized conditions could preparation zinc-glutamate chelate with high chelation rate and stability.%以谷氨酸和硫酸锌为原料,制备谷氨酸锌螯合物.用有机溶剂沉淀法,以螯合率为指标,筛选最佳螯合及分离提纯条件.结果表明,最佳螫合条件为:pH6.5,螯合温度90℃,反应时间30 min;分离最佳条件为:将甲醇与螯合浓缩液按10∶1的比例混合提取谷氨酸锌螯合物,用20%的硫酸溶解该螫合物.试验证明,该条件下谷氨酸螯合锌螯合率可达80%以上.此外,定性试验结果均表明谷氨酸与硫酸锌发生了螯合反应.说明该试验条件下可制得稳定且具较高螯合率的谷氨酸锌产品.

  17. OSU-A9 inhibits angiogenesis in human umbilical vein endothelial cells via disrupting Akt–NF-κB and MAPK signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Omar, Hany A. [Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210 (United States); Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514 (Egypt); Arafa, El-Shaimaa A. [Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514 (Egypt); Salama, Samir A. [Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11511 (Egypt); Arab, Hany H. [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Wu, Chieh-Hsi, E-mail: chhswu@mail.cmu.edu.tw [School of Pharmacy, China Medical University, Taichung 40402, Taiwan (China); Weng, Jing-Ru, E-mail: columnster@gmail.com [Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan (China)

    2013-11-01

    Since the introduction of angiogenesis as a useful target for cancer therapy, few agents have been approved for clinical use due to the rapid development of resistance. This problem can be minimized by simultaneous targeting of multiple angiogenesis signaling pathways, a potential strategy in cancer management known as polypharmacology. The current study aimed at exploring the anti-angiogenic activity of OSU-A9, an indole-3-carbinol-derived pleotropic agent that targets mainly Akt–nuclear factor-kappa B (NF-κB) signaling which regulates many key players of angiogenesis such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Human umbilical vein endothelial cells (HUVECs) were used to study the in vitro anti-angiogenic effect of OSU-A9 on several key steps of angiogenesis. Results showed that OSU-A9 effectively inhibited cell proliferation and induced apoptosis and cell cycle arrest in HUVECs. Besides, OSU-A9 inhibited angiogenesis as evidenced by abrogation of migration/invasion and Matrigel tube formation in HUVECs and attenuation of the in vivo neovascularization in the chicken chorioallantoic membrane assay. Mechanistically, Western blot, RT-PCR and ELISA analyses showed the ability of OSU-A9 to inhibit MMP-2 production and VEGF expression induced by hypoxia or phorbol-12-myristyl-13-acetate. Furthermore, dual inhibition of Akt–NF-κB and mitogen-activated protein kinase (MAPK) signaling, the key regulators of angiogenesis, was observed. Together, the current study highlights evidences for the promising anti-angiogenic activity of OSU-A9, at least in part through the inhibition of Akt–NF-κB and MAPK signaling and their consequent inhibition of VEGF and MMP-2. These findings support OSU-A9's clinical promise as a component of anticancer therapy. - Highlights: • The antiangiogenic activity of OSU-A9 in HUVECs was explored. • OSU-A9 inhibited HUVECs proliferation, migration, invasion and tube formation. • OSU-A9

  18. Dietary Indoles Suppress Delayed-Type Hypersensitivity by Inducing a Switch from Proinflammatory Th17 Cells to Anti-Inflammatory Regulatory T Cells through Regulation of MicroRNA.

    Science.gov (United States)

    Singh, Narendra P; Singh, Udai P; Rouse, Michael; Zhang, Jiajia; Chatterjee, Saurabh; Nagarkatti, Prakash S; Nagarkatti, Mitzi

    2016-02-01

    Aryl hydrocarbon receptor (AhR) has been shown to have profound influence on T cell differentiation, and use of distinct AhR ligands has shown that whereas some ligands induce regulatory T cells (Tregs), others induce Th17 cells. In the present study, we tested the ability of dietary AhR ligands (indole-3-carbinol [I3C] and 3,3'-diindolylmethane [DIM]) and an endogenous AhR ligand, 6-formylindolo(3,2-b)carbazole (FICZ), on the differentiation and functions of Tregs and Th17 cells. Treatment of C57BL/6 mice with indoles (I3C or DIM) attenuated delayed-type hypersensitivity (DTH) response to methylated BSA and generation of Th17 cells while promoting Tregs. In contrast, FICZ exacerbated the DTH response and promoted Th17 cells. Indoles decreased the induction of IL-17 but promoted IL-10 and Foxp3 expression. Also, indoles caused reciprocal induction of Tregs and Th17 cells only in wild-type (AhR(+/+)) but not in AhR knockout (AhR(-/-)) mice. Upon analysis of microRNA (miR) profile in draining lymph nodes of mice with DTH, treatment with I3C and DIM decreased the expression of several miRs (miR-31, miR-219, and miR-490) that targeted Foxp3, whereas it increased the expression of miR-495 and miR-1192 that were specific to IL-17. Interestingly, treatment with FICZ had precisely the opposite effects on these miRs. Transfection studies using mature miR mimics of miR-490 and miR-1192 that target Foxp3 and IL-17, respectively, or scrambled miR (mock) or inhibitors confirmed that these miRs specifically targeted Foxp3 and IL-17 genes. Our studies demonstrate, to our knowledge for the first time, that the ability of AhR ligands to regulate the differentiation of Tregs versus Th17 cells may depend on miR signature profile.

  19. 2010年江苏省现榨果蔬汁中合成着色剂的快速测定与结果分析%Fast Determination and Analysis on Synthetic Colours in Fresh Juice Extracted from Fruits and Vegetables in Jiangsu in 2010

    Institute of Scientific and Technical Information of China (English)

    阮丽萍; 吉文亮; 马永建

    2011-01-01

    目的:建立一种快速、灵敏、准确的HPLC法测定现榨果蔬汁中的合成着色剂,了解江苏省餐饮业现榨果蔬汁中合成着色剂的使用状况。方法:采用HPLC法测定。将样品离心、过滤,以甲醇+乙酸铵(0.02mol/L,pH=4.0)为流动相,梯度淋洗分离,定性、定量分析均采用多波长检测。结果:于260份果蔬汁中检出合成着色剂4种,分别为胭脂红、日落黄、柠檬黄、诱惑红。检出含有一种或多种合成着色剂样品23份,含量范围为0.4—2.2mg/kg,检出率8.85%。结论:该方法简单、准确、灵敏,适用于现榨果蔬汁中合成着色剂的定性、定量分析。%【Objective】To establish a simple,sensitive and accurate method for the determination of synthetical colours in fresh juice extracted from fruits and vegetables.To investigate the sanitary status of them in catering industry in Jiangsu.【Method】The synthetical colours in fresh juice were analyzed by high performance liquid chromatography.The samples were centrifugated and filtered,then separated using mobile phase of carbinol and acetic ammonium solution(0.02mol/L,pH=4) mixture under gradient elution,and quantified by DAD.【Result】Among the 260 samples,Ponceau 4R,Sunset Yellow,Tartrazine,and Allura Red were detected.One or more kinds of synthetical colour were detected in 23 samples,and the amount were from 0.4mg/kg to 2.2mg/kg.The detected rate was 8.85%.【Conclusion】The method was sensitive,simple,accurate and could be used to quantify the 7 kinds of synthetical colour in fresh juice.The method could meet the require for fast and accurate detection of synthetical colour in fresh juice from fruits and vegetables.

  20. Natural pesticides and bioactive components in foods.

    Science.gov (United States)

    Beier, R C

    1990-01-01

    In this review, some common food plants and their toxic or otherwise bioactive components and mycotoxin contaminants have been considered. Crucifers contain naturally occurring components that are goitrogenic, resulting from the combined action of allyl isothiocyanate, goitrin, and thiocyanate. Although crucifers may provide some protection from cancer when taken prior to a carcinogen, when taken after a carcinogen they act as promoters of carcinogenesis. The acid-condensed mixture of indole-3-carbinol (a component of crucifers) binds to the TCDD receptor and causes responses similar to those of TCDD. Herbs contain many biologically active components, with more than 20% of the commercially prepared human drugs coming from these plants. Onion and garlic juices can help to prevent the rise of serum cholesterol. Most herbs used in treatments may have many natural constituents that act oppositely from their intended use. Some herbs like Bishop's week seed contain carcinogens, and many contain pyrrolizidine alkaloids that can cause cirrhosis of the liver. The general phytoalexin response in plants (including potatoes, tomatoes, peppers, eggplant, celery, and sweet potatoes) induced by external stimuli can increase the concentrations of toxic chemical constituents in those plants. In potatoes, two major indigenous compounds are alpha-solanine and alpha-chaconine, which are human plasma cholinesterase inhibitors and teratogens in animals. Because of its toxicity, the potato variety Lenape was withdrawn from the market. Celery, parsley, and parsnips contain the linear furanocoumarin phytoalexins psoralen, bergapten, and xanthotoxin that can cause photosensitization and also are photomutagenic and photocarcinogenic. Celery field workers and handlers continually have photosensitization problems as a result of these indigenous celery furanocoumarins. A new celery cultivar (a result of plant breeding to produce a more pest-resistant variety) was responsible for significant

  1. 回收锂离子电池正极材料的浮选实验研究%Study on flotation of lithium-ion battery anode material

    Institute of Scientific and Technical Information of China (English)

    文瑞明; 刘长辉; 胡拥军; 齐风佩; 林毅辉

    2013-01-01

    The treatment of lithium cobaltate as lithium-ion battery's cathode materials by flotation was studied using diesel as collector and methyl isobutyl carbinol (MIBC) as foaming agent.The effect of the amount of collector and foaming agent,the type and the mount of dispersing agent and inhibitor on the recovery rate of lithium cobaltate were investigated,and the process condition was optimized.Results show that MIBC has good foaming effect and the recovery rate of lithium cobaltate is 98.15% using diesel as collector,sodium sodium hexametapho sphate as dispersing agent,sodium sodium polyacrylate as inhibitor and MIBC as foaming agent under the conditions as follows:the concentration of pulp is 2.000 g/40.00 mL,pH value is 6.00,the amount of diesel,sodium hexametapho sphate,sodium polyacrylate and MIBC is 0.15,0.75,1.0 mg and 0.84 mg,respectively.%采用柴油做捕收剂,甲基异丁基甲醇(MIBC)作起泡剂对锂离子电池正极材料钴酸锂进行了浮选实验研究.研究结果表明:MIBC具有较好的起泡效果.考察了捕收剂的用量、分散剂种类及用量、抑制剂种类及用量,以及起泡剂用量对回收率的影响.当矿浆浓度为2.000 0 g/40.00 mL,pH为6.00时,0.15 mg柴油做捕收剂,0.75 mg六偏磷酸钠做分散剂,1.0 mg聚丙烯酸钠做抑制剂,0.84 mg MIBC为起泡剂钴酸锂回收率达98.15%.

  2. Synthesis of Monomer Hydrogenated Rosin-Acrylic Glycerin Ester%氢化松香-丙烯酸丙三醇酯单体的合成

    Institute of Scientific and Technical Information of China (English)

    李浩; 王春平; 李鹏飞; 雷福厚; 段文贵

    2011-01-01

    Hydrogenated rosin-acrylic glycerin ester is synthesized from hydrogenated rosin modified by thionyl chloride obtained by reaction of hydrogenated rosin and thionyl chloride, glycerin and acryloyl chloride.Hydrogenated rosin acyl chloride is characterized by FTIR spectrum. Hydrogenated rosin glycerin ester obtained by reaction of hydrogenated rosin acyl chloride and glycerin is characterized by FTIR spectrum and determination of acid value, and its optimal synthetic reaction conditions are obtained as follows: molar ratio of hydrogenated rosinacyl chloride to glycerin is 1: 2. 5, pyridine as solvent, reaction time is 3 h, reaction temperature is ll0℃. The acid value of hydrogenated rosin glycerin ester is 21 mg·g-1 under above conditions. The structure of hydrogenated rosin-acrylic glycerin ester is confirmed by FTIR and UV-Vis. The monomer can polymerize in the presence of initiator. For the prepared polymer, its degree of cross linking is 75.1%, its solubility in aviation kerosene, carbinol, methylbenzene or cyclohexane is very small, and its softening point is 235℃.%以氢化松香、二氯亚砜、丙三醇、丙烯酰氯为主要原料,合成了可以均聚的氢化松香-丙烯酸丙三醇酯单体.氢化松香先与二氯亚砜反应制得氢化松香酰氯,通过FTIR对反应过程进行跟踪监测;氢化松香酰氯再与丙三醇经酯化反应合成氢化松香丙三醇酯,优化的反应条件为:吡啶作溶剂、n(氢化松香酰氯):n(丙三醇)=1:2.5、反应温度110℃、反应时间3 h,制得的氢化松香丙三醇酯酸值为21 mg·g-1;最后,氢化松香丙三醇酯与丙烯酰氯经酯化反应制得了氢化松香-丙烯酸丙三醇酯单体,通过FTIR和UV-Vis对其结构进行了表征.单体可以发生均聚反应,生成的颗粒状聚合物交联度为75.1%,在航空煤油、甲醇、甲苯、环己烷中的溶解度均很小,软化点为235℃.

  3. Productive practice and technology optimization of mineral processing for copper-nickel ore in Hami%哈密铜镍矿选矿工艺优化与生产实践

    Institute of Scientific and Technical Information of China (English)

    罗立群; 李金良; 黄红

    2014-01-01

    fine mud is easy to come into being while being process and deteriorate separation environments ,grinding fineness about 78 percent should be appropriate .It was successfully that high modulus of sodium silicate (modulus 3 .1) instead of sodium hexametaphosphate and sodium silicate (modulus 2 .7) strengthened dispersion of slurry ,degree of etherification of methyl-isobutyl-carbinol (M IBC ) enhanced depression of talc and high magnesium oxide minerals as well as synergistic effect was reinforced in addition to a part of new collector Y 89-2 and cancalled foaming agent BK-204 .Production stability ,economic and technical indicators ia good and economic benefitsof over twenty one million seven hundred twenty thousand yuan are gained after productive renovation .

  4. 半乳糖化白蛋白磁性阿霉素纳米粒在家兔体内的药物动力学研究%Pharmacokinetic analysis of galactosylated albumin magnetive Adriamycin nanoparticle(GAMAN) in home rabbits

    Institute of Scientific and Technical Information of China (English)

    张阳德; 王荣兵; 龚连生; 席浩; 刘勤

    2004-01-01

    目的对家兔一次性颈静脉给药,检测自制药物与普通阿霉素在药动力学方面有无差异及了解新药的药动学特点.方法家兔12只,随机分为两组,每组6只,均予颈静脉置管、注射、抽血,一组按3.0mg/kg给予阿霉素;一组按63.2 mg/kg给予半乳糖化白蛋白磁性阿霉素纳米粒,每次抽血1ml,分离血清低温保存,以氯仿-甲醇液萃取阿霉素,在高效液相色谱仪下检测色谱峰高.根据阿霉素标准曲线求血清中阿霉素浓度.以"3P87"进行药动学分析.结果阿霉素与半乳糖化白蛋白磁性阿霉素纳米粒在家兔体内的药动学规律符合三室开放模型;与阿霉素相比,实验组药物的消除相半衰期延长了1.9~3.2倍,清除率是阿霉素的0.5369倍;血药浓度-时间曲线下面积(AUC)是阿霉素的1.3697倍.结论阿霉素经过与白蛋白、磁性微粒结合,并以半乳糖修饰,改变了原药的体内分布特性,延长了药物半衰期,增加了靶器官肝脏的药物浓度.%Objective: Through one-off jugular vein injection on home rabbits with different two drugs, to check up whether the pharmacokinetic of galactosylated albumin magnetive Adriamycin naroparticle (GAMAN)was different to the Adriamycin, and to find out the pharmacokinetic characteristics of the GAMAN. Methods:The twelve home rabbits were divided into two groups in random six in each. Every rabbit was put a pipe in its jugular vein, then injected drugs and phlebotomized. One group was given Adriamycin 3 mg/kg to every rabbit, the other group was given GAMAN 63.2 mg/kg equivalent to Adfiamycin 3 mg/kg to every rabbit. Phlebotomized 1 ml each time, then separated serum and saved 0.3 ml at low temperature, extracted the Adriamycin with chloroform-carbinol, put it under the High Performance Liquid Chromatography (HPLC) to examine the special chromatogram peak value ratio. Finally, the concentration of the Adriamycin in serum was accounted according to the standard curve of

  5. Single-step substitution of all the α, β-positions in pyrrole: choice of binuclear versus multinuclear complex of the novel polydentate ligand.

    Science.gov (United States)

    Ghorai, Debasish; Mani, Ganesan

    2014-04-21

    The α and β-positions of pyrrole were substituted with 3,5-dimethylpyrazolylmethyl groups in a single step that involved the reaction between 2,5-dimethylaminomethylpyrrole and 3,5-dimethylpyrazole-1-carbinol, affording 2,3,4,5-tetrakis(3,5-dimethylpyrazol-1-ylmethyl)pyrrole LH in 40% yield. The coordination chemistry of this new polydentate ligand LH was explored by synthesizing several Pd(II), Cu(I), and Ag(I) complexes. When LH was used as a neutral ligand with [Pd(COD)Cl2], AgBF4, and CuX (X = Cl and I), compartmental type binuclear Pd(II) and Ag(I) complexes such as [Pd2Cl4(μ-C4HN-2,3,4,5-(CH2Me2pz)4-N,N,N,N)] and [Ag2(μ-C4HN-2,3,4,5-(CH2Me2pz)4-N,N,N,N)(CH3CN)2](2+)[BF4(-)]2 and cage-like copper(I) complexes [Cu2(μ-X)(μ-C4HN-2,3,4,5-(CH2Me2pz)4-N,N,N,N)](+)[CuX2](-) (X = Cl and I) containing a halide ion bridging in a bent fashion were obtained, respectively. Conversely, when the same metal precursors were treated with LH in the presence of n-BuLi, the multinuclear complexes [Pd2Cl3(μ-C4N-2,3,4,5-(CH2Me2pz)4-N,N,N,N,N)], [(Cu2(μ-I){μ-C4N-2,3,4,5-(CH2Me2pz)4-N,N,N,N,N})2Cu](+)I(-), and [Ag4(μ-C4N-2,3,4,5-(CH2Me2pz)4-N,N,N,N)2](2+)[BF4(-)]2 were obtained. In addition, the treatment of LH with [Pd(OAc)2] gave the mononuclear complex, [Pd(OAc)(C4N-2,3,4,5-(CH2Me2pz)4-N,N,N)]. The chloride analogue of this complex was obtained by the reaction of LH with [Pd(COD)Cl2] in the presence of triethylamine. The structures of all complexes were determined by single-crystal X-ray diffraction analyses, which revealed interesting structural features, including pyrazole arms adopting different conformations with respect to the pyrrole ring plane and linear two- and three-coordinated copper(I) and silver(I) atoms exhibiting weak interactions between the metal and the pyrrolic carbon atoms and Ag(I)···Ag(I) interactions. The observed shorter metal pyrrolide nitrogen (M-N) bond distances and the elongation of the C-C double and single bond distances of the pyrrole

  6. Simultaneous determination of 10 synthetic colorants in foods with high performance liquid chromatography%高效液相色谱法同时测定食品中10种合成着色剂

    Institute of Scientific and Technical Information of China (English)

    阮丽萍; 吉文亮; 刘华良; 李莉; 马永建

    2011-01-01

    Objective To establish a simple, sensitive and accurate method for the determination of ten kinds of synthetic colorant in food at the same time.Methods Synthetic colorants, including Tartrazine, New Red, Amaranth,Indigo Blue, Ponceau 4R, Sunset Yellow, Allura Red, Brillinat Blue, Quinoline Yellow and Erythrosine B in food samples were prepared with the procedures described in GB/T 5009.35 and were extracted by polyamide adsorption.Sample solutions were separated by reverse phase liquid chromatography with carbinol/acetonitrile ( 3 + 1 ) and acetic ammonium solution (0.02 mol/L, pH =4) mixture as mobile phase under gradient elution, and quantified by DAD (Photodiode Array Detector).Results The calibration curves showed a good linearity with correlation coefficients from 0.999 0 to 1.000 0.The linear range for the quantification of Tartrazine, Amaranth, Indigo Blue, Ponceau 4R and Sunset Yellow was 0.94-30.00 μg/ml, New Red was 0.94-30.00 μg/ml, Allura Red was 1.00-32.10 μg/ml, Brillinat Blue was 0.31-10.00 μg/ml, Quinoline Yellow was 1.21-9.68 μg/ml and Erythrosine was 0.76-24.40 μg/ml.The detection limit was from 0.03 to 0.9 mg/kg.The recovery of the method was from 87.5% to 101.4% , and the relative standard deviation (RSD)was from 1.3% to 5.7%.Conclusion The method is sensitive, simple and accurate, and can be used to quantify these synthetic colorant in foods at the same time.The method could meet the requirement for fast and accurate detection of synthetic colorants in food.%目的 建立一种高效液相色谱法同时测定食品中10种合成着色剂(柠檬黄、新红、觅菜红、靛蓝、胭脂红、日落黄、诱惑红、亮蓝、喹琳黄、赤藓红).方法 用GB/T 5009.35-2003(食品中人工合成着色剂的测定方法)中试样处理方法制备样品溶液,聚酰胺吸附法提取色素,以甲酵/乙睛(3+1)+乙酸铵(0.02 mol/L,pH =4.0)为流动相,梯度淋洗分离,多波长检测定量.结果 线性范围分别为柠檬黄